bluuebunny/crossref_metadata_2025 huggingface dataset:
p27Kip1 inhibits systemic autoimmunity through the control of Treg cell activity and differentiation
Authors: Iglesias Marcos , Postigo Jorge , Santiuste Inés , González Jovanna , Buelta Luis , Tamayo Esther , Merino Jesús , Merino Ramón
Published: November 2012

Objective

Despite the importance of Treg cells in the maintenance of immunologic tolerance, the mechanisms that control their generation and activity are unknown. Since the cell cycle inhibitor p27Kip1 (p27) was involved in T cell anergy, we undertook this study to explore its role in both Treg cell processes.

Methods

The development of type II collagen–induced arthritis (CIA) and lupus‐like abnormalities was compared between transgenic mice overexpressing human Bcl‐2 in T cells (BCL2‐TgT mice) and nontransgenic mice that were deficient or not deficient in p27. The contribution of Treg cells to disease evolution was also explored. Finally, the in vitro activity of Treg cells and their differentiation from naive CD4+ cells was compared between these strains of mice.

Results

BCL2‐TgT mice were protected against CIA by a Treg cell–dependent mechanism. In association with this protection, the overexpression of Bcl‐2 in T cells enhanced the differentiation and activity of Treg cells. Both Bcl‐2 effects were independent of its antiapoptotic activity but dependent on its capacity to induce the expression of p27 that augmented the strength of transforming growth factor β (TGFβ) signaling in T cells. Accordingly, down‐modulation of p27 expression in BCL2‐TgT mice promoted CIA. In addition, p27 deficiency in aged C57BL/6 mice reduced the number and activity of Treg cells and induced the development of mild lupus‐like abnormalities.

Conclusion

Our results point to p27 as a critical regulator of Treg cell differentiation and function through the positive modulation of TGFβ signaling strength in T cells.
β‐catenin regulates parathyroid hormone/parathyroid hormone–related protein receptor signals and chondrocyte hypertrophy through binding to the intracellular C‐terminal region of the receptor
Authors: Yano Fumiko , Saito Taku , Ogata Naoshi , Yamazawa Toshiko , Iino Masamitsu , Chung Ung‐il , Kawaguchi Hiroshi
Published: November 2012

Objective

To investigate the underlying mechanisms of action and functional relevance of β‐catenin in chondrocytes, by examining the role of β‐catenin as a novel protein that interacts with the intracellular C‐terminal portion of the parathyroid hormone (PTH)/PTH‐related protein (PTHrP) receptor type 1 (PTHR‐1).

Methods

The β‐catenin–PTHR‐1 binding region was determined with deletion and mutagenesis analyses of the PTHR1 C‐terminus, using a mammalian two‐hybrid assay. Physical interactions between these 2 molecules were examined with an in situ proximity ligation assay and immunostaining. To assess the effects of gain‐ and loss‐of‐function of β‐catenin, transfection experiments were performed to induce overexpression of the constitutively active form of β‐catenin (ca‐β‐catenin) and to block β‐catenin activity with small interfering RNA, in cells cotransfected with either wild‐type PTHR1 or mutant forms (lacking binding to β‐catenin). Activation of the G protein α subunits Gαs and Gαq in the cells was determined by measurement of the intracellular cAMP accumulation and intracellular Ca2+ concentration, while activation of canonical Wnt pathways was assessed using a TOPflash reporter assay.

Results

In differentiated chondrocytes, β‐catenin physically interacted and colocalized with the cell membrane–specific region of PTHR‐1 (584–589). Binding of β‐catenin to PTHR‐1 caused suppression of the Gαs/cAMP pathway and enhancement of the Gαq/Ca2+ pathway, without affecting the canonical Wnt pathway. Inhibition of Col10a1 messenger RNA (mRNA) expression by PTH was restored by overexpression of ca‐β‐catenin, even after blockade of the canonical Wnt pathway, and Col10a1 mRNA expression was further decreased by knockout of β‐catenin (via the Cre recombinase) in chondrocytes from β‐catenin–floxed mice. Mutagenesis analyses to block the binding of β‐catenin to PTHR1 caused an inhibition of chondrocyte hypertrophy markers.

Conclusion

β‐catenin binds to the PTHR‐1 C‐tail and switches the downstream signaling pathway from Gαs/cAMP to Gαq/Ca2+, which is a possible mechanism by which chondrocyte hypertrophy may be regulated through the PTH/PTHrP signal independent of the canonical Wnt pathway.
Association between thyroxine levels at birth and choanal atresia or stenosis among infants in Texas, 2004–2007
Authors: Lee Laura J. , Canfield Mark A. , Hashmi S. Shahrukh , Moffitt Karen B. , Marengo Lisa , Agopian A. J. , Belmont John W. , Freedenberg Debra , Tanksley Susan M. , Mitchell Laura E. , Lupo Philip J.
Published: November 2012

