bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single Species of Betasatellite is Prevalent in Chilli across North Central Pakistan and Shows Phylogeographic Segregation
Authors: Hussain Mazhar , Iram Shazia , Mansoor Shahid , Briddon Rob W.
Published: March 2009

Chilli leaf curl disease is an important constraint to production of chilli peppers (Capsicum annum L.) across the Indian subcontinent and is caused by begomoviruses in association with betasatellites. Betasatellites are symptom modulating single‐stranded DNA satellites associated with the majority of monopartite begomoviruses and are responsible for diseases of many crops including chilli peppers. Here, we have studied the diversity of a betasatellite of chillies in the Punjab and North Western Frontier Province of Pakistan. Sequence analysis of thirteen full‐length clones showed that a single species of satellite, Chilli leaf curl betasatellite (ChLCB), is prevalent in chilli throughout the surveyed region. ChLCB has only been identified in Pakistan and infecting chilli. It thus probably represents a chilli adapted satellite. The ChLCBs fall into two groups, the first occurs in the less intensively cultivated north and shows a high level of sequence diversity (relative to the second group), while the second occurs in the southern cotton‐growing areas and shows little sequence diversity. Between these two areas there is a region of overlap where both ChLCB types occur. The phylogeographic segregation of ChLCB we attribute to geographic isolation (in the north), leading to divergence and intensive cultivation (in the south), leading to homogenization. However, the lack of diversity (only a single species) bodes well for the prospects of achieving resistance to the disease by either conventional or pathogen‐derived strategies.
Anther Extrusion and Fusarium Head Blight Resistance in European Wheat
Authors: Graham Stewart , Browne Roy A.
Published: March 2009

Anther extrusion has been widely discussed as a factor influencing fusarium head blight (FHB) resistance in wheat. This is despite a paucity of quantitative information on its importance, between cultivars, in contrast to that for heading date and plant height. We describe a method applicable to a plant breeding situation at 10 days postanthesis, for assessing the distinct characteristics of anther retention (anthers held within the spikelet) and trapped anthers (partially extruded and trapped between the lemma and palea of the wheat spikelet). FHB resistance was tested in field experiments in 2004 and 2005. In these experiments designed to resemble applications to a plant breeding selection scheme anther retention was significantly correlated with FHB in 2004 (r = 0.26; P < 0.05) and 2005 (r = 0.26; P < 0.05). A higher proportion of anthers retained relating, albeit weakly, with increased FHB susceptibility in European wheat.
Phenotypic and Genotypic Characterization of Phytophthora infestans Isolates from China
Authors: Li Benjin , Chen Qinghe , Lv Xin , Lan Chengzhong , Zhao Jian , Qiu Rongzhou , Weng Qiyong
Published: March 2009

A total of 288 (202 from potato and 86 from tomato) isolates of Phytophthora infestans were collected from 1998 to 2007 in China. The isolates were characterized based on mating type, in vitro metalaxyl sensitivity, virulence on potato differentials, allozymes of glucose‐6‐phosphate isomerase (Gpi), peptidase (Pep), and mitochondrial DNA (mtDNA) haplotype and examined by DNA‐based simple sequence repeat (SSR) and random amplified polymorphic DNA (RAPD) fingerprinting. The majority (283 of 288) of the isolates were of the A1 mating type, the other three were the A2 mating type and two were the A1A2 mating type. Resistance to metalaxyl was frequently observed, with 248 (86.1%) resistant, 21 (7.3%) intermediate and 19 (6.6%) sensitive isolates identified. Virulence was assessed for 125 isolates on a set of 11 potato differentials and 61 races were detected. Most isolates were virulent on the differential genotype with gene R3, and all known virulence genes were found, with race 3.4.7.11 being the most common. This pattern did not appear to be associated with geographic origin, sample type, mating type or metalaxyl sensitivity. The dominant banding patterns for Gpi were 100/100/111 (176 isolates) and 100/100 (109 isolates), but genotypes 86/100 and 100/111 were also identified. All isolates tested were homozygous (100/100) at the Pep locus. The majority (205 of 288) of isolates tested was of mtDNA haplotype IIb, 76 were haplotype IIa and seven were the rare Ib haplotype. The genetic diversity of 60 representative isolates from China was assayed by two types of molecular markers, RAPD and SSR. A high level of polymorphism was found. The results demonstrated the diverse phenotypic and genotypic structure of the current populations of P. infestans in China.
Alternaria alternata AT Toxin Induces Programmed Cell Death in Tobacco
Authors: Yakimova Elena T. , Yordanova Zhenya. P. , Slavov Slavtcho , Kapchina‐Toteva Veneta M. , Woltering Ernst J.
Published: March 2009

