bluuebunny/crossref_metadata_2025 huggingface dataset:
The planning of appropriate medical and social care in dementia
Authors: Olde-Rikkert Marcel GM , Draskovic Irena , Vernooij-Dassen Myrra
Published: October 2011

• Alzheimer’s disease is probably caused by multiple disease processes that occur simultaneously, have a long preclinical history, and together cause a clinically significant decline of cognitive reserve

• The cognitive reserve theory is an attractive simple theory that may enable clinicians and researcher to formulate innovative research questions, however it still requires an evidence base...
The biochemical properties of the Francisella pathogenicity island (FPI)-encoded proteins IglA, IglB, IglC, PdpB and DotU suggest roles in type VI secretion
Authors: de Bruin Olle M. , Duplantis Barry N. , Ludu Jagjit S. , Hare Rebekah F. , Nix Eli B. , Schmerk Crystal L. , Robb Craig S. , Boraston Alisdair B. , Hueffer Karsten , Nano Francis E.
Published: October 2011

The Francisella pathogenicity island (FPI) encodes proteins thought to compose a type VI secretion system (T6SS) that is required for the intracellular growth of Francisella novicida. In this work we used deletion mutagenesis and genetic complementation to determine that the intracellular growth of F. novicida was dependent on 14 of the 18 genes in the FPI. The products of the iglABCD operon were localized by the biochemical fractionation of F. novicida, and Francisella tularensis LVS. Sucrose gradient separation of water-insoluble material showed that the FPI-encoded proteins IglA, IglB and IglC were found in multiple fractions, especially in a fraction that did not correspond to a known membrane fraction. We interpreted these data to suggest that IglA, IglB and IglC are part of a macromolecular structure. Analysis of published structural data suggested that IglC is an analogue of Hcp, which is thought to form long nano-tubes. Thus the fractionation properties of IglA, IglB and IglC are consistent with the current model of the T6SS apparatus, which supposes that IglA and IglB homologues form an outer tube structure that surrounds an inner tube composed of Hcp (IglC) subunits. Fractionation of F. novicida expressing FLAG-tagged DotU (IcmH homologue) and PdpB (IcmF homologue) showed that these proteins localize to the inner membrane. Deletion of dotU led to the cleavage of PdpB, suggesting an interaction of these two proteins that is consistent with results obtained with other T6SSs. Our results may provide a mechanistic basis for many of the studies that have examined the virulence properties of Francisella mutants in FPI genes, namely that the observed phenotypes of the mutants are the result of the disruption of the FPI-encoded T6SS structure.
Target recognition, resistance, immunity and genome mining of class II bacteriocins from Gram-positive bacteria
Authors: Kjos Morten , Borrero Juan , Opsata Mona , Birri Dagim J. , Holo Helge , Cintas Luis M. , Snipen Lars , Hernández Pablo E. , Nes Ingolf F. , Diep Dzung B.
Published: October 2011

Due to their very potent antimicrobial activity against diverse food-spoiling bacteria and pathogens and their favourable biochemical properties, peptide bacteriocins from Gram-positive bacteria have long been considered promising for applications in food preservation or medical treatment. To take advantage of bacteriocins in different applications, it is crucial to have detailed knowledge on the molecular mechanisms by which these peptides recognize and kill target cells, how producer cells protect themselves from their own bacteriocin (self-immunity) and how target cells may develop resistance. In this review we discuss some important recent progress in these areas for the non-lantibiotic (class II) bacteriocins. We also discuss some examples of how the current wealth of genome sequences provides an invaluable source in the search for novel class II bacteriocins.
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations
Authors: Jing Hua , Kase Julia , Dörr Jan R. , Milanovic Maja , Lenze Dido , Grau Michael , Beuster Gregor , Ji Sujuan , Reimann Maurice , Lenz Peter , Hummel Michael , Dörken Bernd , Lenz Georg , Scheidereit Claus , Schmitt Clemens A. , Lee Soyoung
Published: October 2011

In malignancies, enhanced nuclear factor-κB (NF-κB) activity is largely viewed as an oncogenic property that also confers resistance to chemotherapy. Recently, NF-κB has been postulated to participate in a senescence-associated and possibly senescence-reinforcing cytokine response, thereby suggesting a tumor-restraining role for NF-κB. Using a mouse lymphoma model and analyzing transcriptome and clinical data from lymphoma patients, we show here that therapy-induced senescence presents with and depends on active NF-κB signaling, whereas NF-κB simultaneously promotes resistance to apoptosis. Further characterization and genetic engineering of primary mouse lymphomas according to distinct NF-κB-related oncogenic networks reminiscent of diffuse large B-cell lymphoma (DLBCL) subtypes guided us to identify Bcl2-overexpressing germinal center B-cell-like (GCB) DLBCL as a clinically relevant subgroup with significantly superior outcome when NF-κB is hyperactive. Our data illustrate the power of cross-species investigations to functionally test genetic mechanisms in transgenic mouse tumors that recapitulate distinct features of the corresponding human entity, and to ultimately use the mouse model-derived genetic information to redefine novel, clinically relevant patient subcohorts.
Gene Expression Biomarkers Provide Sensitive Indicators of in Planta Nitrogen Status in Maize
Authors: Yang Xiaofeng S. , Wu Jingrui , Ziegler Todd E. , Yang Xiao , Zayed Adel , Rajani M.S. , Zhou Dafeng , Basra Amarjit S. , Schachtman Daniel P. , Peng Mingsheng , Armstrong Charles L. , Caldo Rico A. , Morrell James A. , Lacy Michelle , Staub Jeffrey M.
Published: October 2011

