bluuebunny/crossref_metadata_2025 huggingface dataset:
Placental-specific
Igf2
knockout mice exhibit hypocalcemia and adaptive changes in placental calcium transport
Authors: Dilworth M. R. , Kusinski L. C. , Cowley E. , Ward B. S. , Husain S. M. , Constância M. , Sibley C. P. , Glazier J. D.
Published: February 2010

Evidence is emerging that the ability of the placenta to supply nutrients to the developing fetus adapts according to fetal demand. To examine this adaptation further, we tested the hypothesis that placental maternofetal transport of calcium adapts according to fetal calcium requirements. We used a mouse model of fetal growth restriction, the placental-specific
Igf2
knockout (P0) mouse, shown previously to transiently adapt placental System-A amino acid transporter activity relative to fetal growth. Fetal and placental weights in P0 mice were reduced when compared with WT at both embryonic day 17 (E17) and E19. Ionized calcium concentration [Ca
2+
] was significantly lower in P0 fetal blood compared with both WT and maternal blood at E17 and E19, reflecting a reversal of the fetomaternal [Ca
2+
] gradient. Fetal calcium content was reduced in P0 mice at E17 but not at E19. Unidirectional maternofetal calcium clearance (
Ca
K
mf
) was not different between WT and P0 at E17 but increased in P0 at E19. Expression of the intracellular calcium-binding protein calbindin-D
9K
, previously shown to be rate-limiting for calcium transport, was increased in P0 relative to WT placentas between E17 and E19. These data show an increased placental transport of calcium from E17 to E19 in P0 compared to WT. We suggest that this is an adaptation in response to the reduced fetal calcium accumulation earlier in gestation and speculate that the ability of the placenta to adapt its supply capacity according to fetal demand may stretch across other essential nutrients.
Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless
Authors: Gureasko Jodi , Kuchment Olga , Makino Debora Lika , Sondermann Holger , Bar-Sagi Dafna , Kuriyan John
Published: February 2010

Membrane-bound Ras is activated by translocation of the Son of Sevenless (SOS) protein to the plasma membrane. SOS is inactive unless Ras is bound to an allosteric site on SOS, and the Dbl homology (DH) and Pleckstrin homology (PH) domains of SOS (the DH-PH unit) block allosteric Ras binding. We showed previously that the activity of SOS at the membrane increases with the density of PIP
2
and the local concentration of Ras-GTP, which synergize to release the DH-PH unit. Here we present a new crystal structure of SOS that contains the N-terminal histone domain in addition to the DH-PH unit and the catalytic unit (SOS
HDFC
, residues 1–1049). The structure reveals that the histone domain plays a dual role in occluding the allosteric site and in stabilizing the autoinhibitory conformation of the DH-PH unit. Additional insight is provided by kinetic analysis of the activation of membrane-bound Ras by mutant forms of SOS that contain mutations in the histone and the PH domains (E108K, C441Y, and E433K) that are associated with Noonan syndrome, a disease caused by hyperactive Ras signaling. Our results indicate that the histone domain and the DH-PH unit are conformationally coupled, and that the simultaneous engagement of the membrane by a PH domain PIP
2
-binding interaction and electrostatic interactions between a conserved positively charged patch on the histone domain and the negatively charged membrane coincides with a productive reorientation of SOS at the membrane and increased accessibility of both Ras binding sites on SOS.
Allosteric gating of Son of sevenless activity by the histone domain
Authors: Yadav Kamlesh K. , Bar-Sagi Dafna
Published: February 2010

Regulated activation of Ras by receptor tyrosine kinases (RTK) constitutes a key transduction step in signaling processes that control an array of fundamental cellular functions including proliferation, differentiation, and survival. The principle mechanism by which Ras is activated down stream of RTKs involves the stimulation of guanine nucleotide exchange by the ubiquitous guanine nucleotide exchange factor Son of sevenless (Sos). In resting conditions, Sos activity is constrained by intramolecular interactions that maintain the protein in an autoinhibited conformation. Structural, biochemical, and genetic studies have implicated the histone domain (Sos-H), which comprises the most N-terminal region of Sos, in the regulation of Sos autoinhibition. However, the molecular underpinnings of this regulatory function are not well understood. In the present study we demonstrate that Sos-H possesses in vitro and in vivo membrane binding activity that is mediated, in part, by the interactions between a cluster of basic residues and phosphatidic acid. This interaction is required for Sos-dependent activation of Ras following EGF stimulation. The inducible association of Sos-H with membranes contributes to the catalytic activity of Sos by forcing the domain to adopt a conformation that destabilizes the autoinhibitory state. Thus, Sos-H plays a critical role in governing the catalytic output of Sos through the coupling of membrane recruitment to the release of autoinhibition.
Effect of deposition rate on device performance and lifetime of planar molecule-based organic light-emitting diodes
Authors: Lee Chih-Chien , Liu Shun-Wei , Chung Yu-Ting
Published: February 2010

