bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of healthy gut microbiota early in life
Authors: Isolauri Erika
Published: June 2012

A healthy intestinal microbiota profile in early life is related to health later in life. An aberrant composition is associated with risks of systemic problems, such as obesity, diabetes and allergic diseases, including asthma and enteric inflammatory conditions, sometimes manifesting at 7 years of age. A healthy and balanced gut microbiota profile in infancy, especially with regard to bifidobacteria, is directly related to mode of delivery (natural birth) and quality of breast milk, which in turn is affected by the mother's own systemic health and nutritional status. Pregnant women of normal body weight and healthy microbiota profiles, both gut microbiota and breast milk microbiota, have greater opportunities to pass on compounds, antigens modified by the mother's gut and other agents that promote the development of a healthy immune system in the breastfed infant.
Missed synchronous gastric neoplasm with endoscopic submucosal dissection for gastric neoplasm: Experience in our hospital
Authors: Kim Hyung Hun , Cho Eun Ju , Noh Eunji , Choi Seok Reyol , Park Seun Ja , Park Moo In , Moon Won
Published: June 2012

Aim

Endoscopic submucosal dissection (ESD) has been widely accepted as a less invasive treatment for early gastric cancer and adenoma, but research on missed synchronous gastric neoplasm (SGN) with ESD has been limited. In the present study, we aimed to investigate the incidence and characteristics of missed SGN during follow‐up endoscopy in patients who have undergone ESD.

Method

We investigated the clinicopathological features of 602 patients and gastric neoplasms treated by ESD from January 2005 through July 2009 at our institution. We defined any second neoplasm found within 1 year after ESD as a missed SGN.

Results

Out of 602 patients, 12 (2.0%) had missed SGN. Among the 12 missed SGN, seven (58.3%) cases were carcinomas. All cases of missed synchronous gastric cancer (SGC) wereexclusively discovered in the posterior wall of the stomach (7 of 7 cases, 100%, P = 0.016). Missed SGN were more frequently observed when the primary gastric neoplasm was adenoma (4.0% vs 1.0%; OR = 4.114; 95% CI = 1.224–13.831). Furthermore, the risk of missed SGC increased 12‐fold in the primary gastric adenoma group compared to the primary gastric carcinoma group (2.9% vs 0.24%; OR = 12.308; 95% CI = 1.472–102.939).

Conclusion

Endoscopists need to make an effort to find SGN, especially when they carry out ESD for an adenoma, which is a less serious lesion. The important blind spot in screening endoscopic examination before ESD is the posterior wall of the upper third and middle third of the stomach.
Pancreatic β‐cell dysfunction, expression of iNOS and the effect of phosphodiesterase inhibitors in human pancreatic islets of type 2 diabetes
Authors: Muhammed S. J. , Lundquist I. , Salehi A.
Published: June 2012

Aims

Induction of inducible nitric oxide synthase (iNOS) in pancreatic islets leads to exaggerated nitric oxide (NO) production associated with dysfunctional β‐cells. We examined insulin secretion, iNOS expression and its relationship to the cAMP system in islets from human type 2 diabetes.

Methods

Insulin, glucagon and cAMP were analysed by RIA; iNOS or phosphodiesterase (PDE) expression by quantitative PCR (qPCR), Western blot and confocal microscopy; cell viability by MTS.

Results

Diabetic islets displayed impaired insulin and glucagon responses to glucose, disturbed cAMP generation and high inducible nitric oxide synthase (iNOS) mRNA and protein expression. Confocal microscopy showed iNOS protein expression in diabetic islets being confined to insulin, glucagon and somatostatin cells. Culture of diabetic islets at 5.5 mmol/l glucose with dibutyryl‐cAMP (Bt2‐cAMP) for 24 h was accompanied by marked suppression of iNOS mRNA, reduced nitrite production and increased insulin secretion. Diabetic islets displayed marked increase in PDE3A and PDE3B mRNA expression. Short‐time incubation of diabetic islets showed, among the PDE inhibitors tested, cilostazol being most favourable to increase insulin secretion. Diabetic islets were most susceptible to long‐term (72 h) culture at high glucose (20 mmol/l) reacting with increased apoptosis. Bt2‐cAMP and the PDE inhibitors cilostazol, milrinone and IBMX efficiently increased cell viability at high glucose during culture. Defective glucose‐stimulated insulin release upon induction of iNOS was restored by iNOS inhibitor aminoguanidine.

Conclusion

Our results suggest that in islets from type 2 diabetes, stimulatory effects in certain cAMP‐compartments induced by PDE inhibitors might play a central role in the suppression of iNOS, resulting in increased β‐cell viability and improved secretory response to glucose.
A content analysis of the portrayal of alcohol in televised music videos in New Zealand: Changes over time
Authors: Sloane Kate , Wilson Nick , Imlach Gunasekara Fiona
Published: June 2012

Introduction and Aims

We aimed to: (i) document the extent and nature of alcohol portrayal in televised music videos in New Zealand in 2010; and (ii) assess trends over time by comparing with a similar 2005 sample.

