bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact recovery from early ‘acquired methylmalonic aciduria’ secondary to maternal atrophic gastritis
Authors: Weber‐Ferro Wencke , Hertzberg Christoph , Röder Helmut , Timme Katharina , Rossi Rainer
Published: February 2011

Aim:  A 6‐month‐old infant with severe hyporegenerative anaemia, muscular hypotonia and developmental delay is reported, and the metabolic, diagnostic and therapeutic implications of this case are discussed.

Results:  Diagnostic work‐up disclosed vitamin B12 depletion with an elevated excretion of methylmalonic acid (MMA), but a normal plasma total homocysteine. MRI showed fronto‐temporal atrophy and a delay in myelinization. The boy’s disease was attributable to a maternal atrophic gastritis. After initiation of vitamin B12 supplementation, he quickly recovered regarding haematopoiesis and MMA excretion. His neurological development completely normalized during 18 months of follow‐up including assessment by Bayley scores.

Conclusion:  As the majority of reported patients with this acquired form of methylmalonic aciduria show a persistent neurological deficit, early diagnosis of this condition is mandatory and should include sensitive markers of vitamin B12 depletion, namely MMA formation and plasma homocysteine.
Outcome in a paediatric cohort receiving ART in Addis Abeba, Ethiopia
Authors: Asfawesen GY , Solomie J , Bisirat T , Berhanu GM , Mebratu B , Rahlenbeck S
Published: February 2011

Aim:  To evaluate pediatric AntiRetroviral Treatment (ART) treatment in a resource‐limited setting.

Methods:  Data from a paediatric ART cohort at the All African Leprosy and Rehabilitation Centre, Addis Abeba, were analysed. Outcome measures included survival, age, gender, WHO stage, weight, regimen and CD4 cell count.

Results:  From April 2005 to December 2008, 482 children initiated ART. Median age was 5.9 years (IQR 3.7–9.8), and median CD4 cell count was 236 cells per mm3. Median follow‐up was 16 months (IQR = 6–24 month). Among those followed for 24 months (n = 188), 160 children were still receiving treatment, six had dropped out, eight had been transferred out, and 13 (7.5%) had died (4.0 deaths per 100 person‐years). Mortality was highest in the first 6 months resulting in a 4.3% mortality rate. Lower age and immune suppression (low CD4) were associated with mortality, while sex, drug regimen, tuberculosis at treatment initiation, application of stavudine and/or zidovudine were not.

Conclusion:  ART treatment of children in resource‐limited settings is possible as demonstrated by low attrition. The high proportion of malnourished children and children admitted at late stage of the disease calls for attention. Efforts to enrol more children and at an earlier stage of the disease should be promoted.
Comparison of Efficacy of an In‐Office Whitening System Used with and without a Whitening Priming Agent
Authors: DA COSTA JULIANA , LUBISICH ERINNE , FERRACANE JACK , HILTON THOMAS
Published: February 2011

Purpose:  The purpose of this study was to compare the whitening efficacy of an in‐office whitening system with and without the whitening primer application and evaluate tooth and soft tissue sensitivity.

Materials and Methods:  This was a randomized, split‐mouth design, single‐blinded, clinical study. Twenty‐five patients received a whitening priming agent (Power Swabs, Power Swabs Corporation, Beaverton, OR, USA) on right or left maxillary incisors prior to in‐office tooth whitening with Opalescence Boost (38% hydrogen peroxide; Ultradent Products, Inc., South Jordan, UT, USA). Color was evaluated with the Bleachedguide 3D Master (Vita Zahnfabrik, Bad Sackingen, Germany) and Vita Easyshade spectrophotometer (Vident, Brea, CA, USA), after 30 minutes, 1 day, and 15 days postwhitening. After each tooth color measurement, the subjects were asked to rate their tooth and soft tissue sensitivity experience using a visual analog scale (1–10 categories). Results were analyzed by two‐way repeated measurements analysis of variance/Tukey's (p < 0.05); Mann–Whitney rank sum test and Kruskal–Wallis.

Results:  The teeth that were treated with the primer prior to tooth whitening did not show significant difference in ΔL*, Δa*, Δb*, ΔE* and delta shade guide from the teeth that were not treated with the primer, at the three time points evaluated (baseline versus 30 minutes after in‐office treatment, baseline versus 1 day, and baseline versus 15 days). None of the subjects experienced soft tissue sensitivity, and those who experienced tooth sensitivity said it was not noticeable after 15 days postwhitening.

CLINICAL SIGNIFICANCE

The primer neither enhanced the whitening effect nor decreased tooth sensitivity when used before vital bleaching with Opalescence Boost (Ultradent Products, Inc., South Jordan, UT, USA). None of the subjects experienced soft tissue sensitivity, and some experienced transient tooth sensitivity.