Electrical and optical characteristics, surface morphology and device lifetime of planar molecule bis(10-hydroxybenzo[h]qinolinato)beryllium (Bebq2) were studied as a function of the deposition rate. These devices exhibited a significant decrease in the photoluminescence (PL) efficiency due to the formation of large aggregation in the emitting layer during a slower deposition process. Time-of-flight studies showed that the molecule-packing configuration in the ordered aggregates could enhance the probability for site-to-site hopping via intermolecular interactions. The effects of the deposition rate on the device performance of an organic light-emitting diode were exhaustively analysed by examining the electrical property, morphology, PL decay and device simulation. These results provide valuable insights into the effects of varying deposition rates on the electroluminescence efficiency and device reliability.
Super-broadband non-diffraction guiding modes in photonic crystals with elliptical rods
Authors: Liang W Y , Wang T B , Yin C P , Dong J W , Leng F C , Wang H Z
Published: February 2010

Non-diffraction guiding modes covering the full broad band of a photonic crystal with elliptical rods for TM mode are reported in this paper. All such modes can be used to effectively guide electromagnetic waves since they have near-zero group velocity components along the ΓX′ direction. In the fourth dispersion surface of the photonic crystal, the two wide flat regions spanning the first Brillouin zone possess unique properties: one dimension corresponds to a broad band, while the other corresponds to full incident angles of 0–90°. These properties have many potential applications; as an example, here a broadband all-angle supercollimation with a bandwidth of 169 nm around 1550 nm is demonstrated. For the inverted structure of elliptical holes in a dielectric, similar results can be achieved over 140 nm around 1550 nm for TE mode.
Charging and the secondary electron–electron emission on a trench surface: broadening and shift of ion energy spectrum at plasma trench etching
Authors: Palov A P , Mankelevich Yu A , Rakhimova T V , Shamiryan D
Published: February 2010

Trench surface charging at the plasma etching of dielectrics and semiconductors is a negative phenomenon because it leads to non-uniform etching of the trench bottom, undesirable etching of its wall, etch stop and breakdown of lower level device elements. To investigate the charging of a SiO2 trench surface by argon radio frequency discharge plasma we applied the 3D Monte Carlo method for modelling the electron and ion trajectories inside a trench and used the 2D analytical method to calculate electric fields and potentials produced by the deposited charges. The secondary electron–electron emission was taken into account as a really important mechanism of electrical charge redistribution on the trench surface. The ion energy spectra were calculated for the trench aspect ratios (depth d/width w) of 1–20 and trench widths of 11, 22 and 45 nm for 180 eV ion flux. The transformation of an initial ion energy spectrum from a delta function at 180 eV into bell-shaped curves with peak shifts of 10–60 eV and broadening of 5–30 eV is obtained.
Optical properties of Dy3+ ion in GGG laser crystal
Authors: Wang Yan , You Zhenyu , Li Jianfu , Zhu Zhaojie , Tu Chaoyang
Published: February 2010

High optical quality Dy3+-doped Gd3Ga5O12 (abbreviated as Dy : GGG below) crystal was grown by the Czochralski technique along the (1 1 1) orientation. The absorption spectrum, fluorescence spectrum and fluorescence decay curve of Dy : GGG have been recorded at room temperature. Based on the Judd–Ofelt (J–O) theory, the intensity parameters from the measured line strengths were determined. The J–O parameters were used to predict radiative transition probabilities, radiative lifetime and branching ratios for various excited levels of the Dy : GGG crystal. In the visible region, one intense fluorescence band was observed at 581 nm, corresponding to the 4F9/2 → 6H13/2 transition. The room-temperature fluorescence lifetime of this transition of Dy3+ ion in the GGG crystal was measured to be 0.79 ms, and the luminescent quantum efficiency of the 4F9/2 level was evaluated to be 71.4 %. The emission cross-sections of the 4F9/2 → 6H13/2 transition were estimated by the use of the Füchtbauer–Ladengurg method. The research on the emission at 581 nm indicates the possibility of using a commercially available laser diode of 353 nm as a pumping source for a solid-state yellow laser.
Growth mechanism and blue shift of Mn2+ luminescence for wurtzite ZnS : Mn2+ nanowires
Authors: Cao Jian , Yang Jinghai , Zhang Yongjun , Yang Lili , Wang Dandan , Wei Maobin , Wang Yaxin , Liu Yang , Gao Ming , Liu Xiaoyan
Published: February 2010

Wurtzite-type ZnS : Mn2+ nanowires were prepared by a hydrothermal method at 180 °C without any surface-active agent. The structure and morphology of the samples were characterized by x-ray diffraction, transmission electron microscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy and energy dispersive spectroscopy. The average diameter of the nanowires was about 10 nm. An ethylenediamine-mediated template was observed and employed to explain the growth mechanism in detail. A strong yellow–orange emission from the Mn2+ 
4T1–6A1 transition was observed in the photoluminescence spectra, which exhibited blue shift as the Mn2+ doped ratio increased.
Extending the class of solvable potentials: II. Screened Coulomb potential with a barrier
Authors: Alhaidari A D
Published: February 2010

