bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular detection and characterisation of fungal heat shock protein 60
Authors: Raggam Reinhard B. , Salzer Helmut J. F. , Marth Egon , Heiling Bettina , Paulitsch Astrid H. , Buzina Walter
Published: July 2010

Heat shock proteins (Hsp) are highly conserved molecules, which are both constitutively expressed and up‐regulated in response to various stress conditions. In particular, fungal Hsp60 can act as immunodominant antigens and facilitate powerful immunological properties. A possible cellular heat shock response was investigated in eight fungi (Aspergillus fumigatus, Aspergillus terreus, Penicillium chrysogenum, Cladosporium cladosporioides, Scedosporium apiospermum, Trichophyton mentagrophytes, Candida albicans and Saccharomyces cerevisiae). Fully automated RNA extraction was followed by quantitative real‐time RT‐PCR targeting fungus‐specific Hsp60 mRNA and sequencing of the amplicon. Levels of temperature‐dependent gene expression were evaluated and rates of similarity and identity were compared. While Hsp60 mRNA was constitutively expressed in all the samples tested, a temperature‐dependent induction was not shown in C. cladosporioides. In the 80‐amino acid fragment from the hypothetical protein, 66% of the amino acids were identical, 20% showed a conserved and 8% a semi‐conserved substitution. Our findings should contribute to a better understanding of host–pathogen relationship and suggest that fungal Hsp60 under temperature‐related stress conditions might act as an immunogenic trigger in orchestrating fungi‐related diseases.
Board Monitoring, Regulation, and Performance in the Banking Industry: Evidence from the Market for Corporate Control
Authors: Hagendorff Jens , Collins Michael , Keasey Kevin
Published: July 2010

Manuscript Type: Empirical

Research Question/Issue: The specific monitoring effect of boards of directors versus industry regulation is unclear. In this paper, we examine how the interaction between bank‐level monitoring and regulatory regimes influences the announcement period returns of acquiring banks in the US and twelve European economies.

Research Findings/Insights: We study three board monitoring mechanisms – independence, CEO‐chair duality, and diversity – and analyze their effectiveness in preventing underperforming merger strategies under bank regulators of varying strictness. Only under strict banking regulation regimes, do board independence and diversity improve acquisition performance. In less strict regulatory environments, corporate governance is virtually irrelevant in improving the performance outcomes of merger activities.

Theoretical/Academic Implications: Our results indicate a complementary role between monitoring by boards and bank regulation. This study is the first to report evidence consistent with complementarity by investigating the effectiveness (rather than the prevalence) of governance arrangements across regulatory regimes.

Practitioner/Policy Implications: Our work offers insights to policymakers charged with improving the quality of decision‐making at financial institutions. Attempts to improve the ability of bank boards to critically assess managerial initiatives are most likely to be successful if internal governance is accompanied by strict industry regulation.
Health‐related quality of life and marital quality of vitiligo patients in China
Authors: Wang K‐Y , Wang K‐H , Zhang Z‐P
Published: July 2010

Background  Vitiligo can adversely affect the quality of life and sexual relationships of patients. Combination of the DLQI with the generic SF‐36 and ENRICH may give further insight in the evaluation of the burden in vitiligo patients.

Objective  We sought to assess the health‐related quality of life (HRQoL) and marital quality of Chinese vitiligo patients and to identify the relevant clinical and socio‐demographic determinants.

Methods  A total of 101 vitiligo patients and 126 healthy controls completed the questionnaires. HRQoL was measured using DLQI and SF‐36, and marital quality was measured using the ENRICH marital inventory.

Results  Patients with vitiligo experienced significantly impaired health‐related quality of life and unstable marital relationships. Gender, distribution pattern of vitiligo and disease severity were independent predictors of DLQI, SF‐36 and ENRICH in this cohort.

Conclusions  Vitiligo is associated with impairment of HRQoL and marital quality among Chinese patients. Alongside the medical interventions, the psychological and sociocultural assessment and intervention should be an essential part of the management of these cases.
Social involvement of children with autism spectrum disorders in elementary school classrooms
Authors: Rotheram‐Fuller Erin , Kasari Connie , Chamberlain Brandt , Locke Jill
Published: July 2010

Background:  Children with autism spectrum disorders (ASD) are increasingly included in general education classrooms in an effort to improve their social involvement.

Methods:  Seventy‐nine children with ASD and 79 randomly selected, gender‐matched peers (88.6% male) in 75 early (K‐1), middle (2nd–3rd), and late (4th–5th) elementary classrooms across 30 schools completed social network surveys examining each child’s reciprocal friendships, peer rejection, acceptance, and social involvement.

Results:  Across grade levels, peers less frequently reciprocated friendships with children with ASD than students in the matched sample. While children with ASD were not more likely to be rejected by peers, they were less accepted and had fewer reciprocal friendships than matched peers at each grade level. Although 48.1% of children with ASD were involved in the social networks of their classrooms, children with ASD were more likely to be isolated or peripheral to social relationships within the classroom across all grade levels, and this difference is even more dramatic in later elementary grades.

