bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: A pilot study
Authors: IKEDA Takaharu , KANAZAWA Nobuo , FURUKAWA Fukumi
Published: December 2011

Hydroxychloroquine (HCQ) is used as the first‐line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment. Arthralgia improved in all three cases with arthralgia and general malaise also improved in two of the three cases who had complained. In three cases who discontinued HCQ therapy after 16 weeks of treatment, their skin lesions and general malaise worsened soon, and after the resumption of HCQ therapy these symptoms improved again. The mean serum triglyceride and total cholesterol levels also decreased significantly at the end of this study. Our results suggest that HCQ might be effective for Japanese SLE skin lesions and CLE, and support the studies which reported that HCQ prevented clinical flare ups of SLE. An additional effect to improve lipid profiles was also observed in our Japanese cases. It is necessary to confirm that these effects are reproducible when Japanese lupus erythematosus cases are given HCQ.
Multicellular tumor spheroid formation in duplex microcapsules for analysis of chemosensitivity
Authors: Sakai Shinji , Inamoto Kazuya , Liu Yang , Tanaka Shinji , Arii Shigeki , Taya Masahito
Published: December 2011

Multicellular tumor spheroids (MTS) are gaining increased recognition as valuable tools and key elements in anticancer drug discovery and tumor therapy test programs. However, the lack of reproducible and uniform MTS sizes is a major problem for pharmaceutical assays. Here, we show the usefulness of duplex microcapsules with a Ca‐alginate gel membrane as a platform for producing MTS with a highly homogeneous size distribution. HeLa cells were enclosed with 86.9% viability within the microcapsules. The enclosed cells grew and formed MTS with the same size as the cavity of the microcapsules by arresting their growth with the microcapsule membrane. The cells in the resultant MTS had a higher proportion in G0/G1 phase (71.2%) than 2‐D cultured cells in the stationary phase (64.3%) or those in MTS formed on a non‐adherent surface (65.3%) (P < 0.01). Furthermore, the cells in MTS formed within microcapsules showed higher tolerance to mitomycin C (1–1000 nM) and gemcitabine (4.5–4500 nM) than 2‐D cultured cells (P < 0.01). In addition, the expression of MDR1, MCT1, HIF‐1α, and GRP78 mRNA was 2.9‐, 3.2‐, 3.8‐, and 5.5‐fold higher, respectively, than those in 2‐D cultured cells (P < 0.04). Cryopreserved encapsulated cells in the microcapsules showed 80.5% viability and formed MTS with a comparable tolerance of 100 and 1000 nM mitomycin C to those that were not cryopreserved (P > 0.09). These findings suggest the duplex microcapsule may be a promising tool for producing MTS for pharmaceutical applications. (Cancer Sci 2012; 103: 549–554)
Does minimum pricing reduce alcohol consumption? The experience of a Canadian province
Authors: Stockwell Tim , Auld M. Christopher , Zhao Jinhui , Martin Gina
Published: December 2011

Aims Minimum alcohol prices in British Columbia have been adjusted intermittently over the past 20 years. The present study estimates impacts of these adjustments on alcohol consumption.

Design Time–series and longitudinal models of aggregate alcohol consumption with price and other economic data as independent variables.

Setting British Columbia (BC), Canada.

Participants The population of British Columbia, Canada, aged 15 years and over.

Measurements Data on alcohol prices and sales for different beverages were provided by the BC Liquor Distribution Branch for 1989–2010. Data on household income were sourced from Statistics Canada.

Findings  Longitudinal estimates suggest that a 10% increase in the minimum price of an alcoholic beverage reduced its consumption relative to other beverages by 16.1% (P < 0.001). Time–series estimates indicate that a 10% increase in minimum prices reduced consumption of spirits and liqueurs by 6.8% (P = 0.004), wine by 8.9% (P = 0.033), alcoholic sodas and ciders by 13.9% (P = 0.067), beer by 1.5% (P = 0.043) and all alcoholic drinks by 3.4% (P = 0.007).

Conclusions Increases in minimum prices of alcoholic beverages can substantially reduce alcohol consumption.
Downregulation of BCL2 by AT‐101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner
Authors: Masood Aisha , Chitta Kasyapa , Paulus Aneel , Khan A. Nazmul H. , Sher Taimur , Ersing Noreen , Miller Kena C. , Manfredi Deborah , Ailawadhi Sikander , Borrelo Ivan , Lee Kelvin P. , Chanan‐Khan Asher
Published: December 2011