Design and Methods

We undertook a content analysis for references to alcohol in 861 music videos shown on a youth‐orientated television channel in New Zealand. This was compared with a sample in 2005 (564 music videos on the same channel plus sampling from two other channels).

Results

The proportion of alcohol content in the music videos was slightly higher in 2010 than for the same channel in the 2005 sample (19.5% vs. 15.7%) but this difference was not statistically significant. Only in the genre ‘Rhythm and Blues’ was the increase over time significant (P = 0.015). In both studies, the portrayal of alcohol was significantly more common in music videos where the main artist was international (not from New Zealand). Furthermore, in the music videos with alcohol content, at least a third of the time, alcohol was shown being consumed and the main artist was involved with alcohol. In only 2% (in 2005) and 4% (in 2010) of these videos was the tone explicitly negative towards alcohol.

Discussion and Conclusions

In both these studies, the portrayal of alcohol was relatively common in music videos. Nevertheless, there are various ways that policy makers can denormalise alcohol in youth‐orientated media such as music videos or to compensate via other alcohol control measures such as higher alcohol taxes.
‘She needs a smack in the gob’: negotiating what is appropriate talk in front of children in family therapy
Authors: O'Reilly Michelle , Parker Nicola
Published: June 2012

Tackling the day‐to‐day challenges of family therapy can prove difficult for professionals. A particular issue arising in family therapy is the notion of what is appropriate for children. Families report events from their social world, out‐there to the therapy in‐here. There are occasions where the content is ‘adult’ in nature and this has to be managed in front of the children. On some occasions family members use derogatory or negative descriptions of their children while their children are present. Drawing upon naturally occurring family therapy sessions, we present a discourse analysis of how this is managed through a range of discursive resources. We show that adult family members construct what is inappropriate for children to be exposed to by positioning blame with others. This has implications for how family therapists deal with inappropriateness when children are present while maintaining the equilibrium of therapeutic alliances.
Moving from the ‘why’ to the ‘how’: reflections on humanitarian response in urban settings
Authors: Lucchi Elena
Published: June 2012

Given the rising numbers of crises in urban settings, Médecins Sans Frontières (MSF) is currently shifting its focus from ‘why’ it should intervene to ‘how’ it should intervene effectively in these contexts. Beyond communities affected by natural disasters and epidemics, MSF has chosen to target populations in urban settings that are affected by violence or by marginalisation and neglect: these groups appear to suffer the greatest number of severe threats to their health and well‐being. Recent reflection within MSF has identified a number of key operational challenges to confront in order to respond efficiently to the needs of these populations. These include: appropriate assessments; measurable indicators of vulnerability and impact; pertinent operational approaches and medical strategies; adapted security management; and responsible closure of activities. This paper summarises the main lessons learned from working in urban settings with the principal aim of mutual sharing and understanding.
BRAIN, MIND AND MACHINE: WHAT ARE THE IMPLICATIONS OF DEEP BRAIN STIMULATION FOR PERCEPTIONS OF PERSONAL IDENTITY, AGENCY AND FREE WILL?
Authors: LIPSMAN NIR , GLANNON WALTER
Published: June 2012

Brain implants, such as Deep Brain Stimulation (DBS), which are designed to improve motor, mood and behavioural pathology, present unique challenges to our understanding of identity, agency and free will. This is because these devices can have visible effects on persons' physical and psychological properties yet are essentially undetectable when operating correctly. They can supplement and compensate for one's inherent abilities and faculties when they are compromised by neuropsychiatric disorders. Further, unlike talk therapy or pharmacological treatments, patients need not ‘do’ anything for the treatment to take effect. If one accepts, as we argue here, that brain implants are unique among implantable types of devices, then this can have significant implications for what it means to persist as the same person and be the source of one's thoughts and actions. By examining two of the most common indications for DBS in current use, namely in the motor (Parkinson's Disease) and psychiatric (Major Depression) domains, we further argue that although DBS, as it is currently applied, does not necessarily represent a unique threat to personal identity and agency per se, it introduces an unprecedented ‘third party’ into the debate on these concepts. In this way, DBS can be used as a tool to begin probing, both conceptually and empirically, some of philosophy's most perennial metaphysical questions.
Equity Under the Knife: Justice and Evidence in Surgery
Authors: Rogers Wendy , Degeling Christopher , Townley Cynthia
Published: June 2012

Surgery is an increasingly common and expensive mode of medical intervention. The ethical dimensions of the surgeon‐patient relationship, including respect for personal autonomy and informed consent, are much discussed; but broader equity issues have not received the same attention. This paper extends the understanding of surgical ethics by considering the nature of evidence in surgery and its relationship to a just provision of healthcare for individuals and their populations.
Family Control and Expropriation at Not‐for‐Profit Organizations: Evidence from Korean Private Universities
Authors: Bae Kee‐Hong , Kim Seung‐Bo , Kim Woochan
Published: June 2012

Manuscript Type

Empirical

Research Question/Issue

We study an agency problem in private universities – the conflict between controlling families and other stakeholders. We investigate whether universities over which controlling families have disproportionately significant power relative to the amount of funds they contribute, that is, universities with high expropriation risk, are associated with lower outside donations and poor quality.