Over the last several decades, increased agricultural production has been driven by improved agronomic practices and a dramatic increase in the use of nitrogen-containing fertilizers to maximize the yield potential of crops. To reduce input costs and to minimize the potential environmental impacts of nitrogen fertilizer that has been used to optimize yield, an increased understanding of the molecular responses to nitrogen under field conditions is critical for our ability to further improve agricultural sustainability. Using maize (Zea mays) as a model, we have characterized the transcriptional response of plants grown under limiting and sufficient nitrogen conditions and during the recovery of nitrogen-starved plants. We show that a large percentage (approximately 7%) of the maize transcriptome is nitrogen responsive, similar to previous observations in other plant species. Furthermore, we have used statistical approaches to identify a small set of genes whose expression profiles can quantitatively assess the response of plants to varying nitrogen conditions. Using a composite gene expression scoring system, this single set of biomarker genes can accurately assess nitrogen responses independently of genotype, developmental stage, tissue type, or environment, including in plants grown under controlled environments or in the field. Importantly, the biomarker composite expression response is much more rapid and quantitative than phenotypic observations. Consequently, we have successfully used these biomarkers to monitor nitrogen status in real-time assays of field-grown maize plants under typical production conditions. Our results suggest that biomarkers have the potential to be used as agronomic tools to monitor and optimize nitrogen fertilizer usage to help achieve maximal crop yields.
Beyond drug use: a systematic consideration of other outcomes in evaluations of treatments for substance use disorders
Authors: Tiffany Stephen T. , Friedman Lawrence , Greenfield Shelly F. , Hasin Deborah S. , Jackson Ron
Published: October 2011

Across the addictions field, the primary outcome in treatment research has been reduction in drug consumption. A comprehensive view of the impact of substance use disorders on human functioning suggests that effective treatments should address the many consequences and features of addiction beyond drug use, a recommendation forwarded by multiple expert panels and review papers. Despite recurring proposals, and a compelling general rationale for moving beyond drug use as the sole standard for evaluating addiction treatment, the field has yet to adopt any core set of ‘other’ measures that are routinely incorporated into treatment research. Among the many reasons for the limited impact of previous proposals has been the absence of a clear set of guidelines for selecting candidate outcomes. This paper is the result of the deliberations of a panel of substance abuse treatment and research experts convened by the National Institute on Drug Abuse to discuss appropriate outcome measures for clinical trials of substance abuse treatments. This paper provides an overview of previous recommendations and outlines specific guidelines for consideration of candidate outcomes. A list of outcomes meeting those guidelines is described and illustrated in detail with two outcomes: craving and quality of life. The paper concludes with specific recommendations for moving beyond the outcome listing offered in this paper to promote the programmatic incorporation of these outcomes into treatment research.
Is alcohol dependence best viewed as a chronic relapsing disorder?
Authors: Cunningham John A. , McCambridge Jim
Published: October 2011

This ‘For Debate’ paper starts by recognizing the growing trend towards considering alcohol dependence as a chronic relapsing disorder. We argue that the adoption of this model results from focusing on those in treatment for alcohol dependence rather than considering the larger number of people in the general population who meet criteria for alcohol dependence at some point in their lives. The majority of the general population who ever experience alcohol dependence do not behave as though they have a chronic relapsing disorder: they do not seek treatment, resolve their dependence themselves and do not relapse repeatedly. We suggest that caution is therefore needed in using the chronic relapsing disorder label. Our primary concerns are that this formulation privileges biological aspects of dependence to the detriment of psychological and social contributions, it inhibits much‐needed developments in understanding alcohol dependence and leads to inefficient distributions of public health and clinical care resources for alcohol dependence. We invite debate on this issue.
RNA‐mediated gene silencing of ToxB in Pyrenophora tritici‐repentis
Authors: ABOUKHADDOUR REEM , KIM YONG MIN , STRELKOV STEPHEN E.
Published: October 2011