This is the second paper in a series where we succeed in enlarging the class of solvable problems in one and three dimensions. We do that by working in a complete square integrable basis that carries a tridiagonal matrix representation of the wave operator. Consequently, the wave equation becomes equivalent to a three-term recursion relation for the expansion coefficients of the wavefunction in the basis. Finding solutions of the recursion relation is equivalent to solving the original problem. This method gives a larger class of solvable potentials. The usual diagonal representation constraint results in a reduction to the conventional class of solvable potentials. However, the tridiagonal requirement allows only very few and special potentials to be added to the solvability class. In the present work, we obtain S-wave solutions for a three-parameter 1/r singular but short-range potential with a nonorbital barrier and study its energy spectrum. We argue that it could be used as a more appropriate model for the screened Coulomb interaction of an electron with extended molecules. We give also its resonance structure for nonzero angular momentum. Additionally, we plot the phase shift for an electron scattering off a molecule modeled by a set of values of the potential parameters.
Evodia rutaecarpa and Three Major Alkaloids Abrogate Influenza A Virus (H1N1)‐Induced Chemokines Production and Cell Migration
Authors: Chiou Wen-Fei , Ko Han-Chieh , Wei Bai-Luh
Published: February 2010

Evodia rutaecarpa is commonly used as an anti‐inflammatory herbal remedy in traditional Chinese medicine. In this study, the ethanol extract of E. rutaecarpa (ER) and three major quinazoline alkaloids dehydroevodiamine (DeHE), evodiamine (Evo) and rutaecarpine (Rut), isolated from ER were employed to study their inhibitory effects against influenza A virus (H1N1)‐induced chemokines production in A549 lung epithelial cells as well as on chemokines‐evoked cell recruitment in HL‐60‐differentiated macrophages. The results showed that ER was a potent inhibitor of RANTES secretion by H1N1‐inoculated A549 cells (IC50: 1.9 ± 0.4 μg ml−1). Three alkaloids, although to differing extents, all concentration dependent, inhibited H1N1‐induced RANTES production with Evo consistently being the most potent among these active components. ER also moderately and significantly inhibited H1N1‐stimulated MCP‐1 production in A549 cells. This was mimicked by Evo and Rut, but not DeHE. In the macrophage recruitment assay, both RANTES and MCP‐1 markedly evoked cell migration and this phenomenon was significantly suppressed by ER. Evo and Rut, but not DeHE, also had the ability to inhibit cell migration toward RANTES and MCP‐1, respectively. In summary, three major alkaloids displayed different potentials for inhibiting chemokines secretion and subsequently cell migration, which could partially explain the activity of ER. As an effective agent to suppress H1N1‐induced chemokines production and block chemokine‐attracted leukocytes recruitment, E. rutaecarpa and its active components may be useful in influenza virus infection‐related inflammatory disorders.
Acupuncture Treatment of a Patient with Persistent Allergic Rhinitis Complicated by Rhinosinusitis and Asthma
Authors: Kim Ae-Ran , Choi Jun-Yong , Kim Jong-In , Jung So-Young , Choi Sun-Mi
Published: February 2010

A pathophysiologic relationship between allergic rhinitis and rhinosinusitis and asthma has long been suggested. However, few clinical studies of acupuncture have been conducted on these comorbid conditions. A 48‐year‐old male suffering from persistent allergic rhinitis with comorbid chronic rhinosinusitis and asthma since the age of 18 years was studied. He complained of nasal obstruction, sneezing, cough, rhinorrhea and moderate dyspnea. He occasionally visited local ear‐nose‐throat clinics for his nasal symptoms, but gained only periodic symptom relief. The patient was treated with acupuncture, infrared radiation to the face and electro‐acupuncture. Needles were inserted at bilateral LI20, GV23, LI4 and EX‐1 sites with De‐qi. Electro‐acupuncture was performed simultaneously at both LI20 sites and additional traditional Korean acupuncture treatments were performed. Each session lasted for 10 min and the sessions were carried out twice a week for 5 weeks. The patient’s Mini‐Rhinoconjunctivitis Quality‐of‐Life Questionnaire score decreased from 38, at the beginning of treatment, to 23, 3 weeks after the last treatment. The Total Nasal Symptom Score was reduced from six (baseline) to five, 3 weeks after the last treatment. There was significant clinical improvement in the forced expiratory volume in 1 s—from 3.01 to 3.50 l—with discontinuation of the inhaled corticosteroid, and no asthma‐related complaints were reported. Further clinical studies investigating the effectiveness of acupuncture for the patients suffering from allergic rhinitis and/or rhinosinusitis with comorbid asthma are needed.
Explosive morphological diversification of spiny-finned teleost fishes in the aftermath of the end-Cretaceous extinction
Authors: Friedman Matt
Published: February 2010

