bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of hematological indices in tannery workers exposed to chromium in Sheikhupura (Pakistan)
Authors: Ramzan Muhammad , Muhammad Anwar Malik  , Iqbal Zaheer , Arshad Najma , Shafaat Yar Khan  , Arshad Muhammad
Published: April 2011

Chromium (Cr), being an excellent tanning agent, is widely used in the leather industry and tannery workers (TW) are exposed to it either in the form of inorganic Cr(III) compounds or Cr bound to proteins (leather dust) in the process of leather production. During the present study, the effect of Cr on the hematological indices in TW was evaluated. In this study, hematological indices of 92 male TW aged 20—60 years were compared with 79 control males who hardly had a chance of exposure to chromium. Both groups were subdivided into four age groups with an interval of 10: group A, 20—29 years; group B, 30—39 years; group C, 40—49 years; group D, 50—60 years. Total erythrocyte count (TEC) was significantly lower (p < 0.05) in TW of age group A, B and C than control subjects. Packed cell volume (PCV) was significantly higher (p < 0.05) in TW of age group B while mean corpuscular hemoglobin (MCH) was significantly lower (p < 0.05) in TW of age group D. Within the TW, MCH was significantly lower (p < 0.05) in the age group D as compared to age group A and B. No significant changes were observed in the values of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration between TW and control individuals. The low values of TEC, PCV and MCH might be a result of chromium exposure in the tannery workers and may act as indicators of chromium toxicity.
The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients
Authors: Altuner Durdu , Ates Ilker , Suzen Sinan H , Koc Gonul Varan , Aral Yalcin , Karakaya Asuman
Published: April 2011

Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants ( p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups ( p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.
Anti-inflammatory effects of the chloroform extract of Pulicaria guestii ameliorated the neutrophil infiltration and nitric oxide generation in rats
Authors: Alghaithy AA , El-Beshbishy HA , AbdelNaim AB , Nagy AA , Abdel-Sattar EM
Published: April 2011

Pulicaria guestii Rech.f. & Rawi is a fragrant, perennial herb, which grows wild, west of Al-Madinah, Saudi Arabia. Several reports were published on the anti-inflammatory activity of the sesquiterpene lactones, phenolics and flavonoids, which constitute the main active constituents of the members of the genus Pulicaria. The present study was designed to explore the potential anti-inflammatory effect of P. guestii in several experimental models. The methanol extract of the dried aerial parts of P. guestii was extracted with petroleum ether, chloroform and n-butanol. The chloroform extract was analysed on TLC and examined under UV and visible light in presence of AlCl3 spray. The free radical scavenging activity and the total phenolic content in the CHCl3 extract were estimated. The crude methanol extract and the CHCl3 fraction were examined against carrageenin-induced paw edema and ear edema induced by croton oil application. The crude methanolic extract significantly reduced carrageenin-induced rat paw edema. After fractionation, the chloroform fraction caused significant reduction in carrageenin-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) in the inflammatory exudates. Topical application of chloroform fraction significantly reduced rat ear edema induced by croton oil application. In the same model, chloroform fraction reduced neutrophil infiltration, as indicated by the significant decrease in myeloperoxidase activity, and ameliorated histopathological changes induced by croton oil application. In lipopolysaccharide-induced inflammation in rat air pouch, chloroform fraction significantly reduced the nitric oxide level and tumor necrosis factor-α release. In conclusion, the chloroform fraction of P. guestii extract possesses anti-inflammatory activity in several experimental models. Further investigations are needed to identify the active constituents responsible for this anti-inflammatory activity.
Occupational health problems of highway restaurant workers of Pune, India
Authors: Kokane S , Tiwari RR
Published: April 2011

To meet the ever-increasing demand for new cuisines, the catering industry in India is becoming more prominent day by day. According to a recent estimate, more than two million restaurants are now dominating the present scenario of the Indian catering industry. The health hazards in restaurants vary according to the place that a worker is employed. The hazards among kitchen staff include several different types of accidents such as burns from deep fryers, slipping on grease and cuts from knives, whereas musculoskeletal disorders are more common among waiters and helpers who usually bear load. The present cross-sectional study included 127 workers from 15 restaurants and dhabas situated at Pune—Mumbai high way. Interview technique followed by clinical examination was the tool for data collection. Musculoskeletal symptoms such as low back pain, fatigue, body ache and pain in limbs were present in 18 (14.2%) of the workers. Gastrointestinal complaints such as heartburn, abdomen pain, stomatitis, etc. were reported by 12 (9.4%) subjects, while skin-related symptoms, such as itching and discoloration were reported in 12 (9.4%) subjects. Seventy-three (57.5%) of the subjects were free from any symptoms.
Effect of selenium pre-treatment on plasma antioxidant vitamins A (retinol) and E (α-tocopherol) in static magnetic field-exposed rats
Authors: Ghodbane Soumaya , Amara Salem , Arnaud Josiane , Garrel Catherine , Faure Henri , Favier Alain , Sakly Mohsen , Abdelmelek Hafedh
Published: April 2011