Research Findings/Insights

Using a sample of Korean private universities, we find that measures of family control in excess of monetary contributions are negatively related to the level of outside donation and measures of university quality. We also find that universities at which the controlling family exerts disproportionate control are more likely to face disputes between the controlling family and other stakeholders. Finally, we show that our results are not driven by reverse causality.

Theoretical/Academic Implications

While the existing literature on not‐for‐profit organizations focuses on the conflict between professional managers and other stakeholders, we study the conflict between controlling families and other stakeholders. We investigate a situation in which the controlling family expropriates other stakeholders, a topic missing from the existing not‐for‐profit literature.

Practitioner/Policy Implications

This study offers insights to policymakers interested in creating private universities in an emerging market setting. The relevance of our results is not limited to Korea. According to Altbach, family control of private universities is prevalent in a number of countries, including Mexico, Thailand, Taiwan, Japan, Korea, the Philippines, Argentina, India, and China.
Board Size and Corporate Risk Taking: Further Evidence from Japan
Authors: Nakano Makoto , Nguyen Pascal
Published: June 2012

Manuscript Type

Empirical

Research Question/Issue

Due to a greater difficulty to achieve compromise, large decision‐making groups tend to adopt less extreme decisions. This implies that larger boards are associated with lower corporate risk taking. We test whether a similar effect applies to the case of Japanese firms. The result is expected to be weaker since Japanese boards form relatively homogeneous groups. We further argue that growth opportunities moderate the relation between board size and risk taking.

Research Findings/Results

Our results indicate that firms with larger boards exhibit lower performance volatility as well as lower bankruptcy risk. However, the effect is not as significant as in the US. The low cross‐sectional variation in risk taking among Japanese firms is found to play a role. In addition, we show that the effect of board size is less significant when firms have plenty of investment opportunities, but much stronger when firms have fewer growth options.

Theoretical Implications

Considering that risk taking contributes to firm performance, our results offer a rationale as to why larger boards might be associated with lower performance. However, they also suggest that this effect should be less detrimental to firms with significant investment opportunities.

Practical Implications

Firms should adapt their decision processes to their business environment. In particular, they may need to adjust the size of their boards to the characteristics of their investment opportunity sets. Firms with fewer growth options would gain most by operating with smaller boards. By restricting their ability to take risks, firms could undermine their growth potential and performance.
Factors associated with self‐efficacy in persons with chronic illness
Authors: BONSAKSEN TORE , LERDAL ANNERS , FAGERMOEN MAY SOLVEIG
Published: June 2012

Bonsaksen, T., Lerdal, A. & Fagermoen, A. S. (2012). Factors associated with self‐efficacy in persons with chronic illness. Scandinavian Journal of Psychology 53, 333–339.

Change of lifestyle may be necessary for persons with chronic illnesses in order to manage their health situation and reduce symptom distress. Success in changing lifestyle partly depends on a person’s self‐efficacy beliefs. This cross‐sectional study explores social support, physical activity, and illness perceptions in relation to self‐efficacy in a sample with morbid obesity and in a sample with chronic obstructive pulmonary disease (COPD). The linear regression analyses showed that higher physical activity and less emotional response to illness were directly associated with higher self‐efficacy among persons with obesity, while more social support; fewer perceived consequences from illness; and more understanding of the illness were directly associated with higher self‐efficacy among persons with COPD. The results indicate that obese persons are likely to benefit from increasing physical activity and from receiving emotional support. Persons with COPD may be empowered by being able to utilize cognitive coping strategies and by receiving social support.
Social Networks and Rural Development: LEADER in Romania
Authors: Marquardt Doris , Möllers Judith , Buchenrieder Gertrud
Published: June 2012

Networking is an inherent part of the European Union (EU) programme Liaison entre actions de développement de l'économie rurale1 (LEADER): through supporting local partnerships, EU‐wide cooperation and information exchange, LEADER aims at strengthening the socioeconomic development of rural regions and improving local governance. Employing Social Network Analysis, we assess how key LEADER features, such as the bottom‐up and the participatory approach, are implemented in a new EU Member State. Focusing on the relevance of social networks for LEADER in Romania, we find that the complexity of the programme, weak administrative networks, political influence, and heritage of the socialist era inhibit the smooth introduction of the LEADER instrument. Clearly, founding formal partnerships and better governance remain generally challenging. While bottom‐up regional networks can more easily establish social capital, initiatives steered by the communal administration are more competitive in the selection for funding, but tend to neglect participation.
Familial Clustering Strongly Suggests that the Phenotypic Variation of the 8344 A>G Lys Mitochondrial tRNA Mutation is Encoded in cis
Authors: Kazakos Kyriakos , Kotsa Kalliopi , Yavropoulou Maria , Dionyssopoulos Alexander , Grabs Rosemary , Yovos John , Polychronakos Constantin
Published: June 2012

The maternally inherited 8344 A>G mutation in the mitochondrial Lys tRNA is classically associated with the myoclonic epilepsy, ragged‐red muscle fiber (MERRF) syndrome. Multiple lipomatosis (Madelung's disease) is occasionally described. Here we report a large kindred with a statistically significant clustering of very unusual clinical manifestations.

