bluuebunny/crossref_metadata_2025 huggingface dataset:
The novel Pseudomonas aeruginosa two‐component regulator BfmR controls bacteriophage‐mediated lysis and DNA release during biofilm development through PhdA
Authors: Petrova Olga E. , Schurr Jill R. , Schurr Michael J. , Sauer Karin
Published: June 2011

Biofilms are surface‐adhered bacterial communities encased in an extracellular matrix composed of polysaccharides, proteins, and extracellular (e)DNA, with eDNA required for biofilm formation and integrity. Here we demonstrate that eDNA release is controlled by BfmR, a regulator essential for Pseudomonas aeruginosa biofilm development. Expression of bfmR coincided with localized cell death and DNA release, and could be stimulated by conditions resulting in membrane perturbation and cell lysis. ΔbfmR mutant biofilms demonstrated increased cell lysis and eDNA release suggesting BfmR to suppress, but not eliminate, these processes. Genome‐wide transcriptional profiling indicated that BfmR was required for repression of genes associated with bacteriophage assembly and bacteriophage‐mediated lysis. Chromatin immunoprecipitation analysis of direct BfmR targets identified the promoter of PA0691, termed here phdA, encoding a previously undescribed homologue of the prevent‐host‐death (Phd) family of proteins. Lack of phdA expression coincided with impaired biofilm development and increased cell death, a phenotype comparable to ΔbfmR. Expression of phdA in ΔbfmR restored eDNA release, cell lysis and biofilm formation to wild‐type levels, with phdA overexpression promoting resistance to the superinfective bacteriophage Pf4, detected only in biofilms. Therefore, we propose that BfmR regulates biofilm development by limiting bacteriophage‐mediated lysis and thus, eDNA release, via PhdA.
Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two‐component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters
Authors: Hiron Aurélia , Falord Mélanie , Valle Jaione , Débarbouillé Michel , Msadek Tarek
Published: June 2011

Two‐component systems (TCSs) are key regulatory pathways allowing bacteria to adapt their genetic expression to environmental changes. Bacitracin, a cyclic dodecylpeptide antibiotic, binds to undecaprenyl pyrophosphate, the lipid carrier for cell wall precursors, effectively inhibiting peptidoglycan biosynthesis. We have identified a novel and previously uncharacterized TCS in the major human pathogen Staphylococcus aureus that we show to be essential for bacitracin and nisin resistance: the BraS/BraR system (Bacitracin resistance associated; SA2417/SA2418). The braRS genes are located immediately upstream from genes encoding an ABC transporter, accordingly designated BraDE. We have shown that the BraSR/BraDE module is a key bacitracin and nisin resistance determinant in S. aureus. In the presence of low antibiotic concentrations, BraSR activate transcription of two operons encoding ABC transporters: braDE and vraDE. We identified a highly conserved imperfect palindromic sequence upstream from the braDE and vraDE promoter sequences, essential for their transcriptional activation by BraSR, suggesting it is the likely BraR binding site. We demonstrated that the two ABC transporters play distinct and original roles in antibiotic resistance: BraDE is involved in bacitracin sensing and signalling through BraSR, whereas VraDE acts specifically as a detoxification module and is sufficient to confer bacitracin and nisin resistance when produced on its own. We show that these processes require functional BraD and VraD nucleotide‐binding domain proteins, and that the large extracellular loop of VraE confers its specificity in bacitracin resistance. This is the first example of a TCS associated with two ABC transporters playing separate roles in signal transduction and antibiotic resistance.
Hsp31 of Escherichia coli K‐12 is glyoxalase III
Authors: Subedi Krishna P. , Choi Dongwook , Kim Insook , Min Bumchan , Park Chankyu
Published: June 2011

Hsp31 encoded by hchA is known as a heat‐inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp‐214, His‐186 and Cys‐185, its enzymatic function, besides weak amino‐peptidase activity, is still unknown. We found that Hsp31 displays glyoxalase activity that catalyses the conversion of methylglyoxal (MG) to d‐lactate without an additional cofactor. The glyoxalase activity was completely abolished in the hchA‐deficient strain, confirming the relationship between the hchA gene and its enzymatic activity in vivo. Hsp31 exhibits Michaelis–Menten kinetics for substrates MG with Km and kcat of 1.43 ± 0.12 mM and 156.9 ± 5.5 min−1 respectively. The highest glyoxalase activity was found at 35–40°C and pH of 6.0–8.0, and the activity was significantly inhibited by Cu2+, Fe3+ and Zn2+. Mutagenesis studies based on our evaluation of conserved catalytic residues revealed that the Cys‐185 and Glu‐77 were essential for catalysis, whereas His‐186 was less crucial for enzymatic function, although it participates in the catalytic process. The stationary‐phase Escherichia coli cells became more susceptible to MG when hchA was deleted, which was complemented by an expression of plasmid‐encoded hchA. Furthermore, an accumulation of intracellular MG was observed in hchA‐deficient strains.
ArsAB, a novel enzyme from Sporomusa ovata activates phenolic bases for adenosylcobamide biosynthesis
Authors: Chan Chi Ho , Escalante‐Semerena Jorge C.
Published: June 2011

