bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor
Authors: Chakraborty Arup R. , Robey Robert W. , Luchenko Victoria L. , Zhan Zhirong , Piekarz Richard L. , Gillet Jean-Pierre , Kossenkov Andrew V. , Wilkerson Julia , Showe Louise C. , Gottesman Michael M. , Collie Nathan L. , Bates Susan E.
Published: March 2013

Key Points

MAPK pathway activation and Bim loss may represent a fundamental mechanism of resistance to histone deacetylase inhibitors. Combination of romidepsin with an MEK inhibitor may lead to greater responses in cancers in which the MAPK pathway is active.
Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium
Authors: Yuan Lei , Janes Lauren , Beeler David , Spokes Katherine C. , Smith Joshua , Li Dan , Jaminet Shou-Ching , Oettgen Peter , Aird William C.
Published: March 2013

Key Points

RNA splicing of the first intron of the von Willebrand factor gene is essential for expression in the endothelium. RNA splicing may play a role in mediating endothelial cell heterogeneity.
Endothelial RAF1/ERK activation regulates arterial morphogenesis
Authors: Deng Yong , Larrivée Bruno , Zhuang Zhen W. , Atri Deepak , Moraes Filipa , Prahst Claudia , Eichmann Anne , Simons Michael
Published: March 2013

Key Points

RAF1 Ser259 phosphorylation is a critical regulator step controlling arterial morphogenesis and arterial-venous patterning. ERK activation controls DLL4/Notch signaling and semaphorin 6A–mediated endothelial cell repulsion.
Chengia laxispicatagen. et sp. nov., a new ephedroid plant from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China: evolutionary, taxonomic, and biogeographic implications
Authors: Yang Yong , Lin Longbiao , Wang Qi
Published: March 2013

Background

The extant Gnetales include three monotypic families, namely, Ephedraceae (Ephedra), Gnetaceae (Gnetum), and Welwitschiaceae (Welwitschia), all of which possess compound female cones that comprise a main axis and 1 to multiple pairs/whorls of bracts subtending a female reproductive unit or having lower pairs/whorls of bracts sterile. However, the evolutionary origin of such a reproductive architecture in Gnetales is controversial in the light of the competing anthophyte versus gnetifer hypotheses of seed plant relationships. Hence, macrofossils demonstrating the structure of compound female cones of the Gnetales should be important to decipher the early evolution of the order.

Results

A new ephedroid plantChengia laxispicatagen. et sp. nov. is described from the Early Cretaceous Yixian Formation of western Liaoning, Northeast China. The fossil represents a part of a leafy shooting system with reproductive organs attached. The main shoot bears internodes and swollen nodes, from which lateral branches arise oppositely. Reproductive organs consist of female spikes terminal to twigs or axillary to linear leaves. Spikes are loosely arranged, having prominent nodes and internodes. Bracts of the spikes are decussately opposite and comprise 4—8 pairs of bracts. Each bract subtends an ellipsoid seed. Seeds are sessile, with a thin outer envelope and a distal micropylar tube.

Conclusions

Chengia laxispicatagen. et sp. nov. provides a missing link between archetypal fertile organs in the crown lineage of the Gnetales and compound female cones of the extant Ephedraceae. Combined with a wealth ofEphedraand ephedroid macrofossils from the Early Cretaceous, we propose a reduction and sterilization hypothesis that the female cone of the extant Ephedraceae may have stemmed from archetypal fertile organs in the crown lineage of the Gnetales. These have undergone sequentially intermediate links similar to female cones of CretaceousSiphonospermum, Chengia, andLiaoxiaby reduction and sterilization of the lower fertile bracts, shortenings of internodes and peduncles as well as loss of reproductive units in all inferior bracts. The basal family Ephedraceae includingEphedraof the extant Gnetales was demonstrated to have considerable diversity by the Early Cretaceous, so an emended familial diagnosis is given here. The Jehol Biota in Northeast China and adjacent areas contains a plethora of well-preserved macrofossils ofEphedraand ephedroids that show different evolutionary stages including primitive and derived characters of Ephedraceae, so Northeast China and adjacent areas may represent either the centre of origination or one of the centres for early diversification of the family.
Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb
Authors: Hori Kazuichiro , Tsujii Masaya , Iino Takahiro , Satonaka Haruhiko , Uemura Takeshi , Akeda Koji , Hasegawa Masahiro , Uchida Atsumasa , Sudo Akihiro
Published: March 2013

Background

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles.

Methods

C57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis.

Results

This model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression.