Over‐expression of anti‐apoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti‐CLL effects of CD20 targeting monoclonal antibody, rituximab. Here, we investigated the mechanism of immune‐directed killing of lenalidomide in CLL and evaluated if concurrent targeting of CD20 and BCL2 can enhance this effect. In vitro treatment with lenalidomide enhanced the antibody‐mediated cellular cytotoxicity (ADCC) directed by rituximab in autologous leukaemic cells. Furthermore, peripheral blood mononuclear cells obtained from patients after treatment with lenalidomide and rituximab showed increased ADCC in vitro versus control (pre‐treatment sample). This effect was further enhanced with pre‐treatment of tumour cells with AT‐101 (a BH3 mimetic that functions as BCL2 antagonist). Our data suggest that AT‐101 in combination with lenalidomide can potentially be an effective therapeutic regimen for CLL.
Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis patients?
Authors: Jamshidian A , Gharagozloo M
Published: December 2011

Plasma exchange is used increasingly as an individual therapeutic decision for treating of severe, steroid-resistant relapses of multiple sclerosis (MS). However, given that its mechanism of action in this CD4+ T cell-mediated autoimmune disease remains unknown, it is not yet considered as a routine therapy for this prevalent neuroimmune disorder. In this regard, we hypothesized that plasma exchange, by depleting the body of inflammatory mediators that acts as providers of co-stimulatory signals for the adaptive immune system, provides the immune system with an exceptional break for de-novo recognition of autoantigens in a tolerogenic manner. This may lead to an increase in the frequency and function of myelin-specific regulatory T cells. For evaluating this we suggest some in vitro and in vivo studies to analyse the effects of varied dilutions of normal and MS plasmas on the induction of regulatory T cells or on the function of isolated and purified regulatory T cells. Clarifying the effects of therapeutic plasma exchange on regulatory T cells as the major controllers of autoimmune responses may provide us with strong evidence to use this procedure as a disease-modifying treatment in remission phase for reducing the rate and severity of future attacks, in addition to more trustworthy therapy in severe relapses of MS.
Hyperthyrotropinemia at 2 weeks of age indicates thyroid dysfunction and predicts the occurrence of delayed elevation of thyrotropin in very low birth weight infants
Authors: Niwa Fusako , Kawai Masahiko , Kanazawa Hoshinori , Iwanaga Kougorou , Matsukura Takashi , Hasegawa Takeshi , Heike Toshio
Published: December 2011

Background  For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important.

Methods  To address the above two issues, we performed thyrotropin‐releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less.

Results  For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10–15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10–15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later.

Conclusions  Thyrotropin‐releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic–pituitary–thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation.
Evolution of the research collaboration network in a productive department
Authors: Katerndahl David
Published: December 2011

Rationale  Understanding collaboration networks can facilitate the research growth of new or developing departments. The purpose of this study was to use social network analysis to understand how the research collaboration network evolved within a productive department.

Methods  Over a 13‐year period, a departmental faculty completed an annual survey describing their research collaborations. Data were analyzed using social network analysis. Network measures focused on connectedness, distance, groupings and heterogeneity of distribution, while measures for the research director and external collaboration focused on centrality and roles within the network. Longitudinal patterns of network collaboration were assessed using Simulation Investigation for Empirical Network Analysis software (University of Groningen, Groningen, Netherlands).

Results  Based upon the number of active research projects, research development can be divided into three phases. The initial development phase was characterized by increasing centralization and collaboration focused within a single subject area. During the maintenance phase, measures went through cycles, possibly because of changes in faculty composition. While the research director was not a ‘key player’ within the network during the first several years, external collaboration played a central role during all phases. Longitudinal analysis found that forming ties was more likely when the opportunity for network closure existed and when those around you are principal investigators (PIs).

Conclusion  Initial development of research relied heavily upon a centralized network involving external collaboration; a central position of the research director during research development was not important. Changes in collaboration depended upon faculty gender and tenure track as well as transitivity and the ‘popularity of PIs’.
The potential for targeted surveillance of live fish movements in Scotland
Authors: Green D M , Werkman M , Munro L A
Published: December 2011

The network structure of the movements of live fish in the Scottish aquaculture industry has recently been demonstrated for 2003. In this paper, we enlarge this analysis to a longer 3‐year period from 2002 to 2004, the new data allowing complete coverage of at least one production cycle. The resulting network contains slightly more sites than that for a single year and is denser with more arcs (directed site‐to‐site connections) present, but otherwise features recognizable in the 1‐year network are still recognizable in the 3‐year network. Arc‐removal algorithms (a proxy for targeted surveillance) were identified that could successfully reduce the portion of the network reachable from a node (a proxy for potential epidemic size) by approximately one‐third by removing as few as four arcs. This results from the high centrality of particular nodes and arcs. A strong community structure was identified in the network, corresponding with species farmed, but only weakly geographical, with a high proportion of arcs occurring between management areas and catchments.
Studies on the effect of temperature and pH on the inactivation of fish viral and bacterial pathogens
Authors: Dixon P F , Smail D A , Algoët M , Hastings T S , Bayley A , Byrne H , Dodge M , Garden A , Joiner C , Roberts E , Verner‐Jeffreys D , Thompson F
Published: December 2011