The spiny-finned teleost fishes (Acanthomorpha) include nearly one-third of all living vertebrate species and assume a bewildering array of bodyplans, but the macroevolutionary assembly of modern acanthomorph biodiversity remains largely unexplored. Here, I reconstruct the trajectory of morphological diversification in this major radiation from its first appearance in the Late Cretaceous to the Miocene using a geometric morphometric database comprising more than 600 extinct species known from complete body fossils. The anatomical diversity (disparity) of acanthomorphs is low throughout the Cretaceous, increases sharply and significantly in the wake of the Cretaceous–Palaeogene (K–P) extinction, and shows little change throughout subsequent Cenozoic intervals. This pattern of morphological diversification appears robust to two potential biasing factors: the ‘Lagerstätten effect’, and the non-random segregation of rare and common taxa along phenotypic axes. Dissecting the trajectory of acanthomorph radiation along phylogenetic lines reveals that the abrupt post-extinction increase in disparity is driven largely by the proliferation of trophically diverse modern groups within Percomorpha, a spiny-fin subclade containing more than 15 000 living species and identified as showing a substantially elevated diversification rate relative to background vertebrate levels. A major component of the Palaeogene acanthomorph radiation reflects colonization of morphospace previously occupied by non-acanthomorph victims of the K–P. However, other aspects of morphological diversification cannot be explained by this simple ecological release model, suggesting that multiple factors contributed to the prolific anatomical radiation of acanthomorphs.
Periodic versus scale-free patterns in dryland vegetation
Authors: von Hardenberg Jost , Kletter Assaf Y. , Yizhaq Hezi , Nathan Jonathan , Meron Ehud
Published: February 2010

Two major forms of vegetation patterns have been observed in drylands: nearly periodic patterns with characteristic length scales, and amorphous, scale-free patterns with wide patch-size distributions. The emergence of scale-free patterns has been attributed to global competition over a limiting resource, but the physical and ecological origin of this phenomenon is not understood. Using a spatially explicit mathematical model for vegetation dynamics in water-limited systems, we unravel a general mechanism for global competition: fast spatial distribution of the water resource relative to processes that exploit or absorb it. We study two possible realizations of this mechanism and identify physical and ecological conditions for scale-free patterns. We conclude by discussing the implications of this study for interpreting signals of imminent desertification.
Typing of Clostridium difficile isolates endemic in Japan by sequencing of slpA and its application to direct typing
Authors: Kato Haru , Kato Hideaki , Ito Yoichiro , Akahane Takayuki , Izumida Sayuri , Yokoyama Toshiyuki , Kaji Chiharu , Arakawa Yoshichika
Published: February 2010

A typing system forClostridium difficileusing sequencing of the surface-layer protein A encoding gene (slpA) was evaluated and used to analyse clinical isolates in Japan. A total of 160 stool specimens from symptomatic patients in Japan was examined and 87C. difficileisolates were recovered.slpAsequence typing was found to have reliable typability and discriminatory power in comparison with PCR ribotyping, and the typing results were highly reproducible and comparable.slpAsequence typing was used to typeC. difficilein DNA extracted directly from stool specimens. Among the 90 stool specimens in which direct typing results were obtained, 77 specimens were positive forC. difficileculture, and typing results from isolated strains agreed with those from direct typing in all 77 specimens. TheslpAsequence type smz was dominant at all four hospitals examined, and this endemic type was detected by culture and/or direct typing in 61 (62 %) of 99 stool specimens positive for toxic culture and/or directslpAsequence typing. Comparison of epidemic strains reported throughout the world revealed one isolate identified asslpAsequence type gc8, which was found to correspond to PCR ribotype 027 (BI/NAP1/027), whereas no isolates were found with theslpAgene identical to that of PCR ribotype 078 strain.slpAsequence typing is valuable for comparison ofC. difficilestrains epidemic in diverse areas because the typing results are reproducible and can easily be shared. In addition,slpAsequence typing could be applied to direct typing without culture.
Identification of two scyllo-inositol dehydrogenases in Bacillus subtilis
Authors: Morinaga Tetsuro , Ashida Hitoshi , Yoshida Ken-ichi
Published: February 2010

scyllo-Inositol (SI) is a stereoisomer of inositol whose catabolism has not been characterized in bacteria. We found thatBacillus subtilis168 was able to grow using SI as its sole carbon source and that this growth was dependent on a functionalioloperon for catabolism ofmyo-inositol (MI; another inositol isomer, which is abundant in nature). Previous studies elucidated the MI catabolic pathway inB. subtilisas comprising multiple stepwise reactions catalysed by a series of Iol enzymes. The first step of the pathway converts MI toscyllo-inosose (SIS) and involves the MI dehydrogenase IolG. Since IolG does not act on SI, we suspected that there could be another enzyme converting SI into SIS, namely an SI dehydrogenase. Within the whole genome, seven genes paralogous toiolGhave been identified and two of these,iolXandiolW(formerly known asyisSandyvaA, respectively), were selected as candidate genes for the putative SI dehydrogenase since they were both prominently expressed whenB. subtiliswas grown on medium containing SI.iolXandiolWwere cloned inEscherichia coliand both were shown to encode a functional enzyme, revealing the two distinct SI dehydrogenases inB. subtilis. Since inactivation ofiolXimpaired growth with SI as the carbon source, IolX was identified as a catabolic enzyme required for SI catabolism and it was shown to be NAD+dependent. The physiological role of IolW remains unclear, but it may be capable of producing SI from SIS with NADPH oxidation.
Digital transcriptome profiling from attomole-level RNA samples
Authors: Ozsolak Fatih , Goren Alon , Gymrek Melissa , Guttman Mitchell , Regev Aviv , Bernstein Bradley E. , Milos Patrice M.
Published: February 2010

