bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Molecules Present Large Opportunities in Plant Biology
Authors: Hicks Glenn R. , Raikhel Natasha V.
Published: May 2012

Since the introduction of chemical genomics to plant biology as a tool for basic research, the field has advanced significantly. There are now examples of important basic discoveries that demonstrate the power and untapped potential of this approach. Given the combination of protein and small-molecule complexity, new phenotypes can be described through the perturbation of cellular functions that can be linked to growth and developmental phenotypes. There are now clear examples of overcoming functional redundancy in plants to dissect molecular mechanisms or critical pathways such as hormone signaling and dynamic intracellular processes. Owing to ongoing advances, including more sophisticated high-content screening and rapid approaches for target identification, the field is beginning to move forward. However, there are also challenges to improve automation, imaging, and analysis and provide chemical biology resources to the broader plant biology community.
Cytokinin Signaling Networks
Authors: Hwang Ildoo , Sheen Jen , Müller Bruno
Published: May 2012

Despite long-standing observations on diverse cytokinin actions, the discovery path to cytokinin signaling mechanisms was tortuous. Unyielding to conventional genetic screens, experimental innovations were paramount in unraveling the core cytokinin signaling circuitry, which employs a large repertoire of genes with overlapping and specific functions. The canonical two-component transcription circuitry involves His kinases that perceive cytokinin and initiate signaling, as well as His-to-Asp phosphorelay proteins that transfer phosphoryl groups to response regulators, transcriptional activators, or repressors. Recent advances have revealed the complex physiological functions of cytokinins, including interactions with auxin and other signal transduction pathways. This review begins by outlining the historical path to cytokinin discovery and then elucidates the diverse cytokinin functions and key signaling components. Highlights focus on the integration of cytokinin signaling components into regulatory networks in specific contexts, ranging from molecular, cellular, and developmental regulations in the embryo, root apical meristem, shoot apical meristem, stem and root vasculature, and nodule organogenesis to organismal responses underlying immunity, stress tolerance, and senescence.
Early Embryogenesis in Flowering Plants: Setting Up the Basic Body Pattern
Authors: Lau Steffen , Slane Daniel , Herud Ole , Kong Jixiang , Jürgens Gerd
Published: May 2012

Early embryogenesis is the critical developmental phase during which the basic features of the plant body are established: the apical-basal axis of polarity, different tissue layers, and both the root pole and the shoot pole. Polarization of the zygote correlates with the generation of apical and basal (embryonic and extraembryonic) cell fates. Whereas mechanisms of zygote polarization are still largely unknown, distinct expression domains of WOX family transcription factors as well as directional auxin transport and local auxin response are known to be involved in early apical-basal patterning. Radial patterning of tissue layers appears to be mediated by cell-cell communication involving both peptide signaling and transcription factor movement. Although the initiation of the shoot pole is still unclear, the apical organization of the embryo depends on both the proper establishment of transcription factor expression domains and, for cotyledon initiation, upward auxin flow in the protoderm. Here we focus on the essential patterning processes, drawing mainly on data from Arabidopsis thaliana and also including relevant data from other species if available.
Photorespiration and the Evolution of C4Photosynthesis
Authors: Sage Rowan F. , Sage Tammy L. , Kocacinar Ferit
Published: May 2012

C4photosynthesis is one of the most convergent evolutionary phenomena in the biological world, with at least 66 independent origins. Evidence from these lineages consistently indicates that the C4pathway is the end result of a series of evolutionary modifications to recover photorespired CO2in environments where RuBisCO oxygenation is high. Phylogenetically informed research indicates that the repositioning of mitochondria in the bundle sheath is one of the earliest steps in C4evolution, as it may establish a single-celled mechanism to scavenge photorespired CO2produced in the bundle sheath cells. Elaboration of this mechanism leads to the two-celled photorespiratory concentration mechanism known as C2photosynthesis (commonly observed in C3–C4intermediate species) and then to C4photosynthesis following the upregulation of a C4metabolic cycle.
Iron Uptake, Translocation, and Regulation in Higher Plants
Authors: Kobayashi Takanori , Nishizawa Naoko K.
Published: May 2012

Iron is essential for the survival and proliferation of all plants. Higher plants have developed two distinct strategies to acquire iron, which is only slightly soluble, from the rhizosphere: the reduction strategy of nongraminaceous plants and the chelation strategy of graminaceous plants. Key molecular components—including transporters, enzymes, and chelators—have been clarified for both strategies, and many of these components are now thought to also function inside the plant to facilitate internal iron transport. Transporters for intracellular iron trafficking are also being clarified. A majority of genes encoding these components are transcriptionally regulated in response to iron availability. Recent research has uncovered central transcription factors, cis-acting elements, and molecular mechanisms regulating these genes. Manipulation of these molecular components has produced transgenic crops with enhanced tolerance to iron deficiency or with increased iron content in the edible parts.
Plant Nitrogen Assimilation and Use Efficiency
Authors: Xu Guohua , Fan Xiaorong , Miller Anthony J.
Published: May 2012