The fungus Pyrenophora tritici‐repentis causes tan spot, a wheat leaf disease of worldwide importance. The pathogen produces three host‐selective toxins, including Ptr ToxB, which causes chlorophyll degradation and foliar chlorosis on toxin‐sensitive wheat genotypes. The ToxB gene, which codes for Ptr ToxB, was silenced in a wild‐type race 5 isolate of the fungus thorough a sense‐ and antisense‐mediated silencing mechanism. Toxin production by the silenced strains was evaluated in culture filtrates of the fungus via Western blotting analysis, and plant bioassays were conducted to test the virulence of the transformants in planta. The chlorosis‐inducing ability of the silenced strains was correlated with the quantity of Ptr ToxB, and transformants in which toxin production was strongly decreased also caused very little disease on toxin‐sensitive wheat genotypes. Cytological analysis of the infection process revealed that, in addition to a reduced capacity to induce chlorosis, the silenced strains with the greatest decrease in the levels of Ptr ToxB produced significantly fewer appressoria than the wild‐type isolate, 12 and 24 h after inoculation onto wheat leaves. The results provide strong support for the suggestion that the amount of Ptr ToxB protein produced by fungal isolates plays a significant role in the quantitative variation in the virulence of P. tritici‐repentis.
Proteomics plus genomics approaches in primary immunodeficiency: the case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
Authors: Zennaro D , Scala E , Pomponi D , Caprini E , Arcelli D , Gambineri E , Russo G , Mari A
Published: October 2011

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare syndrome due to a mutation in the forkhead box protein 3 gene (FOXP3) leading to an impaired regulatory T cell (Treg) activity associated both with skewed T helper type 2 (Th2) response and autoreactive phenomena. The purpose of this study was to describe a combined proteomics and genomics approach to comprehensively evaluate clinical and immunological phenotypes of patients affected by IPEX. T cell receptor (TCR)-Vβ repertoire and peripheral blood lymphocytes phenotype from three brothers affected by IPEX were studied by flow cytometry. Specific immunoglobulin (Ig)E were evaluated by means of an allergenic molecules microarray [immuno solid-phase allergen chip (ISAC)]. Total RNA was extracted and hybridized to Affymetrix oligonucleotide arrays to obtain quantitative gene-expression levels. No FOXP3 protein was detectable within CD127-CD25highCD4+ T cells from peripheral blood. A T cell-naive phenotype (CD62L+CD45R0-) associated with a reduction of both CD26 and CD7 expression and a TCR-Vβ 8 and 22 family expansions were found. B lymphocytes were mainly CD5+ (B1) cells expressing a naive phenotype (tcl1+CD27-). The three IPEX patients had severe food allergy and specific IgE reactivity to cow's milk allergens, a hen's egg allergen and a wheat allergen. Gene expression profile analysis revealed a dysregulation associated mainly with Th1/Th2 pathways. The multiplexing evaluation reported in this study represents a comprehensive approach in the assessment of genetic conditions affecting the immune system such as the IPEX syndrome, paving the way for the development of diagnostic tools to improve the standard clinical and immunological profiling of the disease.
Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs
Authors: Steinborn A , Schmitt E , Kisielewicz A , Rechenberg S , Seissler N , Mahnke K , Schaier M , Zeier M , Sohn C
Published: October 2011

Dysregulations concerning the composition and function of regulatory T cells (Tregs) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six-colour flow cytometric analysis to demonstrate that the total CD4+CD127low+/−CD25+forkhead box protein 3 (FoxP3)+ Treg cell pool contains four distinct Treg subsets: DRhigh+CD45RA-, DRlow+CD45RA-, DR-CD45RA- Tregs and naive DR-CD45RA+ Tregs. During the normal course of pregnancy, the most prominent changes in the composition of the total Treg cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DRhigh+CD45RA- and DRlow+CD45RA- Tregs and a clear increase in the percentage of naive DR-CD45RA+ Tregs. After that time, the composition of the total Treg cell pool did not change significantly. Its suppressive activity remained stable during normally progressing pregnancy, but decreased significantly at term. Compared to healthy pregnancies the composition of the total Treg cell pool changed in the way that its percentage of naive DR-CD45RA+ Tregs was reduced significantly in the presence of pre-eclampsia and in the presence of preterm labour necessitating preterm delivery (PL). Interestingly, its percentage of DRhigh+CD45RA- and DRlow+CD45RA- Tregs was increased significantly in pregnancies affected by pre-eclampsia, while PL was accompanied by a significantly increased percentage of DR-CD45RA- and DRlow+CD45RA- Tregs. The suppressive activity of the total Treg cell pool was diminished in both patient collectives. Hence, our findings propose that pre-eclampsia and PL are characterized by homeostatic changes in the composition of the total Treg pool with distinct Treg subsets that were accompanied by a significant decrease of its suppressive activity.
Use of cone beam computed tomography in the diagnosis, planning and follow up of a type III dens invaginatus case
Authors: Vier‐Pelisser F. V. , Pelisser A. , Recuero L. C. , Só M. V. R. , Borba M. G. , Figueiredo J. A. P.
Published: October 2011

Vier‐Pelisser FV, Pelisser A, Recuero LC, Só MVR, Borba MG, Figueiredo JAP. Use of cone beam computed tomography in the diagnosis, planning and follow up of a type III dens invaginatus case. International Endodontic Journal, 45, 198–208, 2012.

Aim  To present the case of a maxillary left lateral incisor with Oehlers’ type III dens invaginatus in which cone beam computed tomography (CBCT) was used as an adjunctive resource in the diagnosis as well as in the planning and 2‐year follow‐up of the nonsurgical/surgical treatment.