BACKGROUND: The causes of choanal atresia or stenosis (CA) are largely unknown. Infant thyroxine (T4) levels collected during newborn screening may be proxy measures for a risk factor present during the critical period of development. Therefore, we conducted a case‐control study to examine the association between newborn T4 levels and CA. METHODS: Data for cases with CA and controls were obtained from the Texas Birth Defects Registry for the period of 2004 to 2007. Information on infant T4 levels at birth was obtained from the Texas Newborn Screening Program. Controls (n = 3570) were drawn from unaffected births in Texas for the same period and frequency matched to cases (n = 69) on year of birth, then linked to the newborn screening database. Logistic regression was used to evaluate the association between continuous and categorical infant T4 levels and nonsyndromic CA. RESULTS: After adjustment for gestational age and year of birth, infant T4 levels were inversely associated with CA (adjusted odds ratio [AOR], 0.85; 95% confidence interval [CI], 0.80–0.90). We observed a linear trend (p < 0.001) across quartiles of T4; compared to infants with low levels, AORs for CA were 0.50 (95% CI, 0.28–0.91), 0.39 (95% CI, 0.20–0.75), and 0.15 (95% CI, 0.06–0.40) for infants with medium‐to‐low, medium, and high levels, respectively. CONCLUSIONS: Our findings suggest a role of low thyroid hormone levels in the development of CA, or that low newborn T4 levels are potential proxy measures of a risk factor present during the critical period. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.
Moderately high intake of folic acid has a negative impact on mouse embryonic development
Authors: Mikael Leonie G. , Deng Liyuan , Paul Ligi , Selhub Jacob , Rozen Rima
Published: November 2012

BACKGROUND

The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20‐fold higher FA than the recommended intake for rodents had adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10‐fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR).

METHODS

Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA‐supplemented diet (FASD; 10‐fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness.

RESULTS

Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet.

CONCLUSIONS

Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.
Stability of Immobilized Candida sp. 99–125 Lipase for Biodiesel Production
Authors: Lu J. , Deng L. , Nie K. , Wang F. , Tan T.
Published: November 2012

The stability of the immobilized lipase from Candida sp. 99–125 during biodiesel production was investigated. The lipase was separately incubated in the presence of various reaction components such as soybean oil, oleic acid methyl ester, n‐hexane, water, methanol, and glycerol, or the lipase was stored at 60, 80, 100 and 120 °C. Thereafter the residual lipase activity was determined by methanolysis reaction. The results showed that the lipase was rather stable in the reaction media, except for methanol and glycerol. The stability study performed in a reciprocal shaker indicated that enzyme desorption from the immobilized lipase mainly contributed to the lipase inactivation in the water system. So the methanol and glycerol contents should be controlled more precisely to avoid lipase inactivation, and the immobilization method should be improved with regard to lipase desorption.
Direct Synthesis of Dimethyl Carbonate by Carboxylation of Methanol on Ceria‐Based Mixed Oxides
Authors: Hofmann H. J. , Brandner A. , Claus P.
Published: November 2012

The synthesis of ceria‐based mixed oxides via an oxalate‐gel method and the testing of their catalytic activity in the carboxylation of methanol with CO2 are described. The evaluation of their activity is performed in liquid phase. With ceria, the influence of pressure, reaction temperature, and composition of the reactants in the gas and liquid phase are investigated. Moreover, the thermodynamics of the reaction and the structural properties of the catalysts, characterized by X‐ray diffraction, FTIR‐ and UV/VIS spectroscopy, and physisorption, are discussed.
High Cell Density Escherichia coli Cultivation in Different Single‐Use Bioreactor Systems
Authors: Dreher Thomas , Husemann Ute , Zahnow Christian , de Wilde Davy , Adams Thorsten , Greller Gerhard
Published: November 2012

During the last decades single‐use bioreactors have become widely accepted in the biopharmaceutical industry. Single‐use technologies bring many advantages over conventional solutions, such as a reduced investment and operational cost as well as an optimized time‐to‐market. So far, this type of bioreactor is mainly used for cell culture applications. Results for microbial fermentations are rarely found, commonly due to limited oxygen transfer rates. The aim of this study was to establish a high cell density fermentation process for a recombinant Escherichia coli considering a rocking motion type and an adapted stirred 50‐L single‐use bioreactor. By using the design space approach an OTRmax/OURmax model was established. The feeding strategies were optimized and verified based on a model for both single‐use systems to achieve high cell densities. In both single‐use bioreactors a recombinant protein was successfully expressed.
Renal Denervation: A Potential New Treatment for Severe Hypertension
Authors: Huan Yonghong , Cohen Debbie L.
Published: November 2012

Hypertension is a leading cause of cardiovascular morbidity and mortality. Drug‐resistant hypertension remains common despite the availability of several classes of effective antihypertensive agents. Sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, but radical sympathectomy was abandoned several decades ago due to its significant side effects. The newly developed, minimally invasive, catheter‐based renal sympathetic denervation procedure has been shown in recent trials to produce impressive blood pressure reductions and a favorable safety profile in drug‐resistant hypertension. Although the long‐term efficacy and safety of renal denervation remains to be determined, emerging data suggest that the benefits of renal denervation may extend beyond blood pressure control.