Crop productivity relies heavily on nitrogen (N) fertilization. Production and application of N fertilizers consume huge amounts of energy, and excess is detrimental to the environment; therefore, increasing plant N use efficiency (NUE) is essential for the development of sustainable agriculture. Plant NUE is inherently complex, as each step—including N uptake, translocation, assimilation, and remobilization—is governed by multiple interacting genetic and environmental factors. The limiting factors in plant metabolism for maximizing NUE are different at high and low N supplies, indicating great potential for improving the NUE of current cultivars, which were bred in well-fertilized soil. Decreasing environmental losses and increasing the productivity of crop-acquired N requires the coordination of carbohydrate and N metabolism to give high yields. Increasing both the grain and N harvest index to drive N acquisition and utilization are important approaches for breeding future high-NUE cultivars.
Regulation of Seed Germination and Seedling Growth by Chemical Signals from Burning Vegetation
Authors: Nelson David C. , Flematti Gavin R. , Ghisalberti Emilio L. , Dixon Kingsley W. , Smith Steven M.
Published: May 2012

It is well known that burning of vegetation stimulates new plant growth and landscape regeneration. The discovery that char and smoke from such fires promote seed germination in many species indicates the presence of chemical stimulants. Nitrogen oxides stimulate seed germination, but their importance in post-fire germination has been questioned. Cyanohydrins have been recently identified in aqueous smoke solutions and shown to stimulate germination of some species through the slow release of cyanide. However, the most information is available for karrikins, a family of butenolides related to 3-methyl-2H-furo[2,3-c]pyran-2-one. Karrikins stimulate seed germination and influence seedling growth. They are active in species not normally associated with fire, and in Arabidopsis they require the F-box protein MAX2, which also controls responses to strigolactone hormones. We hypothesize that chemical similarity between karrikins and strigolactones provided the opportunity for plants to employ a common signal transduction pathway to respond to both types of compound, while tailoring specific developmental responses to these distinct environmental signals.
Seed Germination and Vigor
Authors: Rajjou Loïc , Duval Manuel , Gallardo Karine , Catusse Julie , Bally Julia , Job Claudette , Job Dominique
Published: May 2012

Germination vigor is driven by the ability of the plant embryo, embedded within the seed, to resume its metabolic activity in a coordinated and sequential manner. Studies using “-omics” approaches support the finding that a main contributor of seed germination success is the quality of the messenger RNAs stored during embryo maturation on the mother plant. In addition, proteostasis and DNA integrity play a major role in the germination phenotype. Because of its pivotal role in cell metabolism and its close relationships with hormone signaling pathways regulating seed germination, the sulfur amino acid metabolism pathway represents a key biochemical determinant of the commitment of the seed to initiate its development toward germination. This review highlights that germination vigor depends on multiple biochemical and molecular variables. Their characterization is expected to deliver new markers of seed quality that can be used in breeding programs and/or in biotechnological approaches to improve crop yields.
Vacuolar Transporters in Their Physiological Context
Authors: Martinoia Enrico , Meyer Stefan , De Angeli Alexis , Nagy Réka
Published: May 2012

Vacuoles in vegetative tissues allow the plant surface to expand by accumulating energetically cheap inorganic osmolytes, and thereby optimize the plant for absorption of sunlight and production of energy by photosynthesis. Some specialized cells, such as guard cells and pulvini motor cells, exhibit rapid volume changes. These changes require the rapid release and uptake of ions and water by the vacuole and are a prerequisite for plant survival. Furthermore, seed vacuoles are important storage units for the nutrients required for early plant development. All of these fundamental processes rely on numerous vacuolar transporters. During the past 15 years, the transporters implicated in most aspects of vacuolar function have been identified and characterized. Vacuolar transporters appear to be integrated into a regulatory network that controls plant metabolism. However, little is known about the mode of action of these fundamental processes, and deciphering the underlying mechanisms remains a challenge for the future.
Polyamines inhibit the assembly of stress granules in normal intestinal epithelial cells regulating apoptosis
Authors: Zou Tongtong , Rao Jaladanki N. , Liu Lan , Xiao Lan , Cui Yu-Hong , Jiang Zhengran , Ouyang Miao , Donahue James M. , Wang Jian-Ying
Published: May 2012