Accurate profiling of minute quantities of RNA in a global manner can enable key advances in many scientific and clinical disciplines. Here, we present low-quantity RNA sequencing (LQ-RNAseq), a high-throughput sequencing-based technique allowing whole transcriptome surveys from subnanogram RNA quantities in an amplification/ligation-free manner. LQ-RNAseq involves first-strand cDNA synthesis from RNA templates, followed by 3′ polyA tailing of the single-stranded cDNA products and direct single molecule sequencing. We applied LQ-RNAseq to profile S. cerevisiae polyA+ transcripts, demonstrate the reproducibility of the approach across different sample preparations and independent instrument runs, and establish the absolute quantitative power of this method through comparisons with other reported transcript profiling techniques and through utilization of RNA spike-in experiments. We demonstrate the practical application of this approach to define the transcriptional landscape of mouse embryonic and induced pluripotent stem cells, observing transcriptional differences, including over 100 genes exhibiting differential expression between these otherwise very similar stem cell populations. This amplification-independent technology, which utilizes small quantities of nucleic acid and provides quantitative measurements of cellular transcripts, enables global gene expression measurements from minute amounts of materials and offers broad utility in both basic research and translational biology for characterization of rare cells.
Temperature and salmonid reproduction: implications for aquaculture
Authors: Pankhurst N. W. , King H. R.
Published: February 2010

Fish reproduction is likely to be affected by increasing water temperatures arising from climate change. Normal changes in environmental temperature have the capacity to affect endocrine function and either advance or retard gametogenesis and maturation, but above‐normal temperatures have deleterious effects on reproductive processes. In Atlantic salmon Salmo salar, exposure to elevated temperature during gametogenesis impairs both gonadal steroid synthesis and hepatic vitellogenin production, alters hepatic oestrogen receptor dynamics and ultimately results in reduced maternal investment and gamete viability. Exposure to high temperature during the maturational phase impairs gonadal steroidogenesis, delaying or inhibiting the preovulatory shift from androgen to maturation‐inducing steroid production. There are also deleterious effects on reproductive development of female broodstock of rainbow trout Oncorhynchus mykiss and Arctic charr Salvelinus alpinus when they are exposed to elevated temperature. Less is known about temperature effects on male fishes but inhibition of spermiation has been observed in S. salar and O. mykiss. Among wild stocks, the response to elevated temperature will involve behavioural thermoregulation with consequent change in geographical ranges and the possibility of local extinctions in some regions. For domesticated stocks, containment in the culture environment precludes behavioural thermoregulation and aquaculturists will be required to develop adaptive strategies in order to maintain productivity. The most direct strategy is to manage the thermal environment using one or more of a range of developing aquaculture technologies. Alternatively, there is potential to mitigate the effects of elevated temperature on reproductive processes through endocrine therapies designed to augment or restore natural endocrine function. Studies largely on S. salar have demonstrated the capacity for synthetic luteinizing hormone‐releasing hormone to offset the inhibitory effects of elevated temperature on maturational events in both sexes, but the potential for hormone therapy to provide protection during gametogenesis is still largely unexplored.
Frenetic activation of fish spermatozoa flagella entails short‐term motility, portending their precocious decadence
Authors: Cosson J.
Published: February 2010

In most species, fish spermatozoa activate their motility on contact with the external medium (sea or fresh water depending of their reproductive habitat). Their flagella immediately develop waves propagated at high beat frequency (up to 70 beats s−1), which propel these sperm cells at high velocity (6–10 mm min−1), but for a quite short period of time, usually limited to minutes. Their specific inability to restore their energy content (mostly adenosine triphosphate) fast enough relatively to their high rate of energy consumption by flagellar contributes mainly to the activity arrest of motility, as the spermatozoa need to rely on early accumulated energy prior to activation. This review of the published data explains the present understanding of physico‐chemical mechanisms by which flagellar motility is activated (mostly through osmotic and ionic regulation) and then propels sperm cells at speed. It aims also to describe the gradual arrest of their motility much of which occurs within a few minutes.
Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress‐independent growth inhibition of pancreatic cancer cells through G2/M cell‐cycle arrest and apoptosis
Authors: Li Wei , Xie Li , Chen Zheng , Zhu Yi , Sun Yujie , Miao Yi , Xu Zekuan , Han Xiao
Published: February 2010

Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. It is a potent and selective inhibitor of protein phosphatase 2A (PP2A) that plays an important role in control of cell cycle, apoptosis, and cell‐fate determination. Owing to its antitumor activity, cantharidin has been frequently used in clinical practice. In the present study, we investigated the therapeutic potential of cantharidin in pancreatic cancer. Cantharidin efficiently inhibited the growth of pancreatic cancer cells, but presented a much lighter toxicity effect against normal pancreatic duct cells. It caused G2/M cell‐cycle arrest that was accompanied by the down‐regulation of cyclin‐dependent kinase 1 (CDK1) and up‐regulation of p21 expression. It induced apoptosis and elevated the expressions of pro‐apoptotic factors tumor necrosis factor‐α (TNF‐α), TNF‐related apoptosis inducing receptor 1 (TRAILR1), TRAILR2, Bad, Bak, and Bid, and decreased the expression of anti‐apoptotic Bcl‐2. Activation of caspase‐8 and caspase‐9 suggested that both extrinsic and intrinsic pathways are involved in the induction of apoptosis. Interestingly, unlike previous studies on other cancer cells, we found that the inhibitory role of cantharidin is independent of oxidative stress in pancreatic cancer cells. Mitogen‐activated protein kinases (MAPKs), including ERK, JNK, and p38, were activated after treatment with cantharidin. Inhibition of JNK, but not ERK or p38, alleviated the cytotoxity effect of cantharidin, suggesting cantharidin exerted its anticancer effect through the JNK‐dependent way. Hence, in addition to being an attractive candidate compound with therapeutic potential, cantharidin also highlighted the possibility of using PP2A as a therapeutic target for pancreatic cancer treatment.