We have studied a Greek family that includes seven symptomatic cases of 8344 A>G. Clinical features, glucose tolerance and heteroplasmy in fat, muscle and blood were analyzed.

The patients, aged 34–76 at the time of assessment, all suffer from progressive proximal limb‐girdle myopathy and extensive lipomatosis. Four of the seven have either impaired glucose tolerance or diabetes but none has had epilepsy, a cardinal feature of MERRF. Heteroplasmy was not higher in adipose tissue than that found in the literature. Compared to literature reports, the familial clustering of this unusual combination of manifestations (lipomatosis in all, epilepsy in none) is statistically significant.

The clustering of unusual manifestations in this large kindred strongly suggests that much of the phenotypic variability of 8344 A>G is determined by mitochondrially encoded modifiers in cis.
Predicting fine root lifespan from plant functional traits in temperate trees
Authors: Luke McCormack M. , Adams Thomas S. , Smithwick Erica A. H. , Eissenstat David M.
Published: June 2012

See also the Commentary by Mommer and Weemstra
Dopamine D1 receptors regulate type 1 inositol 1,4,5‐trisphosphate receptor expression via both AP‐1‐ and NFATc4‐mediated transcriptional processes
Authors: Mizuno Koji , Kurokawa Kazuhiro , Ohkuma Seitaro
Published: June 2012

J. Neurochem. (2012) 122, 702–713.

Although our recent report demonstrates the essential involvement of up‐regulation of a regulator of intracellular Ca2+ concentration, type 1 inositol 1,4,5‐trisphosphate receptors (IP3Rs‐1), mediated via dopamine D1‐like receptor (D1DR) stimulation in the cocaine‐induced psychological dependence, the exact mechanisms of regulation of IP3R‐1 expression by D1DRs have not yet been clarified. This study attempted to clarify these mechanisms using mouse cerebral cortical neurons. An agonist for phosphatidylinositide‐linked D1DRs, SKF83959, induced dose‐ and time‐dependently IP3R‐1 protein up‐regulation following its mRNA increase without cAMP production. U73122 (a phospholipase C inhibitor), BAPTA‐AM (an intracellular calcium chelating reagent), W7 (a calmodulin inhibitor), KN‐93 (a calmodulin‐dependent protein kinases inhibitor), and FK506 (a calcineurin inhibitor), significantly inhibited the SKF83959‐induced IP3R‐1 up‐regulation. Furthermore, immunohistochemical examinations showed that SKF83959 increased expression of both cFos and cJun in nucleus as well as enhanced translocation of both calcineurin and NFATc4 complex to nucleus from cytoplasm. In addition, SKF83959 directly recruited binding of both AP‐1 and NFATc4 to IP3R‐1 promoter region. These results indicate that D1DR activation induces IP3R‐1 up‐regulation via increased translocation of AP‐1 as well as NFATc4 in Gαq protein‐coupled calcium signaling transduction pathway.
Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF‐α) pathways
Authors: Dal Bó Wladmir , Luiz Ana Paula , Martins Daniel F. , Mazzardo‐Martins Leidiane , Santos Adair R.S.
Published: June 2012

Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro‐inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3–300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid‐induced nociception, with ID50 values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3–100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID50 of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF‐α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF‐α. Thus, eugenol could represent an important compound in the treatment for acute pain.
Prognostic value of serum PIIINP, MMP1 and TIMP1 levels in hypertensive patients: a community‐based prospective cohort study
Authors: Agrinier Nelly , Thilly Nathalie , Boivin Jean‐Marc , Dousset Brigitte , Alla François , Zannad Faiez
Published: June 2012

The purpose of this study was to examine the prognostic value of serum ECM biomarkers in hypertensive patients with no history of cardiovascular events. In a community‐based cohort study of 125 hypertensive patients free of cardiovascular events, we collected clinical data and blood samples to assess serum levels of amino‐terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase type 1(MMP1) and tissue inhibitor of MMPs type 1(TIMP1). Left ventricular hypertrophy (LVH) was assessed using the ECG Cornell product. Patients were followed up for death or cardiovascular hospitalisation. We used Cox regression models to assess the prognostic value of ECM biomarkers. The sample included 60.8% women; the mean (±SD) age was 62.9 (±11.4) years. Patients were followed up for a median of 5.5 years, during which 23 events (five deaths) occurred. PIIINP (3.2 ± 1.0 vs. 2.6 ± 0.8 μg/L, P = 0.001) and TIMP1 (886 ± 168 vs. 751 ± 202 μg/L, P < 0.001) levels were higher in the presence of LVH than with no LVH. Basal MMP1 serum levels were significantly associated with CV events (MMP1: HR, 1.06; 95%CI [1.02–1.09]). Adjusting for confounders did not modify this result. Cardiac fibrosis, as assessed with serum ECM biomarkers, might develop early in hypertensive patients and is predictive of cardiovascular events or death.
A template model for studying anticancer drug efflux transporter inhibitors in vitro
Authors: Sostelly Alexandre , Payen Léa , Guitton Jérôme , Pietro Attilio Di , Falson Pierre , Honorat Mylène , Valdameri Glaucio , Geze Annabelle , Boumendjel Ahcène , Freyer Gilles , Tod Michel
Published: June 2012