In the homoacetogenic bacterium Sporomusa ovata, phenol and p‐cresol are converted into α‐ribotides, which are incorporated into biologically active cobamides (Cbas) whose lower ligand bases do not form axial co‐ordination bonds with the cobalt ion of the corrin ring. Here we report the identity of two S. ovata genes that encode an enzyme that transfers the phosphoribosyl group of nicotinate mononucleotide (NaMN) to phenol or p‐cresol, yielding α‐O‐glycosidic ribotides. The alluded genes were named arsA and arsB (for alpha‐ribotide synthesis), arsA and arsB were isolated from a genomic DNA library of S. ovata. A positive selection strategy using an Escherichia coli strain devoid of NaMN:5,6‐dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) activity was used to isolate a fragment of S. ovata DNA that contained arsA and arsB, whose nucleotide sequences overlapped by 8 bp. SoArsAB was isolated to homogeneity, shown to be functional as a heterodimer, and to have highest activity at pH 9. SoArsAB also activated DMB to its α‐N‐glycosidic ribotide. Previously characterized CobT‐like enzymes activate DMB but do not activate phenolics. NMR spectroscopy was used to confirm the incorporation of phenol into the cobamide, and mass spectrometry was used to identify SoArsAB reaction products.
Characterization of DNA‐binding sequences for CcaR in the cephamycin–clavulanic acid supercluster of Streptomyces clavuligerus
Authors: Santamarta I. , López‐García M. T. , Kurt A. , Nárdiz N. , Álvarez‐Álvarez R. , Pérez‐Redondo R. , Martín J. F. , Liras P.
Published: June 2011

RT‐PCR analysis of the genes in the clavulanic acid cluster revealed three transcriptional polycistronic units that comprised the ceaS2–bls2–pah2–cas2, cyp–fd–orf12–orf13 and oppA2–orf16 genes, whereas oat2, car, oppA1, claR, orf14, gcaS and pbpA were expressed as monocistronic transcripts. Quantitative RT‐PCR of Streptomyces clavuligerus ATCC 27064 and the mutant S. clavuligerus ccaR::aph showed that, in the mutant, there was a 1000‐ to 10 000‐fold lower transcript level for the ceaS2 to cas2 polycistronic transcript that encoded CeaS2, the first enzyme of the clavulanic acid pathway that commits arginine to clavulanic acid biosynthesis. Smaller decreases in expression were observed in the ccaR mutant for other genes in the cluster. Two‐dimensional electrophoresis and MALDI‐TOF analysis confirmed the absence in the mutant strain of proteins CeaS2, Bls2, Pah2 and Car that are required for clavulanic acid biosynthesis, and CefF and IPNS that are required for cephamycin biosynthesis. Gel shift electrophoresis using recombinant r‐CcaR protein showed that it bound to the ceaS2 and claR promoter regions in the clavulanic acid cluster, and to the lat, cefF, cefD–cmcI and ccaR promoter regions in the cephamycin C gene cluster. Footprinting experiments indicated that triple heptameric conserved sequences were protected by r‐CcaR, and allowed identification of heptameric sequences as CcaR binding sites.
Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development
Authors: Mishra Arunima , Devarajan Bharanidharan , Reardon Melissa E. , Dwivedi Prabhat , Krishnan Vengadesan , Cisar John O. , Das Asis , Narayana Sthanam V. L. , Ton‐That Hung
Published: June 2011

By combining X‐ray crystallography and modelling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor‐dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG‐like domains, each of which harbours an intramolecular isopeptide bond, previously described in several Gram‐positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell–cell interactions and biofilm formation, they contribute significantly to the proteolytic stability of FimA. Remarkably, FimA harbours two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram‐positive fimbriae.
Antimicrobial peptide sensing and detoxification modules: unravelling the regulatory circuitry of Staphylococcus aureus
Authors: Gebhard Susanne , Mascher Thorsten
Published: June 2011

Investigations into the resistance mechanisms of Firmicutes bacteria against antimicrobial peptides have revealed unique resistance modules comprised of an unusual type of ATP‐binding cassette (ABC) transporter, paired with a two‐component regulatory system. In these systems, the ABC‐transporter is not only involved in detoxification of the peptides, but also in their detection and resulting regulation of gene expression. The manuscript by Hiron et al. (2011) published in this issue describes an intriguing complexity of regulatory circuits and division of labour between the three paralogous modules in Staphylococcus aureus, providing important mechanistic insights and new perspectives for future investigations of these unique systems.
Pervasive post‐transcriptional control of genes involved in amino acid metabolism by the Hfq‐dependent GcvB small RNA
Authors: Sharma Cynthia M. , Papenfort Kai , Pernitzsch Sandy R. , Mollenkopf Hans‐Joachim , Hinton Jay C. D. , Vogel Jörg
Published: June 2011

GcvB is one of the most highly conserved Hfq‐associated small RNAs in Gram‐negative bacteria and was previously reported to repress several ABC transporters for amino acids. To determine the full extent of GcvB‐mediated regulation in Salmonella, we combined a genome‐wide experimental approach with biocomputational target prediction. Comparative pulse expression of wild‐type versus mutant sRNA variants revealed that GcvB governs a large post‐transcriptional regulon, impacting ∼1% of all Salmonella genes via its conserved G/U‐rich domain R1. Complementary predictions of C/A‐rich binding sites in mRNAs and gfp reporter fusion experiments increased the number of validated GcvB targets to more than 20, and doubled the number of regulated amino acid transporters. Unlike the previously described targeting via the single R1 domain, GcvB represses the glycine transporter CycA by exceptionally redundant base‐pairing. This novel ability of GcvB is focused upon the one target that could feedback‐regulate the glycine‐responsive synthesis of GcvB. Several newly discovered mRNA targets involved in amino acid metabolism, including the global regulator Lrp, question the previous assumption that GcvB simply acts to limit unnecessary amino acid uptake. Rather, GcvB rewires primary transcriptional control circuits and seems to act as a distinct regulatory node in amino acid metabolism.
A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP‐43 proteinopathy (FTLD‐TDP)
Authors: Armstrong R. A. , Carter D. , Cairns N. J.
Published: June 2011