(J Esthet Restor Dent 23:97–105, 2011)
Establishment and characterization of a fibroblast cell line derived from Mongolian sheep
Authors: LIU Chang‐Qing , GUO Yu , GUAN Wei‐Jun , MA Yue‐Hui
Published: February 2011

The Mongolian sheep ear marginal tissue fibroblast cell line (MSF32) from 32 samples was successfully established by using primary explants technique and cell cryoconservation technology. MSF32 cells were adherent, with a population doubling time of 28.2 h. Chromosome analysis showed that >90.2% of cells were diploid (2n = 54) prior to cell passage 4. Isoenzyme analyses of lactate dehydrogenase and malate dehydrogenase showed that the MSF22 cells had no cross‐contamination with other species. Tests for cell line contamination with bacteria, fungi, viruses and mycoplasmas were also negative. Plasmids encoding the fluorescent proteins pEGFP‐N3, pEGFP‐C1, pECFP‐N1, pECFP‐mito, pDsRed1‐N1 and pEYFP‐N1 were transfected into cells to study exogenous gene expression in the cells. The plasmid transfection efficiency was between 12.3% and 63.3%. Every index of the MSF32 cell line meets all the standard quality controls of American Type Culture Collection (ATCC). Not only has the genetic resources of the Mongolian sheep been preserved at the cell level, but also valuable materials had been provided for genome, postgenome and somacloning research.
Japanese consumer categorisation of beef into quality grades, based on Meat Standards Australia methodology
Authors: POLKINGHORNE Rod J. , NISHIMURA Takanori , NEATH Kate E. , WATSON Ray
Published: February 2011

The objective was to evaluate the sensory categorisation of beef by Japanese consumers, based on Meat Standards Australia methodology. Various cuts of beef, with a wide range of quality (from Australian and Japanese cattle) and three cooking methods (grill, yakiniku, shabu shabu), were evaluated by 1620 Japanese consumers in Tokyo and Osaka. Consumers rated each sample for four sensory attributes (tenderness, juiciness, flavor and overall satisfaction), then selected one of four grades (unsatisfactory/2‐star, good everyday/3‐star, better than everyday/4‐star, and premium quality/5‐star), based on the quality of the beef within each cooking method. Meat quality scores, denoted as MQ4 scores (weighted combination of the four sensory attributes) were calculated from the Japanese consumer test results, to describe the Japanese consumer rating of beef. The distribution of the Japanese consumer MQ4 scores showed a clear distinction between grades, with the majority of scores being included within the boundaries of each grade. The MQ4 score allocated approximately 64% of the samples to their correct consumer grades. The MQ4 score showed potential to be used as a tool in developing and monitoring a consumer‐focused grading system that is able to predict Japanese consumer satisfaction of individual beef cuts prepared by different cooking methods.
Efficacy of probiotics from anaerobic microflora with prebiotics on growth performance and noxious gas emission in growing pigs
Authors: CHU Gyo Moon , LEE Shin Ja , JEONG Ho Sik , LEE Sung Sill
Published: February 2011

We investigated the effect of probiotics from anaerobic microflora with prebiotics (synbiotics) on growth performance, noxious gas emission and fecal pathogenic bacteria populations in growing pigs. The basal diet, which contained approximately 25% corn, 24% whey, 12% wheat and 12% soybean meal, was supplemented alternatively with 0.15% antibiotics (US diet), prebiotics and 0.2% probiotics from anaerobic bacteria (BS diet), yeast (YS diet), mold (MS diet) or compounds (CS diet). One hundred and fifty pigs were fed an experimental diet for 15 days. Although the growth performance was not affected by supplemental synbiotics, the BS group showed higher dry matter and crude protein digestibility. The BS group decreased fecal ammonia and amine gas emissions, and increased fecal acetate gas emission compared with the US group. All synbiotics groups decreased in fecal propionate gas emission. Fecal Escherichia coli population was lower in the synbiotics groups than in the US group. Therefore, the results of the present study suggest that synbiotics exert similar effects with antibiotics on the nutrient digestibility and fecal microflora composition in growing pigs. Moreover, synbiotics can also decrease the fecal noxious gas emission in growing pigs.
Comparison of feeding systems: feed cost, palatability and environmental impact among hay‐fattened beef, consistent grass‐only‐fed beef and conventional marbled beef in Wagyu (Japanese Black cattle)
Authors: SITHYPHONE Khounsaknalath , YABE Mitsuyasu , HORITA Hiroshi , HAYASHI Keisuke , FUMITA Tomiko , SHIOTSUKA Yuji , ETOH Tetsuji , EBARA Fumio , SAMADMANIVONG Olavanh , WEGNER Jochen , GOTOH Takafumi
Published: February 2011

The objective of this article is to compare feed cost, palatability and environmental impacts among feeding systems of high concentrate (HC), high hay (HH) and grass‐only‐fed (Gof) groups. Feed cost was the sum of costs paid for feed intake times the price of feed per kilogram. Palatability was measured by a panel taste test using HH and Gof beef and analyzed for differences. Environmental impacts were calculated based on 1 kg of Japanese beef yield of CO2 equivalents (eq) and animal end weights at each feeding stage. Results showed that the HH and Gof feeding systems could significantly reduce feed costs by approximately 60% and 78%, respectively, from the HC. In the panel taste test, 50% and 47.50% of panelists indicated that HH beef was ‘extremely delicious’ and ‘acceptable,’ respectively, while 15% indicated that Gof beef was ‘extremely delicious’; 62.50% indicated that Gof beef was ‘acceptable.’ Environmental impacts of each feeding system in terms of CO2 equivalents (eq) were 9.32, 6.10 and 2.04 tonnes of eq for the HC, HH and Gof, respectively. The HH was an economical system that produced moderate impacts on the environment and had impressive taste.
Tissue distribution of albumin‐glucose advanced glycation end products administrated to chickens
Authors: KITA Kazumi
Published: February 2011

