bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropic dissipative effects on the buoyancy instability with background heat flux
Authors: Ren Haijun , Cao Jintao , Wu Zhengwei , Chu Paul K.
Published: March 2011

The linear buoyancy instability in magnetized plasmas is investigated in the presence of anisotropic resistivity and viscosity by taking into account the background heat flux. The magnetic field is assumed to be homogeneous and has both horizontal and vertical components. The heat is primarily transported along the magnetic force lines when the gyro radius is much less than the mean collision free path. The Hall term is examined first and shows a damping effect on the magnetothermal instability. The heat-flux-driven buoyancy instability (HBI) is then investigated by taking into account the parallel resistivity (PR), cross-field resistivity (CR), and the anisotropic viscosity. The general dispersion relation (DR) is derived and discussed in several special cases. We show that only the CR and viscosity exert effects on the DR in the first case. The critical condition for the occurrence of HBI is modified by the CR coupled with the viscosity and the value of the instability growth rate is diminished by them. The effects due to the PR (resp. viscosity) on the HBI are examined next. The PR (resp. viscosity) is shown to alter not only the growth rate but also the instability criterion. There exists an unstable mode when the temperature decreases in the direction of gravity while this case is proven to be magnetothermally stable in the ideal magnetohydrodynamic limit. A new unstable mode is solely induced by the presence of PR (resp. viscosity). When the PR and CR are both taken into account, the resistivity is shown to induce a damping mode rather than an instability. Finally, considering the PR and viscosity simultaneously, it is found that a new unstable mode is excited when the PR is not equal to the viscosity, or else, dissipation effects do not alter the instability criterion and just cut down the growth rate.
Communication: CO oxidation by silver and gold cluster cations: Identification of different active oxygen species
Authors: Popolan Denisia M. , Bernhardt Thorsten M.
Published: March 2011

The oxidation of carbon monoxide with nitrous oxide on mass-selected ${\rm Au}_{3}^{+} $ Au 3+ and ${\rm Ag}_{3}^{+} $ Ag 3+ clusters has been investigated under multicollision conditions in an octopole ion trap experiment. The comparative study reveals that for both gold and silver cations carbon dioxide is formed on the clusters. However, whereas in the case of ${\rm Au}_{3}^{+} $ Au 3+ the cluster itself acts as reactive species that facilitates the formation of CO2 from N2O and CO, for silver the oxidized clusters Ag3Ox+ (n = 1–3) are identified as active in the CO oxidation reaction. Thus, in the case of the silver cluster cations N2O is dissociated and one oxygen atom is suggested to directly react with CO, whereas a second kind of oxygen strongly bound to silver is acting as a substrate for the reaction.
Active control of divertor asymmetry on EAST by localized D2 and Ar puffing
Authors: Wang Dongsheng , Guo Houyang , Wang Huiqian , Luo Guangnan , Wu Zhenwei , Wu Jinhua , Gao Wei , Wang Liang , Li Qiang ,   EAST Team
Published: March 2011

The divertor asymmetry in particle and power fluxes has been investigated on the EAST superconducting tokamak [S. Wu and EAST Team, Fusion Eng. Des. 82, 463 (2007)] for both single null (SN) and double null (DN) divertor configurations. D2 and Ar puffing at various divertor locations has also been explored as an active means to reduce peak target heat load and control divertor asymmetry. For SN, peak heat load on the outer divertor target is 2–3 times that on the inner divertor target under typical ohmic plasma conditions. DN operation leads to a stronger in-out asymmetry favoring the outer divertor. D2 and Ar puffing promotes partial detachment near the strike points, greatly reducing peak target heat load (over 50%), while the far-SOL divertor plasma remains attached. What is remarkable is that the particle flux is even increased away from the strike points when the B×∇B drift is directed toward the divertor target, thus facilitating particle removal.
Qualitative behavioural assessment and quantitative physiological measurement of cattle naïve and habituated to road transport
Authors: Stockman C. A. , Collins T. , Barnes A. L. , Miller D. , Wickham S. L. , Beatty D. T. , Blache D. , Wemelsfelder F. , Fleming P. A.
Published: March 2011

The present study examined whether observers could distinguish between cattle that are naïve to road transport and the same cattle after becoming more habituated to transport. The behavioural expression of cattle was assessed through the method of qualitative behavioural assessment (QBA), and these assessments were correlated with various physiological parameters. Fourteen Angus steers were assessed during their first road trip and then again on their ninth trip, 15 days later. Blood samples were collected immediately before and after transport, and heart rate and core body temperature were measured continuously throughout each trip. Video footage recorded during each trip was edited and clips showing each individual within the first 30 min of departure were randomly ordered and shown to observers for QBA. There was significant (P < 0.001) consensus among 40 observers in their assessment of behavioural expression of the cattle. Transport-naïve cattle were described as more ‘agitated’, while transport-habituated were described as more ‘calm’. Core body temperature (P < 0.01), plasma glucose (P < 0.05) and the neutrophil : lymphocyte ratio (P < 0.01) were higher for the first trip than for the habituated trip (P < 0.01). QBA were significantly correlated with core body temperature (P < 0.01), heart rate (P < 0.01), plasma glucose (P < 0.05) and the neutrophil : lymphocyte ratio (P < 0.01). QBA appears to be a valid and integrative method of assessing cattle welfare under the conditions tested within the present study. There was significant consensus in the ability of human observers to interpret behavioural expression of cattle during this experiment. In addition, observers could identify differences in behavioural expression between cattle that were naïve versus habituated to transport, and these differences were supported by physiological measurements.
Group characteristics influence growth rate and backfat of commercially raised grower pigs
Authors: Jones Robert M. , Crump Ron E. , Hermesch Susanne
Published: March 2011