Conclusions:  In inclusive classrooms, children with ASD are only involved in peers’ social relationships about half of the time, and appear to be even less connected with increasing grade level. Promoting children with ASD’s skills in popular activities to share with peers in early childhood may be a key preventive intervention to protect social relationships in late elementary school grades.
Effect of Seizures Induced by Intra‐Amygdaloid Kainic Acid on Kainic Acid Binding Sites in Rat Hippocampus and Amygdala
Authors: Berger M. L. , Charton G. , Ben‐Ari Y.
Published: July 2010

Abstract:[3H]Kainic acid binding sites with a slow dissociation rate in the rat limbic system were investigated in detail. Extensively washed membranes prepared from the hippocampal formation and from the region comprising the amygdala and the piriform cortex yielded nonlinear Scatchard plots. Microdissection showed that the high‐affinity component (affinity constant around 1 nM) was present in the hippocampal CA3 region (4.2 fmol/mg wet tissue) and the amygdaloid complex (4.6 fmol/mg wet tissue), whereas the remaining part of the hippocampal formation and the piriform lobe contained the low‐affinity component (affinity constant 5–20 nM;11.6 and 11.3 fmol/mg wet tissue, respectively). In the lateral + medial septum we detected only the low‐affinity component. Severe limbic seizures, induced by unilateral injection of 0.7 or 0.8 μg kainic acid in 0.3 μl of phosphate‐buffered saline into the amygdala, reduced kainic acid binding sites in the ipsilateral amygdala and CA3 region. The decline of kainic acid binding sites in the injected amygdala was followed by a similar effect in the contralateral amygdala (“mirror focus”) and later by a moderate loss also in the contralateral CA3 region. Kainic acid receptor autoradi‐ography demonstrated that binding sites were lost from the stratum lucidum in hippocampus. Septal lesion had no effect on kainic acid binding sites in the hippocampus. Comparison with previous results on the histopathological changes after this lesion shows that high‐affinity kainic acid binding sites are preferentially located on neurons that undergo selective degenerations after severe kainic acid‐induced seizures.
Comparative Stereostructure‐Activity Studies on GABAA and GABAB Receptor Sites and GABA Uptake Using Rat Brain Membrane Preparations
Authors: Falch Erik , Hedegaard Anette , Nielsen Lone , Jensen Birger R. , Hjeds Hans , Krogsgaard‐Larsen Povl
Published: July 2010

Abstract: The affinities of a number of analogues of γ‐aminobutyric acid (GABA) for GABAA and GABAB receptor sites and GABA uptake were studied using rat brain membrane preparations. Studies on the (S)‐(+)‐and (R)‐(‐)‐isomers of baclofen, 3‐hydroxy‐4‐aminobutyric acid (3‐OH‐GABA), and 4,5‐dihydromuscimol (DHM) revealed different stereoselectivities of these synaptic mechanisms in vitro. Although (S)‐3‐OH‐GABA and, in particular, (S)‐DHM were more potent than the corresponding (R)‐isomers as inhibitors of GABAA binding, the opposite stereoselectivity was demonstrated for the GABAB binding sites. Thus, (R)‐3‐OH‐GABA and (R)‐baclofen were more potent than the (S)‐isomers as inhibitors of GABAB binding, (R)‐baclofen being some five times more potent than (R)‐3‐OH‐GABA. These two (R)‐isomers actually have opposite orientation of the substituents on the GABA backbones, suggesting that the lipophilic substituent of (R)‐baclofen interacts with a structural element of the GABAB receptor site different from that that binds the very polar hydroxy group of (R)‐3‐OH‐GABA. The O‐methylated analogue of 3‐OH‐GABA, 3‐methoxy‐4‐aminobutyric acid (3‐OCH3‐GABA), did not interact significantly with GABAB sites. The homoiogues of GABA, trans‐4‐aminocrotonic acid (trans‐ACA). muscimol, and 3‐OH‐GABA, that is, 5‐aminovaleric acid (DAVA), trans‐5‐aminopent‐2‐enoic acid, homomuscimol, and 3‐hydroxy‐5‐aminovaleric acid (3‐OH‐DAVA), respectively, were generally much weaker than the parent compounds, whereas 2‐hydroxy‐5‐aminovaleric acid (2‐OH‐DAVA) showed a significantly higher affinity for GABAB sites than the corresponding GABA analogue, 2‐hydroxy‐4‐aminobutyric acid (2‐OH‐GABA). The cyclized analogues of these amino acids, perhydrooxazine‐6‐carboxylic acid and isoxazolidine‐5‐carboxylic acid, respectively, were inactive.
Effects of Osmolality and Ionic Strength on Secretion from Adrenal Chromaffin Cells Permeabilized with Digitonin
Authors: Holz Ronald W. , Senter Ruth A.
Published: July 2010