Conclusions

Edaravone was found to have a protective effect against I/R injury by directly inhibiting lipid peroxidation of the myocyte by free radicals in skeletal muscles and may also reduce the secondary edema and inflammatory infiltration incidence of oxidative stress on tissue.
cAMP-stimulated Cl- secretion is increased by glucocorticoids and inhibited by bumetanide in semicircular canal duct epithelium
Authors: Pondugula Satyanarayana R , Kampalli Suresh B , Wu Tao , De Lisle Robert C , Raveendran Nithya N , Harbidge Donald G , Marcus Daniel C
Published: March 2013

Background

The vestibular system controls the ion composition of its luminal fluid through several epithelial cell transport mechanisms under hormonal regulation. The semicircular canal duct (SCCD) epithelium has been shown to secrete Cl- under β2-adrenergic stimulation. In the current study, we sought to determine the ion transporters involved in Cl- secretion and whether secretion is regulated by PKA and glucocorticoids.

Results

Short circuit current (I

sc
) from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 μM), 8-Br-cAMP (EC50: 180 μM), 8-pCPT-cAMP (100 μM), IBMX (250 μM), and RO-20-1724 (100 μM). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated I

sc
. Partial inhibition of stimulated I

sc
individually by bumetanide (10 & 50 μM), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 μM) were additive and complete. Stimulated I

sc
was also partially inhibited by CFTRinh-172 (5 & 30 μM), flufenamic acid (5 μM) and diphenylamine-2,2′-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR+/− mice showed a stimulation of Isc from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR−/− mice had no responses. Nonetheless, CFTR−/− mice showed no difference from CFTR+/− mice in their ability to balance (rota-rod). Stimulated I

sc
was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 & 0.3 μM), prednisolone (0.3, 1 & 3 μM), hydrocortisone (0.01, 0.1 & 1 μM), and corticosterone (0.1 & 1 μM) and mineralocorticoid aldosterone (1 μM). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.

Conclusions

These results are consistent with a model of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+-K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the regulation of Cl- secretion by protein kinase A and glucocorticoids.
MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1
Authors: Creevey Laura , Ryan Jacqueline , Harvey Harry , Bray Isabella M , Meehan Maria , Khan Adnan R , Stallings Raymond L
Published: March 2013

Background

Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive of neuroblastoma patient survival and has been reported as a tumor suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of the cell cycle and predicted target of miR-497, has emerged as an oncogene in several cancer types and therefore represents an attractive potential target for novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate the potential tumor suppressive role of miR-497 in high-risk neuroblastoma.

Methods

Expression levels of miR-497 and WEE1 in tissues and cells were determined using RT-PCR. The effect of miR-497 and siWEE1 on cell viability was evaluated using MTS assays, apoptosis levels were determined using FACS analysis of Annexin V/PI stained cells, and target protein expression was determined using western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean±S.E.M and differences were tested for significance using 2-tailed Students t-test.

Results

We determined that miR-497 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and that low miR-497 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma. Furthermore, our analysis showed that high WEE1 levels are significantly associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1 in MNA cell lines results in significant levels of apoptosis, supporting an oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR-497 over-expressing cells and WEE1 inhibited cells, resulted in a significant increase in apoptosis in MNA cells, describing a synergistic effect and therefore a potential therapeutic for high-risk neuroblastoma.

Conclusion

Our study’s results are consistent with miR-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. These findings re-enforce the proposal of WEE1 as a therapeutic target in neuroblastoma.
Targeting p53 by small molecules in hematological malignancies
Authors: Saha Manujendra N , Qiu Lugui , Chang Hong
Published: March 2013

p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative activities of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their anti-tumor effects in different types of hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully reached the stage of phase I/II clinical trials in at least one type of hematological cancer. Thus, the pharmacological activation of p53 by these small molecules has a major clinical impact on prognostic use and targeted drug design. In the current review, we present the recent achievements in p53 research using small molecules in hematological malignancies. Anticancer activity of different classes of compounds targeting the p53 signaling pathway and their mechanism of action are discussed. In addition, we discuss how p53 tumor suppressor protein holds promise as a drug target for recent and future novel therapies in these diseases.
Germline deletion of β2 microglobulin or CD1d reduces anti-phospholipid antibody, but increases autoantibodies against non-phospholipid antigens in the NZB/W F1 model of lupus
Authors: Singh Ram Raj , Yang Jun-Qi , Kim Peter J , Halder Ramesh C
Published: March 2013

Introduction

β2-microglobulin (β2m) is required for the surface expression of MHC class I and class I-like proteins such as CD1d, Qa1 and neonatal Fc receptor (FcRn), all of which may impact the development of autoimmunity. Since CD1d is known to bind and present phospholipid antigens to T cells, we asked if the deficiency of β2m or CD1d will impact the development of anti-phospholipid antibodies as compared to other aspects of lupus autoimmunity.