Records from 9429 pigs raised in 353 grower groups in a commercial Australian piggery were analysed to determine whether grower-group characteristics affected daily gain and backfat of individual pigs. Individual and group effects as well as their interactions were tested for significance (P < 0.05) in a mixed model, with sire fitted as a random effect. Group characteristics affected average daily gain (ADG) more than backfat (BF). The proportion of males in a group influenced both traits significantly, as did the average number of full siblings. Groups with 10–30% of the opposite sex had the highest BF and a 21–30 g/day reduction in ADG compared with the highest-performing groups with less than 10% of males. Each additional full sibling per group increased ADG by 5.5 ± 1.60 g/day and BF by 0.12 ± 0.05 mm. Additionally, ADG increased by 9.8 ± 2.64 g/day per second of group mean flight time and by 4.5 g/day per 10% increase in the proportion of Duroc pigs per group. Group size affected ADG (linear and quadratic) and BF (linear); however, the effect on ADG was considerably larger during the warmer grower season. In commercial piggeries, it may be possible to optimise individual daily gain through the manipulation of grower-group characteristics. Advantages for growth rate arose from including a portion of a calmer line of pigs within groups, optimising the stocking density in warmer months and maximising the proportion of quieter, less fearful pigs in grower groups.
Double-lock ratchet mechanism revealing the role of αSER-344 in F
o
F
1
ATP synthase
Authors: Beke-Somfai Tamás , Lincoln Per , Nordén Bengt
Published: March 2011

In a majority of living organisms, F
o
F
1
ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP + P
i
 → ATP + H
2
O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the
γ
P-O
ADP
bond-forming step via a double-proton transfer. At this step, the highly conserved αS344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar

ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a “ratchet” mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.
Temporal view of the costs and benefits of self-deception
Authors: Chance Zoë , Norton Michael I. , Gino Francesca , Ariely Dan
Published: March 2011

Researchers have documented many cases in which individuals rationalize their regrettable actions. Four experiments examine situations in which people go beyond merely explaining away their misconduct to actively deceiving themselves. We find that those who exploit opportunities to cheat on tests are likely to engage in self-deception, inferring that their elevated performance is a sign of intelligence. This short-term psychological benefit of self-deception, however, can come with longer-term costs: when predicting future performance, participants expect to perform equally well—a lack of awareness that persists even when these inflated expectations prove costly. We show that although people expect to cheat, they do not foresee self-deception, and that factors that reinforce the benefits of cheating enhance self-deception. More broadly, the findings of these experiments offer evidence that debates about the relative costs and benefits of self-deception are informed by adopting a temporal view that assesses the cumulative impact of self-deception over time.
Variability, compensation, and modulation in neurons and circuits
Authors: Marder Eve
Published: March 2011

I summarize recent computational and experimental work that addresses the inherent variability in the synaptic and intrinsic conductances in normal healthy brains and shows that multiple solutions (sets of parameters) can produce similar circuit performance. I then discuss a number of issues raised by this observation, such as which parameter variations arise from compensatory mechanisms and which reflect insensitivity to those particular parameters. I ask whether networks with different sets of underlying parameters can nonetheless respond reliably to neuromodulation and other global perturbations. At the computational level, I describe a paradigm shift in which it is becoming increasingly common to develop families of models that reflect the variance in the biological data that the models are intended to illuminate rather than single, highly tuned models. On the experimental side, I discuss the inherent limitations of overreliance on mean data and suggest that it is important to look for compensations and correlations among as many system parameters as possible, and between each system parameter and circuit performance. This second paradigm shift will require moving away from measurements of each system component in isolation but should reveal important previously undescribed principles in the organization of complex systems such as brains.
Cultivation of cereals by the first farmers was not more productive than foraging
Authors: Bowles Samuel
Published: March 2011