Glycation (Maillard reaction) starts from non‐enzymatic amino‐carbonyl reaction binding carbonyl group of reducing sugars to amino group of amino acids. The amino‐carbonyl reaction leads to the formation of the stable Amadori product, which ultimately forms advanced glycation end products (AGE). Acceleration of glycation during hyperglycemia increases the production and accumulation of AGE, which is implicated in the gradual development of diabetic complications in diabetes mellitus. Avian species offers the great advantage of providing animal models for diabetology because high blood glucose concentration should accelerate to generate high concentration of AGE. In the present study, radioactive AGE was prepared from chicken serum albumin and 14C‐glucose. Radioactive AGE was administrated to examine the tissue distribution of AGE in chickens. Administration of radioactive AGE into the circulation of chickens revealed that AGE accumulated into specific tissues, liver, spleen and kidney, which have the function for clearing exogenous substances and endogenous metabolic waste products.
Alizarine derivatives as new dual inhibitors of the HIV‐1 reverse transcriptase‐associated DNA polymerase and RNase H activities effective also on the RNase H activity of non‐nucleoside resistant reverse transcriptases
Authors: Esposito Francesca , Kharlamova Tatyana , Distinto Simona , Zinzula Luca , Cheng Yung‐Chi , Dutschman Ginger , Floris Giovanni , Markt Patrick , Corona Angela , Tramontano Enzo
Published: February 2011

HIV‐1 reverse transcriptase (RT) has two associated activities, DNA polymerase and RNase H, both essential for viral replication and validated drug targets. Although all RT inhibitors approved for therapy target DNA polymerase activity, the search for new RT inhibitors that target the RNase H function and are possibly active on RTs resistant to the known non‐nucleoside inhibitors (NNRTI) is a viable approach for anti‐HIV drug development. In this study, several alizarine derivatives were synthesized and tested for both HIV‐1 RT‐associated activities. Alizarine analogues K‐49 and KNA‐53 showed IC50 values for both RT‐associated functions of ∼ 10 μm. When tested on the K103N RT, both derivatives inhibited the RT‐associated functions equally, whereas when tested on the Y181C RT, KNA‐53 inhibited the RNase H function and was inactive on the polymerase function. Mechanism of action studies showed that these derivatives do not intercalate into DNA and do not chelate the divalent cofactor Mg2+. Kinetic studies demonstrated that they are noncompetitive inhibitors, they do not bind to the RNase H active site or to the classical NNRTI binding pocket, even though efavirenz binding negatively influenced K‐49/KNA‐53 binding and vice versa. This behavior suggested that the alizarine derivatives binding site might be close to the NNRTI binding pocket. Docking experiments and molecular dynamic simulation confirmed the experimental data and the ability of these compounds to occupy a binding pocket close to the NNRTI site.
The histone demethylase JARID1A regulates progesterone receptor expression
Authors: Stratmann Antje , Haendler Bernard
Published: February 2011

Transcriptional control of the progesterone receptor gene by estrogen is a complex mechanism. It involves estrogen receptor α which uses several enzymes that locally modify histone tails as cofactors. Using MCF‐7 cells as a model, we found that Jumonji AT‐rich interactive domain 1A (JARID1A; KDM5A/RBP2), an enzyme that removes the activating H3K4 di‐ and trimethylation marks, was involved in the fine‐tuning of progesterone receptor gene expression. Reduction of JARID1A led to enhanced progesterone receptor expression, at both the basal and estrogen‐stimulated levels. Conversely, overexpression of JARID1A wild‐type, but not the enzymatically inactive mutant, suppressed progesterone receptor promoter activity. Chromatin immunoprecipitation experiments showed JARID1A to bind in a ligand‐independent manner to a progesterone receptor gene upstream region that contains an estrogen response element half‐site as well as the CCGCCC sequence, which is potentially recognized by JARID1A. Estrogen treatment led to RNA polymerase II recruitment to this region and to increased estrogen receptor α binding to the PR enhancer region 1. In addition, elevation of H3K4 trimethylation was detected at the estrogen response element half‐site region. Reduction of JARID1A expression was followed by higher H3K4 trimethylation in this region. Analysis of MDA‐MB‐231 cells, which do not express the progesterone receptor, indicated that H3K4 trimethylation did not take place in the regulatory regions examined. Taken together, the results underscore the importance of epigenetic modifications for regulation of progesterone receptor expression. They suggest that H3K4 tri‐ and dimethylation play an important role and that JARID1A is the histone‐demethylating enzyme responsible for removal of this mark.
Wild‐type p53 enhances annexin IV gene expression in ovarian clear cell adenocarcinoma
Authors: Masuishi Yusuke , Arakawa Noriaki , Kawasaki Hiroshi , Miyagi Etsuko , Hirahara Fumiki , Hirano Hisashi
Published: February 2011