In the present study, we evaluate the effect of the co-exposure to static magnetic field (SMF) and selenium (Se) on the antioxidant vitamins A and E levels and some other parameters of oxidative stress in rat. Sub-acute exposure of male adult rats to a uniform SMF (128 mT, 1 h/day during 5 consecutive days) increased plasma activity of glutathione peroxidase (+35%) but decreased α-tocopherol (−67%) and retinol levels (−41%). SMF exposure failed to alter the plasmatic thiobarbituric acid-reactive species (TBARs), total thiol groups and selenium concentrations. Sub-chronic administration of Se (Na2SeO3, 0.2 mg/L, for 30 consecutive days, per os) ameliorated the antioxidant capacities in SMF-treated rats. Our investigation demonstrated that sub-acute exposure to SMF induced oxidative stress, which may be prevented by a pretreatment with selenium.
Subacute effect of cigarette smoke exposure in rats
Authors: Özkol Halil , Tülüce Yasin , Koyuncu Ismail
Published: April 2011

This study was carried out to determine the preventive effect of Calendula officinalis L. (pot marigold) on rats exposed to cigarette smoke (CS). Rats were divided into three groups as control, CS and CS + pot marigold (PM). The rats in the CS and CS + PM groups were subjected to CS for 1 h twice a day for 23 days. PM (100 mg/kg body weight) was given to rats in the CS + PM group by gavage, 1 h before each administration period. While malondialdehyde, protein carbonyl contents and reduced glutathione level of the CS group increased, their levels diminished by PM administration. In addition, glutathione peroxidase (GPx), superoxide dismutase activities and β-carotene, vitamins A and C levels decreased in the CS group compared to control, however activities of these enzymes and concentration of vitamins were elevated by PM supplementation. This investigation showed that administration of PM supplied relative protection against subacute CS-induced cell injury.
Effect of endostatin on 1,2-dimethylhydrazine-induced colon tumor in mice
Authors: Karaca Omur , Ertekin Tolga , Canoz Ozlem , Ulger Harun , Soysal Handan , Kus Ilter
Published: April 2011

Endostatin, one of the most potent negative regulators of angiogenesis, is naturally occurring as an inhibitor of angiogenesis capable of inhibiting tumor growth and their metastases. We aimed to investigate the in vivo activities of low dose of recombinant human endostatin on 1,2-dimethylhydrazine (DMH)-induced mice colon cancer. Thirty male Balb-c mice were injected with DMH (20 mg/kg/week) subcutaneously once a week for 12 weeks to induce colon cancer. Twelve weeks after the last DMH injection, 7 µg rh-endostatin was injected every day for 6 weeks. The animals were killed after 30 weeks for histopathological examination. The weight of the animals, tumor inhibition rates, death rates and the distribution of the lesions in colon were evaluated after the mice were killed. The mean colonic lesions incidence in single tumor bearing mice was 11 ± 4.0 in those treated with DMH and 8.1 ± 3.7 in those treated with endostatin. When we look at the distribution of lesions in the colon, they occurred in the distal colon. At the end of our study, we noticed that the number of lesions decreased by 25% in the group of endostatin, considering the number of the lesions in the group of DMH. But there was no statistical difference between the mice treated with endostatin and those treated with DMH. It will be very significant to identify endostatin therapeutic effects as long as proper dose of endostatin is administrated at the proper time, duration and proper tumor model.
Taking one day at a time: Temporal experiences in the context of unexpected life course transitions
Authors: Shirani Fiona , Henwood Karen
Published: April 2011

This article explores how unexpected life course events can potentially be experienced as problematic by challenging anticipated future trajectories. Using data from a qualitative longitudinal study of men interviewed about fatherhood, we consider four unanticipated events in the context of family formation which are variously experienced as propelling men forwards, imposing a pause, or regressing to a previous life course phase. In these situations time represents a threat to personal identity, challenging imagined futures and leading to altered behaviour in the present. These unexpected events appear to have a long-term impact on temporal awareness. By highlighting understandings of the future as a fundamental aspect of experience, we illustrate the importance of making time explicit as a tool for elucidating life course transitions.
Between Cries and Flames: Female Sufi Mystics
Authors: Arias Bautista María Teresa
Published: April 2011

For this study, I especially have centred myself on the work of the doctor in psychiatry and professor of the University of Tehran, Javad Nurbakhsh. He was a Master of the Order of Sufi Shah Nematollah Wali and died a year ago. This work, which appeared in 1999, is titled ‘Sufi Women’ and in it, the author compiled the brief biographies, which were sometimes only slight glimpses of existence, of 136 women. I will focus on three principle questions: the women themselves, their relationships with their surroundings, and their relationships with God. I conclude that female Sufi Mystics’ bodies were soaked in tears and their souls in flames. They shed tears because of their distance from God and for being stuck in bodies and because of their desire for transcendence, to drown in Oneness. Since their bodies impeded this desire, they mortified them impiously with fasts and vigils and became unsightly to all who saw them. They did not take care of others, and they did not take care of themselves, they renounced all care.
Feminine Mystique in Flamenco
Authors: Cervini Laura
Published: April 2011

