bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats
Authors: Jia Ning , Yang Kun , Sun Qinru , Cai Qing , Li Hui , Cheng Daxin , Fan Xiaoli , Zhu Zhongliang
Published: November 2009

A substantial number of human epidemiological data, as well as experimental studies, suggest that adverse maternal stress during gestation is involved in abnormal behavior, mental, and cognition disorder in offspring. To explore the effect of prenatal stress (PS) on hippocampal neurons, in this study, we observed the dendritic field of pyramidal neurons in hippocampal CA3, examined the concentration of glutamate (Glu), and detected the expression of synaptotagmin‐1 (Syt‐1) and N‐methyl‐D‐aspartate receptor 1 (NR1) in hippocampus of juvenile female offspring rats. Pregnant rats were divided into two groups: control group (CON) and PS group. Female offspring rats used were 30‐day old. The total length of the apical dendrites of pyramidal neurons in hippocampal CA3 of offspring was significantly shorter in PS than that in CON (p < 0.01). The number of branch points of the apical dendrites of pyramidal neurons in hippocampal CA3 of offspring was significantly less in PS (p < 0.01). PS offspring had a higher concentration of hippocampal Glu compared with CON (p < 0.05). PS offspring displayed increased expression of Syt‐1 and decreased NR1 in hippocampus compared with CON (p < 0.001 and p < 0.01, respectively). The expression of NR1 in different hippocampus subfields of offspring was significantly decreased in PS than that in CON (p < 0.05‐0.01). This study shows that PS increases the Glu in hippocampus and causes apical dendritic atrophy of pyramidal neurons of hippocampal CA3 in offspring rats. The decline of NR1 in hippocampus may be an adaptive response to the increased Glu. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2010
Age differences in genetic and environmental influences on weight and shape concerns
Authors: Klump Kelly L. , Burt S. Alexandra , Spanos Alexia , McGue Matt , Iacono William G. , Wade Tracey D.
Published: November 2009

Objective

Previous research has shown important developmental shifts ingenetic and environmental influences for disordered eating. However, little research has examined age differences for weight/shape concerns, two key components of eating disorders. The goal of this study was to investigate these age differences in preadolescent, adolescent, young adult, and mid‐adult twins.

Method

Participants included 2,618 female twins (ages of 10–41 years) from three large twin registries. Shape and weight concerns were assessed with the Eating Disorders Examination Questionnaire.

Results

Genetic influences were modest in preadolescent twins, but significant from early‐adolescence through middle adulthood. Shared environmental factors showed the opposite pattern, with the largest shared environmental contributions occurring in the youngest age group. Nonshared environmental effects remained relatively constant across age.

Discussion

Findings highlight the importance of age differences in genetic and environmental influences. Possible mechanisms include gene x environment interactions and biological changes associated with key developmental stages. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:679–688
Recurrent acute hepatic dysfunction in severe anorexia nervosa
Authors: Dowman Joanna , Arulraj Ramakrishnan , Chesner Ian
Published: November 2009

Anorexia nervosa (AN) is an eating disorder predominantly affecting young women. Abnormal liver function tests (LFT's) resulting from AN is well‐described but to date few cases of dramatic rises in liver enzymes have been described. We report a 32‐year‐old women with severe anorexia having dramatic rise in LFT's with liver failure during extremely poor nutritional status. Acute rise in liver enzymes observed on several occasions in this patient resulted from ischaemic hepatitis secondary to liver hypoperfusion. Clinicians caring for patients with severe AN should monitor haemodynamic parameters with the knowledge that acute liver failure can be a consequence of sudden liver hypoperfusion. Therapeutic intervention comprising volume support with gradual nutritional support results in normalization of LFT's. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:770–772
Differences in coping across stages of recovery from an eating disorder
Authors: Fitzsimmons Ellen E. , Bardone‐Cone Anna M.
Published: November 2009

Objective

This study examined the relation between coping skills and eating disorder recovery by comparing these skills across healthy controls, fully recovered, partially recovered, and active eating disorder cases. Full recovery was defined using physical, behavioral, and psychological components.

Method

Individuals formerly seen for an eating disorder at a Midwestern clinic were categorized as having an active eating disorder (n= 53), as partially recovered (n= 15), or as fully recovered (n= 20). The coping skills of these groups were compared to each other and to 67 healthy controls.

Results

Healthy controls and fully recovered individuals utilized similarly high levels of task‐ and avoidance‐oriented coping and similarly low levels of emotion‐oriented coping. Partially recovered individuals looked more similar to those with an active eating disorder.