Did foragers become farmers because cultivation of crops was simply a better way to make a living? If so, what is arguably the greatest ever revolution in human livelihoods is readily explained. To answer the question, I estimate the caloric returns per hour of labor devoted to foraging wild species and cultivating the cereals exploited by the first farmers, using data on foragers and land-abundant hand-tool farmers in the ethnographic and historical record, as well as archaeological evidence. A convincing answer must account not only for the work of foraging and cultivation but also for storage, processing, and other indirect labor, and for the costs associated with the delayed nature of agricultural production and the greater exposure to risk of those whose livelihoods depended on a few cultivars rather than a larger number of wild species. Notwithstanding the considerable uncertainty to which these estimates inevitably are subject, the evidence is inconsistent with the hypothesis that the productivity of the first farmers exceeded that of early Holocene foragers. Social and demographic aspects of farming, rather than its productivity, may have been essential to its emergence and spread. Prominent among these aspects may have been the contribution of farming to population growth and to military prowess, both promoting the spread of farming as a livelihood.
Climatological determinants of woody cover in Africa
Authors: Good Stephen P. , Caylor Kelly K.
Published: March 2011

Determining the factors that influence the distribution of woody vegetation cover and resolving the sensitivity of woody vegetation cover to shifts in environmental forcing are critical steps necessary to predict continental-scale responses of dryland ecosystems to climate change. We use a 6-year satellite data record of fractional woody vegetation cover and an 11-year daily precipitation record to investigate the climatological controls on woody vegetation cover across the African continent. We find that—as opposed to a relationship with only mean annual rainfall—the upper limit of fractional woody vegetation cover is strongly influenced by both the quantity and intensity of rainfall events. Using a set of statistics derived from the seasonal distribution of rainfall, we show that areas with similar seasonal rainfall totals have higher fractional woody cover if the local rainfall climatology consists of frequent, less intense precipitation events. Based on these observations, we develop a generalized response surface between rainfall climatology and maximum woody vegetation cover across the African continent. The normalized local gradient of this response surface is used as an estimator of ecosystem vegetation sensitivity to climatological variation. A comparison between predicted climate sensitivity patterns and observed shifts in both rainfall and vegetation during 2009 reveals both the importance of rainfall climatology in governing how ecosystems respond to interannual fluctuations in climate and the utility of our framework as a means to forecast continental-scale patterns of vegetation shifts in response to future climate change.
Quantifying the buildup in extent and complexity of free exploration in mice
Authors: Benjamini Yoav , Fonio Ehud , Galili Tal , Havkin Gregor Z. , Golani Ilan
Published: March 2011

To obtain a perspective on an animal's own functional world, we study its behavior in situations that allow the animal to regulate the growth rate of its behavior and provide us with the opportunity to quantify its moment-by-moment developmental dynamics. Thus, we are able to show that mouse exploratory behavior consists of sequences of repeated motion: iterative processes that increase in extent and complexity, whose presumed function is a systematic active management of input acquired during the exploration of a novel environment. We use this study to demonstrate our approach to quantifying behavior: targeting aspects of behavior that are shown to be actively managed by the animal, and using measures that are discriminative across strains and treatments and replicable across laboratories.
Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer
Authors: Takahashi Sayuri , Watanabe Tomoyuki , Okada Maiko , Inoue Kazuki , Ueda Takashi , Takada Ichiro , Watabe Tetsuro , Yamamoto Yoko , Fukuda Toru , Nakamura Takashi , Akimoto Chihiro , Fujimura Tetsuya , Hoshino Maiko , Imai Yuuki , Metzger Daniel , Miyazono Kohei , Minami Yasuhiro , Chambon Pierre , Kitamura Tadaichi , Matsumoto Takahiro , Kato Shigeaki
Published: March 2011

Prostate cancer development is associated with hyperactive androgen signaling. However, the molecular link between androgen receptor (AR) function and humoral factors remains elusive. A prostate cancer mouse model was generated by selectively mutating the AR threonine 877 into alanine in prostatic epithelial cells through Cre-ER
T2
–mediated targeted somatic mutagenesis. Such AR point mutant mice (

AR
pe-T877A/Y

) developed hypertrophic prostates with responses to both an androgen antagonist and estrogen, although no prostatic tumor was seen. In prostate cancer model transgenic mice, the onset of prostatic tumorigenesis as well as tumor growth was significantly potentiated by introduction of the AR T877A mutation into the prostate. Genetic screening of mice identified Wnt-5a as an activator. Enhanced Wnt-5a expression was detected in the malignant prostate tumors of patients, whereas in benign prostatic hyperplasia such aberrant up-regulation was not obvious. These findings suggest that a noncanonical Wnt signal stimulates development of prostatic tumors with AR hyperfunction.
Chemistry of mycolactones, the causative toxins of Buruli ulcer
Authors: Kishi Yoshito
Published: March 2011

Buruli ulcer is a severe and devastating skin disease caused byMycobacterium ulceransinfection, yet it is one of the most neglected diseases. The causative toxin, referred to as mycolactone A/B, was isolated and characterized as a polyketide-derived macrolide in 1999. The current status of the mycolactone chemistry is described, highlighting the stereochemistry assignment of mycolactone A/B; total synthesis; the structure determination of mycolactone congeners from the human pathogenM. ulcerans, the frog pathogenMycobacterium liflandii, and the fish pathogenMycobacterium marinum; the structural diversity in the mycolactone class of natural products; the highly sensitive detection/structure-analysis of mycolactones; and some biological activity.
The circadian oscillator gene
GIGANTEA
mediates a long-term response of the
Arabidopsis thaliana
circadian clock to sucrose
Authors: Dalchau Neil , Baek Seong J. , Briggs Helen M. , Robertson Fiona C. , Dodd Antony N. , Gardner Michael J. , Stancombe Matthew A. , Haydon Michael J. , Stan Guy-Bart , Gonçalves Jorge M. , Webb Alex A. R.
Published: March 2011