Hyperosmotic solutions inhibit exocytosis of catecholamine from adrenal chromaffin cells at a step after Ca2+ entry into the cells. The possibility that the inhibition resulted from an inability of shrunken secretory granules to undergo exocytosis was investigated in cells with plasma membranes permeabilized by digitonin. The osmoticants and salts used in this study rapidly equilibrated across the plasma membrane and bathed the intracellular organelles. When sucrose was the osmoticant, secretion was not significantly inhibited unless the osmolality was raised above 1,000 mOs. When the osmolality was raised with the tetrasaccharide stachyose or a low‐molecular‐weight maltodextrin fraction (average size a tetrasaccharide), one‐half maximal inhibition occurred at 900–1,000 mOs. Prior treatment of permeabilized cells with Ca2+ in hyperosmotic solution did not result in enhanced secretion when cells were restored to normal osmolality. Increased concentrations of potassium glutamate or sodium isethionate were more potent than carbohydrate in inhibiting secretion. Half‐maximal inhibition occurred at 600–700 mOs or when the ionic strength was approximately doubled. The inhibition by elevated potasium glutamate also occurred when the osmolality was kept constant with sucrose. Increasing the ionic strength did not alter the Ca2+ sensitivity of the secretory response. Reducing the ionic strength by substituting sucrose for salt reduced the Ca2+ concentration required for half‐maximal stimulated secretion from approximately 1.2 μM. Chromaffin granules, the secretory granules, are known to shrink in hyperosmotic solution. The experiments indicate that shrunken chromaffin granules can undergo exocytosis and suggest that in intact cells elevated ionic strength rather than chromaffin granule shrinkage contributes to the inhibition of secretion by hyperosmotic solutions. The experiments place limits on the possible osmotic mechanisms that could be involved in exocytosis.
Metals accelerate production of the aberrant splicing isoform of the presenilin‐2
Authors: Matsuzaki Shinsuke , Manabe Takayuki , Katayama Taiichi , Nishikawa Atsuko , Yanagita Takeshi , Okuda Hiroaki , Yasuda Yuichi , Miyata Shingo , Meshitsuka Shunsuke , Tohyama Masaya
Published: July 2010

Oxidative stress is a major risk factor for Alzheimer's disease (AD) and other neurodegenerative disorders. Metals are known to be one of the factors that contribute to oxidative stress. Recently, we reported that the aberrant splicing isoform (PS2V) generated by skipping exon5 of the presenilin‐2 (PS2) gene is a diagnostic feature of sporadic AD (SAD). PS2V is inducible by exposure of human neuroblastoma to hypoxia. We examined whether this aberrant splicing was caused by metal‐induced oxidative stress, such as exposure to aluminum. As a result, we demonstrated that exposure to aluminum accelerated PS2V production induced by hypoxia. This acceleration of the production of PS2V to hypoxia was caused by chronic aluminum exposure, but was not related to the intracellular content of aluminum. HMGA1a is a mediator of PS2V production, and it was induced by aluminum as well as by hypoxia. Induction of HMGA1a was increased by chronic exposure to aluminum, and a nuclear extract containing HMGA1a bound to a specific sequence on exon5 of PS2 pre‐mRNA, as reported previously. Finally, the acceleration of PS2V production induced by aluminum under hypoxic conditions reflected, but has not yet been directly shown to cause, vulnerability to endoplasmic reticulum stress. These results suggest that exposure to some metals can accelerate and enhance PS2V generation, and that hypoxia plus chronic exposure to metals may promote the development of AD.
GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF‐1‐induced ERK1/2 activation
Authors: Higashi Shinji , Iseki Eizo , Minegishi Michiko , Togo Takashi , Kabuta Tomohiro , Wada Keiji
Published: July 2010

J. Neurochem. (2010) 115, 423–437.

GIGYF2 has been reported as a candidate gene for PARK11‐linked Parkinson’s disease (PD). Heterozygous knockout of GIGYF2 results in neurodegeneration, suggesting important roles for GIGYF2 (Grb10 interacting GYF protein 2) in the CNS. In this study, we used novel GIGYF2 antibodies to clarify the distribution and function of GIGYF2. GIGYF2 was widely expressed, most highly in the pancreas and testis, and moderately in brain, lung, liver, kidney and spleen. In the brain, GIGYF2 was tightly associated with membrane in the S3 fraction, and localised in neuronal perikarya and proximal dendrites. Immunohistochemical analysis indicated sites of GIGYF2 localisation throughout the mouse brain, with high levels in the cerebral cortex, hippocampus, cerebellum, olfactory bulb and brainstem nuclei, but low levels in the substantia nigra and striatum. GIGYF2 was present in endosomes immunopositive for Rab4 and Grb10. Expression of GIGYF2 altered insulin‐like growth factor‐1 (IGF‐1) receptor trafficking and enhanced IGF‐1‐induced extracellular signal‐regulated kinase 1/2 phosphorylation, but not IGF‐1 receptor or serine/threonine protein kinase Akt phosphorylation. There were no significant differences in signalling activation between cells expressing wild‐type and putative PD‐associated mutant GIGYF2. In PD brains, GIGYF2 did not localise to Lewy bodies. Our findings indicate a role for GIGYF2 in the regulation of signalling at endosomes, but no contribution of GIGYF2 to the pathogenesis of PD.
Phosphorus fertilizer form affects phosphorus loss to waterways: a paired catchment study
Authors: McDowell R. W. , Littlejohn R. P. , Blennerhassett J. D.
Published: July 2010

Two catchments were used to test the hypothesis that using reactive phosphate rock (RPR), a low water soluble fertilizer, instead of superphosphate, could decrease phosphorus (P) export in streams. The sheep‐grazed catchments, each ca. 12 ha in size, received 20–25 kg P/ha either as RPR or superphosphate for 3 yr. Filterable (<0.45 μm) reactive P (FRP) and total P (TP) in stream samples were then compared against two subsequent years when both catchments received 20 kg P/ha as superphosphate. On average, during the 5‐yr study, loads of FRP and TP in stream flow were low (110 g FRP/ha and 358 g TP/ha), typical of dry sheep‐grazed hill country. However, FRP (58%) and TP (38%) in stream flow were significantly less when RPR was applied instead of superphosphate. Where appropriate climatic and soil conditions exist to maintain agronomic targets, RPR could be used to decrease P export in streams.
Feeding the family during times of stress: experience and determinants of food insecurity in an Inuit community
Authors: FORD JAMES D , BEAUMIER MAUDE
Published: July 2010