Polyamines regulate multiple signaling pathways and are implicated in many aspects of cellular functions, but the exact molecular processes governed by polyamines remain largely unknown. In response to environmental stress, repression of translation is associated with the assembly of stress granules (SGs) that contain a fraction of arrested mRNAs and are thought to function as mRNA storage. Here we show that polyamines modulate the assembly of SGs in normal intestinal epithelial cells (IECs) and that induced SGs following polyamine depletion are implicated in the protection of IECs against apoptosis. Increasing the levels of cellular polyamines by ectopic overexpression of the ornithine decarboxylase gene decreased cytoplasmic levels of SG-signature constituent proteins eukaryotic initiation factor 3b and T-cell intracellular antigen-1 (TIA-1)-related protein and repressed the assembly of SGs induced by exposure to arsenite-induced oxidative stress. In contrast, depletion of cellular polyamines by inhibiting ornithine decarboxylase with α-difluoromethylornithine increased cytoplasmic eukaryotic initiation factor 3b and TIA-1 related protein abundance and enhanced arsenite-induced SG assembly. Polyamine-deficient cells also exhibited an increase in resistance to tumor necrosis factor-α/cycloheximide-induced apoptosis, which was prevented by inhibiting SG formation with silencing SG resident proteins Sort1 and TIA-1. These results indicate that the elevation of cellular polyamines represses the assembly of SGs in normal IECs and that increased SGs in polyamine-deficient cells are crucial for increased resistance to apoptosis.
Type 2 cGMP-dependent protein kinase regulates proliferation and differentiation in the colonic mucosa
Authors: Wang Rui , Kwon In-Kiu , Thangaraju Muthusamy , Singh Nagendra , Liu Kebin , Jay Philippe , Hofmann Franz , Ganapathy Vadivel , Browning Darren D.
Published: May 2012

Signaling through cGMP has emerged as an important regulator of tissue homeostasis in the gastrointestinal tract, but the mechanism is not known. Type 2 cGMP-dependent protein kinase (PKG2) is a major cGMP effector in the gut epithelium, and the present studies have tested its importance in the regulation of proliferation and differentiation in the mouse colon and in colon cancer cell lines. Tissue homeostasis was examined in the proximal colon of Prkg2 −/− mice using histological markers of proliferation and differentiation. The effect of ectopic PKG2 on proliferation and differentiation was tested in vitro using inducible colon cancer cell lines. PCR and luciferase reporter assays were used to determine the importance of Sox9 downstream of PKG2. The colons of Prkg2 −/− mice exhibited crypt hyperplasia, increased epithelial apoptosis, and reduced numbers of differentiated goblet and enteroendocrine cells. Ectopic PKG2 was able to inhibit proliferation and induce Muc2 and CDX2 expression in colon cancer cells, but did not significantly affect cell death. PKG2 reduced Sox9 levels and signaling, suggesting possible involvement of this pathway downstream of cGMP in the colon. The work presented here demonstrates a novel antiproliferative and prodifferentiation role for PKG2 in the colon. These homeostatic functions of PKG2 were reproducible in colon cancer cells lines where downregulation of Sox9 is a possible mechanism. The similarities in phenotype between PKG2 and GCC knockout mice positions PKG2 as a likely mediator of the homeostatic effects of cGMP signaling in the colon.
Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest
Authors: Aletti Federico , Ferrario Manuela , Xu Da , Greaves Danielle K. , Shoemaker J. Kevin , Arbeille Philippe , Baselli Giuseppe , Hughson Richard L.
Published: May 2012

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (−10 mmHg, −20 mmHg, −30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ∼0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% ( P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to −20 and −30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.
NADPH oxidase inhibition reduces tubular sodium transport and improves kidney oxygenation in diabetes
Authors: Persson Patrik , Hansell Peter , Palm Fredrik
Published: May 2012