Dr. Cohen is the principal investigator for Symplicity 3 study funded by Medtronic; Dr. Huan is the subinvestigator for Symplicity 3 study funded by Medtronic.
Removal of Fluoride from Aqueous Solutions by Adsorption Using a Siliceous Mineral of a Kenyan Origin
Authors: Wambu Enos W. , Onindo Charles O. , Ambusso Willis , Muthakia Gerald K.
Published: November 2012

The problem of high fluoride in water sources in Africa and the rest of the developing world has exacerbated in the latest past due to increasing shortage of water. More people are being exposed to high water fluoride resulting in elevated levels of fluorosis in the societies. Fluoride (F) adsorption from solutions using a siliceous mineral from Kenya (M1) was studied on batch basis and results verified on high fluoride water using fixed‐bed column experiments. About 100% batch F adsorption was achieved at 200 mg/L F concentration, 0.5 g/mL adsorbent dosage, 303–333 K, and pH 3.4 ± 0.2. Based on Giles classifications, F adsorption isotherm was found to be an H3 type isotherm. The equilibrium data was correlated to Freundlich and Langmuir models and the maximum Langmuir adsorption capacity was found to be 12.4 mg/g. Column experiments were conducted for different fluoride concentrations, bed depths, and flow rates. The F breakthrough curves were analyzed using the Thomas model and efficient F adsorption was found to occur at low flow rates and low influent concentrations. The Thomas F adsorption capacity (11.7 mg/g) was consistent with the Langmuir isotherm capacity showing that M1 could be applied as an inexpensive medium for water defluoridation.
Variation Characteristics of Mercury in Speciation during Road Runoff for Different Rainfall Patterns
Authors: Zuo XiaoJun , Fu DaFang , Li He
Published: November 2012

Mercury (Hg) concentration was investigated during 2010 based on road runoff from Nanjing Ring Highway, China. The emphasis was placed on impact of rainfall characteristics on Hg speciation concentration, and on variation characteristics of Hg speciation during road runoff for different rainfall patterns. Results indicated that average concentration of total mercury (THg) was in the range from 0.472 to 1.304 µg/L, and steady Hg (SHg) was the dominant form of Hg. Rainfall and average rainfall intensity were two important factors of determining Hg speciation concentrations during road runoff for different rainfall patterns. Rainfall pattern had significantly influence on variation of available Hg and dissolved Hg during road runoff, and on their proportions in THg. However, the proportion of SHg in THg was not obviously affected by rainfall pattern. On the other hand, toxic degree of Hg to soil environment is various for different rainfall patterns, based on Hg speciation variation.
Adsorption Kinetics of Chloroform from Aqueous Solutions onto Activated Lignite
Authors: Tongur Süheyla , Aydin Mehmet Emin
Published: November 2012

The lignite coal researched by this study was subjected to a two‐stage activation process performed in the scope of obtaining active carbon from domestic resources. “Activation” and “carbonization” stages were used in the experiments. The modified lignite was produced by impregnating lignite with KOH and washing the activation product with 15% HCl solution after thermal treatment. Increasing KOH dosage also increased the removal efficiency. The variables investigated in adsorption experiments were contact time, initial concentration, pH, and sorbent dosage. Adsorption kinetics was fitted by using the pseudo‐first‐order equation, pseudo‐second‐order equation, and intra‐particle diffusion. Isotherm modeling was carried out using Langmuir, Freundlich, and Dubinin–Radushkevich equations. Selected target compound in this work is common environmental pollutant in waters. A commonly known effect of chloroform is its carcinogenic effect. Therefore, removal of these compounds from water is considerably important. Chloroform removal of 97% for was achieved by the use of Konya region activated lignite.
Performances of Reverse Osmosis Membranes for Treatment of Olive Mill Wastewater
Authors: Coskun Tamer , Yildirim Asuman , Balcik Cigdem , Manav Demir Neslihan , Debik Eyup
Published: November 2012

In the following study, two methods were employed in which olive mill wastewaters were treated by using reverse osmosis membranes (BW30 and XLE). In the first, wastewater was centrifuged and then passed through the reverse osmosis whereas in the second, an ultrafiltration was placed between the centrifuge and the reverse osmosis. The reverse osmosis experiments were conducted under 10, 15, 20, and 25 bar. The chemical oxygen demand (COD) removal efficiencies under 25 bar were found to be 97.5% for both BW30 and XLE membranes. The highest conductivity removal rates obtained under 25 bar for BW30 and XLE membranes were found to be 95.6 and 96.2%, respectively. As for the highest permeation flux values obtained under 25 bar, they were separately determined for BW30 and XLE as 15.3 and 21.2 L m−2 h−1, respectively. The performances of the membranes were also evaluated in terms of their mass transfer coefficients. According to this, all mass transfer coefficients were found to be <1 and also in proximate to one another; this clearly reflects the results as COD and conductivity removals were approximate and there was a lack of any significant difference, whether ultrafiltration was applied or not.
Coupling Interactions between Electrokinetics and Bioremediation for Pyrene Removal from Soil under Polarity Reversal Conditions
Authors: Huang Diannan , Guo Shuhai , Li Tingting , Wu Bo
Published: November 2012

This paper investigates the hybrid technology of electrokinetics (EK) coupled with bioremediation (Bio) in the removal of pyrene (PYR) in a soil matrix. Five different treatments were conducted to investigate the coupling interactions between EK and Bio on PYR degradation. A simulated removal curve was obtained by combining the degradation curves in EK‐ and Bio‐only experiments. The results show that the simulated curve fitted well with the actual degradation curve in electro‐bioremediation (EK‐Bio) experiments for the first 30 days of the experiment, while at later stages a discrepancy was found. This discrepancy was caused by adverse effects of low soil pH (3.6) near the anode on bacteria health during EK treatments. With polarity reversal (PR) to control the soil pH, the simulated curve fitted very well (r > 0.99) with the actual degradation curve during the whole treatment period. At the end of the experiment, PYR removal amounted to 63% with EK‐Bio treatments in PR electric fields, which was 1.7 times that of Bio‐only. Moreover, the bacteria counts under electric fields were more than that without EK. The spatial distributions of PYR degradation and bacterial counts were also investigated. The results show that they were both higher nearer the electrodes under PR electric fields.
Identification of the Phytoremediation Potential of Indian mustard Genotypes for Copper, Evaluated from a Hydroponic Experiment
Authors: Ansari Mohd. Kafeel Ahmad , Oztetik Elif , Ahmad Altaf , Umar Shahid , Iqbal Muhammad , Owens Gary
Published: November 2012