This paper uses a mixed methods approach to characterise the experience of food insecurity among Inuit community members in Igloolik, Nunavut, and examine the conditions and processes that constrain access, availability, and quality of food. We conducted semi‐structured interviews (n= 66) and focus groups (n= 10) with community members, and key informant interviews with local and territorial health professionals and policymakers (n= 19). The study indicates widespread experience of food insecurity. Even individuals and households who were food secure at the time of the research had experienced food insecurity in the recent past, with food insecurity largely transitory in nature. Multiple determinants of food insecurity operating over different spatial‐temporal scales are identified, including food affordability and budgeting, food knowledge and preferences, food quality and availability, environmental stress, declining hunting activity, and the cost of harvesting. These determinants are operating in the context of changing livelihoods and climate change, which in many cases are exacerbating food insecurity, although high‐order manifestations of food insecurity (that is, starvation) are no longer experienced.
Aquagenic pruritus: associated diseases and clinical pruritus characteristics
Authors: Heitkemper Tina , Hofmann Tanja , Phan Ngoc Quan , Ständer Sonja
Published: July 2010

Background: Aquagenic pruritus (AP) can be induced by systemic diseases. The distribution of underlying diseases in a representative patient collective has not been investigated. This retrospective study aimed to determine the frequency and pruritus‐specific parameter of systemic diseases in a series of patients.

Patients and methods: Data of 39 patients with AP (24 f, 15 m; mean age: f: 51.3 ± 20.1, m: 57.2 ± 15.0 years) were obtained and statistically evaluated as follows: demographic data, pruritus characteristics, underlying diseases, family history.

Results: 30.8 % of patients exhibited polycythemia vera or myelofibrosis (Group 1: G1), in 69.2 % (G2) no underlying disease was found. 25.6 % had lactose intolerance as possible contributing factor. Women were significantly more common in G2 (p < 0.01), with a lower mean age (p < 0.01) and longer duration of AP (18.9 years, p < 0.01).

Conclusions: AP occurs frequently with polycythemia vera. Other underlying diseases are rare; in over half of the patients no cause can be detected. In 25 % lactose intolerance is present which possibly acts as co‐factor. Demographic parameters (age, gender) allow estimation of the possible underlying disease in AP. Pruritus characteristics are similar in all groups and not helpful in determining the origin of AP.
Identification of a preferred substrate peptide for transglutaminase 3 and detection of in situ activity in skin and hair follicles
Authors: Yamane Asaka , Fukui Mina , Sugimura Yoshiaki , Itoh Miho , Alea Mileidys Perez , Thomas Vincent , El Alaoui Said , Akiyama Masashi , Hitomi Kiyotaka
Published: July 2010

Transglutaminases (TGases) are a family of enzymes that catalyze cross‐linking reactions between proteins. During epidermal differentiation, these enzymatic reactions are essential for formation of the cornified envelope, which consists of cross‐linked structural proteins. Two main transglutaminases isoforms, epidermal‐type (TGase 3) and keratinocyte‐type (TGase 1), are cooperatively involved in this process of differentiating keratinocytes. Information regarding their substrate preference is of great importance to determine the functional role of these isozymes and clarify their possible co‐operative action. Thus far, we have identified highly reactive peptide sequences specifically recognized by TGases isozymes such as TGase 1, TGase 2 (tissue‐type isozyme) and the blood coagulation isozyme, Factor XIII. In this study, several substrate peptide sequences for human TGase 3 were screened from a phage‐displayed peptide library. The preferred substrate sequences for TGase 3 were selected and evaluated as fusion proteins with mutated glutathione S‐transferase. From these studies, a highly reactive and isozyme‐specific sequence (E51) was identified. Furthermore, this sequence was found to be a prominent substrate in the peptide form and was suitable for detection of in situ TGase 3 activity in the mouse epidermis. TGase 3 enzymatic activity was detected in the layers of differentiating keratinocytes and hair follicles with patterns distinct from those of TGase 1. Our findings provide new information on the specific distribution of TGase 3 and constitute a useful tool to clarify its functional role in the epidermis.
Molecular cloning and expression of a Relish gene in Chinese mitten crab Eriocheir sinensis
Authors: Li F. , Wang L. , Zhang H. , Zheng P. , Zhao J. , Qiu L. , Zhang Y. , Song L.
Published: July 2010