Detached tobacco leaves were infiltrated with an AT toxin preparation from the foliar pathogen Alternaria alternata tobacco pathotype. The AT toxin preparation caused formation of necrotic lesions within 5 days post‐infiltration in a concentration‐dependent manner. Cell death was accompanied by increased levels of the stress metabolites hydrogen peroxide, malondialdehyde, free proline and by enhanced total protease activity. Lesion development and the production of stress metabolites were suppressed if the infiltration site was pre‐infiltrated with caspase‐specific peptide inhibitors (irreversible caspase‐1 inhibitor acyl‐Tyr‐Val‐Ala‐Asp‐chloromethylketone (Ac‐YVAD‐CMK) and the broad range caspase inhibitor benzyoxycarbonyl‐Asp‐2,6‐dichlorobenzoyloxymethylketone (Z‐Asp‐CH2‐DCB)), the serine protease inhibitor Nα‐p‐tosyl‐l‐lysine chloromethylketone and the polyamine spermine. Extensive accumulation of reactive oxygen species (ROS), as determined by staining with 3‐3′‐diaminobenzidine and 2′,7′‐dichlorofluorescein diacetate, was found in the AT toxin‐challenged lesions. The data show that AT toxin‐induced cell death in tobacco is a type of programmed cell death in which caspase‐like proteases and ROS signalling play a prominent role.
“Time for dialysis as time to live”: Experiences of time in everyday life of the Swedish next of kin of hemodialysis patients
Authors: Ziegert Kristina , Fridlund Bengt , Lidell Evy
Published: March 2009

Abstract  The aim of this study was to explore the content of time in everyday life as experienced by the next of kin of patients on hemodialysis in Sweden. Chronic renal disease often requires hemodialysis, which is a time‐consuming treatment that makes it necessary to carefully plan everyday life and involves the next of kin to a large degree. This study used a descriptive design with a content analysis approach. The analysis of the data from the twenty interviews revealed the experiences of time in the everyday lives of the next of kin of a patient on hemodialysis. The content of time in everyday life can be described as follows: fragmented time, vacuous time, and uninterrupted time. The findings show how everyday life time for the next of kin is minimized and that the common life space is contracted. The next of kin must be provided with supervision in order to provide them with more of their own time in everyday life, which can benefit their health.
Randomized clinical trial of the influence of local subcutaneous infiltration vs subcutaneous and deep infiltration of local anaesthetic on pain after appendicectomy
Authors: Randall J. K. , Goede A. , Morgan‐Warren P. , Middleton S. B.
Published: March 2009

Introduction  Local anaesthesia is commonly used to provide pain relief after surgery. The aim of this randomized, blinded prospective trial was to evaluate whether local subcutaneous and deep infiltration of local anaesthetic provides better postoperative pain control than subcutaneous infiltration alone.

Method  Eighty‐four patients undergoing open appendicectomy for presumed acute appendicitis were randomly assigned into two groups. Group A received local infiltration of the skin prior to incision with bupivacaine whilst group B received half the bupivacaine infiltrated into the skin and the other half deep‐to‐external oblique to create a local nerve field blockade. Postoperative pain was assessed, on a scale of 1 to 10, at 1, 4, 8 and 24 h postextubation.

Results  At time intervals of 1, 4 and 8 h, there was no significant difference in pain score between group A and group B. At 24 h group B had significantly lower pain scores than group A (2.3 vs 3.4, P = 0.016).

Conclusion  Both methods of administration of local anaesthetic produced consistently low pain scores in the first 24 h after appendicectomy. There may be additional benefit in a local nerve field blockade in combination with local anaesthetic skin infiltration.
British HIV Association (BHIVA) national cohort outcomes audit of patients commencing antiretrovirals from naïve
Authors: Street E , Curtis H , Sabin CA , Monteiro EF , Johnson MA ,   on behalf of the British HIV Association (BHIVA) and BHIVA Audit and Standards Subcommittee.
Published: March 2009

Objectives

The aim of this work was to audit the extent to which routine HIV care in the UK conforms with British HIV Association (BHIVA) guidelines and specifically the proportion of patients starting highly active antiretroviral therapy (HAART) who achieve the outcome of virological suppression below 50 HIV‐1 RNA copies/mL within 6 months.

Methods

A prospective cohort review of adults with HIV infection who started antiretroviral therapy (ART) for the first time between April and September 2006 was carried out using structured questionnaire forms.

Results

A total of 1170 adults from 122 clinical sites participated in the review. Of these patients, 699 (59.7%) started ART at CD4 counts <200 cells/μL and 193 (16.5%) had not been tested for HIV drug resistance. Excluding patients with valid reasons for stopping short‐term ART, 795 (73.5%) of 1081 patients had an undetectable viral load (VL) at follow‐up. Detectable VL was strongly associated with pretreatment CD4 count below 50 cells/μL and pretreatment VL above 100 000 copies/mL, and was not associated with clinic location or case load. About a quarter of patients did not have a VL measurement during the first 6 weeks after starting ART.