The effectiveness of 10 Indian mustard (Brassica juncea L.) genotypes (viz. Agrani, BTO, Kranti, Pusa Bahar, Pusa Basant, Pusa Bold, Pusa Jai Kisan, Vaibhav, Vardhan, and Varuna) were evaluated for their potential to phytoremediate copper from contaminated waters under laboratory controlled conditions. The genotypes were grown for 20 days in aqueous solutions containing various concentrations of copper sulfate (0–50 µM) in a hydroponic chamber. Throughout plant development, changes in growth variables, biomass accumulation, and total Cu content were evaluated. The results suggested that Indian mustard cv. Pusa Jai Kisan possesses the best capacities of Cu sequestration and tolerance amongst all the genotypes studied. Thus, Pusa Jai Kisan has the greatest potential to become a viable candidate in the development of practical phytoremediation technologies for Cu contaminated sites.
The discontinuous nature of neurofilament transport accommodates both establishment and repair of the axonal neurofilament array
Authors: Shea Thomas B. , Lee Sangmook
Published: November 2012

Neurofilaments (NFs) provide structural support to axons. Timely and regional deposition of NFs is essential during axonogenesis, since progressive stabilization of proximal axons is essential to support continued pathfinding of distal axonal regions. NFs undergo short bursts of microtubule‐mediated axonal transport interspersed by prolonged pauses. We demonstrate herein that it is this unique “on‐off” method of axonal transport, coupled with the ability of NFs to form cation‐dependent, phosphomediated lateral associations that allow neurons to mediate the orderly transition from exploratory process to stabilized axon following synaptogenesis. We further demonstrate how this transport method provides for NF maintenance following maturation and encompasses the potential for regeneration. © 2012 Wiley Periodicals, Inc.
Microtubule modifications and stability are altered by cilia perturbation and in cystic kidney disease
Authors: Berbari Nicolas F. , Sharma Neeraj , Malarkey Erik B. , Pieczynski Jay N. , Boddu Ravindra , Gaertig Jacek , Guay‐Woodford Lisa , Yoder Bradley K.
Published: November 2012

Disruption of the primary cilium is associated with a growing number of human diseases collectively termed ciliopathies. Ciliopathies present with a broad range of clinical features consistent with the near ubiquitous nature of the organelle and its role in diverse signaling pathways throughout development and adult homeostasis. The clinical features associated with cilia dysfunction can include such phenotypes as polycystic kidneys, skeletal abnormalities, blindness, anosmia, and obesity. Although the clinical relevance of the primary cilium is evident, the effects that cilia dysfunction has on the cell and how this contributes to disease remains poorly understood. Here, we show that loss of ciliogenesis genes such as Ift88 and Kif3a lead to increases in post‐translational modifications on cytosolic microtubules. This effect was observed in cilia mutant kidney cells grown in vitro and in vivo in cystic kidneys. The hyper‐acetylation of microtubules resulting from cilia loss is associated with both altered microtubule stability and increased α‐tubulin acetyl‐transferase activity. Intriguingly, the effect on microtubules was also evident in renal samples from patients with autosomal recessive polycystic kidneys. These findings indicate that altered microtubule post‐translational modifications may influence some of the phenotypes observed in ciliopathies. © 2012 Wiley Periodicals, Inc
Superresolution STED microscopy reveals differential localization in primary cilia
Authors: Yang T. Tony , Hampilos Perry J. , Nathwani Bhavik , Miller Christine H. , Sutaria Nupur D. , Liao Jung‐Chi
Published: November 2012

The primary cilium is an organelle that serves as a signaling center of the cell and is involved in the cAMP, Wnt, and hedgehog signaling pathways. Adenylyl cyclase type III (ACIII) is enriched in primary cilia and acts as a marker that is involved in cAMP signaling, while also playing an important role in regulating ciliogenesis and sensory functions. Ciliary function relies on the transportation of molecules between the primary cilium and the cell, which is facilitated by intraflagellar transport (IFT). The detailed localization and interactions of these important proteins remain unclear due to the limited resolution of conventional microscopy. We conducted superresolution imaging of immunostained ACIII and IFT88 in human fibroblasts using stimulated emission depletion (STED) microscopy. Instead of a homogeneous distribution along a primary cilium, our STED images revealed that ACIII formed a periodic punctate pattern with a roughly equal spacing between groups of puncta. Superresolution imaging of IFT88, an important protein of the IFT complexes, demonstrated two novel distinct distribution patterns at the basal end: a triangle of three puncta with similar fluorescence intensities, and a Y‐shaped configuration of a bright punctum connected to two branches. We also performed STED imaging of IFT88 in mouse inner medullary collecting duct cells and mouse embryonic fibroblasts. The similar three‐puncta and Y‐shape patterns were observed in these cells, suggesting that these distribution patterns are common among primary cilia of different cell types. Our results demonstrate the ability of superresolution STED microscopy to reveal novel structural characteristics in primary cilia. © 2012 Wiley Periodicals, Inc
Determination of binding curves via protein micropatterning in vitro and in living cells
Authors: Sunzenauer Stefan , Zojer Verena , Brameshuber Mario , Tröls Andreas , Weghuber Julian , Stockinger Hannes , Schütz Gerhard J.
Published: November 2012