Sustained hyperglycemia is associated with increased oxidative stress resulting in decreased intrarenal oxygen tension (Po2) due to increased oxygen consumption (Qo2). Chronic blockade of the main superoxide radicals producing system, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, normalizes Qo2by isolated proximal tubular cells (PTC) and reduces proteinuria in diabetes. The aim was to investigate the effects of acute NADPH oxidase inhibition on tubular Na+transport and kidney Po2in vivo. Glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), Na+excretion, fractional Li+excretion, and intrarenal Po2was measured in control and streptozotocin-diabetic rats during baseline and after acute NADPH oxidase inhibition using apocynin. The effects on tubular transporters were investigated using freshly isolated PTC. GFR was increased in diabetics compared with controls (2.2 ± 0.3 vs. 1.4 ± 0.1 ml·min−1·kidney−1). RBF was similar in both groups, resulting in increased FF in diabetics. Po2was reduced in cortex and medulla in diabetic kidneys compared with controls (34.4 ± 0.7 vs. 42.5 ± 1.2 mmHg and 15.7 ± 1.2 vs. 25.5 ± 2.3 mmHg, respectively). Na+excretion was increased in diabetics compared with controls (24.0 ± 4.7 vs. 9.0 ± 2.0 μm·min−1·kidney−1). In controls, all parameters were unaffected. However, apocynin increased Na+excretion (+112%) and decreased fractional lithium reabsorption (−10%) in diabetics, resulting in improved cortical (+14%) and medullary (+28%) Po2. Qo2was higher in PTC isolated from diabetic rats compared with control. Apocynin, dimethylamiloride, and ouabain reduced Qo2, but the effects of combining apocynin with either dimethylamiloride or ouabain were not additive. In conclusion, NADPH oxidase inhibition reduces tubular Na+transport and improves intrarenal Po2in diabetes.
Modulation of bladder function by luminal adenosine turnover and A1receptor activation
Authors: Prakasam H. Sandeep , Herrington Heather , Roppolo James R. , Jackson Edwin K. , Apodaca Gerard
Published: May 2012

The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A1receptors with 2-chloro- N6-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis.
Olfactory modulation by dopamine in the context of aversive learning
Authors: Dacks Andrew M. , Riffell Jeffrey A. , Martin Joshua P. , Gage Stephanie L. , Nighorn Alan J.
Published: May 2012

The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing.
From anticipation to action, the role of dopamine in perceptual decision making: an fMRI-tyrosine depletion study
Authors: Nagano-Saito Atsuko , Cisek Paul , Perna Andrea S. , Shirdel Fatemeh Z. , Benkelfat Chawki , Leyton Marco , Dagher Alain
Published: May 2012

During simple sensorimotor decision making, neurons in the parietal cortex extract evidence from sensory information provided by visual areas until a decision is reached. Contextual information can bias parietal activity during the task and change the decision-making parameters. One type of contextual information is the availability of reward for correct decisions. We tested the hypothesis that the frontal lobes and basal ganglia use contextual information to bias decision making to maximize reward. Human volunteers underwent functional MRI while making decisions about the motion of dots on a computer monitor. On rewarded trials, subjects responded more slowly by increasing the threshold to decision. Rewarded trials were associated with activation in the ventral striatum and prefrontal cortex in the period preceding coherent dot motion, and the degree of activation predicted the increased decision threshold. Decreasing dopamine transmission, using a tyrosine-depleting amino acid mixture, abolished the reward-related corticostriatal activation and eliminated the correlation between striatal activity and decision threshold. These observations provide direct evidence that some reward-related functional MRI signals in the striatum are the result of dopamine neuron activity and demonstrate that mesolimbic dopamine transmission can influence perceptual and decision-making neural processes engaged to maximize reward harvest.
Modulation of motor control in saccadic behaviors by TMS over the posterior parietal cortex
Authors: Liang Wei-Kuang , Juan Chi-Hung
Published: May 2012

The right posterior parietal cortex (rPPC) has been found to be critical in shaping visual selection and distractor-induced saccade curvature in the context of predictive as well as nonpredictive visual cues by means of transcranial magnetic stimulation (TMS) interference. However, the dynamic details of how distractor-induced saccade curvatures are affected by rPPC TMS have not yet been investigated. This study aimed to elucidate the key dynamic properties that cause saccades to curve away from distractors with different degrees of curvature in various TMS and target predictability conditions. Stochastic optimal feedback control theory was used to model the dynamics of the TMS saccade data. This allowed estimation of torques, which was used to identify the critical dynamic mechanisms producing saccade curvature. The critical mechanisms of distractor-induced saccade curvatures were found to be the motor commands and torques in the transverse direction. When an unpredictable saccade target occurred with rPPC TMS, there was an initial period of greater distractor-induced torque toward the side opposite the distractor in the transverse direction, immediately followed by a relatively long period of recovery torque that brought the deviated trace back toward the target. The results imply that the mechanisms of distractor-induced saccade curvature may be comprised of two mechanisms: the first causing the initial deviation and the second bringing the deviated trace back toward the target. The pattern of the initial torque in the transverse direction revealed the former mechanism. Conversely, the later mechanism could be well explained as a consequence of the control policy in this model. To summarize, rPPC TMS increased the initial torque away from the distractor as well as the recovery torque toward the target.
Motor adaptation following split-belt treadmill walking
Authors: Stubbs Peter W. , Gervasio Sabata
Published: May 2012