The protein annexin IV (ANX4) is elevated specifically and characteristically in ovarian clear cell adenocarcinoma (CCA), a highly malignant histological subtype of epithelial ovarian cancer. On the basis of the hypothesis that the expression of ANX4 in CCA is regulated by a unique transcription mechanism, we explored the cis‐elements involved in CCA‐specific ANX4 expression using a luciferase reporter. We compared the transcriptional activities of the region from −1534 to +1010 relative to the ANX4 transcription start site in CCA and non‐CCA‐type cell lines, and found that two repeated binding motifs for the tumor suppressor protein, p53, in the first intron of ANX4 were involved in CCA‐specific transcriptional activity. Furthermore, chromatin immunoprecipitation showed that endogenous p53 bound to this site in CCA cell lines. Moreover, the use of short interference RNA to silence the p53 gene decreased the transcriptional activity and mRNA expression of ANX4 in CCA cell lines. Thus, the ANX4 gene is, at least in part, regulated by p53 in CCA cells. Mutations in the p53 gene were absent and levels of p53 target genes were higher in several CCA‐derived cell lines. Although the expression of ANX4 is typically low in these non‐CCA cell lines, ANX4 levels were elevated more than three‐fold by the overexpression of wild‐type but not mutant p53. Therefore, we conclude that the ANX4 gene is a direct transcriptional target of p53, and its expression is enhanced by wild‐type p53 in CCA cells.
Proteomic tools for the analysis of transient interactions between metalloproteins
Authors: Martínez‐Fábregas Jonathan , Rubio Silvia , Díaz‐Quintana Antonio , Díaz‐Moreno Irene , De la Rosa Miguel Á.
Published: February 2011

Metalloproteins play major roles in cell metabolism and signalling pathways. In many cases, they show moonlighting behaviour, acting in different processes, depending on the physiological state of the cell. To understand these multitasking proteins, we need to discover the partners with which they carry out such novel functions. Although many technological and methodological tools have recently been reported for the detection of protein interactions, specific approaches to studying the interactions involving metalloproteins are not yet well developed. The task is even more challenging for metalloproteins, because they often form short‐lived complexes that are difficult to detect. In this review, we gather the different proteomic techniques and biointeractomic tools reported in the literature. All of them have shown their applicability to the study of transient and weak protein–protein interactions, and are therefore suitable for metalloprotein interactions.
Alterations in the photoactivation pathway of rhodopsin mutants associated with retinitis pigmentosa
Authors: Bosch‐Presegué Laia , Ramon Eva , Toledo Darwin , Cordomí Arnau , Garriga Pere
Published: February 2011

The visual photoreceptor rhodopsin undergoes a series of conformational changes upon light activation, eventually leading to the active metarhodopsin II conformation, which is able to bind and activate the G‐protein, transducin. We have previously shown that mutant rhodopsins G51V and G89D, associated with retinitis pigmentosa, present photobleaching patterns characterized by the formation of altered photointermediates whose nature remained obscure. Our current detailed UV–visible spectroscopic analysis, together with functional characterization, indicate that these mutations influence the relative stability of the different metarhodopsin photointermediates by altering their equilibria and maintaining the receptor in a nonfunctional light‐induced conformation that may be toxic to photoreceptor cells. We propose that G51V and G89D shift the equilibrium from metarhodopsin I towards an intermediate, recently named as metarhodopsin Ib, proposed to interact with transducin without activating it. This may be one of the causes contributing to the molecular mechanisms underlying cell death associated with some retinitis pigmentosa mutations.
Evidence for a black hole in the X-ray transient XTEJ1859+226
Authors: Corral-Santana J. M. , Casares J. , Shahbaz T. , Zurita C. , Martínez-Pais I. G. , Rodríguez-Gil P.
Published: February 2011

We present the results of time-resolved optical photometry and spectroscopy of the X-ray transient XTEJ1859+226 (V406Vul). Photometric observations taken during 2000 and 2008 reveal the presence of the secondary star's ellipsoidal modulation. Further photometry obtained in 2010 shows the system ≃1mag brighter than its quiescence level and the ellipsoidal modulation diluted by strong flaring activity. Spectroscopic data obtained with the 10.4-m GTC in 2010 reveal radial velocity variations of ∼500kms−1 over 3h. A simultaneous fit to the photometry and spectroscopy using sinusoids to represent the secondary star's ellipsoidal and radial velocity variations, yields an orbital period of 6.58 ± 0.05h and a secondary star's radial velocity semi-amplitude of K2= 541 ± 70kms−1. The implied mass function is f(M) = 4.5 ± 0.6M⊙, significantly lower than previously reported but consistent with the presence of a black hole in XTEJ1859+226. The lack of eclipses sets an upper limit to the inclination of 70° which yields a lower limit to the black hole mass of 5.42M⊙.
Isotopic Mapping of Groundwater Perchlorate Plumes
Authors: Sturchio Neil C. , Hoaglund John R. , Marroquin Roy J. , Beloso Abelardo D. , Heraty Linnea J. , Bortz Sarah E. , Patterson Thomas L.
Published: February 2011