Discussion

Results provide support for a comprehensive definition of eating disorder recovery, of which healthy coping may be an integral component, and for the re‐evaluation of the notion of “maladaptive” coping. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:689–693
PKC‐α controls MYD88‐dependent TLR/IL‐1R signaling and cytokine production in mouse and human dendritic cells
Authors: Langlet Christelle , Springael Cécile , Johnson Jolyn , Thomas Séverine , Flamand Véronique , Leitges Michael , Goldman Michel , Aksoy Ezra , Willems Fabienne
Published: November 2009

Conventional PKC (cPKC)‐α regulates TRIF‐dependent IFN response factor 3 (IRF3)‐mediated gene transcription, but its role in MyD88‐dependent TLR signaling remains unknown. Herein, we demonstrate that PKC‐α is induced by several MyD88‐dependent TLR/IL‐1R ligands and regulates cytokine expression in human and murine DC. First, inhibition of cPKC activity in human DC by cPKC‐specific inhibitors, Gö6976 or HBDDe, downregulated the production of classical inflammatory/immunomodulatory cytokines induced by TLR2, TLR5 or IL‐1R but not by TLR3 stimulation. Similarly, dominant negative PKC‐α repressed Pam3CSK4 induced NF‐κB‐ and AP‐1‐driven promoter activities in TLR2‐expressing human embryonic kidney 293 T cells. Dominant negative PKC‐α inhibited NF‐κB reporter activity mediated by overexpression of MyD88 but not TRIF. Unexpectedly, BM‐derived DC from PKC‐α−/− mice exhibited decreased TNF‐α and IL‐12p40 production induced by both MyD88‐ and TRIF‐dependent ligands. Furthermore, PKC‐α is coupled to TLR2 signaling proximal to MyD88 since MAPK and IκB kinase‐α/β phosphorylations and IκBα degradation were inhibited in PKC‐α−/− BM‐derived DC. Finally, co‐immunoprecipitation assays revealed that PKC‐α physically interacts with Pam3CSK4 activated TLR2 in WT but not in MyD88−/− DC. Collectively this study identifies a species‐specific role of PKC‐α as a key component that controls MyD88‐dependent cytokine gene expression in human and mouse but differentially regulates production of TRIF‐dependent cytokines.
c‐Rel phenocopies PKCθ but not Bcl‐10 in regulating CD8+ T‐cell activation versus tolerance
Authors: Deenick Elissa K. , Po Leslie , Chapatte Laurence , Murakami Kiichi , Lu Yong‐Chen , Elford Alisha R. , Saibil Samuel D. , Ruland Jürgen , Gerondakis Steve , Mak Tak W. , Ohashi Pamela S.
Published: November 2009

Elucidating the signaling events that promote T‐cell tolerance versus activation provides important insights for manipulating immunity in vivo. Previous studies have suggested that the absence of PKCθ results in the induction of anergy and that the balance between the induction of the transcription factors NFAT, AP1 and NF‐κB plays a key role in determining whether T‐cell anergy or activation is induced. Here, we examine whether Bcl‐10 and specific family members of NF‐κB act downstream of PKCθ to alter CD8+ T‐cell activation and/or anergy. We showed that T cells from mice deficient in c‐Rel but not NF‐κB1 (p50) have increased susceptibility to the induction of anergy, similar to T cells from PKCθ‐deficient mice. Surprisingly T cells from Bcl‐10‐deficient mice showed a strikingly different phenotype to the PKCθ‐deficient T cells, with a severe block in TCR‐mediated activation. Furthermore, we have also shown that survival signals downstream of NF‐κB, are uncoupled from signals that mediate T‐cell anergy. These results suggest that c‐Rel plays a critical role downstream of PKCθ in controlling CD8+ T‐cell anergy induction.
Human rhinoviruses induce IL‐35‐producing Treg via induction of B7‐H1 (CD274) and sialoadhesin (CD169) on DC
Authors: Seyerl Maria , Kirchberger Stefanie , Majdic Otto , Seipelt Joachim , Jindra Christoph , Schrauf Catharina , Stöckl Johannes
Published: November 2009

IL‐35 is a heterodimer of EBV‐induced gene 3 and of the p35 subunit of IL‐12, and recently identified as an inhibitory cytokine produced by natural Treg in mice, but not in humans. Here we demonstrate that DC activated by human rhinoviruses (R‐DC) induce IL‐35 production and release, as well as a suppressor function in CD4+ and CD8+ T cells derived from human peripheral blood but not in naïve T cells from cord blood. The induction of IL‐35‐producing T cells by R‐DC was FOXP3‐independent, but blocking of B7‐H1 (CD274) and sialoadhesin (CD169) on R‐DC with mAb against both receptors prevented the induction of IL‐35. Thus, the combinatorial signal delivered by R‐DC to T cells via B7‐H1 and sialoadhesin is crucial for the induction of human IL‐35+ Treg. These results demonstrate a novel pathway and its components for the induction of immune‐inhibitory T cells.
The role of sex hormones in the development of Th2 immunity in a gender‐biased model of Trichuris muris infection
Authors: Hepworth Matthew R. , Hardman Matthew J. , Grencis Richard K.
Published: November 2009