NF‐κB is a B‐cell specific transcription factor that plays crucial roles in inflammation, immunity, apoptosis, development and differentiation. In the present study, a novel NF‐κB‐like transcription factor Relish was cloned from Chinese mitten crab Eriocheir sinensis (designated as EsRelish) by rapid amplification of cDNA ends (RACE) technique based on expressed sequence tag (EST). The full‐length cDNA of EsRelish was of 5034 bp, consisting of a 5′ untranslated region (UTR) of 57 bp, a 3′ UTR of 1335 bp with two mRNA instability motifs (ATTTA), a polyadenylation signal sequence (AATAAA) and a poly (A) tail, and an open reading frame (ORF) of 3645 bp encoding a polypeptide of 1214 amino acids with a calculated molecular mass of 134.8 kDa and a theoretical isoelectric point of 5.26. There were a typical Rel homology domain (RHD), two nuclear localization signal (NLS) sequences (KR), an inhibitor κB (IκB)‐like domain with six ankyrin repeats, a PEST region and a death domain in the deduced amino acid sequence of EsRelish. Conserved domain, higher similarity with other Rel/NF‐κBs and phylogenetic analysis suggested that EsRelish was a member of the NF‐κB family. Quantitative real‐time RT‐PCR was employed to detect the mRNA transcripts of EsRelish in different tissues and its temporal expression in hemocytes of E. sinensis challenged with Pichia methanolica and Listonella anguillarum. The EsRelish mRNA was found to be constitutively expressed in a wide range of tissues. It could be mainly detected in the hemocytes, gonad and hepatopancreas, and less degree in the gill, muscle and heart. The expression level of EsRelish mRNA in hemocytes was up‐regulated from at 3, 6, 9 and 12 h after P. methanolica challenge. In L. anguillarum challenge, it was up‐regulated at 9, 12 and 24 h. The results collectively indicated that EsRelish was potentially involved in the immune response against fungus and bacteria.
Alteration and role of heat shock proteins in acute pancreatitis
Authors: FENG Jia Yan , LI Yong Yu
Published: July 2010

Many etiological factors are involved in the pathogenesis of acute pancreatitis. The pathogenesis of acute pancreatitis has been attributed to such causes as trypsin autodigestion, pancreatic microcirculation malfunction, the calcium overload in pancreatic acinar cells, oxygen free radical injury, cytokine injury, and has been treated in detail in numerous reviews. More recently, heat shock proteins (HSP), particularly heat shock protein 60 (HSP60), have receive increasing attention as another possible factor in the pathogenesis and development of acute pancreatitis. This brief review aims to: (i) outline our current understanding of HSP and their role in pancreatitis; (ii) discuss the available evidences that suggest HSP's interplay between pancreas tissues and etiological agents; (iii) delineate the functional mechanisms of HSP proposed by different research groups, and offer new thinking in preventing and treating acute pancreatitis in general.
Estrogen Receptor Versatility
Authors: Ray L. Bryan
Published: July 2010

The estrogen receptor β functions with and without its estrogen ligand.
TOR Inhibition Promotes Self-Renewal
Authors: VanHook Annalisa M.
Published: July 2010

The TSC1-TSC2 complex represses differentiation of germline stem cells in
Drosophila
.
Inhibiting the Inhibitor of the Inhibitor: Blocking PKC-θ to Enhance Regulatory T Cell Function
Authors: Roybal Kole T. , Wülfing Christoph
Published: July 2010

PKC-θ functions differently in regulatory T cells, which may be linked to its exclusion from immune synapses.
Problem-based learning for professionalism and scientific integrity training of biomedical graduate students: process evaluation
Authors: Jones Nancy L , Peiffer Ann M , Lambros Ann , Eldridge J Charles
Published: July 2010

Objective

We conducted a process evaluation to (a) assess the effectiveness of a new problem-based learning curriculum designed to teach professionalism and scientific integrity to biomedical graduate students and (b) modify the course to enhance its relevance and effectiveness. The content presented realistic cases and issues in the practice of science, to promote skill development and to acculturate students to professional norms of science.

Method

We used 5-step Likert-scaled questions, open-ended questions, and interviews of students and facilitators to assess curricular effectiveness.

Results

Both facilitators and students perceived course objectives were achieved. For example, respondents preferred active learning over lectures; both faculty and students perceived that the curriculum increased their understanding of norms, role obligations and responsibilities of professional scientists. They also reported an increased ability to identify ethical situations and felt that they had developed skills in moral reasoning and effective group work.

Conclusions

These data helped to improve course implementation and instructional material. For example, to correct a negative perception that this was an ‘ethics’ course, we redesigned case debriefing activities to reinforce learning objectives and important skills. We refined cases to be more engaging and relevant for students, and gave facilitators more specific training and resources for each case. The problem-based learning small group strategy can stimulate an environment whereby participants are more aware of ethical implications of science, and increase their socialisation and open communication about professional behaviour.
AN EMERGENCE OF A COMMON CURRENCY AREA IN THE SELECTED EAST ASIAN ECONOMIES: A REVISIT
Authors: SOO SIEW-CHOO , CHOONG CHEE-KEONG
Published: July 2010

The study attempts to re-investigate the possibility of emergence of a single currency area in East Asian (EA) countries by comparing both pre- and post-financial crisis periods. Using variance decomposition and impulse analyses, we investigated whether the selected EA economies — Hong Kong, Indonesia, Korea, Malaysia, the Philippines, and Singapore — are heavily segmented or instead integrated by focusing on the three different shocks, namely global-, regional-, and country-specific shocks. This paper finds that most economies could be described as heavily segmented, especially during the pre-crisis period (before July 1997). However, over time, the degree of segmentation experienced by some of these economies has declined significantly, particularly that of Hong Kong, Korea, and Singapore. The analyses also indicate that few economies, especially Indonesia and the Philippines, are being influenced by the performance of the Japanese economic growth to a greater extent than they were previously.
THE MICROSCOPIC APPROACH TO NUCLEAR MATTER AND NEUTRON STAR MATTER
Authors: SAMMARRUCA FRANCESCA
Published: July 2010