Methods

We introgressed the β2m-null genotype onto the NZB and NZW backgrounds for 12 to 14 generations to generate genetically lupus-susceptible (NZB/NZW)F1 (BWF1) mice that are β2m-deficient (β2m°). Circulating immunoglobulins (Ig), rheumatoid factor (RF), anti-DNA and anti-cardiolipin (anti-CL) antibodies, and renal disease were analyzed in these and CD1d-deficient (CD1d°) BWF1 mice that we had previously generated.

Results

Whereas β2m° BWF1 mice had reduced serum IgG, they had increased mortality, nephritis, serum IgG anti-DNA antibody and RF as compared to heterozygous and wild-type littermates. These effects were recapitulated in CD1d° BWF1 mice, except that they also had increased serum IgG as compared to control littermates. Intriguingly, both β2m° and CD1d° mice had lower serum anti-CL antibody levels than in control littermates. Such CD1d dependence of anti-CL antibody production is not mediated by CD1d/glycolipid-reactive iNKT cells, as these cells reduced the production of RF and anti-DNA antibodies but had no effect on anti-CL antibodies.

Conclusions

We report a novel dichotomous role of β2m and CD1d, whereby these molecules differently regulate autoimmunity against phospholipid versus non-phospholipid autoantigens.
Estimation of optic nerve sheath diameter on an initial brain computed tomography scan can contribute prognostic information in traumatic brain injury patients
Authors: Legrand Aurélien , Jeanjean Patrick , Delanghe Fanny , Peltier Johann , Lecat Benoit , Dupont Hervé
Published: March 2013

Introduction

The aim of this study was to evaluate the prognostic value of optic nerve sheath diameter (ONSD) measured on the initial brain computed tomography (CT) scan for intensive care unit (ICU) mortality in severe traumatic brain injury (TBI) patients.

Methods

A prospective observational study of all severe TBI patients admitted to a neurosurgical ICU (over a 10-month period). Demographic and clinical data and brain CT scan results were recorded. ONSD for each eye was measured on the initial CT scan. The group of ICU survivors was compared to non-survivors. Glasgow Outcome Scale (GOS) was evaluated six months after ICU discharge.

Results

Seventy-seven patients were included (age: 43 ± 18; 81% males; mean Injury Severity Score: 35 ± 15; ICU mortality: 28.5% (n = 22)). Mean ONSD on the initial brain CT scan was 7.8 ± 0.1 mm in non-survivors vs. 6.8 ± 0.1 mm in survivors (P < 0.001). The operative value of ONSD was a good predictor of mortality (area under the curve: 0.805). An ONSD cutoff ≥ 7.3 had a sensitivity of 86.4% and a specificity of 74.6% and was independently associated with mortality in this population (adjusted odds ratio 95% confidence interval: 22.7 (3.2 to 159.6), P = 0.002). There was a relationship between initial ONSD values and six-month GOS (P = 0.03).

Conclusions

ONSD measured on the initial brain CT scan is independently associated with ICU mortality rate (when ≥ 7.3 mm) in severe TBI patients.

See related commentary by Masquère et al.,http://ccforum.com/content/17/3/151
Prediagnosis Soy Food Consumption and Lung Cancer Survival in Women
Authors: Yang Gong , Shu Xiao-Ou , Li Hong-Lan , Chow Wong-Ho , Wen Wanqing , Xiang Yong-Bing , Zhang Xianglan , Cai Hui , Ji Bu-Tian , Gao Yu-Tang , Zheng Wei
Published: March 2013

Purpose

We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer.

Patients and Methods

This analysis included 444 women with incident lung cancer identified from the Shanghai Women's Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival.

Results

Of the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake.

Conclusion

This study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.
Elevated Risk of Prostate Cancer Among Men With Lynch Syndrome
Authors: Raymond Victoria M. , Mukherjee Bhramar , Wang Fei , Huang Shu-Chen , Stoffel Elena M. , Kastrinos Fay , Syngal Sapna , Cooney Kathleen A. , Gruber Stephen B.
Published: March 2013

Purpose

Prostate cancer has been described as a component tumor of Lynch syndrome (LS), with tumors obtained from mutation carriers demonstrating the DNA mismatch repair deficiency phenotype. Previous studies quantifying prostate cancer risk in LS have provided conflicting results.