Quantification of protein interactions in living cells is of key relevance for understanding cellular signaling. With current techniques, however, it is difficult to determine binding affinities and stoichiometries of protein complexes in the plasma membrane. We introduce here protein micropatterning as a convenient and versatile method for such investigations. Cells are grown on surfaces containing micropatterns of capture antibody to a bait protein, so that the bait gets rearranged in the live cell plasma membrane. Upon interaction with the bait, the fluorescent prey follows the micropatterns, which can be readout with fluorescence microscopy. In this study, we addressed the interaction between Lck and CD4, two central proteins in early T‐cell signaling. Binding curves were recorded using the natural fluctuations in the Lck expression levels. Surprisingly, the binding was not saturable up to the highest Lck expression levels: on average, a single CD4 molecule recruited more than nine Lck molecules. We discuss the data in view of protein‐ and lipid‐mediated interactions. © 2012 International Society for Advancement of Cytometry
Resurrected Ceriodaphnia quadrangula highlight differences between pheno‐ and genotypic expressions
Authors: Reinikainen Marko , Åhlén Emma
Published: November 2012

The hatching of cladoceran ephippia from a 15‐cm long sediment core was investigated, and Ceriodaphnia quadrangula clones were isolated from different sediment layers. Bosmina microfossil data were also analyzed, and compared with the corresponding data from a Pb210 dated core, which allowed us to infer the age of the sediment layers. Using changes in Bosmina microfossil morphologies, we were, furthermore, able to infer the presence of different regimes of fish predation. C. quadrangula was found to hatch in layers with an inferred age of approximately a century. Newly hatched individuals had smaller eye‐size in sediment layers corresponding to high predation by young‐of‐the‐year perch. Newly hatched individuals also generally had a marked neck‐spine. In contrast, morphological characters of C. quadrangula clones reared in the laboratory over several generations showed no variation in relation to predation regime, indicating the absence of fixed genotype level changes. Furthermore, the laboratory grown clones only rarely produced a neck‐spine. The results suggest phenotypic variation in response to the regime under which ephippia were produced.
Is the change of winter wheat yield under warming caused by shortened reproductive period?
Authors: Hou Ruixing , Ouyang Zhu , Li Yunsheng , Wilson Glenn V. , Li Hanxia
Published: November 2012

Previous reports from laboratory‐controlled experiments and models considered that a shorter reproductive period could be the main reason for wheat yield reduction in the warmer world. However, this conclusion needs to be proved carefully by field‐scale experiments. In this study, a field‐scale continuous open‐warming experiment was conducted to quantify the adjustment of winter wheat growth and yield under conventional tillage (CT) and no‐till (NT) systems in the North China Plain (NCP). Canopy temperatures were warmed using infrared heaters between 1.0 and 1.6°C (daytime and nighttime, respectively) above the control. Wheat yields under CT were not significantly reduced over the two seasons (2010 and 2011), but yields under NT were 3.3% and 6.1% lower, respectively. The growing seasons for both CT and NT were shortened 6 days in 2010 and 11 days in 2011; however, the reproductive periods were maintained. The shortened days were due to a significantly shorter springtime re‐greening stage followed by minimal changes in other phenological stages (jointing, flag completed, heading, anthesis, and grain‐filling). The temporal advance by warming resulted in lower growing‐season mean air temperatures (MAT) for warmed plots than the control from 0.23 to 4.22°C for the same subsequent phenological stages. Warming increased the number of tillers m−2 and kernel weight, but tended to decrease the number of spikes m−2 in the two tillage systems. The heavier kernels offset the yield reduction from smaller number of spikes. Warming increased the wheat aboveground biomass from 10% to 20% suggesting the potential to sequester more CO2. This study suggests that winter wheat might adjust its growth (shortened vegetative period to maintain reproductive period) to partly compensate for the negative effects from global warming in this temperate irrigated cropland.
Changes in soil bacterial community triggered by drought‐induced gap succession preceded changes in soil C stocks and quality
Authors: Yuste Jorge Curiel , Barba Josep , Fernandez‐Gonzalez Antonio José , Fernandez‐Lopez Manuel , Mattana Stefania , Martinez‐Vilalta Jordi , Nolis Pau , Lloret Francisco
Published: November 2012