(Cancer Sci 2010; 101: 1226–1233)
Expression and prognostic significance of osteopontin and caspase‐3 in hepatocellular carcinoma patients after curative resection
Authors: Huang Hua , Zhang Xiao‐Fei , Zhou Hai‐Jun , Xue Yu‐Hua , Dong Qiong‐Zhu , Ye Qing‐Hai , Qin Lun‐Xiu
Published: February 2010

Osteopontin (OPN) plays an important role in the development, invasion, and metastasis of malignancies. Recently, several studies have reported that OPN enhances chemoresistance in small‐cell lung cancer and breast cancer by blocking caspase‐9 and caspase‐3‐dependent cell apoptosis. The aim of this study was to assess the value of OPN and caspase‐3 for predicting tumor recurrence after curative resection in hepatocellular carcinoma (HCC) patients. We found that OPN expression increased concordantly with increasing metastatic potential in human HCC cell lines, whereas caspase‐3 expression declined. In a tumor tissue microarray immunohistochemical analysis, we found that patients with higher levels of OPN and lower levels of caspase‐3 had a significantly poorer prognosis than patients with lower OPN and higher caspase‐3 levels. The combination of OPN and caspase‐3 expression thus served as an effective prognosticator. These findings suggest that OPN alone or in combination with caspase‐3 may act as an independent indicator for HCC patients after curative resection.

(Cancer Sci 2010; 101: 1314–1319)
Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions
Authors: Haga Naomi , Saito Sakae , Tsukumo Yoshinori , Sakurai Junko , Furuno Aki , Tsuruo Takashi , Tomida Akihiro
Published: February 2010

Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA‐deficient ρ0 cells and electron transport chain blocker‐treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was associated with failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation, but also through modulating the UPR for cell survival.

(Cancer Sci 2010; 101: 1125–1132)
The abuse potential of the synthetic cannabinoid nabilone
Authors: Ware Mark A. , St Arnaud‐Trempe Emmanuelle
Published: February 2010

Aim  Nabilone is a synthetic cannabinoid prescription drug approved in Canada since 1981 to treat chemotherapy‐induced nausea and vomiting. In recent years, off‐label use of nabilone for chronic pain management has increased, and physicians have begun to express concerns about nabilone becoming a drug of abuse. This study evaluates the evidence for abuse of nabilone, which is currently ill‐defined.

Study design  Scientific literature, popular press and internet databases were searched extensively for evidence of nabilone abuse. Focused interviews with medical professionals and law enforcement agencies across Canada were also conducted.

Findings  The scientific literature and popular press reviews found very little reference to nabilone abuse. Nabilone is perceived to produce more undesirable side effects, to have a longer onset of action and to be more expensive than smoked cannabis. The internet review revealed rare and isolated instances of recreational use of nabilone. The database review yielded little evidence of nabilone abuse, although nabilone seizures and thefts have occurred in Canada in the past few years, especially in Ontario. Most law enforcement officers reported no instances of nabilone abuse or diversion, and the drug has no known street value. Medical professionals reported that nabilone is not perceived to be a matter of concern with respect to its abuse potential.

Conclusions  Reports of nabilone abuse are extremely rare. However, follow‐up of patients using nabilone for therapeutic purposes is prudent and should include assessment of tolerance and dependence. Prospective studies are also needed to definitively address the issue of nabilone abuse.
Finnegan neonatal abstinence scoring system: normal values for first 3 days and weeks 5–6 in non‐addicted infants
Authors: Zimmermann‐Baer Urs , Nötzli Ursula , Rentsch Katharina , Bucher Hans Ulrich
Published: February 2010

Objective  The neonatal abstinence scoring system proposed by Finnegan is used widely in neonatal units to initiate and to guide therapy in babies of opiate‐dependent mothers. The purpose of this study was to assess the variability of the scores in newborns and infants not exposed to opiates during the first 3 days of life and during 3 consecutive days in weeks 5 or 6.

Patients and methods  Healthy neonates born after 34 completed weeks of gestation, whose parents denied opiate consumption and gave informed consent, were included in this observational study. Infants with signs or symptoms of disease or with feeding problems were excluded. A modified scoring system was used every 8 hours during 72 hours by trained nurses; 102 neonates were observed for the first 3 days of life and 26 neonates in weeks 5–6. A meconium sample and a urine sample at weeks 5–6 were stored from all infants to be analysed for drugs when the baby scored high. Given a non‐Gaussian distribution the scores were represented as percentiles.