Malone L, Vasudevan E, and Bastian A ( J Neurosci 31: 15136–15143, 2011) investigated the effects of different training paradigms on the day-by-day retention of learned motor patterns. In this Neuro Forum, a description and assessment of the methods used will be presented. The interpretation of the findings will be extended and the possible implications will be discussed. Finally, alternative explanations of the possible regions involved in motor pattern relearning will be provided.
Synthesis of Schiff Bases of 2‐amino‐5‐aryl‐1,3,4‐thiadiazole and Its Analgesic, Anti‐Inflammatory and Anti‐Bacterial Activity
Authors: Pandey Alok , Rajavel R. , Chandraker Sandeep , Dash Deepak
Published: May 2012

Schiff Bases of 2‐amino‐5‐aryl‐1,3,4‐thiadiazole derivatives have been synthesized with different aromatic aldehyde. 1,3,4‐thiadiazole derivatives were prepared by the reaction of thiosemicarbazide, sodium acetate and aromatic aldehyde. The structures of the titled Schiff bases were elucidated by IR and 1H NMR spectral measurements. All the compounds were evaluated for their analgesic activity against swiss albino mice, anti‐inflammatory activity against Wister albino rats. The compounds showed significant antibacterial activity against Staphylococcus aureus (gram‐positive) bacteria and E. coli (gram‐negative) bacteria.
Observations of an 11 September Sahelian Squall Line and Saharan Air Layer Outbreak during NAMMA-06
Authors: Smith J. W. , Reynolds A. E. , Pratt A. S. , Salack S. , Klotz B. , Battle T. L. , Grant D. , Diop A. , Fall T. , Gaye A. , Robertson D. , DeLonge M. S. , Chan S.
Published: May 2012

The 2006 NASA-African Monsoon Multidisciplinary Analyses (NAMMA-06) field campaign examined a compact, low-level vortex embedded in the trough of an AEW between 9–12 September. The vortex triggered a squall line (SL) in southeastern Senegal in the early morning of 11 September and became Tropical Depression 8 on 12 September. During this period, there was a Saharan Air Layer (SAL) outbreak in northwestern Senegal and adjacent Atlantic Ocean waters in the proximity of the SL. Increases in aerosol optical thicknesses in Mbour, Senegal, high dewpoint depressions observed in the Kawsara and Dakar rawinsondes, and model back-trajectories suggest the SAL exists. The close proximity of this and SL suggests interaction through dust entrainment and precipitation invigoration.
Attitudinal Barriers to Analgesic Use among Patients with Substance Use Disorders
Authors: Zallman Leah , Rubens Sonia L. , Saitz Richard , Samet Jeffrey H. , Lloyd-Travaglini Christine , Liebschutz Jane
Published: May 2012

Attitudinal barriers towards analgesic use among primary care patients with chronic pain and substance use disorders (SUDs) are not well understood. We evaluated the prevalence of moderate to significant attitudinal barriers to analgesic use among 597 primary care patients with chronic pain and current analgesic use with 3 subscales from the Barriers Questionaire II: concern about side effects, fear of addiction, and worry about reporting pain to physicians. Concern about side effects was a greater barrier for those with opioid use disorders (OUDs) and non-opioid SUDs than for those with no SUD (OR (95% CI): 2.30 (1.44–3.68), P<0.001 and 1.64 (1.02–2.65), P=0.041, resp.). Fear of addiction was a greater barrier for those with OUDs as compared to those with non-opioid SUDs (OR (95% CI): 2.12 (1.04–4.30), P=0.038) and no SUD (OR (95% CI): 2.69 (1.44–5.03), P=0.002). Conversely, participants with non-opioid SUDs reported lower levels of worry about reporting pain to physicians than those with no SUD (OR (95% CI): 0.43 (0.24–0.76), P=0.004). Participants with OUDs reported higher levels of worry about reporting pain than those with non-opioid SUDs (OR (95% CI): 1.91 (1.01–3.60), P=0.045). Concerns about side effects and fear of addiction can be barriers to analgesic use, moreso for people with SUDs and OUDs.
Electrical Crystallization Mechanism and Interface Characteristics of Nanowire ZnO/Al Structures Fabricated by the Solution Method
Authors: Tseng Yi-Wei , Hung Fei-Yi , Lui Truan-Sheng , Chen Yen-Ting , Xiao Ren-Syuan , Chen Kuan-Jen
Published: May 2012