Not so long ago, when I first became interested in flamenco poetry and was studying it from linguistic and cultural points of view, the question of the female image in the verses began to draw my attention. It is a cornerstone of flamenco poetry yet at the same time is full of contradictions. At that time I wanted to define the difference between the singer and the song: the woman who is the exponent of flamenco and the woman who appears in the lyrics. Today, after translating many ‘coplas’ (flamenco lyrics) and having delved more and more deeply into the words and their hidden meanings I have discovered new aspects of the feminine concept in flamenco. There are nuances whose roots are found in many and different ancient cultures. To describe the combination of elements that place woman both at the heart of flamenco and at the borders, I would like to refer to a very interesting definition of the ‘feminine mystique’.
Identification of biomarkers for diagnosis and progression of MS by MALDI-TOF mass spectrometry
Authors: Teunissen CE , Koel-Simmelink MJA , Pham TV , Knol JC , Khalil M , Trentini A , Killestein J , Nielsen J , Vrenken H , Popescu V , Dijkstra CD , Jimenez CR
Published: April 2011

Introduction: Body fluid biomarkers for clinical subtyping and monitoring of disease progression are of considerable interest in multiple sclerosis (MS). Proteomics tools are optimal for the unbiased simultaneous detection of large series of peptides and proteins.

Objectives: To identify novel candidate biomarkers discriminating patients with MS from patients with other neurological diseases (OND), and for subtyping of relapsing–remitting (RR), secondary progressive (SP) and primary progressive (PP) MS patients using a high-throughput MALDI-TOF-based mass spectrometry method.

Methods: Paired cerebrospinal fluid (CSF) and serum samples of 41 RRMS, 30 SPMS, 13 PPMS patients and 25 patients with OND were analysed.

Results: Out of a total of 100 detected peptides in CSF and 200 peptides in serum, 11 peptides were differentially regulated in serum and two in CSF between patients with MS and the OND control group. Eleven peptides were differentially regulated in both serum and CSF between relapse-onset MS and PPMS patients. Lastly, four peptides were differentially regulated in serum and two in CSF between RRMS and SPMS patients. Specific peaks regulated in MS were tentatively identified as fragments of secretogranin III and complement C3. The peak intensity of the CSF peptide ion with m/z value 8607.7 correlated to atrophy ( r = −0.27, p < 0.005), black hole volumes ( r = 0.31, p < 0.008) and total lesion load ( r = 0.34, p < 0.003). A serum peptide with m/z value of 872.4 elevated in SPMS correlated to Expanded Disability Status Scale ( r = 0.341, p < 0.005) and atrophy ( r = −0.286, p < 0.028).

Conclusions: Using high-throughput body fluid profiling by MALDI-TOF mass spectrometry, small proteins and peptides were detected as promising candidate biomarkers for diagnosis and disease progression of MS.
Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: Implication for plaque progression in diabetic atherosclerosis
Authors: Purushothaman K-Raman , Purushothaman Meerarani , Muntner Paul , Lento Patrick A , O'Connor William N , Sharma Samin K , Fuster Valentin , Moreno Pedro R
Published: April 2011

Sustained inflammation may stimulate a reparative process increasing early reparative type III collagen synthesis, promoting atherosclerotic plaque progression. We evaluated inflammation, neovascularization, intra-plaque hemorrhage (IPH), and collagen deposition in human aortic atherosclerotic plaques from patients with and without diabetes mellitus (DM). Plaques were procured at autopsy from lower thoracic and abdominal aorta from DM ( n = 20) and non-DM ( n = 22) patients. Inflammation and neovascularization were quantified by double-label immunochemistry and the IPH grade was scored using H&E-stained sections. Type I and type III collagens were quantified using Picro-Sirius red stain with polarization microscopy and computerized planimetry. In non-DM plaques, 27%, 40%, and 33% had mild, moderate and severe inflammation in the fibrous cap and shoulder compared with 2%, 30% and 68% in DM plaques ( p < 0.001). The geometric mean neovessel count was increased in DM versus non-DM plaques (140 [95% CI: 119—165] versus 59 [95% CI: 51—70]; p < 0.001). The IPH grade was increased in DM verses non-DM plaques (0.82 ± 0.11 versus 0.29 ± 0.11; p < 0.001) (percentage grade). The density of type III was increased in DM plaques (0.16 ± 0.01 versus 0.06 ± 0.01; p < 0.001) with a non-significant reduction in type I density in DM when compared with non-DM (0.28 ± 0.03 versus 0.33 ± 0.03; p = 0.303) (content per mm2). The increase in type III collagen content correlated with total neovessel content ( r = 0.58; p < 0.001) in DM plaques. In conclusion, our study suggests that enhanced type III collagen deposition was associated with inflammation, neovascularization and IPH, and may be a contributing factor in DM plaque progression.
Mediation among young immigrants in the juvenile penal justice system
Authors: Campo Jaume del , Vilà Ruth , Martí Jaume , Vinuesa M Rosa
Published: April 2011

• Summary: Multicultural modern society shows the necessity for a systematic assessment of needs and the formulation of policies which are based on rigorous and systematic research. Specifically, in Spain juvenile penal justice represents one of the major contexts where the presence of cultural diversity has made itself forcefully felt. This situation has led to an ongoing reappraisal of the way in which the forms of conflict management which currently form part of the Spanish Juvenile Penal Code are applied. This article represents an attempt to take a closer look at the way mediation is used as a policy alternative in the penal context, and in particular how it is used in situations when one part of the process involves a young immigrant. We focus on the meaning attributed to penal mediation from the perspective of the victim or the offender and on the difficulties in applying mediation programs among young immigrants.