Efflux transporters play an important role in drug absorption and also in multidrug resistance. ABCG2 (BCRP) is an efflux transporter conferring cross‐resistance to mitoxantrone (Mit), irinotecan (CPT11), and its active metabolite SN38. MBLI87, a new ABCG2 inhibitor has proven its efficacy against ABCG2‐mediated efflux in vitro and in vivo. This work aimed at modeling and quantifying the cellular interaction between MBLI87 and different substrates using a mechanistic template model. An in vitro competition experiment study was carried out with HEK293 cells overexpressing ABCG2 exposed to fixed concentrations of substrates (Mit, CPT11, SN38) and to MBLI87 at several concentration levels. A nonlinear mixed‐effects transport inhibition model was developed to fit intracellular drug concentrations. In this model, drugs cross the cell membrane through passive diffusion, active drug efflux is ABCG2 mediated, interaction between substrates and inhibitor occurs within the transporter. The interaction was found to be noncompetitive. The MBLI87 Ki was estimated to 141 nm for Mit, 289 nm for CPT11, and 1160 nm for SN38. The ratio of intrinsic transport clearance divided by diffusion clearance was estimated to 2.5 for Mit, 1.01 for CPT11, and 5.4 for SN38. The maximal increase in the intracellular substrate concentration that is possible to achieve by inhibition of the transporter was estimated to 1.5 for Mit, 0.1 for CPT11, and 4.4 for SN38. This mechanistic template model describes both drug accumulation and cellular transport, and the mixed‐effects approach allows an estimation of intra‐ and interassay variability. This model is of great interest to study cytotoxic cellular pharmacokinetics.
Volatile anaesthetics and cardioprotection – lessons from animal studies
Authors: Muntean Danina M. , Ordodi Valentin , Ferrera René , Angoulvant Denis
Published: June 2012

Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre‐ and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies.
Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo
Authors: Attoub Samir , Sperandio Olivier , Raza Haider , Arafat Kholoud , Al‐Salam Suhail , Al Sultan Mahmood Ahmed , Al Safi Maha , Takahashi Takashi , Adem Abdu
Published: June 2012

Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential impact of thymoquinone (TQ), the major constituent of black seed, on survival, invasion of cancer cells in vitro, and tumor growth in vivo. Exposure of cells derived from lung (LNM35), liver (HepG2), colon (HT29), melanoma (MDA‐MB‐435), and breast (MDA‐MB‐231 and MCF‐7) tumors to increasing TQ concentrations resulted in a significant inhibition of viability through the inhibition of Akt phosphorylation leading to DNA damage and activation of the mitochondrial‐signaling proapoptotic pathway. We provide evidence that TQ at non‐toxic concentrations inhibited the invasive potential of LNM35, MDA‐MB‐231, and MDA‐MB231‐1833 cancer cells. Moreover, we demonstrate that TQ synergizes with DNA‐damaging agent cisplatin to inhibit cellular viability. The anticancer activity of thymoquinone was also investigated in athymic mice inoculated with the LNM35 lung cells. Administration of TQ (10 mg/kg/i.p.) for 18 days inhibited the LNM35 tumor growth by 39% (P < 0.05). Tumor growth inhibition was associated with significant increase in the activated caspase‐3. The in silico target identification suggests several potential targets of TQ mainly HDAC2 proteins and the 15‐hydroxyprostaglandin dehydrogenase. In this context, we demonstrated that TQ treatment resulted in a significant inhibition of HDAC2 proteins. In view of the available experimental findings, we contend that thymoquinone and/or its analogues may have clinical potential as an anticancer agent alone or in combination with chemotherapeutic drugs such as cisplatin.
Muslim geographies, violence and the antinomies of community in eastern Sri Lanka
Authors: Hasbullah Shahul , Korf Benedikt
Published: June 2012

This paper studies the intricate relations between violence and the politics of community in a Muslim enclave in the east coast of Sri Lanka. The enclave will not only be studied as a war‐ridden place, but more so in order to explore the antinomies of community that stem from an inherent governmentality that was triggered by the territorial prisonhood of the enclave situation. Violence, as we will show, is not an interruption, but an intensified continuation of politics – of the politics of community and its dynamics of unity and friction, which bring to the fore questions of the relationality of politics/religion, the boundaries of the political in Sri Lanka's Muslim community as well as in Sri Lanka's fragmented and violence‐striven polity more broadly. It will be argued that what is at play is a politics of purification, whereby violence becomes a project of community: violence in the name of purity and an imaginary of community produces ‘antinomies of community’, i.e. the paradoxes of unity and friction that transgress political collectives.
Up‐regulated aldo‐keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha‐fetoprotein and hepatocellular carcinoma
Authors: Sato Shunsuke , Genda Takuya , Hirano Katsuharu , Tsuzura Hironori , Narita Yutaka , Kanemitsu Yoshio , Kikuchi Tetsu , Iijima Katsuyori , Wada Ryo , Ichida Takafumi
Published: June 2012

Background

Elevated serum alpha‐fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC.