Trichuris muris infection is an ideal model for defining T‐cell‐driven immunity, and also provides essential insights that may impact on potential helminth therapies currently in development. Conflicting host variables determine the efficiency of such treatments and we have identified host‐derived sex steroid hormones as key factors in the development of immunity. The female‐associated hormone 17‐β estradiol (E2) significantly enhanced the generation of a Th2 response in vitro; however, this stimulatory effect was found to be dispensable for the generation of immunity to Trichuris in the gender‐biased IL‐4KO mouse model. In contrast, the male‐associated hormone dihydrotestosterone significantly inhibited the T‐cell stimulatory capacity of DC and directly suppressed the immune response of male IL‐4KO mice, with worm expulsion restored following castration. This finding was associated with dramatically reduced IL‐18 mRNA expression suggesting androgens may act via this cytokine to suppress Th2 immunity to Trichuris. This study has critical implications for the development and efficacy of potential helminth therapeutics and identifies host gender – specifically sex hormones – as important factors in the development of Th2 immunity in susceptible and immunocompromised mice.
Apoptotic lymphocytes treated with IgG from Trypanosoma cruzi infection increase TNF‐α secretion and reduce parasite replication in macrophages
Authors: Montalvão Fabricio , Almeida Geisy M. , Silva Elisabeth M. , Borges Valeria M. , Vasconcellos Rita , Takiya Christina M. , Lopes Marcela F. , Nunes Marise P. , DosReis George A.
Published: November 2009

Phagocytic removal of apoptotic lymphocytes exacerbates replication of Trypanosoma cruzi in macrophages. We investigated the presence of Ab against apoptotic lymphocytes in T. cruzi infection and the role of these Ab in parasite replication. Both control and chagasic serum contained IgG Ab that opsonized apoptotic lymphocytes. Treatment of apoptotic lymphocytes with purified IgG from chagasic, but not control serum, reduced T. cruzi replication in macrophages. The protective effect of chagasic IgG depended on Fcγ receptors, as demonstrated by the requirement for the intact Fc portion of IgG, and the effect could be abrogated by treating macrophages with an anti‐CD16/CD32 Fab fragment. Chagasic IgG displayed increased reactivity against a subset of apoptotic cell Ag, as measured by flow cytometry and immunoblot analyses. Apoptotic lymphocytes treated with chagasic IgG, but not control IgG, increased production of TNF‐α, while decreasing production of TGF‐β1 by infected macrophages. Increased control of parasite replication required TNF‐α production. Previous immunization with apoptotic cells or injection of apoptotic cells opsonized with chagasic IgG reduced parasitemia in infected mice. These results indicate that Ab raised against apoptotic cells could play a protective role in control of T. cruzi replication by macrophages.
IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii
Authors: Jones Leigh A. , Roberts Fiona , Nickdel Mohammad B. , Brombacher Frank , McKenzie Andrew N. J. , Henriquez Fiona L. , Alexander James , Roberts Craig W.
Published: November 2009

T1/ST2 is an immunoregulatory protein of the IL‐1 receptor family that has recently been reported as being a component of the IL‐33 receptor. IL‐33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real‐time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN‐γ and TNF‐α in infected T1/ST2−/− mice. These effects were independent of changes in IL‐10 production. This study provides the first evidence of a specific role for IL‐33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.
IL‐7 is superior to IL‐2 for ex vivo expansion of tumour‐specific CD4+ T cells
Authors: Caserta Stefano , Alessi Patrizia , Basso Veronica , Mondino Anna
Published: November 2009

It is well established that tumours hinder both natural and vaccine‐induced tumour‐specific CD4+ T‐cell responses. Adoptive T‐cell therapy has the potential to circumvent functional tolerance and enhance anti‐tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8+ T cells are currently available, data on tumour‐specific CD4+ T cells remain scarce. We report here that CD4+ T cells sensitized to tumour‐associated Ag in vivo, proliferate in vitro in response to IL‐7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory‐like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumour‐sensitized T cells among other memory and naive lymphocytes following exposure to IL‐7. Also IL‐2, previously used to expand anti‐tumour CTL, promotes tumour‐specific CD4+ T‐cell accumulation. However, IL‐7 is superior to IL‐2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4+ T cells to confer therapeutic efficacy upon transplantation in tumour‐bearing hosts. Together our data support a unique role for IL‐7 in retrieving memory‐like CD4+ T cells suitable for adoptive T‐cell therapy.
Specific CD8+ T‐lymphocytes control dissemination of measles virus
Authors: de Vries Rory D. , Yüksel Selma , Osterhaus Albert D. M. E. , de Swart Rik L.
Published: November 2009