Disposal of fish by‐products in the European Community must comply with Regulation (EC) No 1069/2009 which categorizes animal by‐products according to risk, and specifies methods of disposal of by‐products according to that risk. There is provision under the regulation for composting or ensiling to be used for by‐products from aquatic animals. Biosecurity considerations require knowledge of the parameters of time and temperature, or time and pH, required to inactivate any fish pathogens that may be present. To provide those data, we undertook laboratory studies on the inactivation of a number of fish pathogenic viruses and bacteria at 60 °C, pH 4.0 and pH 12.0 as a preliminary to conducting subsequent trials with the most resistant viruses and bacteria in fish tissues. The most resistant bacterium to 60 °C, pH 4.0 as well as pH 12.0 was Lactococcus garvieae. Its concentration was reduced to the level of sensitivity of the test after 24–48 h exposure to 60 °C, but it survived for at least 7 days at pH 4.0 and 14 days at pH 12.0. The most resistant virus to 60 °C was infectious pancreatic necrosis virus, and to pH 12.0 was infectious salmon anaemia virus. The majority of the viruses tested survived exposure to pH 4.0 for up to 28 days. The results suggest that the process of acid ensiling alone is not an effective method for the inactivation of many viral and bacterial pathogens, and fish by‐products would need further treatment by a method approved under the regulation following ensiling, whereas alkaline or heat treatment are likely to provide an increased degree of biosecurity for on‐farm processing of mortalities.
Effect of aging on the morphology of bitumen by atomic force microscopy
Authors: ZHANG H.L. , YU J.Y. , FENG Z.G. , XUE L.H. , WU S.P.
Published: December 2011

Effect of aging on the morphology of bitumen was investigated. Two bitumens were aged according to the thin film oven test (TFOT), pressure aging vessel (PAV) test and ultraviolet (UV) radiation, respectively. The morphology of the binders before and after aging was characterized by atomic force microscopy. The physical properties and chemical compositions of the binders were also measured. The results showed that aging affected the bitumen morphology significantly. Aging increased the overall surface stiffness of the bitumen and made the bitumen surface more solid‐like. The extent of these changes was dependent on aging conditions. TFOT decreased the contrast between the dispersed domains and the matrix, which contributed to the single‐phase trend of the binders. The effect of PAV aging on morphology of the binders was dependent on the base bitumen. In one case, it further accelerated the single‐phase trend of bitumen in comparison with that after TFOT. In the other case, it caused the phase separation of bitumen. In both cases, PAV aging increased the surface roughness of the binders obviously. As a result of UV aging, the contrast between the matrix phase and dispersed phase was increased due to the difference in sensitivity to UV radiation of the bitumen molecules, which caused or further promoted the phase separation in the binders. Regardless of the aging procedure carried out, a strong correlation was observed between the changes in morphology and physical properties as well as chemical compositions of the binders before and after aging.
Quantification of plant cell coupling with three‐dimensional photoactivation microscopy
Authors: LIESCHE J. , SCHULZ A.
Published: December 2011

Plant cells are directly connected by plasmodesmata that form channels through the cell wall and enable the intercellular movement of cytosolic solutes, membrane lipids and signalling molecules. Transport through plasmodesmata is regulated not only by a fixed size‐exclusion limit, but also by physiological and pathological adaptation. To understand plant cell communication, carbon allocation and pathogen attack, the capacities for a specific molecule to pass a specific cell–wall interface is an essential parameter. So far, the degree of cell coupling was derived from frequency and diameter of plasmodesmata in relevant tissues as assessed by electron microscopy of fixed material. However, plasmodesmata functionality and capacity can only be determined in live material, not from electron microscopy, which is static and prone to fixation artefacts. Plasmodesmata functionality was a few times assessed using fluorescent tracers with diffusion properties similar to cytosolic solutes. Here, we used three‐dimensional photoactivation microscopy to quantify plasmodesmata‐mediated cell–wall permeability between living Cucurbita maxima leaf mesophyll cells with caged fluorescein as tracer. For the first time, all necessary functional and anatomical data were gathered for each individual cell from three‐dimensional time series. This approach utilized a confocal microscope equipped with resonant scanner, which provides the high acquisition speed necessary to record optical sections of whole cells and offers time resolution high enough to follow the kinetics of photoactivation. The results were compared to two‐dimensional measurements, which are shown to give a good estimate of cell coupling adequate for homogenous tissues. The two‐dimensional approach is limited whenever tissues interfaces are studied that couple different cell types with diverse cell geometries.
The Role of GABAergic Signalling in Stress‐Induced Suppression of Gonadotrophin‐Releasing Hormone Pulse Generator Frequency in Female Rats
Authors: Lin Y. S. , Li X. F. , Shao B. , Hu M. H. , Goundry A. L. R. , Jeyaram A. , Lightman S. L. , O’Byrne K. T.
Published: December 2011