Analyses of stable isotope ratios of chlorine and oxygen in perchlorate can, in some cases, be used for mapping and source identification of groundwater perchlorate plumes. This is demonstrated here for large, intersecting perchlorate plumes in groundwater from a region having extensive groundwater perchlorate contamination and a large population dependent on groundwater resources. The region contains both synthetic perchlorate derived from rocket fuel manufacturing and testing activities and agricultural perchlorate derived predominantly from imported Chilean (Atacama) nitrate fertilizer, along with a likely component of indigenous natural background perchlorate from local wet and dry atmospheric deposition. Most samples within each plume reflect either a predominantly synthetic or a predominantly agricultural perchlorate source and there is apparently a minor contribution from the indigenous natural background perchlorate. The existence of isotopically distinct perchlorate plumes in this area is consistent with other lines of evidence, including groundwater levels and flow paths as well as the historical land use and areal distribution of potential perchlorate sources.
Diet prescription for non‐alcoholic fatty liver disease: Is it worth the effort? A systematic review
Authors: ROSSI Megan , HICKMAN Ingrid J.
Published: February 2011

Aim:  The objective of this review was to assess the effectiveness of diet interventions for improving disease severity in non‐alcoholic fatty liver disease. A secondary aim was to identify the effectiveness of different methods of dietetic service delivery for achieving weight reduction in this patient group.

Methods:  A review of studies from 1999 to 2009 was conducted. Studies were included if they reported non‐alcoholic fatty liver disease diagnosis by either liver histology analysis, imaging or by persistent hypertransaminasaemia, were English language studies of human adults, ≥18 years, that had implemented a dietary component in the intervention.

Results:  From the 102 papers identified, 20 met inclusion criteria: two randomised controlled trials, two controlled trials (allocation method not disclosed), two non‐randomised experimental studies and 14 case series. Methods of diet prescription differed substantially among studies. Weight reduction appeared to be associated with a reduction in steatosis; however, improvements in other features of liver disease remain unclear. There appeared to be a relationship between the intensity of dietetic contact and weight loss.

Conclusion:  There is limited evidence available to assess the effectiveness of diet interventions on histological severity of non‐alcoholic fatty liver disease. There is good evidence that clinically significant weight reduction can improve steatosis and risk factors for non‐alcoholic fatty liver disease. A relationship may exist between the frequency of dietetic consultations and amount of weight reduction achieved in patients with non‐alcoholic fatty liver disease. Fortnightly intervention for a minimum of three months to achieve at least 5% weight loss is recommended.
Normalization of Proliferation and Tight Junction Formation in Bladder Epithelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome by d‐Proline and d‐Pipecolic Acid Derivatives of Antiproliferative Factor
Authors: Keay Susan , Kaczmarek Piotr , Zhang Chen‐Ou , Koch Kristopher , Szekely Zoltan , Barchi Joseph J. , Michejda Christopher
Published: February 2011

Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopeptide antiproliferative factor or ‘APF’ (Neu5Acα2‐3Galβ1‐3GalNAcα‐O‐TVPAAVVVA) that induces abnormalities in normal cells similar to those in interstitial cystitis/painful bladder syndrome cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated‐APF (‘as‐APF’) in normal bladder cells and determined the ability of as‐APF‐blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of interstitial cystitis/painful bladder syndrome cells. Only two of these derivatives [Galβ1‐3GalNAcα‐O‐TV‐(d‐pipecolic acid)‐AAVVVA and Galβ1‐3GalNAcα‐O‐TV‐(d‐proline)‐AAVVVA] blocked as‐APF antiproliferative activity in normal cells (p < 0.001 for both). Both of these antagonists also 1) significantly increased mRNA expression of ZO‐1, occludin, and claudins 1, 4, 8, and 12 in interstitial cystitis/painful bladder syndrome cells by qRT‐PCR; 2) normalized interstitial cystitis/painful bladder syndrome epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of 14C‐mannitol and 3H‐inulin between confluent interstitial cystitis/painful bladder syndrome epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for the development as interstitial cystitis/painful bladder syndrome therapies.
A New Generation of Potent Complement Inhibitors of the Compstatin Family
Authors: López de Victoria Aliana , Gorham Ronald D. , Bellows‐Peterson Meghan L. , Ling Jun , Lo David D. , Floudas Christodoulos A. , Morikis Dimitrios
Published: February 2011

Compstatin family peptides are potent inhibitors of the complement system and promising drug candidates against diseases involving under‐regulated complement activation. Compstatin is a 13‐residue cyclized peptide that inhibits cleavage of complement protein C3, preventing downstream complement activation. We present three new compstatin variants, characterized by tryptophan replacement at positions 1 and/or 13. Peptide design was based on physicochemical reasoning and was inspired by earlier work, which identified tryptophan substitutions at positions 1 and 13 in peptides with predicted C3c binding abilities [Bellows M.L., Fung H.K., Taylor M.S., Floudas C.A., López de Victoria A., Morikis D. (2010) Biophys J; 98: 2337–2346]. The new variants preserve distinct polar and nonpolar surfaces of compstatin, but have altered local interaction capabilities with C3. All three peptides exhibited potent C3 binding by surface plasmon resonance and potent complement inhibition by enzyme‐linked immunosorbent assay. We also present enzyme‐linked immunosorbent assay data and detailed surface plasmon resonance kinetic data of three peptides from previous computational design.
The views from the hills: fatal accidents, child safety and licensing adventure activities
Authors: McArdle David
Published: February 2011

Two recent fatal accident inquiries (FAIs) in Scotland have potentially far-reaching ramifications for educational provision across the whole of the UK. The deaths of two teenage children during the course of outdoor adventure activities led the sheriff in one of those inquiries to recommend a review of the regulatory framework which governs those activities. This call for an across-the-board review means the outdoor education sector – which includes organisations which provide outdoor education for schools groups as well as those offering more adventurous experiences for children outside term time – is now likely to face a degree of scrutiny greater than any it has experienced since the 1993 Lyme Bay disaster.