Results  During the first 3 days of life median scores remained stable at 2 but the variability increased, with the 95th percentile rising from 5.5 on day 1 to 7 on day 2. At weeks 5–6 median values were higher during daytime (50th percentile = 5, 95th percentile = 8) than night‐time (50th percentile = 2, 95th percentile = 6, P = 0.02).

Conclusion  Scores increase from days 1–3 to weeks 5–6 and show day–night cycles with 5–6 weeks. Values above 8 can be considered pathological. This data may help to raise suspicion of narcotic withdrawal and to guide therapy.
Testing for cannabis in the work‐place: a review of the evidence
Authors: Macdonald Scott , Hall Wayne , Roman Paul , Stockwell Tim , Coghlan Michelle , Nesvaag Sverre
Published: February 2010

Background  Urinalysis testing in the work‐place has been adopted widely by employers in the United States to deter employee drug use and promote ‘drug‐free’ work‐places. In other countries, such as Canada, testing is focused more narrowly on identifying employees whose drug use puts the safety of others at risk.

Aims  We review 20 years of published literature on questions relevant to the objectives of work‐place drug testing (WPDT), with a special emphasis on cannabis, the most commonly detected drug.

Results  We conclude (i) that the acute effects of smoking cannabis impair performance for a period of about 4 hours; (ii) long‐term heavy use of cannabis can impair cognitive ability, but it is not clear that heavy cannabis users represent a meaningful job safety risk unless using before work or on the job; (iii) urine tests have poor validity and low sensitivity to detect employees who represent a safety risk; (iv) drug testing is related to reductions in the prevalence of cannabis positive tests among employees, but this might not translate into fewer cannabis users; and (v) urinalysis has not been shown to have a meaningful impact on job injury/accident rates.

Conclusions  Urinalysis testing is not recommended as a diagnostic tool to identify employees who represent a job safety risk from cannabis use. Blood testing for active tetrahydrocannabinol (THC) can be considered by employers who wish to identify employees whose performance may be impaired by their cannabis use.
A brief alcohol intervention for hazardously drinking incarcerated women
Authors: Stein Michael D. , Caviness Celeste M. , Anderson Bradley J. , Hebert Meg , Clarke Jennifer G.
Published: February 2010

Objective  To test the hypothesis that among hazardously drinking incarcerated women who are returning to the community, a brief alcohol intervention will result in less alcohol use at follow‐up relative to standard of care.

Methods  Eligible participants endorsed hazardous alcohol consumption—four or more drinks at a time on at least 3 separate days in the previous 3 months or a score of 8 or above on the Alcohol Use Disorders Identification Test. Participants were randomized to either an assessment‐only condition or to two brief motivationally focused sessions, the first delivered during incarceration, the second 1 month later after community re‐entry. Participants recalled drinking behaviors at 3 and 6 months after the baseline interview using a 90‐day time‐line follow‐back method.

Results  The 245 female participants averaged 34 years of age, and were 71% Caucasian. The mean percentage of alcohol use days in the 3 months prior to incarceration was 51.7% and heavy alcohol use days was 43.9%. Intervention effects on abstinent days were statistically significant at 3 months (odds ratio = 1.96, 95% confidence interval 1.17, 3.30); the percentage of days abstinent was 68% for those randomized to intervention and 57% for controls. At 6 months the effect of the intervention was attenuated and no longer statistically significant.

Conclusions  Among incarcerated women who reported hazardous drinking, a two‐session brief alcohol intervention increased abstinent days at 3 months, but this effect decayed by 6 months. Study participants continued to drink heavily after return to the community. More intensive intervention pre‐release and after re‐entry may benefit hazardously drinking incarcerated women.
Moderators and mediators of two brief interventions for alcohol in the emergency department
Authors: Barnett Nancy P. , Apodaca Timothy R. , Magill Molly , Colby Suzanne M. , Gwaltney Chad , Rohsenow Damaris J. , Monti Peter M.
Published: February 2010

Objective  To evaluate moderators and mediators of brief alcohol interventions conducted in the emergency department.

Methods  Patients (18–24 years; n = 172) in an emergency department received a motivational interview with personalized feedback (MI) or feedback only (FO), with 1‐ and 3‐month booster sessions and 6‐ and 12‐month follow‐ups. Gender, alcohol status/severity group [ALC+ only, Alcohol Use Disorders Identification Test (AUDIT+) only, ALC+/AUDIT+], attribution of alcohol in the medical event, aversiveness of the event, perceived seriousness of the event and baseline readiness to change alcohol use were evaluated as moderators of intervention efficacy. Readiness to change also was evaluated as a mediator of intervention efficacy, as were perceived risks/benefits of alcohol use, self‐efficacy and alcohol treatment seeking.

Results  Alcohol status, attribution and readiness moderated intervention effects such that patients who had not been drinking prior to their medical event, those who had low or medium attribution for alcohol in the event and those who had low or medium readiness to change showed lower alcohol use 12 months after receiving MI compared to FO. In the AUDIT+ only group those who received MI showed lower rates of alcohol‐related injury at follow‐up than those who received FO. Patients who had been drinking prior to their precipitating event did not show different outcomes in the two interventions, regardless of AUDIT status. Gender did not moderate intervention efficacy and no significant mediation was found.