Methods

We examined cancer histories of probands and their first- through fourth-degree relatives for 198 independent mutation-positive LS families enrolled in two US familial cancer registries. Modified segregation analysis was used to calculate age-specific cumulative risk or penetrance estimates, with accompanying Wald-type CIs. Cumulative lifetime risks and hazard ratio (HR) estimates for prostate cancer were calculated and compared with those of the general population.

Results

Ninety-seven cases of prostate cancer were observed in 4,127 men. Median age at prostate cancer diagnosis was 65 years (range, 38 to 89 years), with 11.53% of affected individuals diagnosed before age 50 years. The cumulative risk of prostate cancer at ages 60 and 80 years was 6.30% (95% CI, 2.47 to 9.96) and 30.0% (95% CI, 16.54 to 41.30), as compared with the population risk of 2.59% and 17.84%, respectively. The overall prostate cancer HR among carriers was 1.99 (95% CI, 1.31 to 3.03).

Conclusion

The cumulative lifetime risk of prostate cancer in individuals with LS is two-fold higher than in the general population and is slightly higher in carriers diagnosed before age 60 years (HR, 2.48; 95% CI, 1.34 to 4.59). These estimates are clinically valuable to quantify risk for both patients and providers.
Effects of ocean acidification on early life-history stages of the intertidal porcelain crab Petrolisthes cinctipes
Authors: Ceballos-Osuna Lina , Carter Hayley A. , Miller Nathan A. , Stillman Jonathon H.
Published: March 2013

Intertidal zone organisms naturally experience daily fluctuations in pH, presently reaching values beyond what is predicted for open ocean surface waters from ocean acidification (OA) by the year 2100, and thus present an opportunity to study the pH sensitivity of organisms that are presumably adapted to an acidified environment. The intertidal zone porcelain crab, Petrolisthes cinctipes, was used to study physiological responses to low pH in embryonic, larval and newly recruited juvenile life-history stages. In these crabs, embryonic development occurs in the pH-variable intertidal zone (pH 6.9–9.5), larvae mature in the more stable pelagic environment (pH 7.9–8.2), and juvenile crabs settle back into the pH-variable intertidal zone. We examined survival, cardiac performance, energetics and morphology in embryonic, larval and juvenile crabs exposed to two pH conditions (pH 7.9 and 7.6). Embryos and larvae were split by brood between the pH treatments for 9 days to examine brood-specific responses to low pH. Hatching success did not differ between pH conditions, but ranged from 30% to 95% among broods. Larval survival was not affected by acidification, but juvenile survival was reduced by ~30% after longer (40 days) exposure to low pH. Embryonic and larval heart rates were 37% and 20% lower at low pH, and there was a brood-specific response in embryos. Embryos did not increase in volume under acidified conditions, compared with a 15% increase in ambient conditions. We conclude that sustained exposure to low pH could be detrimental to P. cinctipes embryos and larvae despite the fact that embryos are regularly exposed to naturally fluctuating hypercapnic water in the intertidal zone. Importantly, our results indicate that early life-history stage responses to OA may be brood specific through as yet undetermined mechanisms.
Hypoxia-induced compression in the tracheal system of the tobacco hornworm caterpillar,Manduca sextaL.
Authors: Greenlee Kendra J. , Socha John J. , Eubanks Haleigh B. , Pedersen Paul , Lee Wah-Keat , Kirkton Scott D.
Published: March 2013

Abdominal pumping in caterpillars has only been documented during molting. Using synchrotron x-ray imaging in conjunction with high-speed flow-through respirometry, we show that Manduca sexta L. caterpillars cyclically contract their bodies in response to hypoxia, resulting in significant compressions of the tracheal system. Compression of tracheae induced by abdominal pumping drives external gas exchange, as evidenced by the high correlation between CO2 emission peaks and body movements. During abdominal pumping, both the frequency and percent diameter change of tracheae increased with body mass. However, abdominal pumping and tracheal compression were only observed in larger, older caterpillars (>0.2 g body mass), suggesting that this hypoxic response increases during ontogeny. The diameters of major tracheae in the thorax increased isometrically with body mass. However, tracheae in the head did not scale with mass, suggesting that there is a large safety margin for oxygen delivery in the head in the youngest animals. Together, these results highlight the need for more studies of tracheal system scaling and suggest that patterns of tracheal investment vary regionally in the body.
Pairs of pigeons act as behavioural units during route learning and co-navigational leadership conflicts
Authors: Flack Andrea , Freeman Robin , Guilford Tim , Biro Dora
Published: March 2013