Measles continues to be an important cause of childhood mortality in developing countries. Measles virus (MV) is lymphotropic and infects high percentages of B‐ and T‐lymphocytes in lymphoid tissues. Cellular immunity is considered crucial for viral clearance; however, MV‐specific T‐lymphocytes generated during primary infection also constitute a potential target for MV infection. We therefore aimed to identify T‐lymphocyte subsets that can clear MV infection without becoming infected. To this end, we infected human EBV transformed B‐lymphoblastic cell lines (B‐LCL) with a recombinant MV strain expressing enhanced GFP, and co‐cultured these with non‐infected B‐LCL resulting in rapid viral spread. MV‐specific CD8+ T‐cell clones efficiently suppressed MV dissemination in autologous and HLA‐matched, but not in HLA‐mismatched B‐LCL. In contrast, CD4+ T‐cell clones could not control MV dissemination but became a target for MV infection themselves. Furthermore, PBMC collected 6–9 months after acute measles and stimulated with autologous MV‐infected B‐LCL also efficiently suppressed MV dissemination; this was mediated by the fraction containing CD8+ T‐lymphocytes. In conclusion, we have developed a powerful tool to study cellular immunity against measles, and demonstrate that control of MV dissemination is mediated by virus‐specific CD8+ rather than by CD4+ T‐lymphocytes.
Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome
Authors: Reimer Thornik , Shaw Michael H. , Franchi Luigi , Coban Cevayir , Ishii Ken J. , Akira Shizuo , Horii Toshihiro , Rodriguez Ana , Núñez Gabriel
Published: November 2009

Cerebral malaria is the most severe complication of Plasmodium falciparum infection in humans and the pathogenesis is still unclear. Using the P. berghei ANKA infection model of mice, we investigated a potential involvement of Nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. Nlrp3 mRNA expression was upregulated in brain endothelial cells after exposure to P. berghei ANKA. Although β‐hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL‐1β in macrophages through Nlrp3, we did not obtain evidence for a role of IL‐1β in vivo. Nlrp3 knock‐out mice displayed a delayed onset of cerebral malaria; however, mice deficient in caspase‐1, the adaptor protein ASC or the IL‐1 receptor succumbed as WT mice. These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL‐1 receptor pathway.
The Extension of the Solid‐Angle Concept to Bidentate Ligands
Authors: Niksch Tobias , Görls Helmar , Weigand Wolfgang
Published: November 2009

In search of an applicable parameter to express the steric requirement of bidentate ligands, the generalised equivalent cone angle Θ–b is established. It is designed in the style of the solid‐angle concept for monodentate ligands, utilising crystal structure data. Its reliability is tested with bidentate phosphanes coordinated to a central platinum atom. Therefore, a detailed evaluation of the Cambridge Database for platinum complexes with bridging phosphanes is performed. Herein, we present the results of the analysis of more than 900 molecular structures and over 280 different bidentate phosphanes. We intend to establish diselenolatoplatinum(II) complexes as model compounds for the fast prediction of Θ–b instead of calculating a multiplicity of molecular structures that is often not available. The complexes reported in Part 1 of this publication turn out to be rather acceptable for rough estimates of the generalised equivalent cone angle. On the other hand, the compounds are used to demonstrate the practicability of the concept, which is easily extended to other bidentate ligands, as is shown for the 2,2‐bis(hydroxymethyl)‐1,3‐diselenolato moiety. In conclusion, the generalised equivalent cone angle Θ–b proves to be a feasible parameter for the steric demand of bidentate ligands.
Formation of Unusual Trinuclear Assemblies: Scope and Mechanism of Zn(salphen)‐Templated Activation of Pyridine‐Alcohol Substrates (Eur. J. Inorg. Chem. 35/2009)
Authors: Martínez Belmonte Marta , Escudero‐Adán Eduardo C. , Benet‐Buchholz Jordi , Kleij Arjan W.
Published: November 2009

The cover picture shows a schematic view of the templated process that is mediated by Zn(salphen) complexes in the presence of pyridine‐alcohol ligands. The products of the templated reactions are unusual trinuclear Zn3 assemblies that comprise a central, nonsymmetrical Zn complex of which the anionic O‐donor atoms coordinate to two Zn(salphen) units. Full details on the stability and structural features of a small library of these supramolecular systems are discussed in the article by A. W. Kleij et al. on p. 5307 ff.
Indirect influence and divergent thinking as a function of member status and task structure in small groups
Authors: Goodman Jeffrey A. , Alexander Michele G. , Chizhik Alexander W. , Chizhik Estella W. , Eidelman Scott
Published: November 2009

A laboratory experiment examined the effect of confederate status and task structure on group members' use of the confederate's problem solving strategies (private/indirect influence) and divergent thinking. Twenty‐eight three‐member, all‐female groups, with an experimental confederate acting as one of the group members, solved an open‐structured or closed‐structured logic problem. The confederate, randomly assigned to be higher‐, lower‐, or of undesignated‐status, presented a scripted but unique solution to the group while solving the task. Lower‐status confederates and open‐structured tasks, relative to higher‐status confederates and closed‐structured tasks, had more private, indirect influence on group members and caused more divergent thinking. We discuss the implications of these findings for group dynamics and social influence literatures. Copyright © 2009 John Wiley & Sons, Ltd.
It could have been better: The effects of counterfactual communication on impression formation
Authors: Wong Elaine M.
Published: November 2009