We review a variety of theoretical and experimental investigations aimed at improving our knowledge of the nuclear matter equation of state. Of particular interest are nuclear matter extreme states in terms of density and/or isospin asymmetry. The equation of state of matter with unequal concentrations of protons and neutrons has numerous applications. These include heavy-ion collisions, the physics of rare, short-lived nuclei and, on a dramatically different scale, the physics of neutron stars. The "common denominator" among these (seemingly) very different systems is the symmetry energy, which plays a crucial role in both the formation of the neutron skin in neutron-rich nuclei and the radius of a neutron star (a system 18 orders of magnitude larger and 55 orders of magnitudes heavier). The details of the density dependence of the symmetry energy are not yet sufficiently constrained. Throughout this article, our emphasis will be on the importance of adopting a microscopic approach to the many-body problem, which we believe to be the one with true predictive power.
A HEURISTIC-INDUCING METHOD FOR GENERATING INITIAL IDEAS FOR OPPORTUNITIES: AN APPLICATION TO THE AUSTRALASIAN DATING MARKET
Authors: VAN GELDEREN MARCO
Published: July 2010

This paper presents a heuristics-inducing method for generating initial ideas for opportunities. It consists of the presentation of snippets of theory and research, selected for their inspirational value and relevance to a particular industry, to business owners in that industry to brainstorm about applications in products and services. In this approach, the researcher bridges the worlds of academia and business, and actively contributes to the opportunity recognition process by selecting, presenting and discussing information. The method is applied to the dating market: searching, matching and/or interacting services, whether internet based or real-life. Participants were ten Australians or New Zealanders dating service owners. The presented information concerns social psychological research outcomes on factors that contribute to attraction and forming bonds, and specific issues relevant to the dating market, e.g., gender imbalances in enrollment. A range of initial ideas for future possibilities in the dating market are presented.
LARGE DEVIATIONS FOR FLOWS OF INTERACTING BROWNIAN MOTIONS
Authors: DOROGOVTSEV A. A. , OSTAPENKO O. V.
Published: July 2010

We establish the large deviation principle (LDP) for stochastic flows of interacting Brownian motions. In particular, we consider smoothly correlated flows, coalescing flows and Brownian motion stopped at a hitting moment.
PERFECT, EFFICIENT, STATE TRANSFER AND ITS APPLICATION AS A CONSTRUCTIVE TOOL
Authors: KAY ALASTAIR
Published: July 2010

We review the subject of perfect state transfer — how one designs the (fixed) interactions of a chain of spins so that a quantum state, initially inserted on one end of the chain, is perfectly transferred to the opposite end in a fixed time. The perfect state transfer systems are then used as a constructive tool to design Hamiltonian implementations of other primitive protocols such as entanglement generation and signal amplification in measurements, before showing that, in fact, universal quantum computation can be implemented in this way.
Role of urocortin 2 secreted by the pituitary in the stress-induced suppression of luteinizing hormone secretion in rats
Authors: Nemoto Takahiro , Iwasaki-Sekino Azusa , Yamauchi Naoko , Shibasaki Tamotsu
Published: July 2010

We have previously shown that urocortin 2 (Ucn 2), a member of the corticotropin-releasing factor (CRF) peptide family that binds to CRF type 2 receptor, is expressed in proopiomelanocortin (POMC) cells of rat pituitary and that its secretion and expression are increased by CRF in both the anterior and intermediate lobes and suppressed by glucocorticoids in the anterior lobe. We have also shown that Ucn 2 secreted by POMC cells acts on gonadotrophs expressing CRF type 2 receptors and inhibits the expression and secretion of gonadotropins. In the present study, we examined whether pituitary Ucn 2 is involved in stress-induced inhibition of gonadotropin secretion. A 90-min period of immobilization stress increased POMC mRNA expression without influencing Ucn 2 mRNA expression and suppressed luteinizing hormone (LH) β-subunit mRNA expression in the anterior lobe and plasma LH levels, while it increased both POMC and Ucn 2 mRNA expression in the intermediate lobe of the pituitary. Pretreatment with anti-CRF IgG blocked immobilization-induced increases in plasma ACTH and corticosterone and in POMC mRNA expression in both pituitary lobes and Ucn 2 mRNA expression in the intermediate pituitary. It also blocked immobilization-induced suppression of plasma LH and LH β-subunit mRNA expression. Pretreatment with anti-Ucn 2 IgG blocked immobilization-induced suppression of plasma LH and LH β-subunit expression without affecting immobilization-induced ACTH and corticosterone release and POMC or Ucn 2 mRNA expression. These results suggest that CRF suppresses the secretion and expression of LH probably through pituitary Ucn 2 in stress.
Physiology of Circadian Entrainment
Authors: Golombek Diego A. , Rosenstein Ruth E.
Published: July 2010

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.
Muscle KATPChannels: Recent Insights to Energy Sensing and Myoprotection
Authors: Flagg Thomas P. , Enkvetchakul Decha , Koster Joseph C. , Nichols Colin G.
Published: July 2010