Both solution nanowire ZnO and sputtered Al thin film on SiO2 as the wire‐film structure and the Al film were a conductive channel for electrical‐induced crystallization (EIC). Direct current (DC) raised the temperature of the Al film and improved the crystallization of the nanostructure. The effects of EIC not only induced Al atomic interface diffusion, but also doped Al on the roots of ZnO wires to form aluminum doped zinc oxide (AZO)/ZnO wires. The Al doping concentration and the distance of the ZnO wire increased with increasing the electrical duration. Also, the electrical current‐induced temperature was ~211°C (solid‐state doped process) and so could be applied to low‐temperature optoelectronic devices.
Dry‐Transfer of Aligned Multiwalled Carbon Nanotubes for Flexible Transparent Thin Films
Authors: Cole Matthew , Hiralal Pritesh , Ying Kai , Li Chi , Zhang Yan , Teo Kenneth , Ferrari Andrea , Milne William
Published: May 2012

Herein we present an inexpensive facile wet‐chemistry‐free approach to the transfer of chemical vapour‐deposited multiwalled carbon nanotubes to flexible transparent polymer substrates in a single‐step process. By controlling the nanotube length, we demonstrate accurate control over the electrical conductivity and optical transparency of the transferred thin films. Uniaxial strains of up to 140% induced only minor reductions in sample conductivity, opening up a number of applications in stretchable electronics. Nanotube alignment offers enhanced functionality for applications such as polarisation selective electrodes and flexible supercapacitor substrates. A capacitance of 17 F/g was determined for supercapacitors fabricated from the reported dry‐transferred MWCNTs with the corresponding cyclic voltagrams showing a clear dependence on nanotube length.
Synthesis and Anti‐Inflammatory Activity of a Novel Series of Diphenyl‐1,2,4‐triazoles and Related Derivatives
Authors: Cherala Swapna , Lingabathula Harikiran , Ganta Rama , Ampati Srinivas , Manda Sarangapani
Published: May 2012

In the present investigation we have synthesized a series of new 1‐[3‐(4‐substitutedphenyl)‐5‐phenyl‐4H‐1,2,4‐triazol‐4‐yl]urea and 1‐[3‐(4‐substitutedphenyl)‐5‐phenyl‐4H‐1,2,4‐triazol‐4‐yl]thiourea derivatives (4Ia ‐ 4IId). The newly synthesised derivatives were characterized by using the data of IR, 1H NMR and Mass Spectral analysis. Thus synthesised and characterized targetted compounds were further screened for their anti‐inflammatory activity by using Carrageenan – induced paw edema rat model. Among all the newly synthesized derivatives, Compounds 4Ia‐4Ic and Compounds 4IIa‐4IId were reduced the inflammation very significantly (p<0.0001), thus these compounds showed promising anti‐inflammatory activity and only one compound (4Id) showed moderate anti‐inflammatory activity (p<0.05).
Rapid Photocatalytic Degradation of Methylene Blue under High Photon Flux UV Irradiation: Characteristics and Comparison with Routine Low Photon Flux
Authors: Zhang Qian , Li Chaolin , Li Ting
Published: May 2012

This study examined the photocatalytic degradation efficiency under high UV photon flux (intensity normalized by photon energy) irradiation; the incident UV photon flux was einstein   made by a super high-intensity UV apparatus. A comparative study between high photon flux photocatalytic process and routine low photon flux photocatalytic process for methylene blue degradation has been made in aqueous solution. The experimental results showed that under the best conditions of high UV photocatalytic reaction 99% decolorization and 95% TOC removal of 20 mg L−1methylene blue could be achieved in 30 s and 120 s of UV irradiation time, respectively. To the best of our knowledge, photocatalytic decolorization and photocatalytic degradation of dyes in such a short time has not been reported. Aiming at the low photonic efficiency in high photon flux photocatalytic process, we found that reducing the density of excited electron-hole appropriately could improve initial apparent photonic efficiency effectively. The TOC experiments under high UV photon flux showed a faster mineralization rate and a different mineralization process compared to that under low UV photon flux.
Biotechnological Tools for Environmental Sustainability: Prospects and Challenges for Environments in Nigeria—A Standard Review
Authors: Ezeonu Chukwuma S. , Tagbo Richard , Anike Ephraim N. , Oje Obinna A. , Onwurah Ikechukwu N. E.
Published: May 2012

The environment is a very important component necessary for the existence of both man and other biotic organisms. The degree of sustainability of the physical environment is an index of the survival and well-being of the entire components in it. Additionally, it is not sufficient to try disposing toxic/deleterious substances with any known method. The best method of sustaining the environment is such that returns back all the components (wastes) in a recyclable way so that the waste becomes useful and helps the biotic and abiotic relationship to maintain an aesthetic and healthy equilibrium that characterizes an ideal environment. In this study, the method investigated includes biological method of environmental sustainability which seeks to investigate the various biotechnological tools (biotools) in current use and those undergoing investigations for future use.
Fast Food Consumption, Quality of Diet, and Obesity among Isfahanian Adolescent Girls
Authors: Rouhani Mohammad Hossein , Mirseifinezhad Maryam , Omrani Nasrin , Esmaillzadeh Ahmad , Azadbakht Leila
Published: May 2012