Stress exerts profound inhibitory effects on reproductive function by suppressing the pulsatile release of gonadotrophin‐releasing hormone (GnRH) and therefore luteinising hormone (LH). This effect is mediated in part via the corticotrophin‐releasing factor (CRF) system, although another potential mechanism is via GABAergic signalling within the medial preoptic area (mPOA) because this has known inhibitory influences on the GnRH pulse generator and shows increased activity during stress. In the present study, we investigated the role of the preoptic endogenous GABAergic system in stress‐induced suppression of the GnRH pulse generator. Ovariectomised oestradiol‐replaced rats were implanted with bilateral and unilateral cannulae targeting toward the mPOA and lateral cerebral ventricle, respectively; blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for the measurement of LH pulses. Intra‐mPOA administration of the specific GABAA receptor antagonist, bicuculline (0.2 pmol each side, three times at 20‐min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS; 25 μg/kg i.v.) but not restraint (1 h) stress on pulsatile LH secretion. By contrast, restraint but not LPS stress‐induced suppression of LH pulse frequency was reversed by application of the selective GABAB receptor antagonist, CGP‐35348, into the mPOA (1.5 nmol each side, three times at 20‐min intervals). However, intra‐mPOA application of either bicuculline or CGP‐35348 attenuated the inhibitory effect of CRF (1 nmol i.c.v.) on the pulsatile LH secretion. These data indicate a pivotal and differential role of endogenous GABAergic signalling in the mPOA with respect to mediating psychological and immunological stress‐induced suppression of the GnRH pulse generator.
Who is eating what: diet assessment using next generation sequencing
Authors: POMPANON FRANCOIS , DEAGLE BRUCE E. , SYMONDSON WILLIAM O. C. , BROWN DAVID S. , JARMAN SIMON N. , TABERLET PIERRE
Published: December 2011

The analysis of food webs and their dynamics facilitates understanding of the mechanistic processes behind community ecology and ecosystem functions. Having accurate techniques for determining dietary ranges and components is critical for this endeavour. While visual analyses and early molecular approaches are highly labour intensive and often lack resolution, recent DNA‐based approaches potentially provide more accurate methods for dietary studies. A suite of approaches have been used based on the identification of consumed species by characterization of DNA present in gut or faecal samples. In one approach, a standardized DNA region (DNA barcode) is PCR amplified, amplicons are sequenced and then compared to a reference database for identification. Initially, this involved sequencing clones from PCR products, and studies were limited in scale because of the costs and effort required. The recent development of next generation sequencing (NGS) has made this approach much more powerful, by allowing the direct characterization of dozens of samples with several thousand sequences per PCR product, and has the potential to reveal many consumed species simultaneously (DNA metabarcoding). Continual improvement of NGS technologies, on‐going decreases in costs and current massive expansion of reference databases make this approach promising. Here we review the power and pitfalls of NGS diet methods. We present the critical factors to take into account when choosing or designing a suitable barcode. Then, we consider both technical and analytical aspects of NGS diet studies. Finally, we discuss the validation of data accuracy including the viability of producing quantitative data.
Identification of a protein kinase A regulatory subunit from Leishmania having importance in metacyclogenesis through induction of autophagy
Authors: Bhattacharya Arijit , Biswas Arunima , Das Pijush K.
Published: December 2011

cAMP‐mediated responses act as modulators of environmental sensing and cellular differentiation of many kinetoplastidae parasites including Leishmania. Although cAMP synthesizing (adenylate cyclase) and degrading (phosphodiesterase) enzymes have been cloned and characterized from Leishmania, no cAMP‐binding effector molecule has yet been identified from this parasite. In this study, a regulatory subunit of cAMP‐dependent protein kinase (Ldpkar1), homologous to mammalian class I cAMP‐dependent protein kinase regulatory subunit, has been identified from L. donovani. Further characterization suggested possible interaction of LdPKAR1 with PKA catalytic subunits and inhibition of PKA activity. This PKA regulatory subunit is expressed in all life cycle stages and its expression attained maximum level in stationary phase promastigotes, which are biochemically similar to the infective metacyclic promastigotes. Starvation condition, the trigger for metacyclogenesis in the parasite, elevates LdPKAR1 expression and under starvation condition promastigotes overexpressing Ldpkar1 attained metacyclic features earlier than normal cells. Furthermore, Ldpkar1 overexpression accelerates autophagy, a starvation‐induced cytological event necessary for metacyclogenesis and amastigote formation. Conditional silencing of Ldpkar1 delays the induction of autophagy in the parasite. The study, for the first time, reports the identification of a functional cAMP‐binding effector molecule from Leishmania that may modulate important cytological events affecting metacyclogenesis.
Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects
Authors: Loke J , Ostrer H
Published: December 2011

Loke J, Ostrer H. Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects.