• Findings: This analysis shows the presence of several asymmetries in intercultural mediation and suggests the importance of intercultural communication in mediation.

• Application: We aim to develop a more comprehensive framework in order to improve the way such processes are implemented in practice, paying special attention to the possible application of mediation in other contexts.
Towards a Manifesto for Machinima
Authors: Harwood Tracy
Published: April 2011

The author examines the past, present and future of machinima, hereby defined as an art form in transition. Although both socially and culturally embedded in gaming cultures, machinima could expand well beyond gaming, as it represents a successful example of convergence of filmmaking, animation and games development. Although the medium has a strong artistic potential, the future trajectory of machinima will remain indelibly tied to games development, reflecting gaming and internet cultures. The author predicts that machinima will further evolve in line with developing curatorial expertise in its presentation to wider audiences and positioning within the digital arts movement.
Machinima is Growing Up
Authors: Fosk Kate
Published: April 2011

The author suggests that machinima is evolving and progressively abandoning its juvenile, playful roots to become a mature form of expression, thanks to the diffusion of specialized animation tools and virtual worlds. The author suggests that this new wave of machinima is experiencing a parallel evolutionary path to mainstream film and broadcast media, expanding into genres that include drama, comedy, documentary, educational material, advertising, art, and political activism. Machinima nowadays includes hybrid works, such as virtual installations and mixed live and online events.
Massively Multiplayer Machinima Mikusuto
Authors: Stern Eddo
Published: April 2011

The author presents a taxonomy of machinima produced within and around Massively Multiplayer Online Games (MMOGs), specifically World of Warcraft ( WoW). The author illustrates three possible categories: in-house machinima, fan-fiction machinima, and nonfiction machinima, examining the difference in style, purpose, and artistic potential of each.
Does Machinima Really Democratize?
Authors: Jones Robert
Published: April 2011

The author questions the apparent democratizing potential of machinima, arguing that this form of expression is limited both in terms of production (creators) and consumption (audience). To make his point, he examines Alex Chan’s The French Democracy, a popular machinima that fictionally reconstructed the Parisian riots of 2005, concluding that this film is an anomaly if compared to the larger machinima production. Moreover, Chan’s point of view, while representative of the marginalized Parisian suburban dwellers vilified during the riots, does not represent all the members of that subaltern group. The author concludes that similar limitations affect other machinima productions.
The Future of Machinima as a Professional Animation Resource and its Growth as Real-Time Animation in Virtual Worlds
Authors: Dellario Frank R.
Published: April 2011

The author argues that although machinima is a relatively specialized field, it offers a newer and faster production pipeline for the commercial animation industry as a whole. Pioneered by individuals who have turned their passion for gaming into a powerful professional animation medium, machinima has a great potential. After comparing the development of machinima to the evolution of the internet, the author concludes that the emergence of virtual worlds such as Second Life was instrumental in the growth of this particular type of real-time computer animation.
Perfect Capture: Three Takes on Replay, Machinima and the History of Virtual Worlds
Authors: Lowood Henry
Published: April 2011

The interactive, immersive and performative aspects of digital games and virtual worlds take the challenges faced by media archivists, curators and historians beyond software preservation to problems that demand new documentation and preservation strategies. The social and performative aspects of online worlds are forcing repositories to develop new strategies for preservation. Of the utmost importance is to preserve and archive practices and performances and not only the software that made these practices and performances possible. The author also argues that the three primary methods for making machinima during its brief history — demo, screen capture, and asset composition — can be matched to three ways for documenting the history of virtual worlds (replay, POV recording, and asset extraction), concluding that machinima provides compelling evidence for the ability of players to turn digital games into their own creative medium.
Examining media effectiveness across cultures and national borders: A review and multilevel framework
Authors: Moustafa Leonard Karen , Van Scotter James R. , Pakdil Fatma , Jbeily Chamseddine Nadine , Esatoglu Ezel , Gumus Murat , Koyuncu Mustafa , Ling Ling Wu  , Mockaitis Audra I. , Salciuviene Laura , Oktem M. Kemal , Surkiene Gene , Tsai Fu-Sheng
Published: April 2011