This paper draws upon research interviews with those who work in outdoor education in some of the more remote areas of Scotland. The data from those interviews indicate that some of the issues that ought to be considered in any such review will not be immediately apparent from reading either the fatal accident inquiries' determinations or the literature which is available either on the Heath and Safety Executive's website or otherwise in the public domain. In particular, it appears that some issues which have only reached a wider audience by virtue of these FAIs have actually been the source of longstanding concerns among the stakeholders, dating back to the mid-1990s when the regulatory framework that came into being in the wake of Lyme Bay was still under discussion. This paper therefore uses the interviewees' responses to help develop a greater understanding of the issues that exist in this particular sector and to illustrate the legal and logistical challenges that it faces.
Ending the life of the act/omission dispute: causation in withholding and withdrawing life-sustaining measures
Authors: McGee Andrew
Published: February 2011

The aim in this paper is to challenge the increasingly common view in the literature that the law on end-of-life decision making is in disarray and is in need of urgent reform. The argument is that this assessment of the law is based on assumptions about the relationship between the identity of the defendant and their conduct, and about the nature of causation, which, on examination, prove to be indefensible. A clarification of the relationship between causation and omissions is provided which proves that the current legal position does not need modification, at least on the grounds that are commonly advanced for the converse view. This paves the way for a clarification, in conclusion, of important conceptual and moral differences between withholding, refusing and withdrawing life-sustaining measures, on the one hand, and assisted suicide and euthanasia, on the other.
Current understanding of increased insulin sensitivity after exercise – emerging candidates
Authors: Maarbjerg S. J. , Sylow L. , Richter E. A.
Published: February 2011

Exercise counteracts insulin resistance and improves glucose homeostasis in many ways. Apart from increasing muscle glucose uptake quickly, exercise also clearly increases muscle insulin sensitivity in the post‐exercise period. This review will focus on the mechanisms responsible for this increased insulin sensitivity. It is believed that increased sarcolemmal content of the glucose transporter GLUT4 can explain the phenomenon to some extent. Surprisingly no improvement in the proximal insulin signalling pathway is observed at the level of the insulin receptor, IRS1, PI3K or Akt. Recently more distal signalling component in the insulin signalling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin sensitivity after exercise. Whereas TBC1D1 does not appear to regulate insulin sensitivity after exercise, correlative evidence in contrast suggests TBC1D4 to be a relevant candidate. Little is known about aPKC and Rac1 in relation to insulin sensitivity after exercise. Besides mechanisms involved in signalling to GLUT4 translocation, factors influencing the trans‐sarcolemmal glucose concentration gradient might also be important. With regard to the interstitial glucose concentration microvascular perfusion is particular relevant as correlative evidence supports a connection between insulin sensitivity and microvascular perfusion. Thus, there are new candidates at several levels which collectively might explain the phenomenon.
Old Chromophores, New Photoactivation Paradigms, Trendy Applications: Flavins in Blue Light‐Sensing Photoreceptors†
Authors: Losi Aba , Gärtner Wolfgang
Published: February 2011

The knowledge on the mechanisms by which blue light (BL) is sensed by diverse and numerous organisms, and of the physiological responses elicited by the BL photoreceptors, has grown remarkably during the last two decades. The basis for this “blue revival” was set by the identification and molecular characterization of long sought plant BL sensors, employing flavins as chromophores, chiefly cryptochromes and phototropins. The latter photosensors are the foundation members of the so‐called light, oxygen, voltage (LOV)‐protein family, largely spread among archaea, bacteria, fungi and plants. The accumulation of sequenced microbial genomes during the last years has added the BLUF (Blue Light sensing Using FAD) family to the BL photoreceptors and yielded the opportunity for intense “genome mining,” which has presented to us the intriguing wealth of BL sensing in prokaryotes. In this contribution we provide an update of flavin‐based BL sensors of the LOV and BLUF type, from prokaryotic microorganisms, with special emphasis to their light‐activation pathways and molecular signal‐transduction mechanisms. Rather than being a fully comprehensive review, this research collects the most recent discoveries and aims to unveil and compare signaling pathways and mechanisms of BL sensors.
Blue and Red Light‐Induced Germination of Resting Spores in the Red‐Tide Diatom Leptocylindrus danicus†
Authors: Shikata Tomoyuki , Iseki Mineo , Matsunaga Shigeru , Higashi Sho‐ichi , Kamei Yasuhiro , Watanabe Masakatsu
Published: February 2011