Background and Objective. Few data are available linking fast food intake to diet quality in developing countries. This study was conducted to determine the association between fast food consumption and diet quality as well as obesity among Isfahani girls.Methods. This cross-sectional study was done among 140 Iranian adolescents selected by the use of systematic cluster random sampling. Dietary intakes were assessed using a validated food frequency questionnaire. Diet quality was defined based on energy density and nutrient adequacy ratios (NARs).Results. Individuals in the highest quartile of fast food intake had significantly lower NARs for vitamin B1(P=0.008), phosphorus (P=0.0250), selenium (P<0.001)and vitamin B2(P=0.012) compared with those in the lowest quartile. Those in top quartile of fast food intake consumed more energy-dense diets than those in the bottom quartile (P=0.022). High intakes of fast foods were significantly associated with overweight (top quartile: 40% versus bottom quartile: 0%,P=0.0001) and obesity (11.4% versus 2.9%,P=0.0001).Conclusion. Fast food consumption is associated with poor diet quality and high prevalence of overweight and obesity among Isfahani adolescents. Prospective data are required to confirm these findings.
Anisotropic Weak Hardy Spaces and Wavelets
Authors: Barrios B. , Betancor J. J.
Published: May 2012

We characterize the anisotropic weak Hardy spacesHAp,∞(ℝn)associated with an expansive matrixAby using square functions involving wavelets coefficients.
Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases
Authors: Kumar Manoj , Nagpal Ravinder , Kumar Rajesh , Hemalatha R. , Verma Vinod , Kumar Ashok , Chakraborty Chaitali , Singh Birbal , Marotta Francesco , Jain Shalini , Yadav Hariom
Published: May 2012

Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especiallyBifidobacteriumspp. andLactobacillusspp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of cholesterol into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile, binding action of bile by fibre, and production of short-chain fatty acids by oligosaccharides. The present paper reviews the mechanisms of action of anti-cholesterolemic potential of probiotic microorganisms and probiotic food products, with the aim of lowering the risks of cardiovascular and coronary heart diseases.
Cancer Cell Secretion of the DAMP Protein HMGB1 Supports Progression in Malignant Mesothelioma
Authors: Jube Sandro , Rivera Zeyana S. , Bianchi Marco E. , Powers Amy , Wang Ena , Pagano Ian , Pass Harvey I. , Gaudino Giovanni , Carbone Michele , Yang Haining
Published: May 2012

Human malignant mesothelioma is an aggressive and highly lethal cancer that is believed to be caused by chronic exposure to asbestos and erionite. Prognosis for this cancer is generally poor because of late-stage diagnosis and resistance to current conventional therapies. The damage-associated molecular pattern protein HMGB1 has been implicated previously in transformation of mesothelial cells. Here we show that HMGB1 establishes an autocrine circuit in malignant mesothelioma cells that influences their proliferation and survival. Malignant mesothelioma cells strongly expressed HMGB1 and secreted it at high levels in vitro. Accordingly, HMGB1 levels in malignant mesothelioma patient sera were higher than that found in healthy individuals. The motility, survival, and anchorage-independent growth of HMGB1-secreting malignant mesothelioma cells was inhibited in vitro by treatment with monoclonal antibodies directed against HMGB1 or against the receptor for advanced glycation end products, a putative HMGB1 receptor. HMGB1 inhibition in vivo reduced the growth of malignant mesothelioma xenografts in severe-combined immunodeficient mice and extended host survival. Taken together, our findings indicate that malignant mesothelioma cells rely on HMGB1, and they offer a preclinical proof-of-principle that antibody-mediated ablation of HMBG1 is sufficient to elicit therapeutic activity, suggesting a novel therapeutic approach for malignant mesothelioma treatment. Cancer Res; 72(13); 3290–301. ©2012 AACR.
Combined EGFR/MET or EGFR/HSP90 Inhibition Is Effective in the Treatment of Lung Cancers Codriven by Mutant EGFR Containing T790M and MET
Authors: Xu Lu , Kikuchi Eiki , Xu Chunxiao , Ebi Hiromichi , Ercan Dalia , Cheng Katherine A. , Padera Robert , Engelman Jeffrey A. , Jänne Pasi A. , Shapiro Geoffrey I. , Shimamura Takeshi , Wong Kwok-Kin
Published: May 2012