Conclusions

The majority of patients who initiated ART at sites participating in this UK national audit were managed within the BHIVA guidelines and achieved virological suppression below 50 copies/mL around 6 months after commencing treatment. Poor VL outcomes were associated with very low CD4 cell count and/or high VL at baseline but not with clinic case load or location. There is an urgent need to diagnose patients at an earlier stage of their HIV disease.
Impact of prior pneumococcal vaccination on clinical outcomes in HIV‐infected adult patients hospitalized with invasive pneumococcal disease
Authors: Imaz A , Falcó V , Peñaranda M , Jordano Q , Martínez X , Nadal C , Curran A , Planes AM , Dalmau D , Ribera E , Riera M , Ruiz de Gopegui E , Pahissa A
Published: March 2009

Background

Recent studies in hospitalized patients with community‐acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23‐valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV‐infected adult patients hospitalized with invasive pneumococcal disease (IPD).

Methods

This was an observational study of all consecutive HIV‐infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome‐related variables were compared according to prior PPV vaccination status.

Results

A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23‐valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011).

Conclusions

Although 23‐valent PPV failed to prevent IPD in some HIV‐infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.
Skin bleaching: highlighting the misuse of cutaneous depigmenting agents
Authors: Dadzie OE , Petit A
Published: March 2009

Hydroquinone and other cutaneous depigmenting agents are widely used by dermatologists to treat pigmentary disorders. On 29 August 2006, the US Food and Drug Administration (FDA) published a monograph in the US Federal Register proposing to ban all hydroquinone products that have not been approved via a New Drug Application process. Reports in the scientific literature on the occurrence of exogenous ochronosis, in relation to the use of hydroquinone, was one of the concerns expressed by the FDA in relation to this agent. However, a review of the English‐language scientific literature reveals that most of the reported cases of hydroquinone‐induced exogenous ochronosis occurs in Africa, where the cultural practice of skin bleaching is highly prevalent. Skin bleaching is the practice of applying hydroquinone and/or other depigmenting agents to specific or widespread areas of the body, the primary function being to lighten normally dark skin. This practice typically occurs in men and women with Fitzpatrick skin phototypes IV to VI. It is a dangerous practice associated with a diverse range of side‐effects, including mercury poisoning. Thus, this current discussion within the dermatological community on the safety of hydroquinone provides a unique opportunity to raise awareness about skin bleaching.
Motor development from 4 to 8 months corrected age in infants born at or less than 29 weeks’ gestation
Authors: PIN TAMIS W , DARRER TANYA , ELDRIDGE BEV , GALEA MARY P
Published: March 2009

Aim  Clinically, preterm infants show motor delay and atypical postures compared with their peers born at term. A longitudinal cohort study was designed to describe the motor development of very preterm infants from 4 to 18 months corrected age (CA). The study was also designed to investigate how the atypical postures observed in early infancy in the preterm infants might be related to their later motor development. Here we report the findings in early motor skills from 4 to 8 months CA.

Method  Early motor skills were assessed in 62 preterm infants (32 males, 30 females, mean gestation 26.94wks, SD 1.11) and 53 term infants (32 males, 21 females, mean gestation 39.55wks, SD 1.17) using the Alberta Infant Motor Scale (AIMS).

Results  The preterm infants demonstrated different motor behaviours from their term peers, with an uneven progression of motor skills in different positions from 4 to 8 months CA. At 8 months CA, 90%of the term infants were able to sit without arm support, but only 56%of the preterm infants could maintain sitting very briefly without arm support.

Interpretation  This uneven progression may have been due to an imbalance between the active flexor and extensor strength and hence inadequate postural control in these positions. The AIMS has also been shown to be a valid assessment tool to demonstrate unique characteristics in movement quality in the preterm population.
Determinants of students’ attitudes towards peers with disabilities
Authors: VIGNES CELINE , GODEAU EMMANUELLE , SENTENAC MARIANE , COLEY NICOLA , NAVARRO FELIX , GRANDJEAN HELENE , ARNAUD CATHERINE
Published: March 2009

Aim  To explore factors associated with students’ attitudes towards their peers with disabilities.

Method  All 7th grade students (aged 12−13y) from 12 schools in the Toulouse area were invited to participate (n=1509). Attitudes were measured using the Chedoke‐McMaster Attitudes Towards Children with Handicaps (CATCH) questionnaire (affective, behavioural, cognitive, and total scores). Personal characteristics, including KIDSCREEN quality of life scores, were recorded. Data regarding information about disabilities received from parents and the media and acquaintance with people with disabilities constituted the ‘disability knowledge’ factors. The characteristics of the schools were obtained from the local education authority. Multivariate multilevel linear regression analyses were conducted to explore the associations between CATCH scores and these three groups of factors.

Results  Responses from 1135 students (612 females, 523 males; mean age 12y 8mo SD 7mo; age range 10y 8mo–15y) were studied (75.2% of the students approached). Factors independently associated with more positive attitudes were being a female, having a good quality of life, being friends with a child with disabilities, or having received information about disabilities from parents and the media. Presence in the school of a special class for children with cognitive disabilities was independently associated with more negative attitudes.