We explore the ways that perceptions of media effectiveness are affected by the societal culture, organizational culture, occupational (professional) culture, individual characteristics, and technology acceptance. This is an important subject to explore, as communication is essential to organizational functioning. The continuous drive for communication to individuals in different national and organizational situations around the world, due in part to globalization, leads us to ask: which medium is perceived as the most effective for each of the tasks a manager may be called upon to perform, particularly in different cultures? In other words, is the receiver getting the message that we intend, when the receiver is not in the same situation (societal, organizational, professional, etc.) as the sender? There are contexts of shared values, rules, and experiences that affect communication; words do not have the same meaning and value across languages and cultures (Macnamara, 2004). This means that the message sent from one context may not be the message received in another. If we are not communicating the messages we intend, then our method of communicating may be efficient, but it is certainly not effective. However, there is little research on the effectiveness of media types. We develop a framework highlighting the intersection of variables salient to effectiveness: societal, organizational, and occupational culture, individual characteristics, and technology the sender? In the conclusion, we suggest future work that might be appropriate, given the increasing interest in global communication.
Special Review Article: Diversity and its not so diverse literature: An international perspective
Authors: Jonsen Karsten , Maznevski Martha L. , Schneider Susan C.
Published: April 2011

This paper reviews workforce diversity literature and its research findings. We identify important gaps between the literature and the challenges of diversity management. These gaps include lack of organizational level analysis, tokenism, and artificially constructed research settings that cannot address a variety of cultural contexts. Furthermore, most studies do not investigate underlying beliefs and values or managerial interventions. We conclude that the diversity field itself is not very diverse and has been dominated by US-centric research. We provide suggestions for future research themes: language diversity, cultural contextualization of diversity, and social class diversity.
New approach to the modelling of motor failure data with application to the engine overhaul decision process
Authors: Jiang R
Published: April 2011

This paper presents a method to transform data on motor failures, that is extensively used in the literature for the benchmarking of reliability models, into the form of time-to-failure (TTF) data. A normal distribution is appropriate for modelling the TTF data. The estimated mean lives are subsequently fitted to a power-law failure point process model, and the life standard deviation after a failure can be obtained using a recursive relation. These are useful for inferring the life distribution after a future failure. The resulting model is applied to optimize the lifespan and predict the number of overhauls in a given operational interval. The approach developed in this paper is not limited to the specific case for which it is derived; it can be applied to similar problems or situations.
Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
Authors: Hubert François-Xavier , Kinkel Sarah A. , Davey Gayle M. , Phipson Belinda , Mueller Scott N. , Liston Adrian , Proietto Anna I. , Cannon Ping Z. F. , Forehan Simon , Smyth Gordon K. , Wu Li , Goodnow Christopher C. , Carbone Francis R. , Scott Hamish S. , Heath William R.
Published: April 2011

To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)–specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter. Aire deficiency reduced the number of mature single-positive OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways to OVA-dependent negative selection depending on the T-cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to medullary thymic epithelial cell (mTEC)–expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTECs can mediate tolerance by direct presentation of Aire-regulated antigens to both CD4 and CD8 T cells.
Proteolytic and genetic variation of the alpha-2-antiplasmin C-terminus in myocardial infarction
Authors: de Willige Shirley Uitte , Miedzak Megan , Carter Angela M. , Lisman Ton , Rosendaal Frits R. , Grant Peter J. , Philippou Helen , Ariëns Robert A. S.
Published: April 2011

Alpha-2-antiplasmin (α2AP) undergoes both N- and C-terminal cleavages, which significantly modify its activities. Compared with other Ser protease inhibitors (serpins), α2AP contains an ∼ 50-residue–extended C-terminus, which binds plasmin(ogen). We developed 2 new ELISAs to measure the antigen levels of free total α2AP and free C-terminally intact α2AP to investigate whether α2AP antigen levels or α2AP C-terminal cleavage were associated with myocardial infarction (MI) in 320 male MI survivors and 169 age-matched controls. Patients had 15.2% reduced total α2AP antigen levels compared with controls (93.8 vs 110.6 U/dL, P < .001), with a 10.1-fold (95% confidence interval [CI]: 5.5-18.9) increased MI risk for levels in the 1st quartile compared with the 4th quartile. The percentage of C-terminal cleavage did not differ between patients and controls (38.7% and 38.1%, respectively, P = .44). In addition, all individuals were genotyped for the polymorphism Arg407Lys, which is located near the start of the extended C-terminus. Arg407Lys was not associated with α2AP C-terminal cleavage, total α2AP antigen levels, or MI risk (odds ratios compared with Arg/Arg: Arg/Lys 0.74, 95% CI: 0.50-1.10; Lys/Lys 0.77, 95% CI: 0.31-1.92). Our data show that levels of free full-length α2AP were decreased in MI, that the percentage of C-terminally cleaved α2AP was unaltered, and that Arg407Lys did not influence α2AP levels or MI risk.
Effects of valproate on Tax and HBZ expression in HTLV-1 and HAM/TSP T lymphocytes
Authors: Belrose Gildas , Gross Antoine , Olindo Stéphane , Lézin Agnès , Dueymes Maryvonne , Komla-Soukha Isabelle , Smadja Didier , Tanaka Yuetsu , Willems Luc , Mesnard Jean-Michel , Peloponese Jean-Marie , Césaire Raymond
Published: April 2011