Summary  The tooth had two root canals: a primary (main) canal with vital pulp that appeared to be closed apically and an invaginated canal that was necrotic, wide‐open at the portal of exit and associated with a large chronic periapical lesion extending to the apex of the maxillary left central incisor. Radiographic tracking of a sinus tract in the labial gingiva of the affected tooth with a gutta‐percha point revealed its origin to be the invagination. The CBCT scans revealed that the periapical radiolucency was significantly larger than seen radiographically as well as an increased thickness of the buccal cortical plate. Conventional root canal treatment of the primary canal was undertaken. As nonsurgical access to the invaginated canal was not possible, endodontic surgery was performed for curettage of the lesion, root‐end cavity preparation using ultrasonic tips and root canal filling with white mineral trioxide aggregate (MTA). CBCT scanning after 17 months and clinical and radiographic follow‐up after 24 months revealed complete periapical repair and absence of symptoms.

Key learning points 

 The combination of nonsurgical and surgical treatments produced periapical repair in a tooth with type III dens invaginatus with two root canals.

 CBCT may aid the diagnosis as well as the management plan and follow‐up of teeth with this developmental anomaly.
Male reproductive success increases with alliance size in Indo‐Pacific bottlenose dolphins (Tursiops aduncus)
Authors: Wiszniewski Joanna , Corrigan Shannon , Beheregaray Luciano B. , Möller Luciana M.
Published: October 2011

1. Determining the extent of variation in male mating strategies and reproductive success is necessary to understand the fitness benefits of social and cooperative behaviour.

2. This study assesses the reproductive success of male Indo‐Pacific bottlenose dolphins in a small embayment population where different behavioural strategies of males have previously been identified. Parentage for 44 sampled calves was examined using 23 microsatellite loci and one mitochondrial DNA marker. Our candidate parent pool of 70 males and 64 females contained individuals sampled from both the embayment and adjacent coastal populations.

3. A moderate level of polygyny was detected in our sample. We assigned paternity of 23 calves to 12 males at the strict 95% confidence level and an additional nine calves to two males at the 80% confidence level. The majority (92%) of successful males were identified as residents to the embayment, and 46% of offspring were located within the same social group or community as their father.

4. Our results suggest that the size of alliances was the best predictor of reproductive success for males in this population, while the strength of association among allied males, alliance stability and male ranging patterns had little influence. In line with predictions for male alliances formed between unrelated individuals, we found that reproductive skew within alliances was not large.

5. Together, our genetic and behavioural analyses demonstrate that alliance formation between male dolphins is a successful strategy to enhance reproductive output.
Changes in Oestrogen Receptor‐β mRNA Expression in Male Rat Brain with Age
Authors: Yamaguchi N. , Yuri K.
Published: October 2011

Oestrogen has important roles not only in the regulation of reproductive function, but also with respect to other functions, such as cognition, emotion and cardiovascular regulation. Oestrogen acts mainly via its oestrogen receptor (ER), namely, ERα and ERβ in target tissues, including the brain. During ageing, the actions of oestrogen are altered in both females and males, raising the possibility that the expression level of ER may be altered with age. Age‐related changes in ER expression in female rat brain have been well demonstrated with regard to reproductive ageing, whereas very little is known about the effects of age on the expression of ERs, especially ERβ, in males. In the present study, which aimed to elucidate the effects of ageing on ERβ expression in the male brain at the transcriptional level, we performed in situ hybridisation using young (10 weeks), middle‐aged (12 months) and old (24 months) gonadally‐intact male rats. We revealed a wide distribution of ERβ mRNA‐positive cells throughout the brain, and found that the number of ERβ mRNA‐positive cells was reduced in several brain regions in males with ageing. ERβ mRNA‐positive cells were decreased with age in layer 6 of the cerebral cortex, hippocampal CA1/CA3 regions, the dorsal endopiriform nucleus, the medial septal nucleus, various subregions of the amygdala (central, lateral, anterior cortical and posterolateral cortical subnuclei), the anteroventral periventricular nucleus, the substantia nigra pars compacta, the raphe magnus nucleus and the locus coeruleus. These results suggest that ERβ expression in male rat brain decreases with age at the transcriptional level and that these ageing effects are region‐specific.
Anatomically‐Specific Actions of Oestrogen Receptor in the Developing Female Rat Brain: Effects of Oestradiol and Selective Oestrogen Receptor Modulators on Progestin Receptor Expression
Authors: Gonzales K. L. , Quadros‐Mennella P. , Tetel M. J. , Wagner C. K.
Published: October 2011