Interpretation  This cross‐sectional study identified different personal and environmental factors upon which interventions aimed at improving students’ attitudes towards their peers with disabilities could be based.
Raf kinase inhibitor protein inhibits cell proliferation but promotes cell migration in rat hepatic stellate cells
Authors: Ma Junji , Li Fangfang , Liu Li , Cui Donglai , Wu Xiaohui , Jiang Xiaoyu , Jiang Huiqing
Published: March 2009

Aim: Hepatic stellate cells (HSCs) play an important role in the pathogenesis of liver fibrosis and cirrhosis. Raf kinase inhibitor protein (RKIP), an inhibitor of extracellular signal‐regulated kinases (ERK)/mitogen‐activated protein kinase (MAPK) signalling pathway, has been proved to suppress tumor metastasis. Interestingly, RKIP promotes cell migration in Madin–Darby canine kidney epithelial cells. However, the effects of RKIP on HSC behaviours are unknown. The purpose of the present study is to investigate the role of RKIP in HSC proliferation, apoptosis and migration.

Methods: Two types of cells, freshly isolated HSC and HSC‐T6 cell line, were used in this study. The amount of RKIP, the phosphorylation of RKIP, Raf and ERK (pRKIP, pRaf and pERK) were analysed in quiescent and activated HSCs by Western blots. HSC‐T6 cells were transfected with RKIP‐expressing plasmid or treated with locostatin, a RKIP inhibitor. HSC proliferation, apoptosis and migration were evaluated with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling (TUNEL) staining and Transwell cell migration assay respectively.

Results: In activated HSCs, RKIP protein expression was downregulated whereas pRKIP, pRaf and pERK were upregulated. RKIP overexpression significantly mitigated the phosphorylation of RKIP, Raf and ERK. This in turn inhibited HSC proliferation. Locostatin not only inhibited RKIP protein expression but also, to some extent, reversed the RKIP‐inhibited phosphorylation of RKIP, Raf and ERK. RKIP augmented HSC migration and enhanced wound closure. Locostatin reversed the effects of RKIP.

Conclusion: Raf kinase inhibitor protein inhibits ERK/MAPK signalling and this inhibition impedes HSC proliferation. RKIP promotes HSC migration and wound closure.
Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass Survey
Authors: Shimoyama Tadashi , Oyama Takao , Matsuzaka Masashi , Danjo Kazuma , Nakaji Shigeyuki , Fukuda Shinsaku
Published: March 2009

Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non‐invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey.

Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori‐specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori, and the level of PGs I and II was also measured to determine the presence of atrophic gastritis.

Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p < .05) in 303 subjects with severe atrophic gastritis.

Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori, would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined.
Retrospective study of teeth with a poor prognosis following non‐surgical periodontal treatment
Authors: Ekuni Daisuke , Yamamoto Tatsuo , Takeuchi Noriko
Published: March 2009

Aim: The aim of this retrospective study was to assess teeth with a poor prognosis and the proximal periodontium of adjacent teeth, and to identify the risk factors associated with the loss of teeth with a poor prognosis following non‐surgical periodontal treatment.

Material and Methods: Teeth with a poor prognosis (n=113), teeth adjacent to those of poor prognosis (n=105) and non‐adjacent teeth (n=51) were evaluated in 25 non‐smoking patients who had received supportive periodontal treatment for 5–16 years following non‐surgical periodontal treatment at a university hospital.

Results: Probing pocket depth (PPD), percentage of alveolar bone loss, presence of tooth mobility and bleeding on probing in all teeth improved significantly after treatment. Logistic regression analysis showed that loss of teeth with a poor prognosis depended on the initial deepest PPD, tooth mobility and multi‐rooted tooth.

Conclusions: Teeth with a poor prognosis did not affect the proximal periodontium of the adjacent teeth, and progression of periodontal disease in these teeth and adjacent teeth can be prevented by non‐surgical periodontal treatment in non‐smokers. The risk factors for loss of teeth with a poor prognosis were the initial deepest PPD, tooth mobility and multi‐rooted tooth.
Change in periodontitis during pregnancy and the risk of pre‐term birth and low birthweight
Authors: Michalowicz Bryan S. , Hodges James S. , Novak Michael John , Buchanan William , DiAngelis Anthony J. , Papapanou Panos N. , Mitchell Dennis A. , Ferguson James E. , Lupo Virginia R. , Bofill James , Matseoane Stephen
Published: March 2009

Aim: Determine whether periodontitis progression during pregnancy is associated with adverse birth outcomes.

Methods: We used clinical data and birth outcomes from the Obstetrics and Periodontal Therapy Study, in which randomly selected women received periodontal treatment before 21 weeks of gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow‐up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as 3 mm loss of clinical attachment. Birth outcomes were compared between non‐progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls.

Results: The distribution of gestational age at the end of pregnancy (p>0.1) and mean birthweight (3295 versus 3184 g, p=0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percentage of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (p>0.05).