The aim of this study was to understand how drought‐induced tree mortality and subsequent secondary succession would affect soil bacterial taxonomic composition as well as soil organic matter (SOM) quantity and quality in a mixed Mediterranean forest where the Scots pine (Pinus sylvestris) population, affected by climatic drought‐induced die‐off, is being replaced by Holm‐oaks (HO; Quercus ilex). We apply a high throughput DNA pyrosequencing technique and 13C solid‐state Nuclear Magnetic Resonance (CP‐MAS 13C NMR) to soils within areas of influence (defined as an surface with 2‐m radius around the trunk) of different trees: healthy and affected (defoliated) pines, pines that died a decade ago and healthy HOs. Soil respiration was also measured in the same spots during a spring campaign using a static close‐chamber method (soda lime). A decade after death, and before aerial colonization by the more competitive HOs have even taken place, we could not find changes in soil C pools (quantity and/or quality) associated with tree mortality and secondary succession. Unlike C pools, bacterial diversity and community structure were strongly determined by tree mortality. Convergence between the most abundant taxa of soil bacterial communities under dead pines and colonizer trees (HOs) further suggests that physical gap colonization was occurring below‐ground before above‐ground colonization was taken place. Significantly higher soil respiration rates under dead trees, together with higher bacterial diversity and anomalously high representation of bacteria commonly associated with copiotrophic environments (r‐strategic bacteria) further gives indications of how drought‐induced tree mortality and secondary succession were influencing the structure of microbial communities and the metabolic activity of soils.
Exploring the genetics of nestling personality traits in a wild passerine bird: testing the phenotypic gambit
Authors: Brommer Jon E. , Kluen Edward
Published: November 2012

When several personality traits covary, they form a behavioral syndrome. Understanding the evolutionary dynamics of a behavioral syndrome requires knowledge of its genetic underpinning. At present, our understanding of the genetic basis of behavioral syndromes is largely restricted to domestic and laboratory animals. Wild behavioral syndromes are mostly inferred on the basis of phenotypic correlations, and thus make the “phenotypic gambit” of assuming that these phenotypic correlations capture the underlying genetic correlations. On the basis of 3 years of reciprocal cross‐fostering of 2896 nestlings of 271 families within a pedigreed population, we show that the nestling personality traits handling aggression, breathing rate, and docility are heritable (h2 = 16–29%), and often have a pronounced “nest‐of‐rearing” variance component (10–15%), but a relatively small “nest‐of‐origin” variance component (0–7%). The three nestling personality traits form a behavioral syndrome on the phenotypic and genetic level. Overall, the phenotypic correlations provide a satisfactory description of the genetic ones, but significantly underestimate the magnitude of one of the pairwise genetic correlations, which mirrors the conclusion based on domestic and laboratory studies.
Differential recruitment and activation of natural killer cell sub‐populations by Mycobacterium bovis‐infected dendritic cells
Authors: Siddiqui Nazneen , Hope Jayne
Published: November 2012

Through complex interplay with APCs, subsets of NK cells play an important role in shaping adaptive immune responses. Bovine tuberculosis, caused by Mycobacterium bovis, is increasing in incidence and detailed knowledge of host–pathogen interactions in the natural host is essential to facilitate disease control. We investigated the interactions of NK‐cell sub‐populations and M. bovis‐infected DCs to determine early innate mechanisms in the response to infection. A sub‐population of NK cells (NKp46+CD2−) selectively expressing lymphoid homing and inflammatory chemokine receptors were induced to migrate towards M. bovis‐infected DCs. This migration was associated with increased expression of chemokines CCL3, 4, 5, 20 and CXCL8 by M. bovis‐infected DCs. Activation of NKp46+CD2− NK cells and secretion of IFN‐γ was observed, a response reliant on localised IL‐12 release and direct cellular interaction. In a reciprocal manner, NKp46+CD2− cells induced an increase in the intensity of cell surface MHC class II expression on DCs. In contrast, NKp46+CD2+ NK cells were unable to secrete IFN‐γ and did not reciprocally affect DCs. This study provides novel evidence to demonstrate distinct effector responses between bovine NK‐cell subsets during mycobacterial infection.
Rational Synthesis of a Family of Neutral Monomeric Heteroleptic Titanium Complexes Based on an Octahedral TiO4N2 Motif
Authors: Weekes David Michael , Baradel Nathalie , Kyritsakas Nathalie , Mobian Pierre , Henry Marc
Published: November 2012

A rational approach leading to a novel family of monomeric heteroleptic titanium complexes formed with two biphenolate derivatives and six different bidentate nitrogenated chelates is proposed. Only one case of loss of structural predictability was observed in the case of a N,O‐coordinating ligand and led to a structure containing two (μ‐O)‐bridged titanium centres. Diffusion‐ordered NMR spectroscopy (DOSY) measurements have been systematically used to prove that the complexes characterised in the solid state remain identical in the liquid phase. All ligands have also been classified quantitatively according to their electron‐withdrawal capabilities. A quantitative thermodynamic analysis using the PACHA software showed that the entropically favoured displacement of two monodentate‐coordinated alcohol molecules needs to be assisted by solvation of the η2‐chelate product to overcome the enthalpically unfavourable replacement of two highly polar Ti–O bonds by less polar Ti–N bonds. The occurrence of dichloromethane molecules in the crystalline state and the existence of more than one crystallographically nonequivalent complex within the unit cell has been associated with a low dipolar moment of the complexes. Other complexes with large dipolar moments (μ > 2 D) seem to have enough dipolar energy in the solid state to remove all the solvating dichloromethane molecules.
A Molecular Precursor Approach to 3D Aligned CuInS2 Chalcopyrite Nanorod Arrays
Authors: Pashchanka Mikhail , Hoffmann Rudolf C. , Schneider Jörg J.
Published: November 2012