Photophysiological and pharmacological approaches were used to examine light‐induced germination of resting spores in the red‐tide diatom Leptocylindrus danicus. The equal‐quantum action spectrum for photogermination had peaks at about 440 nm (blue light) and 680 nm (red light), which matched the absorption spectrum of the resting spore chloroplast, as well as photosynthetic action spectra reported for other diatoms. DCMU, an inhibitor of photosynthetic electron flow near photosystem II, completely blocked photogermination. These results suggest that the photosynthetic system is involved in the photoreception process of light‐induced germination. Results of pharmacological studies of the downstream signal transduction pathway suggested that Ca2+ influx is the closest downstream neighbor, followed by steps involving calmodulin, nitric oxide synthase, guanylyl cyclase, protein‐tyrosine‐phosphatase, protein kinase C and actin polymerization and translation.
An assessment of three noncommercial DNA extraction methods from dried blood spots for beta‐thalassaemia mutation identification
Authors: KARTHIPAN S. N. , GEORGE E. , JAMEELA S. , LIM W. F. , TEH L. K. , LEE T. Y. , CHIN V. K. , LAI M. I.
Published: February 2011

Introduction:  Dried blood spots (DBS) are currently the recommended sample collection method for newborn screening programmes in America. Early diagnosis of beta‐thalassaemia screening is essential as it provides an added advantage especially in sickle cell disease. Beta‐thalassaemia frequency is high in many poor countries, and the cost of using commercial DNA extraction kits can be prohibitive. Our study assessed three methods that use minimal reagents and materials to extract DNA from DBS for beta‐thalassaemia identification.

Methods:  The methods assessed in this study were Tris–EDTA (TE) buffer‐based method by Bereczky et al. (American Journal of Tropical Medicine and Hygiene 72, 2005, 249), NaCL/NaOH/Sodium dodecyl sulphate (SDS) method by Huang et al. (Human Genetics 84, 1990, 129) and NaOH method by Zhou et al. (Analytical Biochemistry 354, 2006, 159). Extracted DNA was amplified for three common beta‐thalassaemia mutations in Malaysia.

Results:  Amplicons derived from TE buffer‐based method were very faint and almost nonexistent while the NaCl/NaOH/SDS method did not produce any visible amplicons. The extraction using NaOH method produced visible bands that were comparable to the standard method using extraction kit.

Conclusion:  The NaOH method is a simple method that uses minimal equipment and reagents that make it labour‐ and cost‐effective. This method could be adopted by poorer countries to extract DNA for beta‐thalassaemia mutation characterization.
ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity
Authors: Landreville Solange , Agapova Olga A. , Kneass Zachary T. , Salesse Christian , William Harbour J.
Published: February 2011

Metastasis of tumor cells to distant organs is the leading cause of death in melanoma. Yet, the mechanisms of metastasis remain poorly understood. One key question is whether all cells in a primary tumor are equally likely to metastasize or whether subpopulations of cells preferentially give rise to metastases. Here, we identified a subpopulation of uveal melanoma cells expressing the multidrug resistance transporter ABCB1 that are highly metastatic compared to ABCB1− bulk tumor cells. ABCB1+ cells also exhibited enhanced clonogenicity, anchorage‐independent growth, tumorigenicity and mitochondrial activity compared to ABCB1− cells. A375 cutaneous melanoma cells contained a similar subpopulation of highly metastatic ABCB1+ cells. These findings suggest that some uveal melanoma cells have greater potential for metastasis than others and that a better understanding of such cells may be necessary for more successful therapies for metastatic melanoma.
Ultrastructure of anterior lens capsule of intumescent white cataract
Authors: Hawlina Marko , Stunf Spela , Hvala Anastazija
Published: February 2011

Purpose:  To analyse the anterior lens capsule thickness and ultrastructure changes of intumescent white cataracts in comparison with nuclear cataracts to prove possible structural reasons for surgical difficulties with the intumescent white cataract.

Methods:  Anterior lens capsules from 35 eyes with intumescent white and 35 eyes with nuclear cataracts were analysed for their thickness by semithin sections technique and for morphological characteristics by transmission electron microscopy.

Results:  Capsule thickness was not significantly different in intumescent white compared to nuclear cataracts (mean values 17.5 and 18.5 μm, respectively, p = 0.369). The main morphological features of capsules were extrusions of capsule at the basement membrane‐epithelial border embedding cellular material which were significantly more frequent in intumescent cataracts. Filaments in the basement membrane as well as rarefication of its structure and lamellae were often concomitant with the extrusions.

Conclusions:  Anterior capsules of white intumescent cataracts do not differ in thickness but have different ultrastructure morphology compared to nuclear cataracts. The extrusions of basement membrane at the basement membrane‐epithelial border towards epithelium, the filamentary inclusions within basement membrane and its rarefication could be the structural causes of tensile weakness and hence additional reason to surgical problems.
Toxoplasma gondii protects against H2O2‐induced apoptosis in ARPE‐19 cells through the transcriptional regulation of apoptotic elements and downregulation of the p38 MAPK pathway
Authors: Choi Si‐Hwan , Park Sung Jun , Cha Guang‐Ho , Quan Juan Hua , Chang Nam‐Sik , Ahn Myoung‐Hee , Shin Dae‐Whan , Lee Young‐Ha
Published: February 2011

Purpose:  Toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii, can lead to severe visual impairment. T. gondii inhibits or delays programmed cell death caused by various apoptotic triggers; however, the mechanisms involved in the T. gondii‐induced suppression of apoptosis in retinal cells have not been analysed in detail.