Tyrosine kinase inhibitors (TKI) that target the EGF receptor (EGFR) are effective in most non–small cell lung carcinoma (NSCLC) patients whose tumors harbor activating EGFR kinase domain mutations. Unfortunately, acquired resistance eventually emerges in these chronically treated cancers. Two of the most common mechanisms of acquired resistance to TKIs seen clinically are the acquisition of a secondary “gatekeeper” T790M EGFR mutation that increases the affinity of mutant EGFR for ATP and activation of MET to offset the loss of EGFR signaling. Although up to one-third of patient tumors resistant to reversible EGFR TKIs harbor concurrent T790M mutation and MET amplification, potential therapies for these tumors have not been modeled in vivo. In this study, we developed a preclinical platform to evaluate potential therapies by generating transgenic mouse lung cancer models expressing EGFR-mutant Del19-T790M or L858R-T790M, each with concurrent MET overexpression. We found that monotherapy targeting EGFR or MET alone did not produce significant tumor regression. In contrast, combination therapies targeting EGFR and MET simultaneously were highly efficacious against EGFR TKI–resistant tumors codriven by Del19-T790M or L858R-T790M and MET. Our findings therefore provide an in vivo model of intrinsic resistance to reversible TKIs and offer preclinical proof-of-principle that combination targeting of EGFR and MET may benefit patients with NSCLC. Cancer Res; 72(13); 3302–11. ©2012 AACR.
Smurf2 Regulates the Senescence Response and Suppresses Tumorigenesis in Mice
Authors: Ramkumar Charusheila , Kong Yahui , Cui Hang , Hao Suyang , Jones Stephen N. , Gerstein Rachel M. , Zhang Hong
Published: May 2012

The E3 ubiquitin ligase Smurf2 mediates ubiquitination and degradation of several protein targets involved in tumorigenesis and induces senescence in human cells. However, the functional role of Smurf2 in tumorigenesis has not been fully evaluated. In this study, we generated a mouse model of Smurf2 deficiency to characterize the function of this E3 ligase in tumorigenesis. Smurf2 deficiency attenuated p16 expression and impaired the senescence response of primary mouse embryonic fibroblasts. In support of a functional role in controlling cancer, Smurf2 deficiency increased the susceptibility of mice to spontaneous tumorigenesis, most notably B-cell lymphoma. At a premalignant stage of tumorigenesis, we documented a defective senescence response in the spleens of Smurf2-deficient mice, consistent with a mechanistic link between impaired senescence regulation and increased tumorigenesis. Taken together, our findings offer the genetic evidence of an important tumor suppressor function for Smurf2. Cancer Res; 72(11); 2714–9. ©2012 AACR.
Oncogenic PI3K Mutations Lead to NF-κB–Dependent Cytokine Expression following Growth Factor Deprivation
Authors: Hutti Jessica E. , Pfefferle Adam D. , Russell Sean C. , Sircar Mayukh , Perou Charles M. , Baldwin Albert S.
Published: May 2012

The phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly misregulated signaling pathways in human cancers, but its impact on the tumor microenvironment has not been considered as deeply as its autonomous impact on tumor cells. In this study, we show that NF-κB is activated by the two most common PI3K mutations, PIK3CA E545K and H1047R. We found that markers of NF-κB are most strongly upregulated under conditions of growth factor deprivation. Gene expression analysis conducted on cells deprived of growth factors identified the repertoire of genes altered by oncogenic PI3K mutations following growth factor deprivation. This gene set most closely correlated with gene signatures from claudin-low and basal-like breast tumors, subtypes frequently exhibiting constitutive PI3K/Akt activity. An NF-κB–dependent subset of genes driven by oncogenic PI3K mutations was also identified that encoded primarily secreted proteins, suggesting a paracrine role for this gene set. Interestingly, while NF-κB activated by oncogenes such as Ras and EGF receptor leads to cell-autonomous effects, abrogating NF-κB in PI3K-transformed cells did not decrease proliferation or induce apoptosis. However, conditioned media from PI3K mutant-expressing cells led to increased STAT3 activation in recipient THP-1 monocytes or normal epithelial cells in a NF-κB and interleukin-6–dependent manner. Together, our findings describe a PI3K-driven, NF-κB–dependent transcriptional profile that may play a critical role in promoting a microenvironment amenable to tumor progression. These data also indicate that NF-κB plays diverse roles downstream from different oncogenic signaling pathways. Cancer Res; 72(13); 3260–9. ©2012 AACR.
Temporary Disruption of the Blood–Brain Barrier by Use of Ultrasound and Microbubbles: Safety and Efficacy Evaluation in Rhesus Macaques
Authors: McDannold Nathan , Arvanitis Costas D. , Vykhodtseva Natalia , Livingstone Margaret S.
Published: May 2012

The blood–brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method. Cancer Res; 72(14); 3652–63. ©2012 AACR.