While research on counterfactuals has closely examined the psychological antecedents and consequences of thinking counterfactually (imagining alternatives to past events), little is known about the effects of counterfactual communication, and in particular, how such thoughts are interpreted by others. In this paper, I argue that counterfactual communication differentially affects impressions formed of speakers by receivers depending on the general content of the counterfactual. Findings from an archival study and a scenario study demonstrated convergent results: Individuals who communicated upward counterfactuals (thoughts of how things could have been better) were more positively perceived by receivers than were individuals who communicated downward counterfactuals (thoughts of how things could have been worse). This difference stemmed from an enhancement effect of upward counterfactuals. Further analysis revealed that the relationship between counterfactual communication and impression formation was mediated by receivers' perceptions of the extent to which speakers took responsibility for their actions. Copyright © 2009 John Wiley & Sons, Ltd.
Antioxidant activity of medicinal and aromatic plants. A review.
Authors: Miguel M. G.
Published: November 2009

Antioxidant properties have been attributed to the essential oils but a great diversity of results has been reported, mainly attributed to the chemical composition of the essential oils and the diversity of tests used. In fact, several in vitro assays for the determination of antioxidant ability have been used. They can be divided into two main groups: those that evaluate lipid peroxidation and that those that measure free radical scavenging ability. In the present study, a brief description of the mechanism involved in the majority of techniques used for the evaluation of antioxidant activity of essential oils is given. At the same time, the antioxidant activities of some essential oils, measured through several methodologies, are presented and compared. Copyright © 2009 John Wiley & Sons, Ltd.
Caveolin-1 Is Enriched in the Peroxisomal Membrane of Rat Hepatocytes
Authors: Woudenberg Jannes , Rembacz Krzysztof P. , van den Heuvel Fiona A. J. , Woudenberg-Vrenken Titia E. , Buist-Homan Manon , Geuken Mariska , Hoekstra Mark , Deelman Leo E. , Enrich Carlos , Henning Rob H. , Moshage Han , Faber Klaas Nico
Published: November 2009

Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression of caveolin-1 in hepatocytes is relatively low, and it has been suggested to also reside at other subcellular locations than the plasma membrane. Recently, we found that the peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular location of caveolin-1 in rat hepatocytes. The subcellular location of rat hepatocyte caveolin-1 was analyzed by cell fractionation procedures, immunofluorescence, and immuno-electron microscopy. Green fluorescent protein (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes. Fenofibric acid–dependent regulation of caveolin-1 was analyzed. Peroxisome biogenesis was studied in rat hepatocytes after RNA interference–mediated silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid–coenzyme A:amino acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP–caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is associated with detergent-resistant microdomains. Caveolin-1 expression is strongly repressed by the peroxisome proliferator-activated receptor-α agonist fenofibric acid. Targeting of peroxisomal matrix proteins and peroxisome number and shape were not altered in rat hepatocytes with 70%-80% reduced caveolin-1 levels and in livers of caveolin-1 knockout mice.

Conclusion:

Caveolin-1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for peroxisome biogenesis, but this unique subcellular location may determine its important role in hepatocyte proliferation and lipid metabolism. (Hepatology 2010.)
Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in A Cohort Chronically Infected With Hepatitis B Virus
Authors: Simonetti Josephine , Bulkow Lisa , McMahon Brian J. , Homan Chriss , Snowball Mary , Negus Susan , Williams James , Livingston Stephen E.
Published: November 2009

Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1,271 Alaska Native persons with chronic HBV infection followed for an average of 19.6 years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A, B, C, D, and F) found in this population. Participants were followed for an average of 108.9 months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3 years after HBsAg clearance (range, 2.0–15.5 years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5–80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1–264.5;

P

< 0.001]). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6 years after clearance.

Conclusion:

HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early. (Hepatology 2010.)
Lactoferrin Protects Against Acetaminophen-Induced Liver Injury in Mice
Authors: Yin Hao , Cheng Linling , Holt Michael , Hail Numsen , MacLaren Robert , Ju Cynthia
Published: November 2009

Acetaminophen-induced liver injury (AILI) is a significant health problem and represents the most frequent cause of drug-induced liver failure in the United States. The development and implementation of successful therapeutic intervention strategies have been demanding, due to significant limitations associated with the current treatment for AILI. Lactoferrin (Lac), a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Our study demonstrated a profound protective effect of Lac in a murine model of AILI, which was not dependent on its iron-binding ability, inhibition of acetaminophen (APAP) metabolism, or a direct cytoprotective effect on hepatocytes. Instead, Lac treatment significantly attenuated APAP-induced liver sinusoidal endothelial cell dysfunction and ameliorated hepatic microcirculation disorder. This protective effect of Lac appeared to be dependent on hepatic resident macrophages (Kupffer cells [KCs]).Conclusion:Collectively, our data indicate that Lac, through activation of KCs, inhibited APAP-induced liver sinusoidal endothelial cell damage and improved hepatic congestion, thereby protecting against AILI. These findings reveal the significant therapeutic potential of Lac during AILI and other types of liver diseases. (Hepatology 2010.)
INSL3 has tumor‐promoting activity in thyroid cancer
Authors: Hombach‐Klonisch Sabine , Bialek Joanna , Radestock Yvonne , Truong Anne , Agoulnik Alexander I. , Fiebig Barbara , Willing Cornelia , Weber Ekkehard , Hoang‐Vu Cuong , Klonisch Thomas
Published: November 2009