A determinant of human T-lymphotropic virus-1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) development is the HTLV-1–infected cell burden. Viral proteins Tax and HBZ, encoded by the sense and antisense strands of the pX region, respectively, play key roles in HTLV-1 persistence. Tax drives CD4+-T cell clonal expansion and is the immunodominant viral antigen recognized by the immune response. Valproate (2-n-propylpentanoic acid, VPA), a histone deacetylase inhibitor, was thought to trigger Tax expression, thereby exposing the latent HTLV-1 reservoir to immune destruction. We evaluated the impact of VPA on Tax, Gag, and HBZ expressions in cultured lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients. Approximately one-fifth of provirus-positive CD4+ T cells spontaneously became Tax-positive, but this fraction rose to two-thirds of Tax-positive–infected cells when cultured with VPA. Valproate enhanced Gag-p19 release. Tax- and Gag-mRNA levels peaked spontaneously, before declining concomitantly to HBZ-mRNA increase. VPA enhanced and prolonged Tax-mRNA expression, whereas it blocked HBZ expression. Our findings suggest that, in addition to modulating Tax expression, another mechanism involving HBZ repression might determine the outcome of VPA treatment on HTLV-1–infected–cell proliferation and survival.
Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma
Authors: Kamper Peter , Ludvigsen Maja , Bendix Knud , Hamilton-Dutoit Stephen , Rabinovich Gabriel A. , Møller Michael Boe , Nyengaard Jens R. , Honoré Bent , d'Amore Francesco
Published: April 2011

Considerable effort has been spent identifying prognostic biomarkers in classic Hodgkin lymphoma (cHL). The aim of our study was to search for possible prognostic parameters in advanced-stage cHL using a proteomics-based strategy. A total of 14 cHL pretreatment tissue samples from younger, advanced-stage patients were included. Patients were grouped according to treatment response. Proteins that were differentially expressed between the groups were analyzed using 2D-PAGE and identified by liquid chromatography mass spectrometry. Selected proteins were validated using Western blot analysis. One of the differentially expressed proteins, the carbohydrate-binding protein galectin-1 (Gal-1), was further analyzed using immunohistochemistry HC and its expression was correlated with clinicopathologic and outcome parameters in 143 advanced-stage cHL cases. At the univariate level, high Gal-1 expression in the tumor microenvironment was correlated with poor event-free survival (P = .02). Among younger (≤ 61 years) patients, high Gal-1 was correlated with poorer overall and event-free survival (both P = .007). In this patient group and at the multivariate level, high Gal-1 expression retained a significant predictive impact on event-free survival. Therefore, in addition to its functional role in cHL-induced immunosuppression, Gal-1 is also associated with an adverse clinical outcome in this disease.
Differentiation, phenotype, and function of interleukin-17–producing human Vγ9Vδ2 T cells
Authors: Caccamo Nadia , La Mendola Carmela , Orlando Valentina , Meraviglia Serena , Todaro Matilde , Stassi Giorgio , Sireci Guido , Fournié Jean Jacques , Dieli Francesco
Published: April 2011

In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17+ Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27−CD45RA+) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17+ Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocytosis of neutrophils and IL-17–dependent production of β-defensin by epithelial cells, indicating that they may be involved in host immune responses against infectious microorganisms. Accordingly, an increased percentage of IL-17+ Vγ9Vδ2 lymphocytes is detected in the peripheral blood and at the site of disease in children with bacterial meningitis, and this pattern was reversed after successful antibacterial therapy. Most notably, the phenotype of IL-17+ Vγ9Vδ2 T cells in children with meningitis matches that of in vitro differentiated IL-17+ Vγ9Vδ2 T cells. Our findings delineate a previously unknown subset of human IL-17+ Vγ9Vδ2 T lymphocytes implicated in the pathophysiology of inflammatory responses during bacterial infections.
Evidence for a purifying selection acting on the β-lactamase locus in epidemic clones of methicillin-resistant Staphylococcus aureus
Authors: Milheiriço Catarina , Portelinha Ana , Krippahl Ludwig , de Lencastre Hermínia , Oliveira Duarte C
Published: April 2011

Background

The β-lactamase (bla) locus, which confers resistance to penicillins only, may control the transcription of mecA, the central element of methicillin resistance, which is embedded in a polymorphic heterelogous chromosomal cassette (the SCCmec element). In order to assess the eventual correlation between bla allotypes and genetic lineages, SCCmec types and/or β-lactam resistance phenotypes, the allelic variation on the bla locus was evaluated in a representative collection of 54 international epidemic methicillin-resistant Staphylococcus aureus (MRSA) clinical strains and, for comparative purposes, also in 24 diverse methicillin-susceptible S. aureus (MSSA) strains.