Conclusions: In these women with periodontitis and within this study's limitations, disease progression was not associated with an increased risk for delivering a pre‐term or a low birthweight infant.
Regulation of interleukin‐12/interleukin‐23 production and the T‐helper 17 response in humans
Authors: Lyakh Lyudmila , Trinchieri Giorgio , Provezza Lisa , Carra Giuseppe , Gerosa Franca
Published: March 2009

Summary: Interleukin‐12 (IL‐12) and IL‐23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL‐12 is involved in the induction or amplification of the T‐helper (Th) type 1 response, whereas IL‐23 has been associated with the generation of the Th17 response and IL‐17 production. Mycobacterium tuberculosis and yeast zymosan induce IL‐23, but in the absence of other stimuli, no IL‐12 is induced in human dendritic cells (DCs). The stimulation of IL‐23 by M. tuberculosis was mostly explained by the triggering of Toll‐like receptor (TLR2) and the cytoplasmic receptor nucleotide oligomerization domain (NOD)‐containing protein 2, whereas zymosan induces IL‐23 primarily by stimulating the β‐glucan receptor dectin‐1 alone or in combination with TLR2. IL‐23, IL‐6, transforming growth factor (TGF‐β1), and IL‐1β in supernatants from activated human DCs induce human naive CD4+ T cells to produce IL‐17. These data are consistent with various recent reports that TGF‐β is an inducer of IL‐17 production both in human and in mouse cells. However, IL‐1 is necessary in combination with some or all of the other cytokines to induce IL‐17 production in human T cells. The ability of various stimuli to induce Th17 cells depends not only on their induction of IL‐23, IL‐6, and TGF‐β production in DCs but also on their ability to activate directly or indirectly the inflammasome and to induce IL‐1β.
Reconciling id, ego, and superego within interleukin‐23
Authors: Tato Cristina M. , Cua Daniel J.
Published: March 2009

Summary: The study of interleukin‐23 (IL‐23) over the past 8 years has led to the realization that cellular immunity is far more complex than previously appreciated, because it is controlled by additional newly identified players. From the analysis of seemingly straightforward cytokine regulation of autoimmune diseases, many limitations of the established paradigms emerged that required reevaluation of the ‘rules’ that govern the initiation and maintenance of immune responses. This information led to a major revision of the T‐helper 1 (Th1)/Th2 hypothesis and discovery of an unexpected link between transforming growth factor‐β‐dependent Th17 and inducible regulatory T cells. The aim of this review is to explore the multiple characteristics of IL‐23 with respect to its ‘id’ in autoimmunity, ‘ego’ in T‐cell help, and ‘superego’ in defense against mucosal pathogens.
Cytometric Analysis of Cytotoxicity of Polyphenols and Related Phenolics to Rat Thymocytes: Potent Cytotoxicity of Resveratrol to Normal Cells
Authors: Fujimoto Aya , Sakanashi Yoko , Matsui Hiroko , Oyama Toshihisa , Nishimura Yumiko , Masuda Toshiya , Oyama Yasuo
Published: March 2009

Abstract:  The chemopreventive and chemotherapeutic actions of polyphenols and related phenolics have received considerable attention since these compounds induce apoptosis in several types of cancer cells in vitro. A plausible criterion for the use of such compounds is that they should not exert any toxic effect on normal cells. However, information about the toxicity of polyphenols and related phenolics to normal cells is limited. In this study, the effects of polyphenols and related phenolics on rat thymocytes were examined by flow cytometric analysis with appropriate fluorescent probes. The compounds examined in this study were caffeic acid, rosmarinic acid, chlorogenic acid, (+)‐catechin, 6‐gingerol, sesamol, resveratrol, and eugenol. Of these, resveratrol was the most cytotoxic on rat thymocytes incubated for 24 hrs with 100 µM of this compound. Resveratrol at a concentration of 10 µM or more (up to 100 µM) led to a significant dose‐dependent increase in the population of dead cells, shrunken living cells, annexin V‐positive cells and cells with hypodiploidal DNA. In the presence of benzyloxycarbonyl‐Val‐Ala‐Asp (OMe) fluoromethylketone (Z‐VAD‐FMK), a pan‐inhibitor of caspases, the resveratrol‐induced increase in the population of cells with hypodiploidal DNA was partially inhibited. Overall, it is suggested that resveratrol at a concentration of 10 µM or more induces apoptosis in normal cells as well as cancer cells (previously reported elsewhere). Thus, at concentrations that are suitable for chemopreventive and chemotherapeutic actions, resveratrol may exert a cytotoxic effect on normal cells.
Morphologic features of the cerebellum of the Atlantic stingray, and their possible evolutionary significance
Authors: PUZDROWSKI Richard L. , GRUBER Stephen
Published: March 2009