R. A. Armstrong, D. Carter and N. J. Cairns (2012) Neuropathology and Applied Neurobiology38, 25–38

A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP‐43 proteinopathy (FTLD‐TDP)

Aims: To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA‐binding protein of 43 kDa (TDP‐43) proteinopathy (FTLD‐TDP). Methods: We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation‐independent TDP‐43 antibody in 32 cases of FTLD‐TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer's disease (AD), and four neuropathological subtypes using TDP‐43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases. Results: These data from FTLD‐TDP cases demonstrate quantitative differences in pathological features between: (i) regions of the frontal and temporal lobe; (ii) upper and lower cortex; (iii) sporadic and progranulin (GRN) mutation cases; (iv) cases with and without AD or HS; and (v) between assigned subtypes. Conclusions: The data confirm that the dentate gyrus is a major site of neuropathology in FTLD‐TDP and that most laminae of the cerebral cortex are affected. GRN mutation cases are quantitatively different from sporadic cases, while cases with associated HS and AD have increased densities of dystrophic neurites and abnormally enlarged neurones respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data.
Review: The architecture of inflammatory demyelinating lesions: implications for studies on pathogenesis
Authors: Lassmann H.
Published: June 2011

H. Lassmann (2011) Neuropathology and Applied Neurobiology37, 698–710

The architecture of inflammatory demyelinating lesions: implications for studies on pathogenesis

Recent technological advances provided the chance to analyse the molecular events involved in the pathogenesis of lesions in human disease. A major prerequisite for such studies is, however, that the pathological material used is exactly defined and characterized. In multiple sclerosis (MS), this is difficult, as several types of active lesions exist, depending upon the stage of the disease, the age and location of these lesions and the inter‐individual differences between patients. In addition, within an active lesion, different closely adjacent zones are present reflecting initial tissue injury, debris removal or repair. Here evidence is reviewed, showing that distinct subareas of active MS lesions reflect different pathological hallmarks of lesion evolution. These data provide the basis for our understanding of the pathogenesis of tissue injury in MS and imply that studies on MS pathogenesis have to rely on a clear definition of the lesions analysed and have to focus on specific lesion areas, isolated by microdissection. In addition, these data also imply that molecules, identified in these studies, must be confirmed and validated in the correct context of lesion initiation and/or progression.
BRAF‐KIAA1549 fusion transcripts are less frequent in pilocytic astrocytomas diagnosed in adults
Authors: Hasselblatt M. , Riesmeier B. , Lechtape B. , Brentrup A. , Stummer W. , Albert F. K. , Sepehrnia A. , Ebel H. , Gerß J. , Paulus W.
Published: June 2011

M. Hasselblatt, B. Riesmeier, B. Lechtape, A. Brentrup, W. Stummer, F. K. Albert, A. Sepehrnia, H. Ebel, J. Gerß and W. Paulus (2011) Neuropathology and Applied Neurobiology37, 803–806

BRAF‐KIAA1549 fusion transcripts are less frequent in pilocytic astrocytomas diagnosed in adults

Aim: Duplication of 7q34 resulting in generation of BRAF‐KIAA1549 fusion transcripts is a characteristic event in pilocytic astrocytoma that may also aid distinction from diffuse astrocytic tumours. As data on BRAF‐KIAA1549 fusion transcript status remain mainly limited to children, we aimed to examine the diagnostic value of BRAF‐KIAA1549 fusion transcripts across all age groups. Methods:BRAF‐KIAA1549 fusion transcript status was examined using reverse transcription polymerase chain reaction on formalin‐fixed paraffin‐embedded samples of 105 primary pilocytic astrocytomas [median patient age: 17 years (1–74 years)]. Results: Informative results (distinct wildtype BRAF bands detectable) were obtained in 105/124 cases (85%). Fusion transcripts were detected in 53 of cases (51%). They were more often encountered in tumours of infratentorial location [42/67 (63%) vs. 11/38 (29%)] and comprised KIAA1549‐Ex16_BRAF‐Ex9 (32 cases), KIAA1549‐Ex15_BRAF‐Ex9 (14 cases) and KIAA1549‐Ex16_BRAF‐Ex11 (seven cases). Fusion transcripts were present in 79% of tumours diagnosed in the first decade of life, but only in 51% of patients aged 11–20 years, 42% of patients aged 21–30 years, 30% of patients aged 31–40 years and 7% of patients older than 40 years. On multivariate logistic regression analysis, the association of fusion transcript status and age was confirmed adjusting for tumour location (P = 0.006). Conclusions: The frequency of BRAF‐KIAA1549 fusion transcripts is significantly lower in adult patients with pilocytic astrocytoma, weakening the sensitivity of this specific diagnostic marker in that age group.
Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease
Authors: Orimo S. , Uchihara T. , Kanazawa T. , Itoh Y. , Wakabayashi K. , Kakita A. , Takahashi H.
Published: June 2011