In many species, group members obtain benefits from moving collectively, such as enhanced foraging efficiency or increased predator detection. In situations where the group's decision involves integrating individual preferences, group cohesion can lead to more accurate outcomes than solitary decisions. In homing pigeons, a classic model in avian orientation studies, individuals learn habitual routes home, but whether and how co-navigating birds acquire and share route-based information is unknown. Using miniature GPS loggers, we examined these questions by first training pairs (the smallest possible flocks) of pigeons together, and then releasing them with other pairs that had received separate pair-training. Our results show that, much like solitary individuals, pairs of birds are able to establish idiosyncratic routes that they recapitulate together faithfully. Also, when homing with other pairs they exhibit a transition from a compromise- to a leadership-like mechanism of conflict resolution as a function of the degree of disagreement (distance separating the two preferred routes) between the two pairs, although pairs tolerate a greater range of disagreements prior to the transition than do single birds. We conclude that through shared experiences during past decision-making, pairs of individuals can become units so closely coordinated that their behaviour resembles that of single birds. This has implications for the behaviour of larger groups, within which certain individuals have closer social affiliations or share a history of previous associations.
Immune function is related to adult carotenoid and bile pigment levels, but not dietary carotenoid access during development, in female mallard ducks
Authors: Butler Michael W. , McGraw Kevin J.
Published: March 2013

Immune function can be modulated by multiple physiological factors, including nutrition and reproductive state. Because these factors can vary throughout an individual’s lifetime due to environmental conditions (e.g. nutrition) or life-history stage (e.g. adult reproduction), we must carefully examine the degree to which developmental versus adult conditions shape performance of the immune system. We investigated how variation in dietary access to carotenoid pigments – a class of molecules with immunostimulatory properties that females deposit into egg yolks – during three different developmental time points affected adult immunological and reproductive traits in female mallard ducks (Anas platyrhynchos). In males and females of other avian species, carotenoid access during development affects carotenoid assimilation ability, adult sexual ornamentation, and immune function, while carotenoid access at adulthood can increase immune response and reproductive investment (e.g. egg-laying capacity, biliverdin deposition in eggshells). We failed to find effects of developmental carotenoid supplementation on adult immune function (phytohemagglutinin-induced cutaneous immune response, antibody production in response to the novel antigen keyhole limpet hemocyanin [KLH], or oxidative burst, assessed by change in circulating nitric oxide levels), carotenoid-pigmented beak coloration, ovarian development, circulating carotenoid levels, or concentration of bile pigments in the gall bladder. However, we did uncover positive relationships between circulating carotenoid levels at adulthood and KLH-specific antibody production, and a negative relationship between biliverdin concentration in bile and KLH-specific antibody production. These results are consistent with the view that adult physiological parameters better predict current immune function than do developmental conditions and highlight a possible, previously unstudied relationship between biliverdin and immune system performance.
The response of the scleractinian coralTurbinaria reniformisto thermal stress depends on the nitrogen status of the coral holobiont
Authors: Béraud Eric , Gevaert François , Rottier Cécile , Ferrier-Pagès Christine
Published: March 2013

The physiological response of the scleractinian coral Turbinaria reniformis to ammonium enrichment (3 µM) was examined at 26°C as well as during a 7d increase in temperature to 31°C (thermal stress). At 26°C, ammonium supplementation slightly changed the coral physiology. It induced a decrease in symbiont density, compensated by an increase in chlorophyll content per symbiont cell. Organic carbon release was reduced, likely due to a better utilization of the photosynthesized carbon (i.e. incorporation into proteins, kept into the coral tissue). The δ15N signature of the ammonium-enriched symbionts and host tissue was also significantly decreased by 4 and 2‰ respectively, compared to the non enriched conditions, suggesting an important uptake of inorganic nitrogen by the holobiont. Under thermal stress, coral colonies that were not nitrogen enriched experienced a drastic decrease in photosynthetic and photoprotective pigments (chlorophyll a, β carotene, diadinoxanthin, diatoxanthin, peridinin), followed by a similar decrease in the rates of photosynthesis and calcification. Organic carbon release was not affected by this thermal stress. Conversely, nitrogen-enriched corals showed an increase in their pigment concentrations, which maintained rates of photosynthesis and calcification to ca. 60% and 100% of those obtained under control conditions respectively. These corals however lost more organic carbon into the environment. Overall, these results indicate that inorganic nitrogen availability can be important to determine the resilience of some scleractinian coral species to thermal stress, and can have an equivalent function as heterotrophic feeding concerning the maintenance of coral metabolism under stress conditions.
Texting Bans and Fatal Accidents on Roadways: Do They Work? Or Do Drivers Just React to Announcements of Bans?
Authors: Abouk Rahi , Adams Scott
Published: March 2013