Circadian clocks are 24-h timing devices that phase cellular responses; coordinate growth, physiology, and metabolism; and anticipate the day–night cycle. Here we report sensitivity of the
Arabidopsis thaliana
circadian oscillator to sucrose, providing evidence that plant metabolism can regulate circadian function. We found that the
Arabidopsis
circadian system is particularly sensitive to sucrose in the dark. These data suggest that there is a feedback between the molecular components that comprise the circadian oscillator and plant metabolism, with the circadian clock both regulating and being regulated by metabolism. We used also simulations within a three-loop mathematical model of the
Arabidopsis
circadian oscillator to identify components of the circadian clock sensitive to sucrose. The mathematical studies identified
GIGANTEA
(
GI
) as being associated with sucrose sensing. Experimental validation of this prediction demonstrated that
GI
is required for the full response of the circadian clock to sucrose. We demonstrate that
GI
acts as part of the sucrose-signaling network and propose this role permits metabolic input into circadian timing in
Arabidopsis
.
Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways
Authors: Hatori Megumi , Hirota Tsuyoshi , Iitsuka Michiko , Kurabayashi Nobuhiro , Haraguchi Shogo , Kokame Koichi , Sato Ryuichiro , Nakai Akira , Miyata Toshiyuki , Tsutsui Kazuyoshi , Fukada Yoshitaka
Published: March 2011

The circadian clock is phase-delayed or -advanced by light when given at early or late subjective night, respectively. Despite the importance of the time-of-day–dependent phase responses to light, the underlying molecular mechanism is poorly understood. Here, we performed a comprehensive analysis of light-inducible genes in the chicken pineal gland, which consists of light-sensitive clock cells representing a prototype of the clock system. Light stimulated expression of 62 genes and 40 ESTs by >2.5-fold, among which genes responsive to the heat shock and endoplasmic reticulum stress as well as their regulatory transcription factors heat shock factor (HSF)1, HSF2, and X-box-binding protein 1 (XBP1) were strongly activated when a light pulse was given at late subjective night. In contrast, the light pulse at early subjective night caused prominent induction of
E4bp4
, a key regulator in the phase-delaying mechanism of the pineal clock, along with activation of a large group of cholesterol biosynthetic genes that are targets of sterol regulatory element-binding protein (SREBP) transcription factor. We found that the light pulse stimulated proteolytic formation of active SREBP-1 that, in turn, transactivated
E4bp4
expression, linking SREBP with the light-input pathway of the pineal clock. As an output of light activation of cholesterol biosynthetic genes, we found light-stimulated pineal production of a neurosteroid, 7α-hydroxypregnenolone, demonstrating a unique endocrine function of the pineal gland. Intracerebroventricular injection of 7α-hydroxypregnenolone activated locomotor activities of chicks. Our study on the genome-wide gene expression analysis revealed time-of-day–dependent light activation of signaling pathways and provided molecular connection between gene expression and behavior through neurosteroid release from the pineal gland.
Structure of bacteriophage
ϕ
29 head fibers has a supercoiled triple repeating helix-turn-helix motif
Authors: Xiang Ye , Rossmann Michael G.
Published: March 2011

The tailed bacteriophage
ϕ
29 capsid is decorated with 55 fibers attached to quasi-3-fold symmetry positions. Each fiber is a homotrimer of gene product 8.5 (gp8.5) and consists of two major structural parts, a pseudohexagonal base and a protruding fibrous portion that is about 110 Å in length. The crystal structure of the C-terminal fibrous portion (residues 112–280) has been determined to a resolution of 1.6 Å. The structure is about 150 Å long and shows three distinct structural domains designated as head, neck, and stem. The stem region is a unique three-stranded helix-turn-helix supercoil that has not previously been described. When fitted into a cryoelectron microscope reconstruction of the virus, the head structure corresponded to a disconnected density at the distal end of the fiber and the neck structure was located in weak density connecting it to the fiber. Thin section studies of
Bacillus subtilis
cells infected with fibered or fiberless
ϕ
29 suggest that the fibers might enhance the attachment of the virions onto the host cell wall.
Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein
Authors: Lu Jinghua , Marjon Kristopher D. , Marnell Lorraine L. , Wang Ruipeng , Mold Carolyn , Du Clos Terry W. , Sun Peter
Published: March 2011