S. Orimo, T. Uchihara, T. Kanazawa, Y. Itoh, K. Wakabayashi, A. Kakita and H. Takahashi (2011) Neuropathology and Applied Neurobiology37, 791–802

Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease

Aims: We recently demonstrated accumulation of α‐synuclein aggregates of the cardiac sympathetic nerve in Parkinson's disease (PD) and a possible relationship between degeneration of the cardiac sympathetic nerve and α‐synuclein aggregates. The aim of this study is to determine whether there is a difference in the degenerative process between unmyelinated and myelinated axons of the cardiac nerve. Methods: We immunohistochemically examined cardiac tissues from four pathologically verified PD patients, nine patients with incidental Lewy body disease (ILBD) and five control subjects, using antibodies against neurofilament, myelin basic protein (MBP) and α‐synuclein. First, we counted the number of neurofilament‐immunoreactive axons not surrounded by MBP (unmyelinated axons) and those surrounded by MBP (myelinated axons). Next, we counted the number of unmyelinated and myelinated axons with α‐synuclein aggregates. Results: (i) The percentage of unmyelinated axons in PD (77.5 ± 9.14%) was significantly lower compared to that in control subjects (92.2 ± 2.40%). (ii) The ratio of unmyelinated axons with α‐synuclein aggregates to total axons with α‐synuclein aggregates in ILBD ranged from 94.4 to 100 (98.2 ± 2.18%). Among axons with α‐synuclein aggregates, unmyelinated axons were the overwhelming majority, comprising 98.2%. Conclusion: These findings suggest that in PD unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve, because α‐synuclein aggregates accumulate much more abundantly in unmyelinated axons.
Septic metastatic encephalitis: coexistence of brain damage and repair
Authors: Tauber S. C. , Bunkowski S. , Brück W. , Nau R.
Published: June 2011

S. C. Tauber, S. Bunkowski, W. Brück and R. Nau (2011) Neuropathology and Applied Neurobiology37, 768–776

Septic metastatic encephalitis: coexistence of brain damage and repair

Aims: Septic metastatic encephalitis (SME) arises from systemic bacterial infections and is a severe complication of sepsis with a high mortality. In this study, we examined the neuropathological findings in humans suffering from SME including white matter pathology and proliferation of neural precursor cells in the hippocampal dentate gyrus. Methods: The brains of 10 autopsy cases with SME and 10 control cases after sudden death from non‐neurological causes were studied by means of immunohistochemistry. Results: We found diffuse axonal injury and demyelination in the frontal cortex (P = 0.01) as well as increased numbers of recently generated TUC‐4 expressing neurones in the hippocampal dentate gyrus in SME cases (P = 0.01). The median density of apoptotic granule cells in the dentate gyrus also was higher in SME cases, the difference, however, failed to reach statistical significance (P = 0.25). Conclusion: The coexistence of degenerative processes predominantly in the neocortex and regenerative activity in the hippocampal formation known from bacterial meningitis also characterizes the pathology of SME.
S100β as a novel and accessible indicator for the presence of monocyte‐driven encephalitis in AIDS
Authors: Renner N. A. , Redmann R. K. , Moroney‐Rasmussen T. , Sansing H. A. , Aye P. P. , Didier P. J. , Lackner A. A. , MacLean A. G.
Published: June 2011

N. A. Renner, R. K. Redmann, T. Moroney‐Rasmussen, H. A. Sansing, P. P. Aye, P. J. Didier, A. A. Lackner and A. G. MacLean (2012) Neuropathology and Applied Neurobiology38, 162–174

S100β as a novel and accessible indicator for the presence of monocyte‐driven encephalitis in AIDS

Aims: The pathogenesis of human/simian immunodeficiency virus encephalitis (HIVE/SIVE) remains incompletely understood, but is associated with alterations in the blood–brain barrier. At present, it is not possible to easily determine if an individual has HIVE/SIVE before post mortem examination. Methods: We have examined serum levels of the astroglial protein S100β in SIV‐infected macaques and show that it can be used to determine which animals have SIVE. We also checked for correlations with inflammatory markers such as CCL2/MCP‐1, IL‐6 and C‐reactive protein. Results: We found that increased S100β protein in serum correlated with decreased expression of the tight junction protein zonula occludens‐1 on brain microvessels. Furthermore, the decrease in zonula occludens‐1 expression was spatially related to SIVE lesions and perivascular deposition of plasma fibrinogen. There was no correlation between encephalitis and plasma levels of IL‐6, MCP‐1/CCL2 or C‐reactive protein. Conclusions: Together, these data indicate that SIVE lesions are associated with vascular leakage that can be determined by S100β protein in the periphery. The ability to simply monitor the presence of SIVE will greatly facilitate studies of the neuropathogenesis of AIDS.
Cytokinin antagonizes ABA suppression to seed germination of Arabidopsis by downregulating ABI5 expression
Authors: Wang Yanping , Li Lin , Ye Tiantian , Zhao Shujuan , Liu Zhao , Feng Yu‐Qi , Wu Yan
Published: June 2011