Results

Internal fragments of blaZ (the β-lactamase structural gene) were sequenced for all strains. A subset of strains, representative of blaZ allotypes, was further characterized by sequencing of internal fragments of the blaZ transcriptional regulators, blaI and blaR1. Thirteen allotypes for blaZ, nine for blaI and 12 for blaR1 were found. In a total of 121 unique single-nucleotide polymorphisms (SNP) detected, no frameshift mutations were identified and only one nonsense mutation within blaZ was found in a MRSA strain. On average, blaZ alleles were more polymorphic among MSSA than in MRSA (14.7 vs 11.4 SNP/allele). Overall, blaR1 was the most polymorphic gene with an average of 24.8 SNP/allele. No correlation could be established between bla allotypes and genetic lineages, SCCmec types and/or β-lactam resistance phenotypes. In order to estimate the selection pressure acting on the bla locus, the average dN/dS values were computed. In the three genes and in both collections dN/dS ratios were significantly below 1.

Conclusions

The data strongly suggests the existence of a purifying selection to maintain the bla locus fully functional even on MRSA strains. Although, this is in agreement with the notion that in most clinical MRSA strains mecA gene is under the control of the bla regulatory genes, these findings also suggest that the apparently redundant function of blaZ gene for the MRSA resistant phenotype is still important for these strains. In addition, the data shows that the sensor-inducer blaR1 is the primary target for the accumulation of mutations in the bla locus, presumably to modulate the response to the presence of β-lactam antibiotic.
Differential disease resistance response in the barley necrotic mutant nec1
Authors: Keisa Anete , Kanberga-Silina Krista , Nakurte Ilva , Kunga Laura , Rostoks Nils
Published: April 2011

Background

Although ion fluxes are considered to be an integral part of signal transduction during responses to pathogens, only a few ion channels are known to participate in the plant response to infection. CNGC4 is a disease resistance-related cyclic nucleotide-gated ion channel.Arabidopsis thalianaCNGC4 mutantshlm1anddnd2display an impaired hypersensitive response (HR), retarded growth, a constitutively active salicylic acid (SA)-mediated pathogenesis-related response and elevated resistance against bacterial pathogens. Barley CNGC4 shares 67% aa identity with AtCNGC4. The barley mutantnec1comprising of a frame-shift mutation of CNGC4 displays a necrotic phenotype and constitutively over-expressesPR-1, yet it is not known what effect thenec1mutation has on barley resistance against different types of pathogens.

Results

nec1mutant accumulated high amount of SA and hydrogen peroxide compared to parental cv. Parkland. Experiments investigatingnec1disease resistance demonstrated positive effect ofnec1mutation on non-host resistance againstPseudomonas syringaepv.tomato(Pst) at high inoculum density, whereas at normalPstinoculum concentrationnec1resistance did not differ from wt. In contrast to augmentedP. syringaeresistance, penetration resistance against biotrophic fungusBlumeria graminisf. sp.hordei(Bgh), the causal agent of powdery mildew, was not altered innec1. Thenec1mutant significantly over-expressed race non-specificBghresistance-related genesBI-1andMLO. Induction ofBI-1andMLOsuggested putative involvement ofnec1in race non-specificBghresistance, therefore the effect ofnec1onmlo-5-mediatedBghresistance was assessed. Thenec1/mlo-5double mutant was as resistant toBghasNec1/mlo-5plants, suggesting thatnec1did not impairmlo-5race non-specificBghresistance.

Conclusions

Together, the results suggest thatnec1mutation alters activation of systemic acquired resistance-related physiological markers and non-host resistance in barley, while not changing rapid localized response during compatible interaction with host pathogen. Increased resistance ofnec1against non-host pathogenPstsuggests thatnec1mutation may affect certain aspects of barley disease resistance, while it remains to be determined, if the effect on disease resistance is a direct response to changes in SA signaling.
Supramolecular assemblies of rifampicin and cationic bilayers: preparation, characterization and micobactericidal activity
Authors: Barbassa Lilian , Mamizuka Elsa M , Carmona-Ribeiro Ana M
Published: April 2011

Background

Cationic bilayers based on the inexpensive synthetic lipid dioctadecyldimethylammonium bromide (DODAB) have been useful as carriers for drug delivery, immunoadjuvants for vaccines and active antimicrobial agents.

Methods

Rifampicin (RIF) or isoniazid (ISO) interacted with DODAB bilayer fragments (BF) or large vesicles (LV). Dispersions were evaluated by dynamic light-scattering for zeta-average diameter (Dz) and zeta-potential (ζ) analysis; dialysis for determination of drug entrapment efficiency; plating and CFU counting for determination of cell viability of Mycobacterium smegmatis or tuberculosis, minimal bactericidal concentration (MBC) and synergism index for DODAB/drug combinations.

Results

DODAB alone killed micobacteria over a range of micromolar concentrations. RIF aggregates in water solution were solubilised by DODAB BF. RIF was incorporated in DODAB bilayers at high percentiles in contrast to the leaky behavior of ISO. Combination DODAB/RIF yielded MBCs of 2/2 and 4/0.007 μg/mL against Mycobacterium smegmatis or Mycobacterium tuberculosis, respectively. Synergism indexes equal to 0.5 or 1.0, indicated synergism against the former and independent action, against the latter species.