The functional role of INSL3 and its receptor RXFP2 in carcinogenesis is largely unknown. We have previously demonstrated (pro‐)cathepsin‐L as a target of INSL3 in human thyroid cancer cells facilitating penetration of tumor cells through elastin matrices. We demonstrate the expression of RXFP2 in human thyroid tissues and in mouse follicular thyroid epithelial cells using Cre‐recombinase transgene driven by Rxfp2 promoter. Recombinant and secreted INSL3 increased the motility of thyroid carcinoma (TC) cells in an autocrine/paracrine manner. This effect required the presence of RXFP2. We identified S100A4 as a novel INSL3 target molecule and showed that S100A4 facilitated INSL3‐induced enhanced motility. Stable transfectants of the human follicular TC cell line FTC‐133 expressing and secreting bioactive human INSL3 displayed enhanced anchorage‐independent growth in soft agar assays. Xenotransplant experiments in nude mice showed that INSL3, but not EGFP‐mock transfectants, developed fast‐growing and highly vascularized xenografts. We used human umbilical vein endothelial cells in capillary tube formation assays to demonstrate increased 2‐dimensional tube formations induced by recombinant human INSL3 and human S100A4 comparable to the effect of vascular endothelial growth factor used as positive control. We conclude that INSL3 is a powerful and multifunctional promoter of tumor growth and angiogenesis in human thyroid cancer cell xenografts. INSL3 actions involve RXFP2 activation and the secretion of S100A4 and (pro‐)cathepsin‐L.
Targeting Gene‐ViroTherapy for prostate cancer by DD3‐driven oncolytic virus‐harboring interleukin‐24 gene
Authors: Fan Jun Kai , Wei Na , Ding Miao , Gu Jin Fa , Liu Xin Ran , Li Bing Hua , Qi Rong , Huang Wei Dan , Li Yu Hua , Xiong Xiao Quan , Wang Jian , Li Run Sheng , Liu Xin Yuan
Published: November 2009

Prostate cancer (PCa) is the second leading cause of cancer‐related deaths in Western male population. Previous studies have demonstrated that differential display code 3 (DD3 or DD3PCA3) is one of the most PCa‐specific genes; therefore, it has been used as a clinical diagnostic marker for PCa. In this study, we constructed an oncolytic adenovirus Ad.DD3‐E1A by using the minimal DD3 promoter to replace the native viral promoter of E1A gene. In addition, Ad.DD3‐E1A was armed with therapeutic gene IL‐24 to enhance its antitumor activity. The resulting adenovirus, Ad.DD3‐E1A‐IL‐24, demonstrated PCa specificity and excellent antitumor effect. Further analyses on its antitumor mechanism revealed that it has the capacity to induce apoptosis in PCa cells and inhibit angiogenesis. These results suggest that Ad.DD3‐E1A‐IL‐24 is a promising antitumor agent that may be able to be used in the future as a treatment for PCa.
Integrating “invisible” farmers in a regional debate on water productivity: The case of informal water and land markets in the Algerian Mitidja plain
Authors: Imache A. , Bouarfa S. , Kuper M. , Hartani T. , Dionnet M.
Published: November 2009

In the irrigated scheme of West Mitidja, access to land and water is ensured through countless local informal arrangements. The assignees of small collective farms have subdivided the land informally, and rent out part of it to lessees, thereby circumventing current legislation. The surface irrigation system provides only a small proportion of irrigation water to farmers, who rely mainly on groundwater for irrigation. The results of our analyses show that the agricultural dynamics of this perimeter are to a large extent ensured by “invisible” farmers cultivating land obtained through informal land markets and using groundwater via “illicit” tubewells. These farmers are also important vectors for innovation (new irrigated cropping systems, drip irrigation). We organized a series of workshops with farmers (assignees and lessees) and government agencies to explore agricultural development and water management perspectives in the area. Our work showed that it is land and water markets that should be formalized rather than land or water property so that lessees will be considered as actors for water management and agricultural development in the area. Copyright © 2009 John Wiley & Sons, Ltd.
Finding a way to legality, local coordination modes and public policies in large‐scale irrigation schemes in Algeria and Morocco
Authors: Errahj M. , Kuper M. , Faysse N. , Djebbara M.
Published: November 2009