Polycrystalline ternary CuInS2 (CIS) nanorods with stoichiometric composition have been synthesized by using a nanocasting approach employing track‐etched polycarbonate films as soft templates. The CuInS2 chalcopyrite phase was obtained by using molecular copper and indium oximato complexes and thiourea as single‐source precursors.
C,N‐Palladacycles Containing N‐Heterocyclic Carbene and Azido Ligands – Effective Catalysts for Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Kim Yong‐Joo , Lee Jung‐Hyun , Kim Taejung , Ham Jungyeob , Zheng Zhen Nu , Lee Soon W.
Published: November 2012

Azido‐palladacycles containing C,N‐donor and N‐heterocyclic carbene ligands, [(C,N‐L)Pd(N3)(NHC)] [NHC = IPr; 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene], were prepared from (i) IPr and dinuclear PdII azides, [Pd(μ‐N3)(C,N‐Ln)]2 [C,N‐L1H = N,N′‐dimethylbenzylamine; C,N‐L2H = 2‐(2′‐thienyl)pyridine; C,N‐L3H = azobenzene; C,N‐L4H = 2‐(p‐tolyl)pyridine], or from (ii) NaN3 and mononuclear PdII chloride, [Pd(Cl)(IPr)(C,N‐Ln)], in aqueous solution. The structures of two of these products were determined by X‐ray crystallography. The palladacycles showed high catalytic efficiency toward activated and nonactivated aryl bromides (at room temperature) as well as aryl chlorides (at 80 °C) in Suzuki–Miyaura cross‐coupling reactions. In addition, coupling reactions of aryl chlorides using potassium aryl trifluoroborates instead of phenyl boronic acid gave good‐to‐excellent product yields.
A Polyoxometalate‐Based Coordination Polymer with the Diamondoid Topology
Authors: Mandic Susanna , Healey Merinda R. , Gotthardt Jan M. , Alley Kerwyn G. , Gable Robert W. , Ritchie Chris , Boskovic Colette
Published: November 2012

The new coordination polymer [ϵ‐PMo12O37(OH)3{La(H2O)3}4(L)]·28H2O [H4L = tetrakis(4‐carboxyphenyl)silane] can be synthesized by combining equal quantities of two types of 4‐connecting building blocks: organic L4– ligands and inorganic polyoxometalate‐derived [ϵ‐PMo12O37(OH)3{La(H2O)4}4]4+ polyoxocations. The resulting coordination polymer exhibits the diamondoid topology, where both building blocks act as pseudotetrahedral nodes. The structural and spectroscopic characteristics of the parent polyoxocation are retained in the coordination polymer.
Synthesis of Cyclotriveratrylene–Phenylacetylene Derivatives and a Photophysical Investigation of Rigid Conjugated Cyclotriveratrylene Dendrimers
Authors: Han Xiao‐Na , Chen Jian‐Ming , Huang Zhi‐Tang , Zheng Qi‐Yu
Published: November 2012

Various functionalized host molecules and building blocks can be derived from the cone‐shaped cyclotriveratrylene (CTV). In this article, we report on the synthesis of CTV‐I3 derivatives 3a and 3b and their Sonogashira cross‐coupling with various terminal aryl‐alkynes, to synthesize CTV‐phenylacetylene derivatives in moderate to good yields. In this way, three star‐like conjugated dendrimers with rigid macrocyclic cores 4k–m, which showed good photophysical properties, were also synthesized. The band gaps of 4k–m are 3.49, 3.49 and 3.45 eV, and the fluorescence quantum yields are 0.64, 0.78, 0.48 (2‐aminopyridine as a standard and excited at 310 nm), respectively. Electrochemical studies revealed their HOMO and LUMO energy levels. Our research disclosed that these CTV dendrimers could potentially be used as host materials in OLEDs.
One‐Pot Catalyst‐Free Synthesis of β‐ and γ‐Hydroxy Sulfides Using Diaryliodonium Salts and Microwave Irradiation
Authors: Vaddula Buchi Reddy , Varma Rajender S. , Leazer John
Published: November 2012

A simple and rapid one‐pot protocol is described for the preparation of α‐ and β‐hydroxy sulfides. The direct solvent‐free microwave irradiation of diaryliodonium salts, potassium thiocyanate, and ethylene glycol/β‐propylene glycol without any catalyst or base affords the final compounds in good yields (65–95 %) in around 10–25 min.
Modified silver staining in 2DE improves protein detection even at extremely low sample concentration
Authors: Liew Yun Khoon , Neela Vasanthakumari , Hamat Rukman Awang , Nordin Syafinaz Amin , Chong Pei Pei
Published: November 2012

The typical concentration of protein loaded varies from 0.13 to 1.40 μg/μL for a classical silver staining method in 2DE gel. Here, we present a simple modified classical silver staining method by modifying the silver impregnation and development reaction steps. This modified method detects the protein spots at extremely low loaded concentrations, ranging from 0.0048 to 0.0480 μg/μL. We recommend this modified silver staining as an excellent method for the limited biological samples used for silver‐stained 2DE analysis. Altogether, the protocol takes close to two days from first dimension separation to second dimension separation, followed by silver staining, scanning, and analysis.
3D numerical simulation of a Coulter counter array with analysis of electrokinetic forces
Authors: Guo Jinhong , Pui Tze Sian , Rahman Abdur Rub Abdur , Kang Yuejun
Published: November 2012