DNA sequencing of candidate genes or whole exomes on a diagnostic or investigational basis will yield a plethora of variants of uncertain significance whose potential phenotypic roles cannot be readily demonstrated by prediction programs, SNP databases nor conventional genetic analysis. Many variants may produce phenotypic changes in the encoded proteins by affecting the quantity, post‐translational modification or protein interactions. Here, we establish the application of the method of flow cytometry following immunoprecipitation to show that known protein interactions are altered in the B‐lymphoblastoid cells of patients with 46,XY gonadal dysgenesis arising from mutations in the MAP3K1 gene. This method can be scaled readily to test multiple interactions for many variants simultaneously from available tissues as well as quantify the effects of variants on protein accumulation and post‐translational modification, thus providing an efficient means for screening variants of uncertain significance for phenotypic effects.
Islet isolation from adult designated pathogen‐free pigs: use of the newer bovine nervous tissue–free enzymes and a revised donor selection strategy would improve the islet graft function
Authors: Jin Sang‐Man , Shin Jun Seop , Kim Kang Seok , Gong Chang‐Hoon , Park Su Kyoung , Kim Jung‐Sik , Yeom Su‐Cheong , Hwang Eung Soo , Lee Choon Taek , Kim Sang‐Joon , Park Chung‐Gyu
Published: December 2011

Jin S‐M, Shin JS, Kim KS, Gong C‐H, Park SK, Kim J‐S, Yeom S‐C, Hwang ES, Lee CT, Kim S‐J, Park C‐G. Islet isolation from adult designated pathogen‐free pigs: use of the newer bovine nervous tissue–free enzymes and a revised donor selection strategy would improve the islet graft function. Xenotransplantation 2011; 18: 369–379. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  In clinical trials using adult porcine islet products, islets should be isolated from the designated pathogen‐free (DPF) pigs under the current good manufacturing practice (GMP) regulations. Our previous studies suggested that male DPF pigs are better donors than retired breeder pigs and histomorphometrical parameters of donor pancreas predict the porcine islet quality. We aimed to investigate whether the use of the newer bovine nervous tissue–free enzymes and a revised donor selection strategy could improve the islet graft function in the context of islet isolation with DPF pigs.

Methods:  Using 30 DPF pigs within a closed herd, we compared the islet yield of porcine islets isolated with Liberase PI (n = 11, as a historical control group), Liberase MTF C/T, which is a GMP‐grade enzyme (n = 12), and CIzyme collagenase MA/BP protease (n = 7). We analyzed the relationship between the diabetes reversal rate of recipient NOD/SCID mice (n = 75) and histomorphometric parameters of each donor pancreas as well as donor characteristics.

Results:  Proportion of islets larger than 200 μm from the biopsied donor pancreas (P = 0.006) better predicted islet yield than age (P = 0.760) or body weight (P = 0.371) of donor. The proportion of islets larger than 200 μm from the biopsied donor pancreas was not related to the sex of the donor miniature pig (P = 0.358). The islet yield obtained with the three enzymes did not differ, even after stratification of the donor with the histomorphometric parameters of the biopsied donor pancreas and the sex of donor. The use of the newer bovine nervous tissue–free enzymes (P < 0.001), a higher proportion of large islets in donor pancreas (P = 0.006), and a male sex of the donor (P = 0.025) were independent predictors of earlier diabetes reversal.

Conclusions:  Use of the newer bovine nervous tissue–free enzymes including a GMP‐grade enzyme resulted in better islet quality than that of islet isolated using Liberase PI. To obtain high‐quality islet from DPF pigs, the donor should be male pig and histomorphometrical parameters from donor pancreas should be considered.
Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes
Authors: Hawthorne Wayne J. , Simond Denbigh M. , Stokes Rebecca , Patel Anita T. , Walters Stacey , Burgess Jane , O’Connell Philip J.
Published: December 2011

Hawthorne WJ, Simond DM, Stokes R, Patel AT, Walters S, Burgess J, O’Connell PJ. Pre‐clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 2011; 18: 390–399. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  Development of a limitless source of β cells for xenotransplantation into patients suffering type 1 diabetes and renal failure that can control their diabetes and provide normal renal function in one procedure would be a major achievement. For the islet tissue to survive transplantation, as an islet‐kidney composite graft this would have significant advantages. It would simplify the surgical procedure; remove the complications caused by the exocrine pancreas whilst reversing diabetes and uraemia. It was our hypothesis that a composite foetal porcine pancreas fragment (FPPF)/renal graft could achieve these objectives in a large pre‐clinical animal model as a means to establish whether this would be feasible before moving to the clinic.