Conclusions  Findings may help practitioners target patients for whom brief interventions will be most effective. More research is needed to understand how brief interventions transmit their effects.
Predictors of hangover during a week of heavy drinking on holiday
Authors: Hesse Morten , Tutenges Sébastien
Published: February 2010

Aims  To investigate predictors of hangover during a week of heavy drinking in young adults.

Design  Observational prospective study.

Methods  A total of 112 young Danish tourists were interviewed on three occasions during their holiday. They completed the Acute Hangover Scale and answered questions about their alcohol consumption and rest duration. The incidence of hangover was analysed as the proportion of heavy drinkers (i.e. those reporting drinking more than 12 standard units of alcohol during the night before) scoring above the 90th percentile of light drinkers (i.e. those who had consumed fewer than seven standard units the night before). We estimated the course and predictors of hangover using random effects regression.

Results  The incidence of hangover was 68% after drinking more than 12 standard units in the whole sample. The severity of hangover increased significantly during a week of heavy drinking and there was a time × number of drinks interaction, indicating that the impact of alcohol consumed on hangover became more pronounced later in the week. Levels of drinking before the holiday did not predict hangover.

Conclusions  Hangovers after heavy drinking during holidays appear to be related both to amount drunk and time into the holiday.
Genetic and environmental influences on cannabis use initiation and problematic use: a meta‐analysis of twin studies
Authors: Verweij Karin J. H. , Zietsch Brendan P. , Lynskey Michael T. , Medland Sarah E. , Neale Michael C. , Martin Nicholas G. , Boomsma Dorret I. , Vink Jacqueline M.
Published: February 2010

Background  Because cannabis use is associated with social, physical and psychological problems, it is important to know what causes some individuals to initiate cannabis use and a subset of those to become problematic users. Previous twin studies found evidence for both genetic and environmental influences on vulnerability, but due to considerable variation in the results it is difficult to draw clear conclusions regarding the relative magnitude of these influences.

Methods  A systematic literature search identified 28 twin studies on cannabis use initiation and 24 studies on problematic cannabis use. The proportion of total variance accounted for by genes (A), shared environment (C) and unshared environment (E) in (i) initiation of cannabis use and (ii) problematic cannabis use was calculated by averaging corresponding A, C and E estimates across studies from independent cohorts and weighting by sample size.

Results  For cannabis use initiation, A, C and E estimates were 48%, 25% and 27% in males and 40%, 39% and 21% in females. For problematic cannabis use A, C and E estimates were 51%, 20% and 29% for males and 59%, 15% and 26% for females. Confidence intervals of these estimates are considerably narrower than those in the source studies.

Conclusions  Our results indicate that vulnerability to both cannabis use initiation and problematic use was influenced significantly by A, C and E. There was a trend for a greater C and lesser A component for cannabis use initiation compared to problematic use for females.
Clinical trial: interferential electric stimulation in functional dyspepsia patients – a prospective randomized study
Authors: KÖKLÜ S. , KÖKLÜ G. , ÖZGÜÇLÜ E. , KAYANI G. U. , AKBAL E. , HASÇELIK Z.
Published: February 2010

Aliment Pharmacol Ther 31, 961–968

Background  There are several studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with gastroparesis and chronic constipation.

Aim  To analyse whether transcutaneous electrical stimulation is an effective procedure in functional dyspepsia patients.

Methods  Functional dyspepsia patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Upper gastrointestinal system symptoms were documented at the beginning, during and after the treatment sessions.

Results  Patients in therapy (23 cases) and placebo (21 cases) groups were homogeneous with respect to demographic data and upper gastrointestinal system symptoms. In the therapy group, all symptoms other than early satiation improved significantly during and after the treatment sessions, whereas in the placebo group, symptoms including heartburn and vomiting did not change significantly. IFC therapy was superior to placebo with respect to epigastric discomfort, pyrosis, bloating, early satiation and postprandial fullness during the treatment sessions. One month after the treatment sessions, vacuum IFC proved to be superior to placebo with regard to early satiation and heartburn.

Conclusions  Vacuum IFC is a non‐invasive and effective therapy for functional dyspepsia. Transcutaneous electrical stimulation may represent a new treatment modality for drug‐refractory functional dyspepsia patients.
Women's traditional fishery and alternative aquatic resource livelihood strategies in the Southern Cameroonian Rainforest
Authors: BRUMMETT R. E. , YOUALEU J. L. N. , TIANI A.‐M. , KENMEGNE M. M.
Published: February 2010

Abstract  To inform the development of alternative livelihoods, the women’s traditional alok fishery in the Campo‐Ma’an National Park and buffer zone of southern Cameroon were studied over 15 months. Participatory rural appraisal was used to characterise livelihood strategies among 45 households. Thirty‐three cultured crops, nine farmed animal species and 65 non‐timber forest products, including 31 bushmeat species are cultivated in, or harvested from, the forest. Transport is a major impediment to commercial trade of all local products. In 16 alok fishing events, average weight of fish harvested was 5.14 kg per 280 m of stream distributed among an average of 23 fishers for a return of 220 g person−1 or 40 g fish h−1 over 5 h of work. Fish and crustacean standing stock was 25 g per linear metre or 167 t when extrapolated to the zone. Implications for rainforest livelihoods in light of the Millennium Development Goals are discussed.