Aim

The aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC.

Methods

Liver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo‐keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) and immunohistochemical analyses. A matched case‐control study was performed to evaluate the risk of AKR1B10 expression for HCC development.

Results

Distinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (≥10 ng/mL) and normal AFP (<10 ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT‐PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case‐control study identified that AKR1B10 up‐regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001).

Conclusion

AKR1B10 was up‐regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis.
Ocular Problems in the Patient with End‐Stage Renal Disease
Authors: Mullaem Gaia , Rosner Mitchell H.
Published: June 2012

The patient with end‐stage renal disease (ESRD) is at risk for development of eye disease. This risk is related to the comorbid conditions that are often seen in ESRD patients as well as to the unique effects of hemodialysis and the uremic state in leading to changes in the conjunctivae, cornea, retina, and macula. The most common ocular complaints in ESRD patients include red, irritated eyes, and may be associated with elevations in the calcium‐phosphate product. In those patients with chronically elevated calcium‐phosphate products, band keratopathy may result. Other eye conditions include macular edema, ischemic optic neuropathy, elevated intraocular pressure, retinal detachment, and retinal hemorrhage. Prompt recognition of these conditions that may threaten a patient’s vision is required. This may prove challenging to the nephrologist in the dialysis unit where a detailed ophthalmological examination is difficult. However, a basic knowledge of the common ocular diseases encountered in the dialysis patient forms a framework for deciding which patients require urgent consultation with an ophthalmologist.
IDENTIFICATION OF CRYPTIC SPECIES IN THE LESSONIA NIGRESCENS COMPLEX (PHAEOPHYCEAE, LAMINARIALES)1
Authors: González Alejandra , Beltrán Jessica , Hiriart‐Bertrand Luciano , Flores Verónica , de Reviers Bruno , Correa Juan A. , Santelices Bernabé
Published: June 2012

The kelp Lessonia nigrescens Bory is the most ecologically and economically important seaweed in rocky intertidal and shallow subtidal habitats along the temperate Pacific South American coasts. Recent molecular studies suggest the existence of two lineages, one (northern lineage) from 17° S to 30° S and a second (central lineage) from 29° S to 41° S. To identify and name these lineages we performed morphological, nomenclatural and field studies. Four external and three internal anatomical traits permitted a morphological separation of the two lineages. The internal structure of both lineages was different from the isolectotype of Lessonia nigrescens. It is therefore concluded that the name Lessonia nigrescens should not be used for the Chilean material. Chordaria spicata Suhr appears as the oldest available name for the central lineage, while Lessonia berteroana Montagne is the oldest name for the northern lineage. In both cases, the type material consisted of small‐sized, apical branches of larger plants. The new combination Lessonia spicata (Suhr) Santelices is proposed for the central lineage and we reinstate Lessonia berteroana for the northern lineage. Laminaria scissa Suhr is reduced to synonym of L. spicata. Representative specimens of Lessonia nigrescens were not found during new visits to its type locality in Cape Horn and along Chile. Future studies should verify the status of this species.
Economic Development and Environmental Intentions: A Comment on Liu and Sibley (2011)
Authors: Arbuthnott Katherine D. , Devoe Daniel , Lawrie Tricia
Published: June 2012

In a sample of university students from 34 countries, Liu and Sibley (2011) observed that the association between concern about climate change and willingness to pay for protection of the natural environment was moderated by countries’ human development index (HDI). Two concerns with this research are outlined, the use of a single, biased question to measure environmental action intentions and the authors’ framing of the results using a disconfirmed version of Maslow's hierarchy of needs model. When considered outside the framework of Maslow's hierarchy, HDI seems to influence concern about climate change but not willingness to pay for environmental protection.
The Embodied Liminalities of Occupational Overuse Syndrome
Authors: Jaye Chrystal , Fitzgerald Ruth
Published: June 2012