Steroid hormones largely exert their actions by activating nuclear receptors, which, as transcription factors, powerfully influence fundamental processes of neural development. Often, steroid receptor action demonstrates remarkable specificity under different developmental, anatomical or hormonal conditions. Yet, the mechanisms underlying such specificity are poorly understood. The present study examined the anatomically‐specific regulation of progestin receptor (PR) expression by oestrogen receptor (ER) activation in the ventromedial nucleus (VMN) of the hypothalamus and the medial preoptic nucleus (MPN) of the neonatal female rat brain, using the selective oestrogen receptor modulators (SERMs), tamoxifen and ICI 182 780 (ICI), in the presence or absence of oestradiol benzoate (EB) treatment. The results demonstrate that PR immunoreactivity (PR‐ir) in the neonatal female MPN was significantly increased by EB and this increase was abolished by either tamoxifen or ICI treatment. In contrast, within the VMN of the same animals, EB had no effect on PR‐ir and the SERMs only modestly decreased PR‐ir. Interestingly, ICI acted as a true antagonist regardless of EB treatment, whereas tamoxifen acted as an ER agonist in the absence of EB in the MPN, but not the VMN, representing one of the first in vivo demonstrations of tissue‐specific and oestradiol‐independent effects of tamoxifen on ER activation. The present results indicate that PR expression is highly dependent on oestradiol and its receptor in the MPN, although it is independent of both oestradiol and ER activation within the neonatal VMN. These findings demonstrate the anatomically‐specific actions of oestradiol and its receptor to induce PR in two brain regions controlling different aspects of female reproductive behaviours in adulthood.
Up‐Regulation of Neurosteroid Biosynthesis as a Pharmacological Strategy to Improve Behavioural Deficits in a Putative Mouse Model of Post‐Traumatic Stress Disorder
Authors: Pinna Graziano , Rasmusson Ann M.
Published: October 2011

Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however, their use is associated with the development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with post‐traumatic stress disorder (PTSD). For these nonresponders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalise decreased brain levels of neurosteroids in patients with depression and PTSD; in particular, the progesterone derivative allopregnanolone, which potently, positively and allosterically modulates the action of GABA at GABAA receptors. Preclinical studies using the socially‐isolated mouse as an animal model of PTSD have demonstrated that fluoxetine and congeners ameliorate anxiety‐like behaviour, fear responses and aggressive behaviour expressed by such mice by increasing corticolimbic levels of allopregnanolone. This is a novel and more selective mechanism than serotonin reuptake inhibition, which, for half a century, has been considered to be the main molecular mechanism for the therapeutic action of SSRIs. Importantly, this finding may shed light on the high rates of SSRI resistance among patients with PTSD and depression, comprising disorders in which there appears to be a block in allopregnanolone synthesis. There are several different mechanisms by which such a block may occur, and SSRIs may only be corrective under some conditions. Thus, the up‐regulation of allopregnanolone biosynthesis in corticolimbic neurones may offer a novel nontraditional pharmacological target for a new generation of potent nonsedating, anxiolytic medications for the treatment of anxiety, depression, and PTSD: selective brain steroidogenic stimulants.
Immunohistochemistry for the diagnosis of hepatitis E virus infection
Authors: Gupta P. , Jagya N. , Pabhu S. B. , Durgapal H. , Acharya S. K. , Panda S. K.
Published: October 2011

Summary. Hepatitis E virus (HEV) is an emerging pathogen and the most common cause of acute viral hepatitis all over the world. We describe here an immunohistochemical method for the detection of HEV antigens (pORF2 and pORF3) in formalin‐fixed, paraffin‐embedded liver tissues using monoclonal antibodies raised against two of the virus proteins (pORF2 and pORF3). We analysed their specificity and sensitivity in comparison with serology and nucleic acid detection in cases of acute liver failure (ALF). We used this test on 30 liver biopsies collected post‐mortem from the patients of ALF caused by HEV infection. These cases were selected on the basis of positive results for enzyme immunoassay (IgM anti‐HEV). Of the 30 cases taken from the archives of the Department of Pathology, the antibodies successfully stained all. However, only 25 serum samples (83.3%) of these were positive for HEV RNA. Fifteen controls used (Five noninfected liver tissues, five HBV‐ and five hepatitis C virus‐infected liver tissues) were all negative. The immunohistochemical assay described here may prove a valuable tool for the detection of HEV infection in biopsy, autopsy and explant liver tissues and can serve as a link along with other available tests to delineate the extent of HEV‐associated problem worldwide.
Genetics of resistance to downy mildew in Brassica oleracea and breeding towards durable disease control for UK vegetable production
Authors: Vicente J. G. , Gunn N. D. , Bailey L. , Pink D. A. C. , Holub E. B.
Published: October 2011