Methods:  Inbred ‘Westran’ pig FPPF were transplanted under the kidney capsule of syngeneic Westran pig recipients without immunosuppression. Following maturation of the FPPF under the renal subcapsular space of this recipient, this kidney bearing the composite FPPF piggyback graft was removed and transplanted into another nephrectomized and pancreatectomized recipient to demonstrate function.

Results:  Under the kidney capsule of the first transplant group (n = 6), the FPPF‐transplanted tissue developed and matured to form islet cell nests. These composite FPPF/renal grafts were then successfully removed and transplanted into the second functional assessment recipient group. This second group of six composite FPPF/renal‐grafted pigs had normal renal function for more than 44 days and normal glucose homoeostasis without exogenous insulin as assessed by normal glucose tolerance tests, K values and normal glucagon secretion. Histological analysis showed despite the ischaemic insult during the composite kidney transplant procedure, there was appropriate development of islet‐like structures up to and beyond 224 days after the original transplantation under the kidney capsule.

Conclusions:  This study shows that the use of composite FPPF/renal grafts can cure both diabetes and renal failure with a single‐transplant procedure. Using such composite grafts for xenotransplantation would simplify the surgical procedure and protect the islet graft from the immediate innate immune response.
Xenotransplantation literature update, July–October 2011
Authors: Schneider Mårten K. J. , Seebach Jörg D.
Published: December 2011

Schneider MKJ, Seebach JD. Xenotransplantation literature update, July–October 2011. Xenotransplantation 2011; 18: 400–404. © 2011 John Wiley & Sons A/S.
The Evolution of Large Testes: Sperm Competition or Male Mating Rate?
Authors: Vahed Karim , Parker Darren J.
Published: December 2011

A positive relationship across species between the extent to which females mate with more than one male and relative testes mass has been demonstrated in a wide range of vertebrate taxa and certain insects. At least two hypotheses, which are not necessarily mutually exclusive, could account for this pattern: (1) the numerical sperm competition hypothesis, which assumes that larger testes enable the male to transfer more sperm to each female, giving the male an advantage in sperm competition and (2) the male mating rate hypothesis, which proposes that larger testes allow the male to produce a greater number of (potentially smaller) ejaculates to engage in frequent copulations with different females. Of these hypotheses, the former has won broad acceptance, while the latter has tended to be dismissed. Here, we argue that the lines of evidence commonly used to support the numerical sperm competition hypothesis in favour of the male mating rate hypothesis are not as clear cut or generally applicable as they are purported to be and that, consequently, the male mating rate hypothesis cannot be excluded with confidence on the basis of the current evidence. Furthermore, some evidence, such as the finding that ejaculate mass and/or sperm number is negatively correlated with testes mass across species in some insects and that larger testes in Drosophila can evolve in response to an increase in the number of females available for mating in the laboratory, provides support for the male mating rate hypothesis. Further work is needed to disentangle the relative effects of these selective pressures on the evolution of testes size.
Aggressive Signal Design in the Jacky Dragon (Amphibolurus muricatus): Display Duration Affects Efficiency
Authors: Woo Kevin L. , Rieucau Guillaume
Published: December 2011

Design characteristics of signals, such as their duration, may have evolved to maximize signal efficiency. It is commonly assumed that constraints on signal design have usually shaped the most optimal display characteristics to improve signal transmission and information transfer of the signaller, and detection by intended receivers. In this study, we tested whether the characteristics (duration, speed and frequency) of an aggressive display, the push‐up body rock, exhibited by the Jacky dragon (Amphibolurus muricatus) have likely evolved for optimal signal efficiency, as it is able to draw attention to the signaller. We performed two video playback experiments using high‐resolution 3D animations testing the effect of variation in push‐up body rock structure. In experiment 1, we manipulated push‐up body rock display structure. We gradually increased the number of push‐ups exhibited by a digitally animated Jacky dragon increasing the overall display duration. In experiment 2, we developed four stimuli based on population‐typical push‐up body rock display for duration (short and long), and frequency of push‐ups (1 or 5 consecutive push‐ups) by manipulating push‐ups’ speed. In both experiments, we measured the probability of an orienting response and response latency of focal lizards when being exposed to the different stimuli. Our results showed that display duration is critically important for signal efficiency in the aggressive push‐up body rock display. If we are to understand the design characteristics of signals used in animal communication, then it appears important to consider the possible trade‐off between signal efficiency and costs.
Mallards Feed Longer to Maintain Intake Rate under Competition on a Natural Food Distribution
Authors: van Dijk Jacintha G. B. , Duijns Sjoerd , Gyimesi Abel , de Boer Willem F. , Nolet Bart A.
Published: December 2011