Drawing on interviews with sufferers of OOS (occupational overuse syndrome) in Aoteraoa/New Zealand, this article explores the liminalities associated with OOS and the ways in which this liminality is embodied. While successful rehabilitation could lead back to employment, the respondents’ fragility while living with OOS and its accompanying social stigma render such rehabilitation both literally and symbolically “out of reach.” Their situations reveal social isolation, loss of identities, pain, and functional disability that have been incorporated into renegotiated identities and biographies in which respondents have become exquisitely self‐absorbed, exercising constant bodily surveillance and discipline in order to manage their symptoms. We suggest that this problematic extends beyond biographical disruption to encompass the concept of injury to an embodied sense of integrity for people who were notable prior to their affliction for their reputations as extremely competent and conscientious workers. The embodied meaning of OOS in this environment is not so much to have fallen “out of culture” as Hilbert (Ewan et al. 1991) suggests, but to be liminal in Turner's sense of “threshold people” (Turner 1969:56) “ground down to a uniform condition to be fashioned anew.”[liminality, New Zealand, occupational overuse syndrome, embodiment]
Thyroid hormone induces sprouting angiogenesis in adult heart of hypothyroid mice through the PDGF‐Akt pathway
Authors: Chen Jinghai , Ortmeier Steven B. , Savinova Olga V. , Nareddy Vijaya B. , Beyer April J. , Wang Dajun , Gerdes A. Martin
Published: June 2012

Study of physiological angiogenesis and associated signalling mechanisms in adult heart has been limited by the lack of a robust animal model. We investigated thyroid hormone‐induced sprouting angiogenesis and the underlying mechanism. Hypothyroidism was induced in C57BL/6J mice by feeding with propylthiouracil (PTU). One year of PTU treatment induced heart failure. Both 12 weeks‐ (young) and 1 year‐PTU (middle age) treatment caused a remarkable capillary rarefaction observed in capillary density. Three‐day Triiodothyronine (T3) treatment significantly induced cardiac capillary growth in hypothyroid mice. In cultured left ventricle (LV) tissues from PTU‐treated mice, T3 also induced robust sprouting angiogenesis where pericyte‐wrapped endothelial cells formed tubes. The in vitro T3 angiogenic response was similar in mice pre‐treated with PTU for periods ranging from 1.5 to 12 months. Besides bFGF and VEGF164, PDGF‐BB was the most robust angiogenic growth factor, which stimulated notable sprouting angiogenesis in cultured hypothyroid LV tissues with increasing potency, but had little effect on tissues from euthyroid mice. T3 treatment significantly increased PDGF receptor beta (PDGFR‐β) protein levels in hypothyroid heart. PDGFR inhibitors blocked the action of T3 both on sprouting angiogenesis in cultured LV tissue and on capillary growth in vivo. In addition, activation of Akt signalling mediated in T3‐induced angiogenesis was blocked by PDGFR inhibitor and neutralizing antibody. Our results suggest that hypothyroidism leads to cardiac microvascular impairment and rarefaction with increased sensitivity to angiogenic growth factors. T3‐induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF‐BB, PDGFR‐β and downstream activation of Akt.
CBCT device dependency on the transfer accuracy from computer‐aided implantology procedures
Authors: Dreiseidler Timo , Tandon Daniel , Kreppel Matthias , Neugebauer Jörg , Mischkowski Robert A. , Zinser Max J. , Zöller Joachim E.
Published: June 2012

Objectives

To evaluate the potential influence of different cone‐beam computed tomography (CBCT) devices on the transfer accuracy of an open‐source system for computer‐aided implantology (CAI).

Material and methods

A total of 108 implants in 18 partially edentulous patient‐equivalent models were planned and fully guided implants were inserted using an open‐source CAI system with three different CBCT devices. After follow‐up CBCT and fiducial marker‐matching procedure, linear horizontal, vertical, and maximal three‐dimensional deviations, as well as angle deviations between the virtual planning data and the surgical results were calculated. Variance analysis was carried out to prove whether or not the observed differences between the CBCT devices were statistically significant.

Results

The observed mean three‐dimensional deviation rates between virtually planned and achieved implant positions varied by around 400 μm (45%) at the implant's base and around 540 μm (50%) at the implant's tip in dependence to the applied CBCT device. Mean vertical deviations varied around 370 μm (76%) at the implant's base and 350 μm (69%) at the implant's tip, whereas axes deviations varied around 0.81° (40%) between the three investigated CBCT devices. Except for the axes deviations and the horizontal linear deviations at the implants base, observed differences reached significance level between the CBCT devices.

Conclusions

Until now, the potential influence from different CBCT devices on the transfer accuracy of CAI systems has not yet been investigated. Data from the present study confirm for the first time the in vitro CBCT device dependency on the transfer accuracy of CAI systems reaching up to axes deviations of 0.6 angle degree and linear deviations around half a millimeter.
Identification of subpopulations from connectivity matrices
Authors: Jacobi Martin Nilsson , André Carl , Döös Kristofer , Jonsson Per R.
Published: June 2012