C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, FcαRI, as a ligand for pentraxins. CRP recognized FcαRI both in solution and on cells, and the pentraxin binding site on the receptor appears distinct from that recognized by IgA. Further competitive binding and mutational analysis showed that FcαRI bound to the effector face of CRP in a region overlapping with complement C1q and Fcγ receptor (FcγR) binding sites. CRP cross-linking of FcαRI resulted in extracellular signal-regulated kinase (ERK) phosphorylation, cytokine production, and degranulation in FcαRI-transfected RBL cells. In neutrophils, CRP induced FcαRI surface expression, phagocytosis, and TNF-α secretion. The ability of CRP to activate FcαRI defines a function for pentraxins in inflammatory responses involving neutrophils and macrophages. It also highlights the innate aspect of otherwise humoral immunity-associated antibody receptors.
Population trends of grassland birds in North America are linked to the prevalence of an agricultural epizootic in Europe
Authors: Nocera Joseph J. , Koslowsky Hannah M.
Published: March 2011

Globalization of trade has dramatic socioeconomic effects, and, intuitively, significant ecological effects should follow. However, few quantitative examples exist of the interrelationship of globalization, socioeconomics, and ecological patterns. We present a striking illustration of a cascade in which bovine spongiform encephalopathy (BSE; “mad cow disease”) outbreaks in Europe exerted pressure on global beef markets, subsequently affecting North American hayfields and grassland bird populations. We examined competing models, which linked the prevalence of BSE in five focal countries, volume of beef exports to those countries from North America, and the amount of hayfield harvested and the abundance of grassland birds in North America. We found that (
i
) imports from North America increased 1 y after BSE outbreaks; (
ii
) probably because fewer cattle remained, the hay harvest in North America was reduced 2 y after the outbreak; (
iii
) the reduced hay harvest yielded a positive response in grassland bird populations 3 y after the outbreak.
Genetic elimination of dengue vector mosquitoes
Authors: Wise de Valdez Megan R. , Nimmo Derric , Betz John , Gong Hong-Fei , James Anthony A. , Alphey Luke , Black William C.
Published: March 2011

An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector,
Aedes aegypti
, was engineered to have a repressible female-specific flightless phenotype. This strain circumvents the need for radiation-induced sterilization, allows genetic sexing resulting in male-only releases, and permits the release of eggs instead of adult mosquitoes. OX3604C males introduced weekly into large laboratory cages containing stable target mosquito populations at initial ratios of 8.5–10∶1 OX3604C∶target eliminated the populations within 10–20 weeks. These data support the further testing of this strain in contained or confined field trials to evaluate mating competitiveness and environmental and other effects. Successful completion of the field trials should facilitate incorporation of this approach into area-wide dengue control or elimination efforts as a component of an integrated vector management strategy.
Ion clustering in aqueous solutions probed with vibrational energy transfer
Authors: Bian Hongtao , Wen Xiewen , Li Jiebo , Chen Hailong , Han Suzee , Sun Xiuquan , Song Jian , Zhuang Wei , Zheng Junrong
Published: March 2011

Despite prolonged scientific efforts to unravel the hydration structures of ions in water, many open questions remain, in particular concerning the existences and structures of ion clusters in 1∶1 strong electrolyte aqueous solutions. A combined ultrafast 2D IR and pump/probe study through vibrational energy transfers directly observes ion clustering in aqueous solutions of LiSCN, NaSCN, KSCN and CsSCN. In a near saturated KSCN aqueous solution (water/KSCN molar ratio = 2.4/1), 95% of the anions form ion clusters. Diluting the solution results in fewer, smaller, and tighter clusters. Cations have significant effects on cluster formation. A small cation results in smaller and fewer clusters. The vibrational energy transfer method holds promise for studying a wide variety of other fast short-range molecular interactions.
Nitric oxide prevents axonal degeneration by inducing HIF-1–dependent expression of erythropoietin
Authors: Keswani Sanjay C. , Bosch-Marcé Marta , Reed Nicole , Fischer Angela , Semenza Gregg L. , Höke Ahmet
Published: March 2011

Nitric oxide (NO) is a signaling molecule that can trigger adaptive (physiological) or maladaptive (pathological) responses to stress stimuli in a context-dependent manner. We have previously reported that NO may signal axonal injury to neighboring glial cells. In this study, we show that mice deficient in neuronal nitric oxide synthase (nNOS
−/−
) are more vulnerable than WT mice to toxin-induced peripheral neuropathy. The administration of NO donors to primary dorsal root ganglion cultures prevents axonal degeneration induced by acrylamide in a dose-dependent manner. We demonstrate that NO-induced axonal protection is dependent on hypoxia-inducible factor (HIF)-1–mediated transcription of erythropoietin (EPO) within glial (Schwann) cells present in the cultures. Transduction of Schwann cells with adenovirus AdCA5 encoding a constitutively active form of HIF-1α results in amelioration of acrylamide-induced axonal degeneration in an EPO-dependent manner. Mice that are partially deficient in HIF-1α (HIF-1α
+/−
) are also more susceptible than WT littermates to toxic neuropathy. Our results indicate that NO→HIF-1→EPO signaling represents an adaptive mechanism that protects against axonal degeneration.
Glucose transporters and ATP-gated K
+
(K
ATP
) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells
Authors: Yee Karen K. , Sukumaran Sunil K. , Kotha Ramana , Gilbertson Timothy A. , Margolskee Robert F.
Published: March 2011

Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on (
a
) activation of sugar-gated cation channels and/or (
b
) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium–glucose cotransporter (SGLT1), and two components of the ATP-gated K
+
(K
ATP
) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K
ATP
channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K
ATP
channels constitute a major portion of K
+
channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K
ATP
may serve as mediators of the T1r-independent sweet taste of sugars.
Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK
Authors: Shang Libin , Chen She , Du Fenghe , Li Shen , Zhao Liping , Wang Xiaodong
Published: March 2011

Macroautophagy (herein referred to as autophagy) is an evolutionarily conserved self-digestive process cells adapt to starvation and other stress responses. Upon starvation, autophagy is induced, providing cells with needed nutrient supplies. We report here that Unc-51-like kinase 1 (Ulk1), a key initiator for mammalian autophagy, undergoes dramatic dephosphorylation upon starvation, particularly at serine 638 and serine 758. Phosphorylations of Ulk1 are mediated by mammalian target-of-rapamycin (mTOR) kinase and adenosine monophosphate activated protein kinase (AMPK). AMPK interacts with Ulk1 in a nutrient-dependent manner. Proper phosphorylations on Ulk1 are crucial for Ulk1/AMPK association, as a single serine-to-alanine mutation (S758A) at Ulk1 impairs this interaction. Compared to the wild-type ULK1, this Ulk1-S758A mutant initiates starvation-induced autophagy faster at an early time point, but does not alter the maximum capacity of autophagy when starvation prolongs. This study therefore revealed previously unnoticed acute autophagy response to environmental changes.
Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability
Authors: Ho King Ching , Zhou Zhonghua , She Yi-Min , Chun Alex , Cyr Terry D. , Yang Xiaolong
Published: March 2011

The large tumor suppressor 1 (LATS1) is a serine/threonine kinase and tumor suppressor found down-regulated in a broad spectrum of human cancers. LATS1 is a central player of the emerging Hippo-LATS suppressor pathway, which plays important roles in cell proliferation, apoptosis, and stem cell differentiation. Despite the ample data supporting a role for LATS1 in tumor suppression, how LATS1 is regulated at the molecular level remains largely unknown. In this study, we have identified Itch, a HECT class E3 ubiquitin ligase, as a unique binding partner of LATS1. Itch can complex with LATS1 both in vitro and in vivo through the PPxY motifs of LATS1 and the WW domains of Itch. Significantly, we found that overexpression of Itch promoted LATS1 degradation by polyubiquitination through the 26S proteasome pathway. On the other hand, knockdown of endogenous Itch by shRNAs provoked stabilization of endogenous LATS1 proteins. Finally, through several functional assays, we also revealed that change of Itch abundance alone is sufficient for altering LATS1-mediated downstream signaling, negative regulation of cell proliferation, and induction of apoptosis. Taking these data together, our study identifies E3 ubiquitin ligase Itch as a unique negative regulator of LATS1 and presents a possibility of targeting LATS1/Itch interaction as a therapeutic strategy in cancer.
Mutated β-catenin evades a microRNA-dependent regulatory loop
Authors: Veronese Angelo , Visone Rosa , Consiglio Jessica , Acunzo Mario , Lupini Laura , Kim Taewan , Ferracin Manuela , Lovat Francesca , Miotto Elena , Balatti Veronica , D'Abundo Lucilla , Gramantieri Laura , Bolondi Luigi , Pekarsky Yuri , Perrotti Danilo , Negrini Massimo , Croce Carlo M.
Published: March 2011

hsa-mir-483
is located within intron 2 of the
IGF2
gene. We have previously shown oncogenic features of miR-483-3p through cooperation with IGF2 or by independently targeting the proapoptotic gene BBC3/PUMA. Here we demonstrate that expression of miR-483 can be induced independently of IGF2 by the oncoprotein β-catenin through an interaction with the basic helix–loop–helix protein upstream stimulatory transcription factor 1. We also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulatory loop that becomes ineffective in cells harboring an activating mutation of β-catenin. These results provide insights into the complex regulation of the
IGF2/miR-483
locus, revealing players in the β-catenin pathway.
The wrong suspect?
Authors: Short Ben
Published: March 2011

Parkinson's disease may be caused by microtubule, rather than mitochondrial complex I, dysfunction.
OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation
Authors: Itoh Takashi , Kanno Eiko , Uemura Takefumi , Waguri Satoshi , Fukuda Mitsunori
Published: March 2011