Abscisic acid (ABA) and cytokinin are key hormones controlling plant development. How ABA and cytokinin interplay to control the transition from a dry seed into a young seedling remains elusive. Here we undertook a gain‐of‐function genetic screen to identify ABA‐insensitive mutants during seed germination in Arabidopsis using an estradiol‐inducible approach. In the presence of estradiol, one of these mutants gim1 (germination insensitive to ABA mutant 1) exhibited an elevated level of cytokinin that was attributed to the estradiol‐induced expression of AtIPT8 that encodes an isopentenyltransferase for the biosynthesis of cytokinins. Our data on OE‐2 and Com‐1 transgenic plants carrying the ectopically expressing AtIPT8 gene indicated that the elevation of cytokinin level was responsible for the ABA‐insensitivity of gim1 seed germination. Further analyses on alterations of gene transcriptomes in the gim1 mutant demonstrated that the expression of some ABA‐inducible genes, including ABI5, was reduced, and could not be restored by exogenous ABA treatment. Moreover, we also failed to observe the ABA‐mediated repression of a family of cytokinin signal transducers and transcription repressors called type‐A ARR4, ARR5 and ARR6 in the gim1 seedlings. Further analysis demonstrated that type‐A ARR4, ARR5 and ARR6 could negatively regulate ABI5 expression, and the physical interaction of ABI5 and type‐A ARR4, ARR5 and ARR6 proteins was detected. In summary, our study suggests that the interaction of ABA and cytokinin during seed germination and seedling growth can be mediated by the interplay of transcriptional regulators in Arabidopsis.
Knowledge, attitude and practice towards blood donation in Iranian population
Authors: Mousavi F. , Tavabi A. A. , Golestan B. , Ammar‐Saeedi E. , Kashani H. , Tabatabaei R. , Iran‐Pour E.
Published: June 2011

Background: The increase in demand for blood products because of new surgical and medical procedures seeks more research to find new ways to recruit people to donate blood.

Objective/Aim: To determine the level of people's knowledge about donating blood considering its relation with infectious and chronic diseases, drug abuse, unsafe sexual intercourse, menstruation and anaemia. In addition, their attitude towards blood donation regarding their previous behaviour and factors such as altruism, religion, family, fears and availability of blood donation centres has been evaluated.

Methods: This study was conducted in Tehran, Iran in 2009 on 1000 respondents. Data were collected through questionnaires that comprised 37 questions considering demographic and background characteristics, level of knowledge and positive and negative attitudes towards blood donation. Finally, data were analysed using SPSS software.

Results: Of 1000 in this study, 26% were donors, of whom 55% had donated blood more than once. The mean knowledge score of the participants was 8·6, which was associated with the subjects' gender and level of education (P = 0·031 and P < 0·001, respectively). Age, gender and level of education were significantly associated with one's attitude towards blood donation (P = 0·021, P < 0·001 and P = 0·003,respectively). Ninety‐five percent of people have stated that their main motivation to donate blood was altruism.

Conclusion: Altruism and being encouraged by others had the leading roles in peoples' positive attitude towards blood donation; whereas hard access to blood donation centres seemed to be the main inhibitory factor.
Genotype–phenotype correlation in colorectal polyposis
Authors: Newton KF , Mallinson EKL , Bowen J , Lalloo F , Clancy T , Hill J , Evans DGR
Published: June 2011

Newton KF, Mallinson EKL, Bowen J, Lalloo F, Clancy T, Hill J, Evans DGR. Genotype–phenotype correlation in colorectal polyposis.

Familial adenomatous polyposis (FAP) has been divided into three clinical subtypes: mild, classical and severe. This study aimed to investigate for a correlation between genotype and phenotype. A codon‐specific survival difference is unknown. A retrospective longitudinal study of 492 patients on the Manchester Polyposis Registry was conducted. Patients were grouped according to genotypes: 0, unknown mutation; 1, adenomatous polyposis coli (APC) 0–178 (and 312–412 of exon 9); 2, APC >1550; 3, APC 179–1249; 4, APC 1250–1549; and 5, MutYH. Date of onset of polyposis, incidence of colorectal cancer (CRC), survival and actuarial time to surgery were calculated. Median age of onset of polyposis for genotype 0 was 20.3 years, genotype 1 35.6 years, genotype 2 32.2, genotype 3 15.9 years, and genotype 4 14.8 years (p < 0.0001). Age of onset of CRC was similar between genotypes. Median survival for genotype 0 was 56.6 years, genotype 1 74.9 years, genotype 2 61.0 years, genotype 3 63.0 years, genotype 4 48.1 years, and genotype 5 69.7 years (p = 0.003). This survival difference was also seen when patients who underwent screening and those who did not were analysed separately. Survival in the screened population was 53.9 years in genotype 4 and 72.9 years in genotype 3. Patients with genotype 4 (APC 1249–1549) have a significantly worse survival despite screening and early prophylactic surgery. This analysis supports a genotype–phenotype correlation. Patients with a mutation APC 1249–1549 develop polyposis at an early age and have a worse survival. Patients with a mutation APC 0–178 or 312–412 develop polyposis later and have an improved survival. This survival difference has not previously been documented.
High frequency of autosomal‐recessive DFNB59 hearing loss in an isolated Arab population in Israel
Authors: Borck G , Rainshtein L , Hellman‐Aharony S , Volk AE , Friedrich K , Taub E , Magal N , Kanaan M , Kubisch C , Shohat M , Basel‐Vanagaite L
Published: June 2011

Borck G, Rainshtein L, Hellman‐Aharony S, Volk AE, Friedrich K, Taub E, Magal N, Kanaan M, Kubisch C, Shohat M, Basel‐Vanagaite L. High frequency of autosomal‐recessive DFNB59 hearing loss in an isolated Arab population in Israel.