Animals foraging in groups may benefit from a faster detection of food and predators, but competition by conspecifics may reduce intake rate. Competition may also alter the foraging behaviour of individuals, which can be influenced by dominance status and the way food is distributed over the environment. Many studies measuring the effects of competition and dominance status have been conducted on a uniform or highly clumped food distribution, while in reality prey distributions are often in‐between these two extremes. The few studies that used a more natural food distribution only detected subtle effects of interference and dominance. We therefore conducted an experiment on a natural food distribution with focal mallards Anas platyrhynchos foraging alone and in a group of three, having a dominant, intermediate or subordinate dominance status. In this way, the foraging behaviour of the same individual in different treatments could be compared, and the effect of dominance was tested independently of individual identity. The experiment was balanced using a 4 × 4 Latin square design, with four focal and six non‐focal birds. Individuals in a group achieved a similar intake rate (i.e. number of consumed seeds divided by trial length) as when foraging alone, because of an increase in the proportion of time feeding (albeit not significant for subordinate birds). Patch residence time and the number of different patches visited did not differ when birds were foraging alone or in a group. Besides some agonistic interactions, no differences in foraging behaviour between dominant, intermediate and subordinate birds were measured in group trials. Possibly group‐foraging birds increased their feeding time because there was less need for vigilance or because they increased foraging intensity to compensate for competition. This study underlines that a higher competitor density does not necessarily lead to a lower intake rate, irrespective of dominance status.
Movements and Conflicts in a Flock of Foraging Black‐Tailed Godwits (Limosa limosa): The Influence of Feeding Rates on Behavioural Decisions
Authors: Sirot Etienne , Maes Philippe , Gélinaud Guillaume
Published: December 2011

We studied movements and conflicts within a small flock of free‐living black‐tailed godwits foraging on benthic invertebrates in a brackish lagoon. To interpret our results in the framework of foraging theory, we studied the influence of individual feeding rate on the decisions to move and to attack flock companions. Birds changed their position within the flock more often when their intake rate was low and sometimes attacked conspecifics to supplant them from their feeding place. Aggressors significantly avoided front attacks and were almost always successful. They attacked individuals having higher feeding rates than themselves and their own feeding rate significantly increased after the attack, although victims were not chased off to particularly poor sites. Our results suggest that aggressors could obtain reliable information about the quality of the foraging site they coveted by observing their victim’s feeding activity before attacking. Although aggression seemed to be caused by a low intake rate, we show that displacing another bird was more time‐consuming than independent foraging. We conclude that it was not the most profitable behaviour in terms of energy intake. Foraging site displacement probably also had social functions, such as reinforcement of social status in a flock of birds preparing for pre‐breeding migration.
Shelter Availability, Occupancy, and Residency in Size‐Asymmetric Contests Between Rusty Crayfish,Orconectes rusticus
Authors: Klar Nathan M. , Crowley Philip H.
Published: December 2011

Contest outcomes are usually determined by differences in resource‐holding potential, the social histories of the combatants, and perceptions of resource value. One aspect of gaining an advantage is the residency effect. Prior occupancy of a particular place can affect the knowledge and motivation of the resident. There could be a tactical advantage in knowing the terrain or an increased willingness to fight to maintain control of a familiar area. In this study, we evaluated the importance of shelter residency effects relative to size differences between rusty crayfish (Orconectes rusticus) as potential competitors for access to shelter. The intensity of any residency effects was manipulated by altering the number of shelters in the arena. Our results suggest that any residency effect is very weak in this system, and if present, may often be masked by the strong and pervasive influence on contest outcome of the relative body sizes of the contestants. We also found that both shelter number and crayfish size asymmetries had strong, independent effects on levels of aggression. Dominance, but not residency status, was a factor in shelter use.
Isotopic Data Do Not Support Food Sharing Within Large Networks of Female Vampire Bats (Desmodus rotundus)
Authors: Voigt Christian C. , Voigt‐Heucke Silke L. , Schneeberger Karin
Published: December 2011

Reciprocal altruism is considered to be particularly stable when occurring in small networks. Using a stable isotope approach, we tested in colonies of vampire bats (Desmodus rotundus) whether food sharing occurs among few or many females; vampires are known to regurgitate recently ingested blood for starving conspecifics. Accordingly, the isotopic signatures of vampires depend not only on individual prey choice but also on the extent of food sharing among isotopically contrasting conspecifics. By measuring the stable carbon isotope ratio in tissues with varying isotopic retention in individual vampires (blood: approx. 2 wk; wing membrane tissue: approx. 2 mo; fur: >6 mo), we estimated the variation in the percentages of carbon derived from pasture (via blood from cattle and horses). We expected to find narrow ranges of percentages in individual vampires, because we anticipated food sharing only within small female networks if food sharing happened at all. Overall, vampire bats obtained 79.2 ± 12.3% of carbon from grazers. The range of percentages was small within the majority of individuals in relation to that across all individuals, suggesting that most vampires were isotopic specialists. We expected females to be more isotopically generalistic than males, as food sharing was observed to occur more often between females than between males. Indeed, stable isotope evidence suggested that more females obtained carbon from isotopically contrasting sources than males. This pattern is consistent with food sharing in small groups of female vampires, provided that food sharing occurred at all.
Efficacy and tolerability of pegylated interferon‐α‐2a in chronic hepatitis B: A multicenter clinical experience
Authors: Ratnam Dilip , Dev Anouk , Nguyen Tin , Sundararajan Vijaya , Harley Hugh , Cheng Wendy , Lee Alice , Rusli Ferry , Chen Robert , Bell Sally , Pianko Stephen , Sievert William
Published: December 2011

Background and Aim:  Pegylated interferon‐α (PEG‐IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non‐controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG‐IFN‐α2A in CHB patients in a clinical setting.