The design of public policy related to irrigation sectors in North Africa was often based on the state view. Local farmers' organizations, made up of family farms, did not contribute to building the legal framework, which was in turn unable to propose specific solutions for family farming. Legal reforms currently underway in Morocco and Algeria show how difficult it is to integrate field realities. Access to land and water resources is often obtained through informal local coordination modes. The purpose of this paper is to clarify how collective action can integrate the dynamics of local coordination modes and contribute to the formulation of public policies. The underlying hypothesis is that by doing so, the public policies can be continuously renewed and will be more appropriate and robust, and consequently favour rural development. We show that local coordination modes, presently often invisible or even illegal, can help farmers to go beyond survival strategies by providing access to more formal development spheres and policy making. These results should encourage development and extension agencies to redefine collective action as a tool of learning and empowerment centred on the co‐construction of public policies. Copyright © 2009 John Wiley & Sons, Ltd.
Farmers' perceptions and engineering approach in the modernization of a community‐managed irrigation scheme. A case study from an oasis of the Nefzawa (South of Tunisia)
Authors: Ghazouani W. , Marlet S. , Mekki I. , Vidal A.
Published: November 2009

Irrigation programmes are usually based on technical and economic considerations without substantial involvement of the target farmers. This study aimed to investigate farmers' discourse, practices and perceptions, and to emphasize progress, limit and synergy of farmers' representation in the modernization programme undertaken by engineers in the Fatnassa oasis in southern Tunisia. Analyses of constraints were based on the modernization programmes and on farmers' interviews. Causal relationships were represented separately as problem trees according to farmers' and engineers' perceptions. The technical solutions implemented by engineers did not achieve the expected enhancement because they disregarded inappropriate community management of the oasian system. Farmers were aware of constraints related to waterlogging and hot irrigation water since they can link causes and effects. The low frequency of delivery water turns was cited as the main constraint in spite of the fact that the farmers were themselves accountable for some inefficient irrigation practices and continuous extension of date palm plantation. Farmers failed to mention soil degradation and salinity, which were only perceived indirectly, or because they applied corrective measures. This case study allowed a critical reflection on the limitations of each approach and for the combination of experts and farmers' knowledge. Copyright © 2009 John Wiley & Sons, Ltd.
Local transformation of a state‐initiated institutional innovation: The example of water users' associations in an irrigation scheme in Morocco
Authors: Kadiri Zakaria , Kuper Marcel , Faysse Nicolas , Errahj Mostafa
Published: November 2009

The international debate on participatory management and irrigation management transfer has mainly focused on ex‐ante/ex‐post evaluations that rely on quantitative performance indicators to measure the failure or success of management transfer and the functioning of water users' associations (WUAs). This article focuses on the appropriation by farmers of state‐initiated WUAs illustrated by the case of the Moyen Sebou irrigation scheme in Morocco. This scheme, which was designed for agency‐managed water distribution, was implemented at the height of the debate on participatory management in the early 1990s, and was transformed into a farmer‐managed irrigation scheme. The results revealed the gradual adoption of the water institutions (WUAs and the federations of WUAs) by farmers, who continuously crafted and adapted rules for the management of water distribution, collection of water fees, and governance of the irrigation scheme. In addition, there were a number of indirect spin‐offs generated by the collective learning process in terms of leadership, collective action, local democracy and local development. Copyright © 2009 John Wiley & Sons, Ltd.
Water productivity through dual purpose (milk and meat) herds in the Tadla irrigation scheme, Morocco
Authors: Sraïri Mohamed Taher , Rjafallah Marouane , Kuper Marcel , Le Gal Pierre‐Yves
Published: November 2009

This study aims to characterize water productivity in cattle farms facing severe water stress. Agricultural practices were monitored on six farms in a large‐scale Moroccan irrigation scheme. Results showed marked variability in forage yields, milk production and live weight gain. Mean forage biomass yields represented less than two‐thirds of their potential productivity. Alfalfa was the most common forage crop, and its yield was significantly correlated to the amounts of water used for irrigation. The annual mean milk yield per cow was low (2170 kg), whereas the average live weight gain per cow and its progeny was 308 kg. Off‐farm feed provided variable amounts of virtual water which represented 33% of total water uses. Results showed that 1.7 m3 of total water was needed to produce 1 kg of milk, whereas 9.1 m3 were needed for 1 kg of live weight gain. The economic productivity of water through milk was less efficient than through meat (respectively €0.07 and €0.25 m−3). Finally, the overall water productivity of cattle farming (both milk and live weight gain) was €0.14 m−3 of water. Taken together, the results pointed to possible ways of improving water productivity, as many constraints were identified, from water management to farming practices. Copyright © 2009 John Wiley & Sons, Ltd.
A crop needs more than a drop: Towards a new praxis in irrigation management in North Africa
Authors: Kuper M. , Bouarfa S. , Errahj M. , Faysse N. , Hammani A. , Hartani T. , Marlet S. , Zairi A. , Bahri A. , Debbarh A. , Garin P. , Jamin J.‐Y. , Vincent B.
Published: November 2009