The morphology of the cerebellar corpus in cartilaginous fishes varies from a smooth, relatively simple structure to a complex, multilobed structure. Atlantic stingrays possess a trilobed corpus that includes an anterior lobe, divided into rostral and caudal lobules, and a posterior lobe. The corpus in this stingray is assymetrical. This asymmetry was examined in the stingray population of Galveston Bay. In 49% of the animals the axis of the caudal lobule was right of the midline, in 27% it was across the midline, and in 24% it was to the left. This variation is not related to size, sex, or an asymmetry in the cranial volume, but might reflect a variation in the cerebellar developmental program. To gain insight into the factors that have driven cerebellar hypertrophy in cartilaginous fishes, the neural connections of the lobules of the cerebellum of the Atlantic stingray were examined using biotinylated dextrans. It was found that, for the most part, the stingray cerebellum receives inputs from the same diencephalic and brainstem nuclei as in cartilaginous fishes with a bilobed cerebellum. However, in stingrays there is greater segregation of inputs. The anterior lobe rostral lobule receives inputs from the accessory optic nuclei, the caudal lobule receives inputs from trigeminal and octavolateral nuclei, and the posterior lobe receives inputs from the spinal cord. The rostral lobule and posterior lobe also receive input from midbrain nuclei that do not appear to be present in cartilaginous fishes with a morphologically simple corpus. Therefore, it is proposed that the complex hypertrophy of the corpus in stingrays might result from a combination of functional specialization of the lobes, and the acquisition of new inputs.
Adaptive hearing in the vocal plainfin midshipman fish: getting in tune for the breeding season and implications for acoustic communication
Authors: SISNEROS Joseph A.
Published: March 2009

The plainfin midshipman fish (Porichthys notatusGirard, 1854) is a vocal species of batrachoidid fish that generates acoustic signals for intraspecific communication during social and reproductive activity and has become a good model for investigating the neural and endocrine mechanisms of vocal‐acoustic communication. Reproductively active female plainfin midshipman fish use their auditory sense to detect and locate “singing” males, which produce a multiharmonic advertisement call to attract females for spawning. The seasonal onset of male advertisement calling in the midshipman fish coincides with an increase in the range of frequency sensitivity of the female's inner ear saccule, the main organ of hearing, thus leading to enhanced encoding of the dominant frequency components of male advertisement calls. Non‐reproductive females treated with either testosterone or 17β‐estradiol exhibit a dramatic increase in the inner ear's frequency sensitivity that mimics the reproductive female's auditory phenotype and leads to an increased detection of the male's advertisement call. This novel form of auditory plasticity provides an adaptable mechanism that enhances coupling between sender and receiver in vocal communication. This review focuses on recent evidence for seasonal reproductive‐state and steroid‐dependent plasticity of auditory frequency sensitivity in the peripheral auditory system of the midshipman fish. The potential steroid‐dependent mechanism(s) that lead to this novel form of auditory and behavioral plasticity are also discussed.
Understanding the Russian Health Crisis: a Sociological Perspective
Authors: Cockerham William
Published: March 2009

This essay applies a sociological perspective to the health crisis in Russia by delving increasingly deeper into the layers of causes. The major characteristic of this crisis is the decline in life expectancy among men and the relative stagnation of longevity among women. The primary cause is increased cardiovascular disease and alcohol‐related poisoning and accidents. However, in order to determine the ultimate cause, it is necessary to examine secondary level factors to explain what is responsible for the rise in heart disease and alcohol‐based afflictions. Several secondary factors were considered, including infectious disease, poor medical care, environmental pollution, policy, and stress, but the strongest evidence supported negative health lifestyles. The next step is find what is causing a lifestyle harmful to male health in particular and while stress is likely important – the best tertiary level cause is the deeply embedded working‐class style of heavy drinking that is normative in Russia.
Microsatellite markers for mungbean developed from sequence database
Authors: SEEHALAK WORAPA , SOMTA PRAKIT , SOMMANAS WARUNEE , SRINIVES PEERASAK
Published: March 2009

A novel set of microsatellite markers for mungbean [Vigna radiata (L.) Wilczek] was developed from the public sequence database. Seventy‐eight primers were designed and evaluated for polymorphism among 22 cultivated accessions. Eight polymorphic loci detected two to three alleles per locus with an average of 2.25. The observed heterozygosity varied from 0.00 to 0.18, while the expected heterozygosity ranged from 0.09 to 0.46. Among them, all eight loci showed significant departuring from Hardy–Weinberg equilibrium, while four pairs of loci displayed significant pairwise linkage disequilibrium values. All eight loci except DMB‐SSR1 showed heterozygote deficiency.
SURFACE RESPONSE OF SPHERICAL CORE–SHELL STRUCTURED NANOPARTICLE BY OPTICALLY INDUCED ELASTIC OSCILLATIONS OF SOFT SHELL AGAINST HARD CORE
Authors: BASTRUKOV S. I. , LAI P.-Y. , MOLODTSOVA I. V. , CHANG H.-K. , PODGAINY D. V.
Published: March 2009