Autosomal‐recessive non‐syndromic hearing impairment (DFNB) is usually of prelingual onset with a moderate to profound degree of hearing loss. More than 70 DFNB loci have been mapped and ∼40 causative genes have been identified. Non‐syndromic hearing impairment caused by mutations of DFNB59 (encoding pejvakin) has been described in a couple of families in which affected individuals presented with either auditory neuropathy or hearing loss of cochlear origin. We have identified and clinically evaluated three consanguineous families of Israeli Arab origin with prelingual non‐syndromic hearing impairment and absent otoacoustic emissions in a total of eight affected individuals. All the families originate from the same village and bear the same family name. We have identified a c.406C>T (p.R136X) nonsense mutation in the DFNB59 gene in affected individuals from these families. Among the inhabitants of the village, we found an exceptionally high carrier frequency of ∼1 in 12 individuals (7/85; 8.2%). The high prevalence of hearing impairment can be explained by a founder effect and the high consanguinity rate among the inhabitants of this village.
Novel mutation in ATP13A2 widens the spectrum of Kufor‐Rakeb syndrome (PARK9)
Authors: Eiberg H , Hansen L , Korbo L , Nielsen IM , Svenstrup K , Bech S , Pinborg LH , Friberg L , Hjermind LE , Olsen OR , Nielsen JE
Published: June 2011

Eiberg H, Hansen L, Korbo L, Nielsen IM, Svenstrup K, Bech S, Pinborg LH, Friberg L, Hjermind LE, Olsen OR, Nielsen JE. Novel mutation in ATP13A2 widens the spectrum of Kufor‐Rakeb syndrome (PARK9).

Kufor‐Rakeb syndrome (KRS) is a rare autosomal recessive inherited juvenile parkinsonian syndrome caused by mutations in ATP13A2. We describe six patients from a consanguineous Greenlandic Inuit family, homozygous for a novel frame‐shift mutation in exon 22 of ATP13A2 (c.2473C>AA, p.Leu825AsnfsX32). Disease onset varied from 10 to 29 years of age, the latest reported, and the clinical features were highly variable within a wide spectrum of an extrapyramidal–pyramidal syndrome with cognitive/psychiatric features. Ataxia was seen in two patients and axonal neuropathy in one, features not previously related to KRS. Dopamine transporter scans showed symmetrical, severely reduced uptake in striatum in two patients. Magnetic resonance imaging was without atrophy in one patient despite disease duration of 17 years, and cerebral and cerebellar atrophy was seen in another patient after 4 years of disease duration. The molecular pathogenic mechanisms of ATP13A2 mutations are discussed. The observation that the mutant transcript is not degraded by nonsense‐mediated RNA decay and the fact that none of the eight heterozygous carriers from the family have KRS symptoms suggest that the mutant protein does not interfere and destroy the function of the wild‐type ATP13A2 protein.
Infectious risk in xenotransplantation – what post‐transplant screening for the human recipient?
Authors: Denner Joachim
Published: June 2011

Denner J. Infectious risk in xenotransplantation – what post‐transplant screening for the human recipient? Xenotransplantation 2011; 18: 151–157. © 2011 John Wiley & Sons A/S.

Abstract:  Xenotransplantation may be associated with the transmission of pig microorganisms including viruses, bacteria, fungi, and parasites. As the recipient may be immunosuppressed, infection and pathologic consequences may be more pronounced compared to non‐immunosuppressed individuals. Transmission of most microorganisms with exception of porcine endogenous retroviruses (PERV) may be prevented by screening the donor pig and qualified pathogen‐free breeding. PERVs represent a special risk as they are present in the genome of all pigs and infect human cells in vitro. Until now, no PERV transmission was observed in experimental and clinical xenotransplantations as well as in numerous infection experiments. Nevertheless, several strategies have been developed to prevent PERV transmission.
Attitudinal study of organ xenotransplantation in patients on the kidney and liver transplant waiting list in a country with a high rate of deceased donation
Authors: Martínez‐Alarcón Laura , Ríos Antonio , Pons Jose A. , González Maria J. , Ramis Guillermo , Ramírez Pablo , Parrilla Pascual
Published: June 2011

Martínez‐Alarcón L, Ríos A, Pons JA, González MJ, Ramis G, Ramírez P, Parrilla P. Attitudinal study of organ xenotransplantation in patients on the kidney and liver transplant waiting list in a country with a high rate of deceased donation. Xenotransplantation 2011; 18: 168–175. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  The organ transplant deficit is leading to an increase in the importance of solid organ xenotransplantation. However, the use of animals for human transplantation causes a certain amount of opposition in patients and the general public. The objective of this study was to analyze the attitude of patients on the kidney and liver waiting list toward xenotransplantation and the variables affecting this attitude.

Methods:  Patients on the kidney and liver waiting list (January 2003 – December 2005) were surveyed. Attitude toward xenotransplantation was assessed using a psychosocial questionnaire about the donation of organs of animal origin administered by a healthcare professional from the Transplant Unit.

Results:  A total of 373 patients were interviewed (kidney [n = 214] and liver patients [n = 158]). In the case of kidney patients, if the results of xenotransplantation were as effective as those attained using human organs, 76% (n = 162) would be in favor. If the results were worse, only 8% (n = 17) would be in favor. Two factors affected this attitude: a high level of education (P = 0.007) and a positive attitude toward organ donation upon death (P < 0.001). In the case of liver patients, 67% (n = 106) would be in favor if the results of xenotransplantation were as effective as those attained using human organs, decreasing to 16% (n = 25) if the results were worse. Attitude toward deceased organ donation also affected the attitude of these patients (P < 0.043).