Since 2007, many states passed laws prohibiting text messaging while driving. Using vehicular fatality data from across the United States and standard difference-in-differences techniques, bans appear moderately successful at reducing single-vehicle, single-occupant accidents if bans are universally applied and enforced as a primary offense. Bans enforced as secondary offenses, however, have at best no effect on accidents. Any reduction in accidents following texting bans is short-lived, however, with accidents returning to near former levels within a few months. This is suggestive of drivers reacting to the announcement of the legislation only to return to old habits shortly afterward. (JEL D12, K42, R41)
Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction
Authors: Lovren Fina , Verma Subodh
Published: March 2013

BACKGROUND

Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation.

CONTENT

This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells.

MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.
Laterality and Symmetry in Rat Olfactory Behavior and in Physiology of Olfactory Input
Authors: Parthasarathy Kalyanasundaram , Bhalla Upinder S.
Published: March 2013

Many species use bilateral sampling for odor-guided navigation. Bilateral localization strategies typically involve balanced and lateralized sensory input and early neuronal processing. For example, if gradient direction is estimated by differential sampling, then any asymmetry could bias the perceived direction. Subsequent neuronal processing can compensate for this asymmetry but requires the presence of mechanisms to track changes in asymmetry. A high degree of laterality is also important for differential sampling because spillover of signals will dilute the perceived odor gradient. In apparent contradiction to this model, both symmetry and laterality of nasal air flow have been reported to be incomplete in rats. Here, we measured symmetry and laterality in early olfactory processing in the rat. We first established behavioral readouts of precisely controlled bilateral odorant stimuli. We found that rats could rapidly and accurately report the direction of a wide range of odor gradients, presented in random sequence. We then showed that nasal air flow was symmetric over an entire day in awake rats. Furthermore, odor sampling from the two nostrils in the behavioral task was highly lateralized. This lateralization extended to the receptor epithelium responses as measured by electro-olfactograms. We finally observed strong lateralization of intrinsic signal responses from the glomerular layer of the olfactory bulb. We confirmed that a differential comparison of glomerular responses was sufficient to localize odorants. Together, these results suggest that the rat olfactory system is symmetric, with highly lateralized odor flow and neuronal responses. In combination, these attributes support odor localization by differential comparison.
Alzheimer's Disease Neurodegenerative Biomarkers Are Associated with Decreased Cognitive Function but Not β-Amyloid in Cognitively Normal Older Individuals
Authors: Wirth Miranka , Madison Cindee M. , Rabinovici Gil D. , Oh Hwamee , Landau Susan M. , Jagust William J.
Published: March 2013

β-Amyloid (Aβ) plaque deposition and neurodegeneration within temporoparietal and hippocampal regions may indicate increased risk of Alzheimer's disease (AD). This study examined relationships between AD biomarkers of Aβ and neurodegeneration as well as cognitive performance in cognitively normal older individuals. Aβ burden was quantified in 72 normal older human subjects from the Berkeley Aging Cohort (BAC) using [11C] Pittsburgh compound B (PIB) positron emission tomography. In the same individuals, we measured hippocampal volume, as well as glucose metabolism and cortical thickness, which were extracted from a template of cortical AD-affected regions. The three functional and structural biomarkers were merged into a highly AD-sensitive multimodality biomarker reflecting neural integrity. In the normal older individuals, there was no association between elevated PIB uptake and either the single-modality or the multimodality neurodegenerative biomarkers. Lower neural integrity within the AD-affected regions and a control area (the visual cortex) was related to lower scores on memory and executive function tests; the same association was not found with PIB retention. The relationship between cognition and the multimodality AD biomarker was stronger in individuals with the highest PIB uptake. The findings indicate that neurodegeneration occurs within AD regions regardless of Aβ deposition and accounts for worse cognition in cognitively normal older people. The impact of neural integrity on cognitive functions is, however, enhanced in the presence of high Aβ burden for brain regions that are most affected in AD.
Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in the endometrium of the post-partum dairy cow
Authors: Swangchan-Uthai Theerawat , Chen Qiusheng , Kirton Sally E , Fenwick Mark A , Cheng Zhangrui , Patton Joe , Fouladi-Nashta Ali A , Wathes D Claire
Published: March 2013