ATP-sensitive potassium (KATP) channels are present in the surface and internal membranes of cardiac, skeletal, and smooth muscle cells and provide a unique feedback between muscle cell metabolism and electrical activity. In so doing, they can play an important role in the control of contractility, particularly when cellular energetics are compromised, protecting the tissue against calcium overload and fiber damage, but the cost of this protection may be enhanced arrhythmic activity. Generated as complexes of Kir6.1 or Kir6.2 pore-forming subunits with regulatory sulfonylurea receptor subunits, SUR1 or SUR2, the differential assembly of KATPchannels in different tissues gives rise to tissue-specific physiological and pharmacological regulation, and hence to the tissue-specific pharmacological control of contractility. The last 10 years have provided insights into the regulation and role of muscle KATPchannels, in large part driven by studies of mice in which the protein determinants of channel activity have been deleted or modified. As yet, few human diseases have been correlated with altered muscle KATPactivity, but genetically modified animals give important insights to likely pathological roles of aberrant channel activity in different muscle types.
Hepatocyte Death: A Clear and Present Danger
Authors: Malhi Harmeet , Guicciardi Maria Eugenia , Gores Gregory J.
Published: July 2010

The hepatocyte is especially vulnerable to injury due to its central role in xenobiotic metabolism including drugs and alcohol, participation in lipid and fatty acid metabolism, its unique role in the enterohepatic circulation of bile acids, the widespread prevalence of hepatotropic viruses, and its existence within a milieu of innate immune responding cells. Apoptosis and necrosis are the most widely recognized forms of hepatocyte cell death. The hepatocyte displays many unique features regarding cell death by apoptosis. It is quite susceptible to death receptor-mediated injury, and its death receptor signaling pathways involve the mitochondrial pathway for efficient cell killing. Also, death receptors can trigger lysosomal disruption in hepatocytes which further promote cell and tissue injury. Interestingly, hepatocytes are protected from cell death by only two anti-apoptotic proteins, Bcl-xLand Mcl-1, which have nonredundant functions. Endoplasmic reticulum stress or the unfolded protein response contributes to hepatocyte cell death during alterations of lipid and fatty acid metabolism. Finally, the current information implicating RIP kinases in necrosis provides an approach to more fully address this mode of cell death in hepatocyte injury. All of these processes contributing to hepatocyte injury are discussed in the context of potential therapeutic strategies.
A Two-Zone Multigrid Model for SI Engine Combustion Simulation Using Detailed Chemistry
Authors: Ge Hai-Wen , Juneja Harmit , Shi Yu , Yang Shiyou , Reitz Rolf D.
Published: July 2010

An efficient multigrid (MG) model was implemented for spark-ignited (SI) engine combustion modeling using detailed chemistry. The model is designed to be coupled with a level-set-G-equation model for flame propagation (GAMUT combustion model) for highly efficient engine simulation. The model was explored for a gasoline direct-injection SI engine with knocking combustion. The numerical results using the MG model were compared with the results of the original GAMUT combustion model. A simpler one-zone MG model was found to be unable to reproduce the results of the original GAMUT model. However, a two-zone MG model, which treats the burned and unburned regions separately, was found to provide much better accuracy and efficiency than the one-zone MG model. Without loss in accuracy, an order of magnitude speedup was achieved in terms of CPU and wall times. To reproduce the results of the original GAMUT combustion model, either a low searching level or a procedure to exclude high-temperature computational cells from the grouping should be applied to the unburned region, which was found to be more sensitive to the combustion model details.
A Cancer Detection Platform Which Measures Telomerase Activity from Live Circulating Tumor Cells Captured on a Microfilter
Authors: Xu Tong , Lu Bo , Tai Yu-Chong , Goldkorn Amir
Published: July 2010

Circulating tumor cells (CTC) quantified in cancer patients' blood can predict disease outcome and response to therapy. However, the CTC analysis platforms commonly used cannot capture live CTCs and only apply to tumors of epithelial origin. To address these limitations, we have developed a novel cancer detection platform which measures telomerase activity from live CTCs captured on a parylene-C slot microfilter. Using a constant low-pressure delivery system, the new microfilter platform was capable of cell capture from 1 mL of whole blood in less than 5 minutes, achieving 90% capture efficiency, 90% cell viability, and 200-fold sample enrichment. Importantly, the captured cells retained normal morphology by scanning electron microscopy and could be readily manipulated, further analyzed, or expanded on- or off-filter. Telomerase activity—a well-recognized universal cancer marker—was reliably detected by quantitative PCR from as few as 25 cancer cells added into 7.5 mL of whole blood and captured on the microfilter. Moreover, significant telomerase activity elevation was also measured from patients' blood samples and from single cancer cells lifted off of the microfilter. Live CTC capture and analysis is fast and simple yet highly quantitative, versatile, and applicable to nearly all solid tumor types, making this a highly promising new strategy for cancer detection and characterization. Cancer Res; 70(16); 6420–6. ©2010 AACR.
Dvl2 Promotes Intestinal Length and Neoplasia in the Apc
Min Mouse Model for Colorectal Cancer
Authors: Metcalfe Ciara , Ibrahim Ashraf E.K. , Graeb Michael , de la Roche Marc , Schwarz-Romond Thomas , Fiedler Marc , Winton Douglas J. , Corfield Anthony , Bienz Mariann
Published: July 2010