Macroautophagy is a bulk degradation system conserved in all eukaryotic cells. A ubiquitin-like protein, Atg8, and its homologues are essential for autophagosome formation and act as a landmark for selective autophagy of aggregated proteins and damaged organelles. In this study, we report evidence demonstrating that OATL1, a putative Rab guanosine triphosphatase–activating protein (GAP), is a novel binding partner of Atg8 homologues in mammalian cells. OATL1 is recruited to isolation membranes and autophagosomes through direct interaction with Atg8 homologues and is involved in the fusion between autophagosomes and lysosomes through its GAP activity. We further provide evidence that Rab33B, an Atg16L1-binding protein, is a target substrate of OATL1 and is involved in the fusion between autophagosomes and lysosomes, the same as OATL1. Because both its GAP activity and its Atg8 homologue–binding activity are required for OATL1 to function, we propose a model that OATL1 uses Atg8 homologues as a scaffold to exert its GAP activity and to regulate autophagosomal maturation.
Principles of chromosomal organization: lessons from yeast
Authors: Zimmer Christophe , Fabre Emmanuelle
Published: March 2011

The spatial organization of genes and chromosomes plays an important role in the regulation of several DNA processes. However, the principles and forces underlying this nonrandom organization are mostly unknown. Despite its small dimension, and thanks to new imaging and biochemical techniques, studies of the budding yeast nucleus have led to significant insights into chromosome arrangement and dynamics. The dynamic organization of the yeast genome during interphase argues for both the physical properties of the chromatin fiber and specific molecular interactions as drivers of nuclear order.
On emerging nuclear order
Authors: Rajapakse Indika , Groudine Mark
Published: March 2011

Although the nonrandom nature of interphase chromosome arrangement is widely accepted, how nuclear organization relates to genomic function remains unclear. Nuclear subcompartments may play a role by offering rich microenvironments that regulate chromatin state and ensure optimal transcriptional efficiency. Technological advances now provide genome-wide and four-dimensional analyses, permitting global characterizations of nuclear order. These approaches will help uncover how seemingly separate nuclear processes may be coupled and aid in the effort to understand the role of nuclear organization in development and disease.
Leveraging Electronic Medical Records for Surveillance of Surgical Site Infection in a Total Joint Replacement Population
Authors: Inacio Maria C. S. , Paxton Elizabeth W. , Chen Yuexin , Harris Jessica , Eck Enid , Barnes Sue , Namba Robert S. , Ake Christopher F.
Published: March 2011

Objective.

TO evaluate whether a hybrid electronic screening algorithm using a total joint replacement (TJR) registry, electronic surgical site infection (SSI) screening, and electronic health record (EHR) review of SSI is sensitive and specific for SSI detection and reduces chart review volume for SSI surveillance.

Design.

Validation study.

Setting.

A large health maintenance organization (HMO) with 8.6 million members.

Methods.

Using codes for infection, wound complications, cellullitis, procedures related to infections, and surgeon-reported complications from the International Classification of Diseases, Ninth Revision, Clinical Modification, we screened each TJR procedure performed in our HMO between January 2006 and December 2008 for possible infections. Flagged charts were reviewed by clinical-content experts to confirm SSIs. SSIs identified by the electronic screening algorithm were compared with SSIs identified by the traditional indirect surveillance methodology currently employed in our HMO. Positive predictive values (PPVs), negative predictive values (NPVs), and specificity and sensitivity values were calculated. Absolute reduction of chart review volume was evaluated.

Results.

The algorithm identified 4,001 possible SSIs (9.5%) for the 42,173 procedures performed for our TJR patient population. A total of 440 case patients (1.04%) had SSIs (PPV, 11.0%; NPV, 100.0%). The sensitivity and specificity of the overall algorithm were 97.8% and 91.5%, respectively.

Conclusion.

An electronic screening algorithm combined with an electronic health record review of flagged cases can be used as a valid source for TJR SSI surveillance. The algorithm successfully reduced the volume of chart review for surveillance by 90.5%.
Universal Admission Screening for Methicillin-Resistant Staphylococcus aureus in a Level HID Neonatal Intensive Care Unit: The First 9 Months
Authors: Myers Patrick J. , Marcinak John , David Michael Z. , Zychowski Diana L. , Boyle-Vavra Susan , Weber Stephen , Daum Robert S.
Published: March 2011

In response to epidemic methicillin-resistant Staphylococcus aureus (MRSA) in the community, the Illinois General Assembly mandated that all patients admitted to intensive care units statewide be screened for MRSA. Screening was instituted at our neonatal intensive care unit (NICU) in September 2007 by a polymerase chain reaction (PCR)-based strategy. The law created an opportunity to determine the rate of MRSA colonization among neonates, to gather information about subsequent MRSA infections, and to evaluate risk factors for MRSA colonization on admission to the NICU.
Antibiotic Resistance in Pseudomonas aeruginosa Related to Quinolone Formulary Changes: An Interrupted Time Series Analysis
Authors: Church E. Chandler , Mauldin Patrick D. , Bosso John A.
Published: March 2011