Methods:  Chronic hepatitis B patients treated with PEG‐IFN‐α2A (180 µg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on‐treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA < 351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion.

Results:  Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post‐treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50–75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs.

Conclusion:  In everyday clinical practice PEG‐IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.
Body mass index distribution affects discrepancies in weight classifications in children
Authors: Tuan Nguyen T , Butte Nancy F , Nicklas Theresa A
Published: December 2011

Background:  The aim of the present study was to investigate the effect of body mass index (BMI) distribution, ethnicity and age at menarche on the consistency in the prevalence of underweight and overweight defined by the Centers for Disease Control and Prevention (CDC) and the International Obesity Task Force (IOTF) cut‐off points in 2–17‐year‐old Chinese and US children.

Methods:  Data from the China Health and Nutrition Survey (CHNS) 1991 (n= 3895), CHNS 2004 (n= 1902), and the National Health and Nutrition Examination Survey (NHANES) 2003–2004 (n= 3344) were used to define the prevalence of underweight and overweight using the CDC and IOTF BMI cut‐off points.

Results:  An upward shift in the BMI distribution was observed from the CHNS 1991 to CHNS 2004, and between the CHNS and NHANES 2004. The prevalence of underweight defined by the IOTF cut‐off points was higher than that obtained using the CDC cut‐off points; absolute differences between IOTF and CDC classifiers were 7%, 5%, and 2% in boys, and 12%, 11%, and 4% in girls in the CHNS 1991, CHNS 2004, and NHANES 2004, respectively. There was a greater consistency in the prevalence of overweight. The consistency of the two classification systems increased with the higher BMI distribution and was not affected significantly by ethnicity or age at menarche.

Conclusions:  The BMI distribution of a population can affect the classification of childhood underweight and overweight differentially as defined by the CDC and IOTF cut‐off points, and thus should be considered in the interpretation of results in clinical and population settings.
New technique with combination of felt, Hem‐o‐lok and Lapra‐Ty for suturing the renal parenchyma in laparoscopic partial nephrectomy
Authors: Masumori Naoya , Itoh Naoki , Takahashi Satoshi , Kitamura Hiroshi , Nishida Sachiyo , Tsukamoto Taiji
Published: December 2011

We reported a new technique for closure of the renal parenchyma in laparoscopic partial nephrectomy, shortening the suturing time. Between 2009 and 2011, 41 patients with renal masses 4 cm or smaller in diameter underwent transabdominal laparoscopic partial nephrectomy by a single surgeon in a single institution. The sutures were carried out using 2‐0 vicryl CT‐1 with a 1.2 × 1.2 cm piece of felt, and both sutures were temporarily held using a Hem‐o‐lok. After all sutures (median 3) were completed, they were sequentially fixed by sliding the Hem‐o‐lok, and then locked using the Lapra‐Ty. The median times for suturing the renal parenchyma and ischemic time were 13 min and 28 min, respectively. The arrangement of the wound and hemostasis were good. No patients developed urinoma or postoperative bleeding.
Fracture mechanics of surface fatigue crack growth by ductile striation space measurement in notched Waspaloy
Authors: SUH CHANG‐MIN , SUH MIN‐SOO , KIM SEON‐GAB
Published: December 2011

Ductile striation space (DSS), a parameter to predict actual cracks in both direction of length and depth, is proposed for the surface fatigue crack behaviors on notched Waspaloy. Three different lengths (1, 2 and 4 mm) of artificial notches are formed as the initial surface crack for an applied maximum stress of 1,103 MPa at the stress ratio R of 0.05. These notches are similar with the appearance of the surface cracks found from the survey of compressor disk. The results show that, all initial crack sites in the depth direction started from the multiple origination sites. The DSS parameter was clearly confirmed, and it also proves the high effectiveness of the measurement in the range of the stress intensity factors for acquiring the crack growth rate on the fractured surface. The surface cracks on Waspaloy at room temperature in an atmosphere perfectly follow the relation of ΔK versus da/dN and db/dN, even though there are, respectively, earlier and later timing differences on the initiation of cracks for the notch sizes of 1 and 4 mm. The results of ΔK versus da/dN and db/dN relations show a similar slope for three different kinds of notches.