Conclusions:  The attitude toward xenotransplantation of patients on the kidney and liver transplant waiting list was favorable and associated with a positive attitude toward human organ donation.
Effect of αGal on corneal xenotransplantation in a mouse model
Authors: Choi Hyuk Jin , Kim Mee Kum , Lee Hyun Ju , Jeong So Hee , Kang Hee Jung , Park Chan‐Sik , Park Chung‐Gyu , Joon Kim Sang , Wee Won Ryang
Published: June 2011

Choi HJ, Kim MK, Lee HJ, Jeong SH, Kang HJ, Park C‐S, Park C‐G, Kim SJ, Wee WR. Effect of αGal on corneal xenotransplantation in a mouse model. Xenotransplantation 2011; 18: 176–182. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  It has been reported that hyperacute rejection (HAR) does not occur after pig‐to‐nonhuman corneal xenotransplantation. However, considering that immune privilege is already disrupted in most human corneal recipients, and the expression of αGal can be gradually reduced after pig‐to‐rat corneal transplantation, the long‐term survival of corneal grafts from wild‐type pigs cannot be guaranteed. Accordingly, we aimed to investigate the effect of αGal on the change in anti‐Gal antibodies, using sensitized α1,3‐galactosyltransferase gene‐knockout (GTKO) mice recipients.

Methods:  C57BL/6 (B6) and GTKO mice were divided into 5 groups and underwent orthotopically full thickness cormeal transplantation as follows (n=4 for each group): (1) group 1: B6 to B6; (2) group 2: fresh porcine posterior corneal lamella to B6; (3) fresh porcine posterior corneal lamella to GTKO; (4) group 4: decellularized porcine posterior corneal lamella to GTKO, and (5) group 5: B6 to GTKO. Before transplantation, all GTKO recipients were sensitized using intraperitoneal injections of rabbit blood cells. Median survival times (MST) for the corneal grafts of the different groups were compared and plasma concentrations of IgG/IgM anti‐Gal antibodies were evaluated at 1 week, 2 weeks and 3 weeks post‐transplantation.

Results:  There were no differences in MSTs between groups. Although there was no HAR of fresh porcine posterior corneal grafts even in sensitized GTKO recipients, αGal expression was induced in the transplanted fresh porcine corneal grafts and plasma concentration of IgG anti‐Gal antibody was gradually increased in fresh porcine cornea‐grafted GTKO recipients. On the contrary, αGal expression did not increase in the grafts and plasma concentration of anti‐Gal antibodies did not change after transplantation using decellularized porcine corneas.

Conclusions:  Our findings suggest that αGal may affect the long‐term survival of porcine corneal xenografts via antibody‐mediated rejection, although αGal does not have an effect on acute rejection and decellularized porcine corneas may enable the long‐term survival of porcine corneal xenografts.
Discoid lupus erythematosus at a site of previous injury
Authors: Ruocco Eleonora , Brunetti Giampiero , Sangiuliano Sonia , Caccavale Stefano , Lo Schiavo Ada
Published: June 2011

A 71‐year‐old man with three patches of discoid lupus erythematosus (DLE) confined to the right preauricular region drew our attention because of the unusual linear arrangement of the lesions. Twenty‐five years previously, the patient had suffered a trauma in the same area from falling off his motorcycle. We believe that, despite the great lapse in time, this injury may have facilitated the onset of DLE in the very same area, through long‐term destabilization of the local neuroimmune network. The case fits the recently coined concept of the immunocompromised district, a cutaneous region with altered immune control, more susceptible to harbouring opportunistic infections, tumours, and immune disorders.
Coexistence of congenital linear porokeratosis and disseminated superficial porokeratosis
Authors: Cho Eujin , Lee Young Bok , Park Hyun Jeong , Cho Baik Kee
Published: June 2011

The coexistence of two or more forms of porokeratosis in a single individual is rarely reported. We report here on a patient exhibiting the coexistence of congenital linear porokeratosis and disseminated superficial porokeratosis. To our knowledge, this entity has been previously reported only once.
Establishment and characterization of a novel dedifferentiated liposarcoma cell line, NDDLS‐1
Authors: Ariizumi Takashi , Ogose Akira , Kawashima Hiroyuki , Hotta Tetsuo , Li Guidong , Xu Yongjun , Hirose Takanori , Endo Naoto
Published: June 2011

We established a dedifferentiated liposarcoma cell line (NDDLS‐1) that produces interleukin‐6 (IL‐6) and granulocyte‐colony stimulating factor (G‐CSF). The parental tumor showed high leukemoid reactions. The NDDLS‐1 cell line was established from a pleural effusion associated with a lung metastasis. Pleomorphic tumor cells arranged in a haphazard growth pattern were seen in xenograft tumors. Numerous inflammatory cells including neutrophils or eosinophils were present throughout the tumor cells. This finding resembled the dedifferentiated area of the parental tumor. The mice bearing NDDLS‐1 showed marked leukocytosis. In addition, the NDDLS‐1 cells expressed IL‐6 and G‐CSF at both the mRNA and protein levels, while the NDDLS‐1 cells produced near normal levels of tumor necrosis factor alpha (TNF‐α). In the cytogenetic analysis, both the parental tumor and the NDDLS‐1 cells showed a ring or giant marker chromosomes. The NDDLS‐1 cell line demonstrated the amplification and expression of both MDM2 and CDK4 by fluorescence in situ hybridization and immunohistochemical analysis. The NDDLS‐1 cell line is consistent with the parental dedifferentiated liposarcoma, and it should therefore be useful for further investigations of human dedifferentiated liposarcomas.
Experiences of women who have a vaginal birth after requesting a Cesarean section due to a fear of birth: A biographical, narrative, interpretative study
Authors: Ramvi Ellen , Tangerud Margrethe
Published: June 2011