Downy mildew resistance was previously identified from screening a Brassica oleracea collection against two standard UK isolates of Hyaloperonospora parasitica. Sources of resistance were chosen from this material and developed further in this study by generating doubled haploid (DH) and inbred lines. Seedlings from the new lines were tested for resistance to a larger collection of H. parasitica isolates collected in 2001–2002 and 2007–2008 from the main broccoli and cauliflower production regions of the UK. Three lines (derived from borecole or summer cabbage) were broadly resistant to the pathogen isolates. Three of the remaining lines exhibited strong isolate‐specific resistance; several examples of weak or basal level of resistance to some isolates were observed. A new H. parasitica variant collected in 2008 was virulent in the broadly resistant lines, but was avirulent in a line with narrow specificity of resistance. The F2 and BC1 seedlings derived from outcrossing each of the three broadly resistant lines to susceptible broccoli and cauliflower lines segregated in a manner indicating that the resistance was controlled by a single dominant gene. No susceptibility was observed amongst F2 seedlings derived from intercrossing the three resistant lines, indicating that they all share the same or closely linked broad‐spectrum resistance gene(s). DH lines were produced from F1 plants, and resistant plants were further backcrossed to produce broccoli and cauliflower‐like lines that could be useful pre‐breeding material. A combination of resistance from lines with broad and narrow specificity is recommended for controlling downy mildew in UK brassica production.
Novel p.M96T variant of NRL and shRNA‐based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa
Authors: Hernan I , Gamundi MJ , Borràs E , Maseras M , García‐Sandoval B , Blanco‐Kelly F , Ayuso C , Carballo M
Published: October 2011

Hernan I, Gamundi MJ, Borràs E, Maseras M, García‐Sandoval B, Blanco‐Kelly F, Ayuso C, Carballo M. Novel p.M96T variant of NRL and shRNA‐based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa.

Mutations in the gene encoding the transcription factor neural retina leucine zipper (NRL) are known to cause autosomal dominant (adRP) or recessive (arRP) retinitis pigmentosa (RP). In an adRP Spanish family, we detected a novel sequence variation (c.287T>C) in the NRL gene that results in the p.M96T protein change. A functional test of the ability of NRL, in conjunction with cone‐rod homeobox (CRX), to transactivate a human rhodopsin (RHO) promoter was used to evaluate the pathogenic mechanisms of NRL. We found upregulation of the RHO promoter by p.M96T protein similar to that shown by other missense NRL mutations that cause adRP. Affected RP patients of the family carry the nucleotide change, although two other family members that also carry the c.287T>C variation remain asymptomatic. This result complicates the genetic counselling of the family.

The pathogenic mechanisms associated with adRP NRL mutations appear to be caused by a gain of function. To suppress the negative effect of an NRL mutant, the suppression and replacement strategy seems to be the most suitable therapeutic approach capable of overcoming the mutational heterogeneity associated with NRL‐linked adRP. Thus, we evaluated this methodology in the NRL gene for the first time.
A novel genus of multicellular magnetotactic prokaryotes from the Yellow Sea
Authors: Zhou Ke , Zhang Wen‐Yan , Yu‐Zhang Kui , Pan Hong‐Miao , Zhang Sheng‐Da , Zhang Wei‐Jia , Yue Hai‐Dong , Li Ying , Xiao Tian , Wu Long‐Fei
Published: October 2011

Multicellular magnetotactic prokaryotes (MMPs) are a group of magnetotactic microorganisms composed of 10–40 Gram‐negative cells. Currently, all the identified MMPs show a spherical morphology and synthesize mainly iron sulfide magnetosomes. In this study, we report a novel genus of MMPs with peculiar ellipsoidal morphology and iron oxide magnetosomes, which were discovered in intertidal sediment of the Yellow Sea in China. Optical and fluorescence microscopy revealed that this organism was ∼10 × 8 µm in size and composed of ∼40 cells enveloped by an outer layer. Scanning electron microscopy showed that the cells were arranged in 4–6 interlaced circles. Bullet‐shaped magnetite magnetosomes were organized in chains roughly parallel to the long axis of the ellipsoidal MMPs when analysed by transmission electron microscopy. These MMPs displayed special escape motility, i.e. swimming rapidly from the edge to the centre of the droplet and then slowly back to the edge. In addition, they exhibited negative phototaxis. Light microscopy observations showed that the ellipsoidal MMPs reproduced by division along the body long axis. Both analysis of 16S rRNA gene sequence and fluorescence in situ hybridization revealed the ellipsoidal MMPs as a new genus of the Deltaproteobacteria. In summary, this novel genus of MMPs exhibit unique morphology, peculiar division process and distinct phylogenetic affiliation compared with the other MMPs.
The atypical cannabinoid O‐1602 stimulates food intake and adiposity in rats
Authors: Díaz‐Arteaga A. , Vázquez M. J. , Vazquez‐Martínez R. , Pulido M. R. , Suarez J. , Velásquez D. A. , López M. , Ross R. A. , de Fonseca F. Rodriguez , Bermudez‐Silva F. J. , Malagón M. M. , Diéguez C. , Nogueiras R.
Published: October 2011

Aims: Cannabinoids are known to control energy homeostasis. Atypical cannabinoids produce pharmacological effects via unidentified targets. We sought to investigate whether the atypical cannabinoid O‐1602 controls food intake and body weight.

Methods: The rats were injected acutely or subchronically with O‐1602, and the expression of several factors involved in adipocyte metabolism was assessed by real‐time polymerase chain reaction. In vivo findings were corroborated with in vitro studies incubating 3T3‐L1 adipocytes with O‐1602, and measuring intracellular calcium and lipid accumulation. Finally, as some reports suggest that O‐1602 is an agonist of the putative cannabinoid receptor GPR55, we tested it in mice lacking GPR55.