Coulter counters have played an important role in biological cell assays since their introduction decades ago. Several types of high throughput micro‐Coulter counters based on lab‐on‐chip devices have been commercialized recently. In this paper, we propose a highly integrated micro‐Coulter counter array working under low DC voltage. The real‐time electrical current change, including the pulse amplitude and width, of the micro‐Coulter counter with novel structure is systematically investigated numerically. The major types of forces exerted on the particle in the micro‐Coulter counter, including hydrodynamic force and electrokinetic force are quantitatively analyzed. The simulation in this study shows the pulse profile, such as width and amplitude, is affected by both particle size and the flow condition. The special cases of multiple particle aggregation and cross‐talk between neighboring channels are also considered for their effects on the electric current pulses. This simulation provides critical insight and guidance for developing next new generations of micro‐Coulter counter.
miR‐10b*, a master inhibitor of the cell cycle, is down‐regulated in human breast tumours
Authors: Biagioni Francesca , Bossel Ben‐Moshe Noa , Fontemaggi Giulia , Canu Valeria , Mori Federica , Antoniani Barbara , Di Benedetto Anna , Santoro Raffaela , Germoni Sabrina , De Angelis Fernanda , Cambria Anna , Avraham Roi , Grasso Giuseppe , Strano Sabrina , Muti Paola , Mottolese Marcella , Yarden Yosef , Domany Eytan , Blandino Giovanni
Published: November 2012

Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA‐10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA‐10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR‐10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease‐free survival, relapse‐free survival and metastasis‐free survival when compared to patients with low expression. This also suggests that restoration of microRNA‐10b* expression might have therapeutic promise.
Personalised medicine: challenges in development and delivery
Authors: Montgomery David A , Heathfield Adam , Moledina Altaf
Published: November 2012

On 9 December 1969, in an open letter to President Nixon published in the Washington Post, Dr Sidney Farber, past president of the American Cancer Society was quoted as saying: ‘We are so close to a cure for cancer’.1 So what happened? Copyright © 2012 John Wiley & Sons, Ltd.
Drugs in development for the management of dyslipidaemia
Authors: Wierzbicki Anthony , Hardman Timothy , Viljoen Adie
Published: November 2012

Lipid‐lowering is established as proven intervention to reduce atherosclerosis. Statins form the basis of care but are not able to treat all aspects of dyslipidaemia. Many novel therapeutic compounds are being developed. These include additional therapeutics for low‐density lipo protein cholesterol (LDL‐C), eg antisense oligonucleotides or microsomal transfer protein inhibitors (MTPI); triglycerides, eg novel peroxisomal proliferator activating receptors (PPAR) agonists, MTPIs; HDL: delipidation strategies and cholesterol ester transfer protein inhibitors (CETPIs) and modulators of inflammation, eg phospholipase inhibitors. Copyright © 2012 John Wiley & Sons, Ltd.
Aflibercept – a novel agent for VEGF‐driven macular disease
Authors: Morphis George
Published: November 2012

Aflibercept is a novel vascular endothelial growth factor (VEGF) inhibitor that has recently been approved by the US Food and Drug Administration (FDA) for the treatment of wet age‐related macular degeneration (AMD). In this Drug profile Mr George Morphis presents the clinical data relating to its efficacy and adverse events, and discusses its potential place in therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Diffuse reflectance spectroscopy in Barrett’s Esophagus: developing a large field‐of‐view screening method discriminating dysplasia from metaplasia
Authors: Douplik Alexandre , Zanati Simon , Saiko Guennadi , Streutker Catherine , Loshchenov Maxim , Adler Desmond , Cho Sarah , Chen Dean , Cirocco Maria , Marcon Norman , Fengler John , Wilson Brian C.
Published: November 2012

We evaluated diffuse reflectance spectroscopy implemented as a small field‐of‐view technique for discrimination of dysplasia from metaplasia in Barrett’s esophagus as an adjuvant to autofluorescence endoscopy. Using linear discriminant analysis on 2579 spectra measured in 54 patients identified an optimum a 4‐wavelength classifier (at 485, 513, 598 and 629 nm). Sensitivity and specificity for a test data set were 0.67 and 0.85, respectively. Spectroscopic results show that this technique could be implemented in wide‐field imaging mode to improve the accuracy of existing endoscopy techniques for finding early pre‐malignant lesions in Barrett’s esophagus. Results show that the discrimination occurs likely due to redistribution of blood content in the tissue sensed by the optical probing with the wavelength‐dependent sampling depth. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characterisation of a label‐free biosensor based on long period grating
Authors: Chiavaioli Francesco , Trono Cosimo , Giannetti Ambra , Brenci Massimo , Baldini Francesco
Published: November 2012

Optical fibre gratings, especially long period gratings, have been recently proposed as optical devices for biochemical sensing. A biochemical interaction along the grating portion induces a refractive index change and hence a change in the fiber transmission spectrum. This provides an alternative methodology with respect to other label‐free optical approaches, such as surface plasmon resonance, interferometric configurations and optical resonators. The fibre biofunctionalization has been carried out by means of a novel chemistry using Eudragit L100 copolymer as opposed to the commonly used silanization procedure. Antigen‐antibody interaction has been analysed by means of an IgG/anti‐IgG bioassay. The biosensor was fully characterised, monitoring the kinetics during the antibody immobilization and the antigen interaction and achieving the calibration curve of the assay. A comparison of the biosensor performance was made by using two different long period gratings with distinct periods. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)