Conclusions

In vitro, DODAB acted effectively both as micobactericidal agent and carrier for rifampicin. The novel assemblies at reduced doses may become valuable against tuberculosis.
Use of multivitamins, folic acid and herbal supplements among breast cancer survivors: the black women's health study
Authors: Bright-Gbebry Mireille , Makambi Kepher H , Rohan JoyAnn Phillips , Llanos Adana A , Rosenberg Lynn , Palmer Julie R , Adams-Campbell Lucile L
Published: April 2011

Background

Complementary and alternative medicine (CAM) use, including herbals and multivitamin supplements, is quite common in the U.S., and has been shown to be highest in breast cancer survivors. However, limited data are currently available for CAM usage among African Americans. Thus, we sought to determine the prevalence of multivitamins, folic acid and herbal supplement usage in African American breast cancer survivors, and to compare the characteristics of users and nonusers.

Methods

A cohort study of breast cancer survivors, who completed the 1999 Black Women's Health Study questionnaire and self-reported having been diagnosed with breast cancer between 1995 and 1999, comprised the study population. In this study, the intake of natural herbs, multivitamins and folic acid at least three days per week within the past two years was used as a proxy for typical usage of this complimentary alternative medicine (CAM) modality.

Results

A total of 998 breast cancer survivors were identified. Overall, 68.2% had used either herbals or multivitamin supplements or both. The three most frequently used herbals were garlic (21.2%), gingko (12.0%), and echinacea (9.4%). The multivariate analysis determined that single marital status (OR = 1.58; 95%CI: 1.04-2.41), and alcohol consumption of 1-3 drinks per week (OR = 1.86, 95%CI: 1.28-2.68) were significantly associated with increased herbal use. Multivitamin use was significantly lower among obese women (OR = 0.66, 95%CI: 0.46-0.94) and current smokers (OR = 0.53, 95%CI: 0.34-0.82).

Conclusions

A significant number of African American breast cancer survivors are using herbals and multivitamins as CAM modality. Additional research is needed to understand the impact of herbals and multivitamins in African American breast cancer survivors.
CMOS-compatible dense arrays of Ge quantum dots on the Si(001) surface: hut cluster nucleation, atomic structure and array life cycle during UHV MBE growth
Authors: Arapkina Larisa V , Yuryev Vladimir A
Published: April 2011

We report a direct observation of Ge hut nucleation on Si(001) during UHV molecular beam epitaxy at 360°C. Nuclei of pyramids and wedges were observed on the wetting layer (WL) (M × N) patches starting from the coverage of 5.1 Å and found to have different structures. Atomic models of nuclei of both hut species have been built as well as models of the growing clusters. The growth of huts of each species has been demonstrated to follow generic scenarios. The formation of the second atomic layer of a wedge results in rearrangement of its first layer. Its ridge structure does not repeat the nucleus. A pyramid grows without phase transitions. A structure of its vertex copies the nucleus. Transitions between hut species turned out to be impossible. The wedges contain point defects in the upper corners of the triangular faces and have preferential growth directions along the ridges. The derived structure of the {105} facet follows the paired dimer model. Further growth of hut arrays results in domination of wedges, and the density of pyramids exponentially drops. The second generation of huts arises at coverages > 10 Å; new huts occupy the whole WL at coverages ~14 Å. Nanocrystalline Ge 2D layer begins forming at coverages > 14 Å.
A 5'-proximal Stem-loop Structure of 5' Untranslated Region of Porcine Reproductive and Respiratory Syndrome Virus Genome Is Key for Virus Replication
Authors: Lu Jiaqi , Gao Fei , Wei Zuzhang , Liu Ping , Liu Changlong , Zheng Haihong , Li Yanhua , Lin Tao , Yuan Shishan
Published: April 2011

Background

It has been well documented that the 5' untranslated region (5' UTR) of many positive-stranded RNA viruses contain key cis-acting regulatory sequences, as well as high-order structural elements. Little is known for such regulatory elements controlling porcine arterivirus replication. We investigated the roles of a conserved stem-loop 2 (SL2) that resides in the 5'UTR of the genome of a type II porcine reproductive and respiratory syndrome virus (PRRSV).

Results

We provided genetic evidences demonstrating that 1) the SL2 in type II PRRSV 5' UTR, N-SL2, could be structurally and functionally substituted by its counterpart in type I PRRSV, E-SL2; 2) the functionality of N-SL2 was dependent upon the G-C rich stem structure, while the ternary-loop size was irrelevant to RNA synthesis; 3) serial deletions showed that the stem integrity of N-SL2 was crucial for subgenomic mRNA synthesis; and 4) when extensive base-pairs in the stem region was deleted, an alternative N-SL2-like structure with different sequence was utilized for virus replication.

Conclusion

Taken together, we concluded that the phylogenetically conserved SL2 in the 5' UTR was crucial for PRRSV virus replication, subgenomic mRNA synthesis in particular.