Results: Central and peripheral administration of O‐1602 acutely stimulates food intake, and chronically increases adiposity. The hyperphagic action of O‐1602 is mediated by the downregulation of mRNA and protein levels of the anorexigenic neuropeptide cocaine‐ and amphetamine‐regulated transcript. The effects on fat mass are independent of food intake, and involve a decrease in the expression of lipolytic enzymes such as hormone sensitive lipase and adipose triglyceride lipase in white adipose tissue. Consistently, in vitro data showed that O‐1602 increased the levels of intracellular calcium and lipid accumulation in adipocytes. Finally, we injected O‐1602 in GPR55 −/− mice and found that O‐1602 was able to induce feeding behaviour in GPR55‐deficient mice.

Conclusions: These findings show that O‐1602 modulates food intake and adiposity independently of GPR55 receptor. Thus atypical cannabinoids may represent a novel class of molecules involved in energy balance.
Reference values for Schirmer tear tests I and II in clinically normal pigs
Authors: Trbolova Alexandra , Ghaffari Masoud Selk
Published: October 2011

Objective  To determine reference values for Schirmer tear tests I and II in clinically normal pigs.

Animal studied  Twenty clinically normal Landrace pigs (10 males and females) without ocular abnormalities were used in this study.

Procedures  In all pigs, Schirmer tear tests (STT) I and II were performed by using a sterile Schirmer tear test standardized strip (Schirmer‐Tränentest®, Germany) placed in the lower conjunctival fornix for 1 min.

Results  For each test (STT I and STT II), no differences were observed between the right and left eyes (P ≥ 0.5). The mean ± SD STT I value was 15.6 ± 3.7 mm/min (range, 10–22 mm/min), while the mean STT II value was 12.4 ± 3.8 mm/minute (range, 5–18 mm/min). The mean STT II value was significantly lower than the STT I level (P < 0.001). Animal gender did not have a significant effect on STT I and II values (P = 0.52). The mean ± SD STT I/II values of 10 juvenile pigs were significantly lower than the mean ± SD STT I/II values of 10 adult pigs (P < 0.001).

Conclusions  This study of 20 Landrace pigs provided valuable information on normal STT I/II in this species. Knowledge of normal STT reference values in pigs enables the clinician to evaluate corneal pathology and diagnose tear deficiency syndromes with greater accuracy.
Intracorporeal neobladder reconstruction: pressure‐flow urodyamic studies in cadaveric orthotopic neobladders
Authors: Blute Jr Michael L. , George Arvin , Herati Amin , Srinivasian Arun , Vira Manish A. , Kavoussi Louis R. , Richstone Lee
Published: October 2011

Study Type – Therapy (case series)

Level of Evidence 4

OBJECTIVE

• To determine the pressure‐flow characteristics of neobladders created in various configurations that may be constructed intra‐abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set.

MATERIALS AND METHODS

• Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W‐pouch, and U‐pouch with stapled anastamoses.

• Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined.

RESULTS

• The cystometric capacities of the stapled U‐pouch, W‐pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL.

• The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U‐pouch, with the W‐pouch revealing a compliance of 3.44 mL/cmH2O.

• The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O).

CONCLUSION

• The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure‐flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo.
Biochemical outcome after high‐dose‐rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience
Authors: Prada Pedro J. , González Herminio , Fernández José , Jiménez Isabel , Iglesias Aránzazu , Romo Inmaculada
Published: October 2011

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal.

The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.

The mean (median) follow‐up was 71 (68) months.

Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).

The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).

The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.

Gleason score was the only factor to significantly affect distant metastases.

Grade ≥3 late toxicity was not detected.

CONCLUSION

The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.
Global Warming with Green and Brown Consumers
Authors: Wirl Franz
Published: October 2011

In this paper, I investigate how much green polluters mitigate the familiar dynamic “tragedy of the commons” (“global warming”). Green consumers feel penalized (“pain”) for any consumption in excess of the social optimum; this can arise, for example, from Kant’s categorical moral imperative. Interplays among and between green and brown consumers are investigated as differential games. Green preferences, the heterogeneity of consumers, and the irreversibility of emissions lead to discontinuous strategies. Associated with these are a number of non‐trivial and even puzzling features (e.g., the possibility of another “green paradox”).
Ways of knowing for ‘response‐ability’ in more‐than‐human encounters: the role of anticipatory knowledges in outdoor access with dogs
Authors: Brown Katrina , Dilley Rachel
Published: October 2011