Methods:  We investigated the role of T. gondii infection in H2O2‐induced apoptosis in human retinal pigment epithelial cells (ARPE‐19) by monitoring the activities of apoptosis‐regulating molecules and mitogen‐activated protein kinases (MAPKs), including p38 MAPK. We also examined the gene downstream from p38 MAPK.

Results:  T. gondii infection significantly inhibited the cellular toxicity of H2O2 (500 μm) and increased cell viability in a multiplicity of infection (MOI)‐dependent manner by reducing DNA fragmentation and reactive oxygen species (ROS) generation in ARPE‐19 cells. Western blot analysis also showed that T. gondii infection prevented the host cell expression of pro‐apoptotic factors, such as Bad and Bax, and the activation of caspase‐3. Infection with T. gondii increased the expression of the anti‐apoptotic factor Bcl‐2 in ARPE‐19 cells under oxidative stress. In accordance with these findings, Toxoplasma infection was protective enough to suppress the phosphorylation of p38 MAPK following H2O2 treatment. Exposure to H2O2 increased the expression of heme oxygenase‐1 (HO‐1) in ARPE‐19 cells, and its expression was significantly inhibited in H2O2‐treated infected cells.

Conclusion:  The protective function of T. gondii infection against ROS‐induced apoptosis results from changes in the expression of apoptotic molecules and the downregulation of stress‐induced intracellular signalling.
Clinical Efficacy of Aniracetam, Either as Monotherapy or Combined with Cholinesterase Inhibitors, in Patients with Cognitive Impairment: A Comparative Open Study*
Authors: Koliaki Chrysi C. , Messini Chaido , Tsolaki Magda
Published: February 2011

Introduction: Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. Aims: In the present study, we aimed to evaluate the efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. Results: In our prospective, open‐label study, we enrolled a total of 276 patients (mean age 71 ± 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between aniracetam and ChEIs in patients with relatively mild dementia (15 ≤ MMSE ≤ 25) revealed a significantly better cognitive performance with aniracetam at 6 months and improved functionality at 3 months. Comparing aniracetam monotherapy with combined treatment in the same population, aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. Conclusions: Our findings indicate that aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients.
Stem Cell Challenges in the Treatment of Neurodegenerative Disease
Authors: Feng Zhongling , Gao Feng
Published: February 2011

Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. The rapidly advancing stem cell field is providing attractive alternative options for fighting these diseases. Results have provided proof of principle that cell replacement can work in humans with Parkinson's disease (PD). However, three clinical studies of cell transplantation were published that found no net benefit, while patients in two of the studies developed dyskinesias that persisted despite reductions in treatment. Induced pluripotent stem cells (iPSC) have major potential advantages because patient‐specific neuroblasts are suitable for transplantation, avoid immune reactions, and can be produced without the use of human ES cells (hESC). Although iPSCs have not been successfully used in clinical trials for PD, patients with amyotrophic lateral sclerosis (ALS) were treated with autologous stem cells and, though they had some degree of decline one year after treatment, they were still improved compared with the preoperative period or without any drug therapy. In addition, neural stem cells (NSCs), via brain‐derived neurotrophic factor (BDNF), have been shown to ameliorate complex behavioral deficits associated with widespread Alzheimer's disease (AD) pathology in a transgenic mouse model of AD. So far, the FDA lists 18 clinical trials treating multiple sclerosis (MS), but most are in preliminary stages. This article serves as an overview of recent studies in stem cell and regenerative approaches to the above chronic neurodegenerative disorders. There are still many obstacles to the use of stem cells as a cure for neurodegenerative disease, especially because we still don't fully understand the true mechanisms of these diseases. However, there is hope in the potential of stem cells to help us learn and understand a great deal more about the mechanisms underlying these devastating neurodegenerative diseases.
Metabolic Syndrome and Bipolar Disorder: What Should Psychiatrists Know?
Authors: de Almeida Karla M. , Moreira Camila L. R. L. , Lafer Beny
Published: February 2011

This paper reviews the association between bipolar disorder (BD) and metabolic syndrome (MetS), focusing on the etiopathogenetic and pathophysiological aspects of this association and on the recommendations for preventing and managing MetS in patients with BD. We conducted a nonsystematic literature review by means of a MEDLINE search. The exact causal relationship between MetS and BD is still uncertain. The side effects of psychotropic medications may be a major contributor to the increased rates of MetS in patients with BD. Other factors such as unhealthy lifestyles, common neuroendocrine and immuno‐inflammatory abnormalities, and genetic vulnerability may also play a role in explaining the high rates of MetS in BD. Strategies to prevent and treat the MetS and its cardiovascular consequences in patients with BD include accurate screening and monitoring of the patient and appropriate psychoeducation on weight control, healthy nutrition, and increased physical activity. When deciding on pharmacological therapy for the treatment of the components of the MetS, drug interactions and the effects of the medications on mood must be taken into account.