Uterine inflammation occurs after calving in association with extensive endometrial remodelling and bacterial contamination. If the inflammation persists, it leads to reduced fertility. Chronic endometritis is highly prevalent in high-yielding cows that experience negative energy balance (NEB) in early lactation. This study investigated the effect of NEB on the antimicrobial peptides S100A8 and S100A9 in involuting uteri collected 2 weekspost partum. Holstein-Friesian cows (six per treatment) were randomly allocated to two interventions designed to produce mild or severe NEB (MNEB and SNEB) status. Endometrial samples were examined histologically, and the presence of neutrophils, macrophages, lymphocytes and natural killer cells was confirmed using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of uterine inflammation. Samples of previously gravid uterine horn were used to localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were present in bovine endometrium with strong staining in epithelial and stromal cells and in infiltrated leucocytes. Immunostaining was significantly higher in SNEB cows along with increased numbers of segmented neutrophils. These results suggest that the metabolic changes of apost-partumcow suffering from NEB delay uterine involution and promote a chronic state of inflammation. We show that upregulation of S100A8 and S100A9 is clearly a key component of the early endometrial response to uterine infection. Further studies are warranted to link the extent of this response after calving to the likelihood of cows developing endometritis and to their subsequent fertility.
The Legal Authority of Mature Minors to Consent to General Medical Treatment
Authors: Coleman Doriane Lambelet , Rosoff Philip M.
Published: March 2013

The nature and scope of mature adolescents’ legal authority to consent to general medical treatment without parental involvement is often misrepresented by commentators. This state of affairs is further complicated by the law itself, which has developed a broad “mature minor exception” to the general requirement of parental consent in abortion cases and which has additionally carved out numerous specific status-based and condition-based exceptions to that requirement. In these circumstances, it is not always a simple matter for physicians and other medical professionals who treat adolescents to ascertain the applicable law. In this article, we discuss the underlying differences between medical ethics and law, which have caused some of the confusion in this area, and we set out the most current legal rules governing adolescent decision-making authority in general medical settings. A comprehensive analysis of both statutory and common law demonstrates that in such settings, parental consent continues to be required by most jurisdictions, even when the minor can be considered cognitively “mature.”
Electronic Prescribing in Pediatrics: Toward Safer and More Effective Medication Management
Authors: Johnson Kevin B. , Lehmann Christoph U. ,   the COUNCIL ON CLINICAL INFORMATION TECHNOLOGY, Del Beccaro Mark A. , Alexander Gregg , Drummond Willa H. , Francis Anne B. , Handler Eric G. , Johnson Timothy D. , Kim George R. , Leu Michael , Tham Eric , Weinberg Stuart T. , Zuckerman Alan E.
Published: March 2013

This Technical Report was retired.

This technical report discusses recent advances in electronic prescribing (e-prescribing) systems, including the evidence base supporting their limitations and potential benefits. Specifically, this report acknowledges that there are limited but positive pediatric data supporting the role of e-prescribing in mitigating medication errors, improving communication with dispensing pharmacists, and improving medication adherence. On the basis of these data and on the basis of federal statutes that provide incentives for the use of e-prescribing systems, the American Academy of Pediatrics recommends the adoption of e-prescribing systems with pediatric functionality. This report supports the accompanying policy statement from the American Academy of Pediatrics recommending the adoption of e-prescribing by pediatric health care providers.
Constructing Religion in Unexpected Places
Authors: Beckford James A.
Published: March 2013

This paper aims to respond positively to the criticism sometimes expressed in forms of realism in Religious Studies—that social constructionist perspectives throw relatively little light on religion. These perspectives frame social and cultural phenomena as the result of the claims making, negotiation and contestation that underlie all social processes, structures and interactions—both formal and informal. After considering the philosophical objections to constructionism, the paper will present a range of empirical evidence showing that investigation of the social processes involved in negotiating and challenging the meaning of religion should be central to sociological analysis of religious phenomena. Special attention will be given to the incidence of religion in unexpected places.
The Enchanting Dream of “Spiritual Capital”
Authors: Montemaggi Francesca E.S.
Published: March 2013

Spiritual capital has gained prominence in the past decade as the social capital of faith based organizations (FBOs). In a previous issue of Implicit Religion, Chris Baker and Jonathan Miles-Watson, of the William Temple Foundation (WTF), presented an exhaustive review of the relevant literature on social capital and spiritual capital, and proposed a notion of spiritual capital that includes religious culture motivating social action (Baker and Miles-Watson 2010). This interpretation has transformed the original notion of spiritual capital into a normative concept that seeks to celebrate spirituality rather than understand it. This paper presents a critical reflection on the implications of such an approach and argues for the differentiation and analysis of religious phenomena.
Response to Montemaggi’s Dream of Spiritual Capital
Authors: Baker Chris , Miles Watson J.
Published: March 2013