The optically induced oscillatory response of a spherical two-component, shell–core structured, nanoparticle by nodeless elastic vibrations of soft peripheral shell against hard and dynamically immobile inner core is considered. The eigenfrequencies of the even-parity, spheroidal, and odd-parity torsional vibrational modes trapped in the finite-depth shell are obtained, which are of practical interest for modal specification of individual resonances in spectra of resonant scattering of long wavelength ultrafine particles.
STRUCTURAL AND OPTICAL FEATURES OF POROUS SILICON PREPARED BY ELECTROCHEMICAL ANODIC ETCHING
Authors: CHUAH L. S. , HASSAN Z. , YAM F. K. , ABU HASSAN H.
Published: March 2009

Porous silicon (PS) samples were prepared by electrochemical anodic etching of n-type (111) silicon wafers in HF solution. The structural, optical, and chemical features of the PS were investigated in terms of different etching durations. The porous samples were investigated by scanning electron microscopy (SEM), photoluminescence (PL), and Raman scattering. SEM images indicated that the pores increased with the etching duration; however, the etching duration has significant effect on the shape of the pores. PL measurements revealed that the porosity-induced PL intensity enhancement was only observed in the porous samples. Raman spectra showed shifting of PS Raman peak to lower frequency relative to non-porous silicon Raman peak.
ENDOHEDRAL FULLERENES C60 AND C82 WITH SILVER
Authors: GURIN V. S.
Published: March 2009

The models of endofullerenes C 60 and C 82 with silver atom or diatomic silver are calculated with ab initio methods including the full geometry optimization. Ag @ C 60 is the bound system with positive binding energy while Ag 2@ C 60 is not bound because of strong geometrical strain. In Ag @ C 60 silver atom has the off-center position for the lowest energy model, and the whole structure reduces the symmetry from I h down to C 1. The endo-structures with the C 82 cage can exist with both mono- and diatomic silver interiors. Electronic charge is transferred from the carbon cage to silver.
Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats
Authors: Postler Thomas S. , Budak Murat T. , Khurana Tejvir S. , Rubinstein Neal A.
Published: March 2009

Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone 3,3′,5-triiodo-l-thyronine (T3); subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated control animals. The expression of 468 transcripts was found to be significantly altered, with 466 of these transcripts downregulated in EOMs from T3-treated animals. The biological processes into which the affected genes could be grouped included cellular metabolism, transport, biosynthesis, protein localization, and cell homeostasis. Moreover, 15 distinct biochemical canonical pathways were represented among the genes with altered transcription levels. Strikingly, myostatin ( Gdf8), a potent negative regulator of muscle growth, was found to be strongly downregulated in EOMs from T3-treated animals. Together, these findings suggest that pathological concentrations of thyroid hormone have a unique effect on gene expression in EOMs, which is likely to play a hitherto neglected role in thyroid-associated ophthalmopathies.
Recognition of Live Phosphatidylserine-Labeled Tumor Cells by Dendritic Cells: A Novel Approach to Immunotherapy of Skin Cancer
Authors: Shurin Michael R. , Potapovich Alla I. , Tyurina Yulia Y. , Tourkova Irina L. , Shurin Galina V. , Kagan Valerian E.
Published: March 2009

Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor “cargoes” into DC, we developed a new approach based on the “labeling” of tumors with a phospholipid “eat-me” signal, phosphatidylserine. Expression of phosphatidylserine on live tumor cells mediated their recognition and endocytosis by DC resulting in the presentation of tumor antigens to antigen-specific T cells. In mice, topical application of phosphatidylserine-containing ointment over melanoma induced tumor-specific CTL, local and systemic antitumor immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy. [Cancer Res 2009;69(6):2487–96]
Hypoxia-Inducible Factor-1α Suppresses Squamous Carcinogenic Progression and Epithelial-Mesenchymal Transition
Authors: Scortegagna Marzia , Martin Rebecca J. , Kladney Raleigh D. , Neumann Robert G. , Arbeit Jeffrey M.
Published: March 2009