Geographical scholarship is increasingly concerned with how knowledges count in human–nonhuman relations, including questions of what it takes to achieve responsible practice, and the forms of expertise that shape corporeal encounters. This paper highlights how the outdoors comes to be known matters for the integrity of human and non‐human bodies performing and encountered in outdoor spaces. It examines some of the ways of knowing demanded in accomplishing responsible outdoor access with dogs, in terms of constituting response‐ability – or the capacity to respond – across species and geographical difference. Through mobile and visual ethnographic methods enabling episodes and repertoires of canine–human enactments to be witnessed and recounted, we identify ways of knowing the outdoors that exceed cognition of the formal scriptings of conduct, yet are crucial to preventing its transgression through engendering capacities to respond. We identify in particular the role of anticipatory knowledges, and argue that better account needs to be taken of the embodied preparatory and pre‐emptory ways of knowing that make the mutual doings of response‐ability across spatial and species difference possible. These encompass a set of temporally interleaving spatio‐corporeal competencies that render the crux time‐spaces of ‘irresponsible’ human–nonhuman ruptures preventable rather than merely recognisable. They work by shaping and being attuned to how dog and human bodies become articulate to each other in relation to the shifting ecologies, topographies, terrains and proximities of an outdoor excursion. Consequently, we raise the question of the work of responsibility done (or not) in terms of our human obligations to animals when attentions become focused on codified rather than the broader range of outdoor knowledges.
Cell quality of apheresis‐derived platelets treated with riboflavin‐ultraviolet light after resuspension in platelet additive solution
Authors: Picker Susanne M. , Tauszig Marie E. , Gathof Birgit S.
Published: October 2011

BACKGROUND: Previously, we evaluated the Mirasol pathogen reduction technology (PRT) system on platelet (PLT) function before resuspension. We now evaluated this system in the presence of PLT additive solution (PAS).

STUDY DESIGN AND METHODS: Double‐dose PLTs (n = 15) were generated using a commercially available apheresis system (Trima, Version 5.2, CaridianBCT) allowing for the resuspension in SSP+ (MacoPharma) immediately after collection. Paired units (n = 30) were PRT treated (M) or remained untreated (C) and analyzed for metabolism (pH, pO2, glucose, lactate, adenosine triphosphate [ATP]), swirl, hypotonic shock response (HSR), turbidometric aggregation, CD62P expression, annexin A5 and lactate dehydrogenase (LDH) release, mitochondrial enzymatic reduction activity (MTS), transmembrane mitochondrial potential (Δψ), and surface coverage (SC) during shear‐induced adhesion throughout 8 days of storage.

RESULTS: As seen previously, PRT treatment of PLT units, containing a mean of 3.9 × 1011 ± 0.3 × 1011 PLTs in 397 ± 10 mL with a 32% to 34% plasma carryover, was associated with significantly (p < 0.001) increased cell activation, acidity, and glycolytic flux. PRT treatment appeared to up regulate both oxidative pathway and adhesional properties as evidenced by significantly higher MTS reduction, oxygen consumption, and shear‐induced SC on Day 1 (p ≤ 0.016). While no significant differences were found for LDH release and ATP content (except for Day 8), M units were significantly inferior (p ≤ 0.021) for aggregation (TRAP‐6); for Δψ and annexin A5 release (by Day 5); and for swirl, HSR, and MTS reduction (by Day 7).

CONCLUSION: PRT treatment in the presence of PAS was comparable to PRT treatment before resuspension preserving ATP content and mitochondrial function.
Immunosuppressive effects of red blood cells on monocytes are related to both storage time and storage solution
Authors: Muszynski Jennifer , Nateri Jyotsna , Nicol Kathleen , Greathouse Kristin , Hanson Lisa , Hall Mark
Published: October 2011

BACKGROUND: Reduced monocyte function is associated with adverse outcomes from critical illness. Red blood cells (RBCs) are thought to impair monocyte function but relationships between RBC storage solution and monocyte suppression are unknown. This study was designed to test the hypothesis that immunosuppressive effects of RBCs on monocytes are related to both storage time and preservative solution.

STUDY DESIGN AND METHODS: Monocytes from healthy adult donors were co‐cultured with RBCs that had been stored in AS‐1, AS‐3, or CPD only for 7, 14, or 21 days. Cells were then stimulated with lipopolysaccharide (LPS) and their supernatants assayed for tumor necrosis factor (TNF)‐α and interleukin (IL)‐10. Transwell experiments were performed to evaluate the role of cell‐to‐cell contact. Monocyte mRNA expression was quantified by real‐time–polymerase chain reaction.

RESULTS: LPS‐induced TNF‐α production capacity was reduced compared to controls for all groups, but CPD‐only RBCs suppressed monocyte function more than RBCs stored in AS‐1 (p = 0.007) and AS‐3 (p = 0.006). IL‐10 production was preserved or augmented in all groups. A longer storage time was associated with reduced TNF‐α production capacity for AS‐1 and AS‐3 groups but not CPD. Preventing cell‐to‐cell contact did not eliminate the inhibitory effect of RBCs on monocyte responsiveness. RBC exposure was associated with decreased LPS‐induced TNFA mRNA expression (p < 0.05 for all groups).

CONCLUSIONS: CPD‐only RBCs suppressed monocyte function more than RBCs stored with additive solutions. TNF‐α production was reduced even in the absence of cell‐to‐cell contact and was impaired at the mRNA level. Further work is needed to understand the role of preservative solutions in this process.