We designed and implemented an action–research programme in large‐scale irrigation schemes in Algeria, Morocco and Tunisia, aiming to develop a regional network of competences by conducting research, training and development activities, and involving local actors. We worked on three issues: (i) the sustainability of North Africa's growing groundwater economy, (ii) the integration of environmental constraints in the management of irrigated agriculture, and(iii) the analysis of new coordination modes of agricultural production and rural development in traditionally centrally managed irrigation schemes. Based on 11 empirical studies, we contributed to operationalizing a new praxis in irrigation management; this learning‐oriented and network‐based approach enables mobilization of the knowledge of a wide range of actors, as well as linking local knowledge systems to more universal ones. This approach is necessary to support family‐based agriculture to continue to face recurrent droughts, feed the urban and rural populations, develop rural territories and integrate the rural youth. Copyright © 2009 John Wiley & Sons, Ltd.
BBR induces apoptosis in HepG2 cell through an Akt‐ASK1‐ROS‐p38MAPKs‐linked cascade
Authors: Hyun Mee‐Sun , Hur Jung‐Mu , Mun Yeun‐Ja , Kim Dongho , Woo Won‐Hong
Published: November 2009

Berberine (BBR) has indicated significant antimicrobial activity against a variety of organisms including bacteria, viruses, and fungi. The mechanism by which BBR initiates apoptosis remains poorly understood. In the present study, we demonstrated that BBR exhibited significant cytotoxicity in human hepatoma HepG2 cells. Herein, we investigated cytotoxicity mechanism of BBR in HepG2 cells. The results showed that the induction of apoptosis in HepG2 cells by BBR was characterized by DNA fragmentation, an increased percentage of annexin V, and the activation of caspase‐3. The expressions of Bcl‐2 protein and pro‐caspase‐3 were reduced by BBR in HepG2 cells. However, Bax protein was increased in the cells. BBR‐induced apoptosis was preceded by increased generation of reactive oxygen species (ROS). NAC treatment, a scavenger of ROS, reversed BBR‐induced apoptosis effects via inhibition of Bax activation and Bcl‐2 inactivation. BBR‐induced, dose‐dependent induction of apoptosis was accompanied by sustained phosphorylation of MAP Kinases (JNK and p38 MAPK), ASK1, Akt, and p53. Furthermore, SB203580, p38 inhibitor, reduced the apoptotic effect of BBR, and blocks the generation of ROS and NO as well as activation of Bax. We found that the treatment of HepG2 cells with BBR triggers generation of ROS through Akt phosphorylation, resulting in dissociation of the ASK1‐mediated activation of JNK and p38 pathways. J. Cell. Biochem. 109: 329–338, 2010. © 2009 Wiley‐Liss, Inc.
Non‐resorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells
Authors: Kreja L. , Brenner R.E. , Tautzenberger A. , Liedert A. , Friemert B. , Ehrnthaller C. , Huber‐Lang M. , Ignatius A.
Published: November 2009

Osteoclast activity has traditionally been regarded as restricted to bone resorption but there is some evidence that also non‐resorbing osteoclasts might influence osteoblast activity. The aim of the present study was to further investigate the hypothesis of an anabolic function of non‐resorbing osteoclasts by investigating their capability to recruit mesenchymal stem cells (MSC) and to provoke their differentiation toward the osteogenic lineage. Bone‐marrow‐derived human MSC were exposed to conditioned media (CM) derived from non‐resorbing osteoclast cultures, which were generated from human peripheral blood monocytes. Osteogenic marker genes (transcription factor Runx2, bone sialoprotein, alkaline phosphatase (AP), and osteopontin) were significantly increased. Osteogenic differentiation (OD) was also proved by von Kossa and AP staining occurred in the same range as in MSC cultures stimulated with osteogenic supplements. Chemotactic responses of MSC were measured with a modified Boyden chamber assay. CM from osteoclast cultures induced a strong migratory response in MSC, which was greatly reduced in the presence of an anti‐human platelet‐derived growth factor (PDGF) receptor β antibody. Correspondingly, significantly increased PDGF‐BB concentrations were measured in the CM using a PDGF‐BB immunoassay. CM derived from mononuclear cell cultures did not provoke MSC differentiation and had a significantly lower migratory effect on MSC suggesting that the effects were specifically mediated by osteoclasts. In conclusion, it can be suggested that human non‐resorbing osteoclasts induce migration and OD of MSC. While effects on MSC migration might be mainly due to PDGF‐BB, the factors inducing OD remain to be elucidated. J. Cell. Biochem. 109: 347–355, 2010. © 2009 Wiley‐Liss, Inc.
BMP4 regulates vascular progenitor development in human embryonic stem cells through a smad‐dependent pathway
Authors: Bai Hao , Gao Yongxing , Arzigian Melanie , Wojchowski Don M. , Wu Wen‐shu , Wang Zack Z.
Published: November 2009

The signals that direct pluripotent stem cell differentiation into lineage‐specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum‐free condition, hESCs sequentially differentiated into CD34+CD31−, CD34+CD31+, and then CD34−CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. BMP4 promoted hESC differentiation into CD34+CD31+ cells at an early stage. In contrast, TGFβ suppressed BMP4‐induced CD34+CD31+ cell development, and promoted CD34+CD31− cells that failed to give rise to either endothelial or smooth muscle cells. The BMP‐Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad‐dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate into vascular cells. J. Cell. Biochem. 109: 363–374, 2010. © 2009 Wiley‐Liss, Inc.