APC mutations cause activation of Wnt/β-catenin signaling, which invariably leads to colorectal cancer. Similarly, overexpressed Dvl proteins are potent activators of β-catenin signaling. Screening a large tissue microarray of different staged colorectal tumors by immunohistochemistry, we found that Dvl2 has a strong tendency to be overexpressed in colorectal adenomas and carcinomas, in parallel to nuclear β-catenin and Axin2 (a universal transcriptional target of Wnt/β-catenin signaling). Furthermore, deletion of Dvl2 reduced the intestinal tumor numbers in a dose-dependent way in the ApcMin model for colorectal cancer. Interestingly, the small intestines of Dvl2 mutants are shortened, reflecting in part a reduction of their crypt diameter and cell size. Consistent with this, mammalian target of rapamycin (mTOR) signaling is highly active in normal intestinal crypts in which Wnt/β-catenin signaling is active, and activated mTOR signaling (as revealed by staining for phosphorylated 4E-BP1) serves as a diagnostic marker of ApcMin mutant adenomas. Inhibition of mTOR signaling in ApcMin mutant mice by RAD001 (everolimus) reduces their intestinal tumor load, similarly to Dvl2 deletion. mTOR signaling is also consistently active in human hyperplastic polyps and has a significant tendency for being active in adenomas and carcinomas. Our results implicate Dvl2 and mTOR in the progression of colorectal neoplasia and highlight their potential as therapeutic targets in colorectal cancer. Cancer Res; 70(16); 6629–38. ©2010 AACR.
Suppression of Neurotensin Receptor Type 1 Expression and Function by Histone Deacetylase Inhibitors in Human Colorectal Cancers
Authors: Wang Xiaofu , Jackson Lindsey N. , Johnson Sara M. , Wang Qingding , Evers B. Mark
Published: July 2010

Neurotensin, a gut peptide, stimulates the growth of colorectal cancers that possess the high-affinity neurotensin receptor (NTR1). Sodium butyrate (NaBT) is a potent histone deacetylase inhibitor (HDACi) that induces growth arrest, differentiation, and apoptosis of colorectal cancers. Previously, we had shown that NaBT increases nuclear GSK-3β expression and kinase activity; GSK-3β functions as a negative regulator of extracellular signal-regulated kinase (ERK) signaling. The purpose of our current study was to determine: (a) whether HDACi alters NTR1 expression and function, and (b) the role of GSK-3β/ERK in NTR1 regulation. Human colorectal cancers with NTR1 were treated with various HDACi, and NTR1 expression and function were assessed. Treatment with HDACi dramatically decreased endogenous NTR1 mRNA, protein, and promoter activity. Overexpression of GSK-3β decreased NTR1 promoter activity (> 30%); inhibition of GSK-3β increased NTR1 expression in colorectal cancer cells, indicating that GSK-3β is a negative regulator of ERK and NTR1. Consistent with our previous findings, HDACi significantly decreased phosphorylated ERK while increasing GSK-3β. Selective MAP/ERK kinase/ERK inhibitors suppressed NTR1 mRNA expression in a time- and dose-dependent fashion, and reduced NTR1 promoter activity by ∼70%. Finally, pretreatment with NaBT prevented neurotensin-mediated cyclooxygenase-2 and c-myc expression and attenuated neurotensin-induced interleukin-8 expression. HDACi suppresses endogenous NTR1 expression and function in colorectal cancer cell lines; this effect is mediated, at least in part, through the GSK-3β/ERK pathway. The downregulation of NTR1 in colorectal cancers may represent an important mechanism for the anticancer effects of HDACi. Mol Cancer Ther; 9(8); 2389–98. ©2010 AACR.
Systematic Interpretation of Comutated Genes in Large-Scale Cancer Mutation Profiles
Authors: Gu Yunyan , Yang Da , Zou Jinfeng , Ma Wencai , Wu Ruihong , Zhao Wenyuan , Zhang Yuannv , Xiao Hui , Gong Xue , Zhang Min , Zhu Jing , Guo Zheng
Published: July 2010

By high-throughput screens of somatic mutations of genes in cancer genomes, hundreds of cancer genes are being rapidly identified, providing us abundant information for systematically deciphering the genetic changes underlying cancer mechanism. However, the functional collaboration of mutated genes is often neglected in current studies. Here, using four genome-wide somatic mutation data sets and pathways defined in various databases, we showed that gene pairs significantly comutated in cancer samples tend to distribute between pathways rather than within pathways. At the basic functional level of motifs in the human protein-protein interaction network, we also found that comutated gene pairs were overrepresented between motifs but extremely depleted within motifs. Specifically, we showed that based on Gene Ontology that describes gene functions at various specific levels, we could tackle the pathway definition problem to some degree and study the functional collaboration of gene mutations in cancer genomes more efficiently. Then, by defining pairs of pathways frequently linked by comutated gene pairs as the between-pathway models, we showed they are also likely to be codisrupted by mutations of the interpathway hubs of the coupled pathways, suggesting new hints for understanding the heterogeneous mechanisms of cancers. Finally, we showed some between-pathway models consisting of important pathways such as cell cycle checkpoint and cell proliferation were codisrupted in most cancer samples under this study, suggesting that their codisruptions might be functionally essential in inducing these cancers. All together, our results would provide a channel to detangle the complex collaboration of the molecular processes underlying cancer mechanism. Mol Cancer Ther; 9(8); 2186–95. ©2010 AACR.