We are grateful for Francesca Montemaggi’s extended critique of our literature review. We are also grateful to the Editor of Implicit Religion for giving us the opportunity to respond to her critique. Our response will have two emphases. One is a review of Montemaggi’s interpretation of our original article. The other takes a broader and more thematic perspective.
There and Back Again
Authors: Geraci Robert M.
Published: March 2013

Popular science and science-fiction depictions of immortality through uploading minds are “authentic fakes”: secular practices that do authentic religious work for transhumanist communities. Although in the 1980s science fiction departed from this practice and rejected transhuman promises of “mind-uploading” and immortality through technology, in the twenty-first century science fiction has rejoined pop science as a genre advocating transhumanist salvation. Accelerando by Charles Stross and Down and Out in the Magic Kingdom by Cory Doctorow illustrate the powerful way in which science fiction once again normalizes radical visions of our future, and thereby encourages belief in key transhuman concepts such as a scarcity-free economy, the Singularity, and an immortality obtained by uploading human consciousnesses into machines.
Don Cupitt’s Ethical Jesus and a Secular Transcendence
Authors: Hey John
Published: March 2013

In his latest book, Jesus and Philosophy, Don Cupitt looks for a “reform and renewal of Christianity.” He envisages this transformation by means of a recognition of the emotive foundation of ethics, a recognition which ousts a traditional moral realism. Examination of the teaching of Jesus reveals that he also evoked the emotive humanitarian nature of ethics over against a rigid divine law. Ethics, like Christianity, should be understood horizontally, rather than vertically. On this basis Jesus looked for a new world-order, based on an extravagant love.

There is much to be said for Cupitt’s demythologising of a metaphysical religion, particularly in the light of the recent scientific appreciation and development of Darwin’s work. There is merit also in Cupitt’s stress on the prophetic message, present in the teaching of Jesus, that knowledge of God is synonymous with love of the neighbour. However, his central thesis is damaged by a confusing epistemology, which fails to explain how an ethic of extravagant love can be derived merely from feeling, and by an uprooting of Jesus from his place in first-century Judaism and locating him in a post Enlightenment sceptical modernity.

Cupitt’s secular transcendence offers us the vision of a “secular Jesus” promoting a “quite new moral world.” However this important idea is undermined by a lack of clarity concerning the ethical transcendence, and an autonomous ethic which is compromised by reliance upon an eccentric interpretation of Jesus.
Review: The Death of Christian Britain: Understanding Secularisation, edited by C. Brown, Routledge, 2009 (2nd ed.) and Pulling out of the Nosedive: What the 2005 English Church Census Reveals, London Christian Research, 2006.
Authors: Collins Mike
Published: March 2013

The Death of Christian Britain: Understanding Secularisation, edited by Callum Brown, Routledge, 2009 (2nd ed.). 304pp., Pb. $35.95/£19.99, ISBN-13: 9780415471343; Hb. $115.00/£70.00, ISBN-13: 9780415471336.

Pulling out of the Nosedive: What the 2005 English Church Census Reveals, London Christian Research, 2006. Pb. 320pp., £8.99. ISBN-13: 9781853211683.
Assaying the Pope
Authors: Arya Rina
Published: March 2013

The artist Francis Bacon vehemently denied that he was religious and yet in his art he employed numerous examples of Christian symbols, such as the Crucifixion and the Pope. The use of religious symbols by artists who profess either atheism or a mere lack of a religious interest is uncontroversial. However, Bacon did not use isolated examples of religious symbols: he employed them throughout his career. His use was ongoing and frequent and this raises questions about his motivation. I am not disputing his atheism but believe that his attitude towards religion was reactive and complex. Religion, with the existential issues it raises, needs to be addressed and this is what his art does. Bacon worked with and through religious ideas and symbols to express his unbelief. One indisputable and paradoxical notion is that, in order to articulate his unbelief, he was dependent on the very tradition that he denounced. Bacon spent the early part of his career, particularly the 1930s and 1940s, articulating his interpretations of the Crucifixion, before moving on to the symbol of the Pope, a subject that he concentrated on in the 1950s. For reasons of space I have limited my study to the symbol of the Pope. In his pursuit of the Pope, Bacon traps and strips him down to reveal “the scream of the abyss.”