Hypoxia-inducible factor-1 (HIF-1) is a known cancer progression factor, promoting growth, spread, and metastasis. However, in selected contexts, HIF-1 is a tumor suppressor coordinating hypoxic cell cycle suppression and apoptosis. Prior studies focused on HIF-1 function in established malignancy; however, little is known about its role during the entire process of carcinogenesis from neoplasia induction to malignancy. Here, we tested HIF-1 gain of function during multistage murine skin chemical carcinogenesis in K14-HIF-1αPro402A564G (K14-HIF-1αDPM) transgenic mice. Transgenic papillomas appeared earlier and were more numerous (6 ± 3 transgenic versus 2 ± 1.5 nontransgenic papillomas per mouse), yet they were more differentiated, their proliferation was lower, and their malignant conversion was profoundly inhibited (7% in transgenic versus 40% in nontransgenic mice). Moreover, transgenic cancers maintained squamous differentiation whereas epithelial-mesenchymal transformation was frequent in nontransgenic malignancies. Transgenic basal keratinocytes up-regulated the HIF-1 target N-myc downstream regulated gene-1, a known tumor suppressor gene in human malignancy, and its expression was maintained in transgenic papillomas and cancer. We also discovered a novel HIF-1 target gene, selenium binding protein-1 (Selenbp1), a gene of unknown function whose expression is lost in human cancer. Thus, HIF-1 can function as a tumor suppressor through transactivation of genes that are themselves targets for negative selection in human cancers. [Cancer Res 2009;69(6):2638–46]
CBL Exon 8/9 Mutants Activate the FLT3 Pathway and Cluster in Core Binding Factor/11q Deletion Acute Myeloid Leukemia/Myelodysplastic Syndrome Subtypes
Authors: Reindl Carola , Quentmeier Hilmar , Petropoulos Konstantin , Greif Philipp A. , Benthaus Tobias , Argiropoulos Bob , Mellert Gudrun , Vempati Sridhar , Duyster Justus , Buske Christian , Bohlander Stefan K. , Humphries Keith R. , Hiddemann Wolfgang , Spiekermann Karsten
Published: March 2009

Purpose: CBL is a negative regulator of activated receptor tyrosine kinases (RTK). In this study, we determined the frequency of CBL mutations in acute leukemias and evaluated the oncogenic potential of mutant CBL.

Experimental Design: The cDNA of 300 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL) patients and 82 human leukemic cell lines was screened for aberrations in the linker and RING finger domain of CBL. The oncogenic potential of identified mutants was evaluated in hematopoietic cells.

Results: We identified 3 of 279 AML/MDS patients expressing CBL exon 8/9 deletion mutants. Three of four cases at diagnosis expressed deleted transcripts missing exon 8 or exon 8/9. In remission samples a weak or no expression of mutant CBL was detected. No aberrations were found in normal hematopoietic tissues. One of 116 sequenced AML/MDS cases carried a R420G missense mutation. All AML/MDS patients with identified CBL mutants belonged to the core binding factor and 11q deletion AML subtypes. Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. Expression of CBLΔexon8 and CBLΔexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor–independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). FLT3 ligand–dependent hyperproliferation of CBL mutant cells could be abrogated by treatment with the FLT3 PTK inhibitor PKC412 (midostaurin).

Conclusion: CBL exon8/9 mutants occur in genetically defined AML/MDS subtypes and transform hematopoietic cells by constitutively activating the FLT3 pathway. This phenotype resembles the one of mutated RTKs and suggests that CBL mutant AML patients might benefit from treatment with FLT3 PTK inhibitors.
The Topoisomerase I Poison CPT-11 Enhances the Effect of the Aurora B Kinase Inhibitor AZD1152 both In vitro and In vivo
Authors: Nair Jayasree S. , de Stanchina Elisa , Schwartz Gary K.
Published: March 2009

Purpose: AZD1152 is an Aurora B kinase inhibitor currently in clinical trials. As the topoisomerase I poison CPT-11 induces a G2 arrest, a mechanistic understanding of the cell cycle interactions between these agents may prove critical for combination therapy.

Methods: AZD1152 was tested in vitro and in vivo with SN-38 and CPT-11 against HCT-116 cells. Inhibition of clonogenicity, induction of apoptosis, effects on polyploidy, and tumor growth were examined.

Results: AZD1152 alone induced polyploidy of HCT-116 cells at low nanomolar concentrations. The induction of apoptosis required prolonged exposure (48 hours) and higher concentrations of drug. When SN-38 was given before or concomitantly with AZD1152, SN-38 blocked the AZD1152 effect by arresting cells in G2 and inhibiting cells from undergoing polyploidy. With the reverse combination (AZD1152 followed by SN-38), there was a significant induction of polyploidy and apoptosis, even with shorter exposure (24 hours) of AZD1152. In vivo, AZD1152 alone suppressed HCT-116 xenograft tumor growth in a dose-dependent manner with target inhibition of phosphoH3, induction of multinucleated giant cells, but without induction of apoptosis. In combination, both sequences in vivo (CPT->AZD, AZD->CPT, P = 0.008, AUC/d) proved superior to either single agent therapy. However, AZD->CPT still showed a greater increase in apoptosis and greater suppression of tumor regrowth than CPT->AZD (P = 0.02, AUC/d).

Conclusions: The results from these studies indicate a promising therapeutic strategy for combining AZD1152 with CPT-11, and suggest that the sequence of drug administration is pivotal when an Aurora B kinase inhibitor is administered with a topoisomerase I poison.
Effective Prostate Cancer Chemopreventive Intervention with Green Tea Polyphenols in the TRAMP Model Depends on the Stage of the Disease
Authors: Adhami Vaqar Mustafa , Siddiqui Imtiaz Ahmad , Sarfaraz Sami , Khwaja Sabih Islam , Hafeez Bilal Bin , Ahmad Nihal , Mukhtar Hasan
Published: March 2009

Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP.

Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling.

Results: Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common.

Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.