A fear of childbirth is a reason for a Cesarean section on request without a medical indication. The law for patients' rights in Norway does not give women the opportunity to choose a Cesarean section, only the potential to participate in the decision‐making process. This requires cooperation between health professionals and patients. The present study explores the experience of women who had a vaginal birth after requesting a Cesarean section due to a fear of birth. A biographical, narrative, interpretative method was used. Through five women's stories, it is evident that the practice of decision‐making constitutes a challenge for both the women and the health professionals. The importance of a woman's right to be taken seriously, even if she does not want to understand the reason behind her fear of birth, is emphasized. An open mind from midwives and physicians is required, although this seems difficult to achieve.
Fatigue strength analysis of notched aluminium specimens using the highly stressed volume method
Authors: VAN HOOREWEDER BRECHT , MOENS DAVID , BOONEN RENE , SAS PAUL
Published: June 2011

This paper describes a methodology to analyse the fatigue strength of notched aluminium 7075 T7531 specimens using the highly stressed volume method. A straightforward test setup was developed to load test samples with different stress concentrations in repeated bending at high frequency. The highly stressed volumes are precisely determined using static finite element analysis in combination with Matlab for post‐processing. Mean values of the local endurable stress amplitudes are calculated by means of the staircase method. The results indicate that the highly stressed volume can be used as an accurate and efficient design parameter to take the notch‐effect in aluminium components into account.
Messenger RNA processing and its role in diabetes
Authors: Harries L. W.
Published: June 2011

Diabet. Med. 28, 1010–1017 (2011)

The past few years have seen huge advances in our understanding of the genetics of diabetes. However, definition of the mechanisms that underpin these observations is less clear. It is now becoming apparent that the processes that mediate these effects are complex and interlinked, and will require consideration of other factors in addition to the DNA sequence. The information in our genes is conveyed to the cellular machinery via an intermediate molecule, RNA. However, we now understand that RNA is not merely a messenger, as RNA‐based mechanisms are responsible for a large proportion of the fine‐tuning of gene expression and gene regulation. The initial RNA transcript produced undergoes a series of modifications known as RNA processing to generate a mature messenger RNA (mRNA). This includes addition of the 5’ cap sequences and the poly‐A tail of the mRNA molecule, and removal of its intronic sequences. The exact pattern of mRNA processing may vary from cell type to cell type and differ in response to internal and external stimuli. In this review, using examples from my own work, I will outline how mRNA processing mechanisms can sometimes provide a mode of action for mutations causing monogenic diabetes, and also suggest potential explanations for phenotypic variation in this condition. The potential for mRNA processing to impact on more complex causes of diabetes as well will also be considered.
As Autumn Turns to Winter – in Search of the Archive Without an Address
Authors: MAIR KIMBERLY
Published: June 2011

This paper reflects upon absences in the institutional archive and considers the problems associated with the search for non‐textual records. Speculating on the potential of the city street, or spaces as such, as sites of collection, this paper aims to perform a displacement of public forms of memorialization, such as the formal archive, the gravestone, or the public monument and argues that institutional forms of memorialization tend to trade the ontological accumulation of imprints, echoes, and trajectories embodied in everyday spaces for both physical and conceptual containment in a form that is subject to hierarchies of meaning to which public space is ultimately accountable.
Motivated Closed‐Mindedness Mediates the Effect of Threat on Political Conservatism
Authors: Thórisdóttir Hulda , Jost John T.
Published: June 2011

In this article we synthesize theory and research from several areas of psychology and political science to propose and test a causal model of the effects of threat on political attitudes. Based in part on prior research showing that fear, threat, and anxiety decrease cognitive capacity and motivation, we hypothesize that under high (vs. low) threat, people will seek to curtail open‐ended information searches and exhibit motivated closed‐mindedness (one aspect of the need for cognitive closure). The subjective desire for certainty, control, and closure, in turn, is expected to increase the individual's affinity for political conservatism, insofar as resistance to change and adherence to authority figures and conventional forms of morality are assumed to satisfy these epistemic motives more successfully than their ideological opposites. Consistent with this account, we find in Studies 1a and 1b that putting people into a highly threatened mindset leads them to exhibit an increase in motivated closed‐mindedness and to perceive the world as more dangerous. Furthermore, in Study 2 we demonstrate that a subtle threat manipulation increases self‐reported conservatism (or decreases self‐reported liberalism), and this effect is mediated by closed‐mindedness. In Study 3, we manipulated closed‐mindedness directly and found that high (vs. low) cognitive load results in a greater affinity for the Republican (vs. Democratic) party. Finally, in Study 4 we conducted an experiment involving political elites in Iceland and found that three different types of threat (to the self, group, and system) all led center‐right politicians to score higher on closed‐mindedness and issue‐based political conservatism. Implications for society and for the theory of ideology as motivated social cognition are discussed.