Dispersal on the landscape/seascape scale may lead to complex spatial population structure with non‐synchronous demography and genetic divergence. In this study we present a novel approach to identify subpopulations and dispersal barriers based on estimates of dispersal probabilities on the landscape scale. A theoretical framework is presented where the landscape connectivity matrix is analyzed for clusters as a signature of partially isolated subpopulations. Identification of subpopulations is formulated as a minimization problem with a tuneable penalty term that makes it possible to generate population subdivisions with varying degree of dispersal restrictions. We show that this approach produces superior results compared to alternative standard methods. We apply this theory to a dataset of modeled dispersal probabilities for a sessile marine invertebrate with free‐swimming larvae in the Baltic Sea. For a range of critical connectivities we produce a hierarchical partitioning into subpopulations spanning dispersal probabilities that are typical for both genetic divergence and demographic independence. The mapping of subpopulations suggests that the Baltic Sea includes a fine‐scale (100–600 km) mosaic of invisible dispersal barriers. An analysis of the present network of marine protected areas reveal that protection is very unevenly distributed among the suggested subpopulations. Our approach can be used to assess the location and strength of dispersal barriers in the landscape, and identify conservation units when extensive genotyping is prohibitively costly to cover necessary spatial and temporal scales, e.g. in spatial management of marine populations.
Sp1 and Sp3 are involved in the full transcriptional activity of centromere protein H in human nasopharyngeal carcinoma cells
Authors: Zhao Wei‐feng , Wang Hong‐bo , Xie Bo , Hu Li‐juan , Xu Li‐hua , Kuang Bo‐hua , Li Man‐zhi , Zhang Xing
Published: June 2012

The overexpression of centromere protein H (CENPH), one of the fundamental components of the human active kinetochore, has been shown to be closely associated with human cancers. However, the mechanism of its transcriptional regulation has not been reported. The aim of the present study was to investigate the regulatory elements for the transcriptional regulation of CENPH in nasopharyngeal carcinoma cells. To characterize the CENPH promoter and identify regulatory elements, we cloned 1015 bp (−975/+40 bp) of the 5′‐flanking region of the CENPH gene from immortalized normal nasopharyngeal epithelial cells (Bmi‐1/NPEC). Functional analysis established a minimal region (−140/−87 bp) involved in the regulation of human CENPH promoter activity. Through site‐directed mutagenesis, a transactivation assay, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we found that the Sp1/Sp3 transcription factors could bind to the CENPH promoter in vitro and in vivo, and that they regulated CENPH promoter activation in human nasopharyngeal carcinoma cells. Furthermore, Sp1 and Sp3 were highly expressed in nasopharyngeal carcinoma cells. Knockdown of Sp1 and Sp3 by small interfering RNA or inhibition of Sp1 and Sp3 activity by mithramycin A decreased CENPH mRNA expression, whereas the exogenous expression of Sp1 and Sp3 upregulated CENPH mRNA expression. Taken together, our results indicate that Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas.
Fermi's SIBYL: mining the gamma-ray sky for dark matter subhaloes
Authors: Mirabal N. , Frías-Martinez V. , Hassan T. , Frías-Martinez E.
Published: June 2012

Dark matter annihilation signals coming from Galactic subhaloes may account for a small fraction of unassociated point sources detected in the second Fermi-LAT Catalogue (2FGL). To investigate this possibility, we present sibyl, a Random Forest classifier that offers predictions on class memberships for unassociated Fermi-LAT sources at high Galactic latitudes using gamma-ray features extracted from the 2FGL. sibyl generates a large ensemble of classification trees that are trained to vote on whether a particular object is an active galactic nucleus (AGN) or a pulsar. After training on a list of 908 identified/associated 2FGL sources, sibyl reaches individual accuracy rates of up to 97.7 per cent for AGNs and 96.5 per cent for pulsars. Predictions for the 269 unassociated 2FGL sources at |b|≥ 10° suggest that 216 are potential AGNs and 16 are potential pulsars (with majority votes greater than 70 per cent). The remaining 37 objects are inconclusive, but none is an extreme outlier. These results could guide future quests for dark matter Galactic subhaloes.
Supplementations of dl‐Methionine and Methionine Dipeptide in Diets are Effective for the Development and Growth of Larvae and Juvenile Red Sea Bream, Pagrus major
Authors: Mamauag Roger Edward P. , Gao Jian , Thanh Nguyen Binh , Ragaza Janice A. , Koshio Shunsuke , Ishikawa Manabu , Yokoyama Saichiro
Published: June 2012

Growth trials for larvae and juvenile red sea bream, Pagrus major, were conducted to elucidate the efficacy of two molecular forms of methionine; dl‐methionine (dl‐Met) and methionine dipeptide (Met‐Met). For the larvae experiment, five experimental diets were formulated and fed to fish (42 mg) for 30 days. A diet which has 15% soy protein isolate served as the control diet. Similarly, test diets supplemented with dl‐Met and Met‐Met at 0.5%, which were either precoated by zein or intact, were also formulated. For the juvenile experiment, five experimental diets were formulated wherein the control diet contained 25% soy protein isolate. Test diets were supplemented with dl‐Met and Met‐Met at 0.75%, which were either coated by carboxymethycellulose or intact and fed to juveniles (0.75 g) for 56 days. The results of two feeding trials showed both dl‐Met and Met‐Met can be equally utilized by red sea bream larvae and juveniles. Coating the amino acid significantly improved both fish larval and juvenile growth performance. The development of digestive protease activity of larvae was significantly influenced by coating the amino acid, but the type of methionine was not a factor in changing the protease activity of larvae.