Pseudomonas aeruginosa is a nosocomial pathogen capable of exhibiting a variety of resistance mechanisms against multiple classes of antibiotics. Fluoroquinolones, commonly used to treat a variety of infections in both ambulatory and hospitalized patients, have been increasingly linked to the development of resistance, both to fluoroquinolones and to other classes of antibiotics including β-lactams, cephalosporins, and carbapenems. In turn, as many as 95% of multidrug-resistant pseudomonal isolates may be resistant to fluoroquinolones. Although research has examined the effect of fluoroquinolone use on P. aeruginosa resistance, to our knowledge, no work has been published describing possible differences among individual fluoroquinolones related to resistance to other antibiotic classes. The purpose of this analysis was to assess the possible effects of varying usage of levofloxacin, gatifloxacin, and moxifloxacin on P. aeruginosa susceptibility to piperacillin-tazobactam, cefepime, and tobramycin. Data from January 2000 through December 2008 were obtained from clinical microbiology and pharmacy databases of the Medical University of South Carolina Medical Center, which is a 689-bed academic medical center and level 1 trauma center with adult and pediatric beds. This study was approved by the institution's institutional review board.
Does Adaptation to Climate Change Provide Food Security? A Micro‐Perspective from Ethiopia
Authors: Di Falco Salvatore , Veronesi Marcella , Yesuf Mahmud
Published: March 2011

We examine the driving forces behind farm households’ decisions to adapt to climate change, and the impact of adaptation on farm households’ food productivity. We estimate a simultaneous equations model with endogenous switching to account for the heterogeneity in the decision to adapt or not, and for unobservable characteristics of farmers and their farm. Access to credit, extension and information are found to be the main drivers behind adaptation. We find that adaptation increases food productivity, that the farm households that did not adapt would benefit the most from adaptation.
Estimating the Environmental Impact of Land and Production Decisions with Multivariate Selection Rules and Panel Data
Authors: Lacroix Anne , Thomas Alban
Published: March 2011

We propose an estimation procedure dealing with multivariate selection and dynamics in land choice and unobserved heterogeneity in structural and crop selection equations. The method is applied to a multi‐output profit function with multiple corner solutions and farm‐level panel data. Estimation results reveal that the single selection rule associated with the Tobit procedure is rejected in favor of our multivariate selection treatment. Inconsistent estimates are expected with the Tobit procedure, or if farmer fixed effects are omitted, which can have important consequences for policy recommendations, as illustrated in an evaluation of nitrogen runoff elasticities with respect to economic variables.
First Report of Botrytis cinerea Causing Gray Mold of Tobacco in Guizhou Province of China
Authors: Wang H.-C. , Li W.-H. , Wang M.-S. , Chen Q.-Y. , Feng Y.-G. , Shi J.-X.
Published: March 2011

Tobacco (Nicotiana tabacum L.) is a leafy, annual, solanaceous plant grown commercially for its leaves. Guizhou Province produces more than 30% of the total Chinese tobacco crop. In July 2010, a disease was observed in a commercial field of 5-month-old N. tabacum plants in Bijie, Guizhou in southwestern China. Symptoms first appeared on the leaves as small spots that later increased in size and developed into expanded, dark brown lesions covered with green-gray spore masses. Lesions expanded rapidly under cool, humid conditions. Isolates of Botrytis cinerea were collected from diseased leaves with typical symptoms. Diseased leaf samples were washed with distilled water three times, placed in a moist chamber, and incubated at 25°C in darkness for 48 h to encourage sporulation. Spores produced on leaves were transferred to individual agar discs (5 mm in diameter) with an inoculating needle and then the agar discs were transferred to potato dextrose agar (PDA) and incubated at 25°C for 7 days. Fungal colonies were at first colorless and later became gray to brown when the conidia differentiated. The size of conidia ranged from 5.0 to 9.5 × 6.5 to 12.5 μm (average 7.3 × 8.7 μm) based on 50 spore measurements. Microsclerotia produced in the culture were round or irregular and ranged from 1.2 to 3.0 × 1.0 to 2.5 mm (average 2.1 × 2.0 mm). The pathogen was identified as B. cinerea Pers.:Fr on the basis of morphology and sequence of ITS1-5.8s-ITS2 region of rDNA amplified by PCR using universal primers ITS-1 (5′-TCCGTAGGTGAACCTGCGG-3′) and ITS-4 (5′-TCCTCCGCTTATTGATATGC-3′). The sequence (GenBank Accession No. HQ902163) exactly matched the sequences of two Botryotinia fuckeliana (anamorph B. cinerea) accessions, (e.g., GenBank Accession Nos. HM849615.1 and HM849047.1). Koch's postulates were conducted by wound inoculating five tobacco leaves (cv. K326) after surface disinfesting them with 5% NaOCl. Plugs of the fungus (5 mm in diameter) obtained from the colony margins were transferred onto 3 × 3 mm wounds made with a needle on the surface of five sterilized leaves. Inoculated leaves were incubated at 25°C, 100 to 120 μE·m–2·s–1, relative humidity >80%, and 16 h light per day for disease development. Typical symptoms developed on leaves within 7 days after inoculation. The pathogen was reisolated from affected leaves but not from the noninoculated control leaves. Botrytis gray mold blight has been recorded on N. tabacum in New Zealand, the United Kingdom, and northern China (1–3). However, to our knowledge, this is the first report of Botrytis blight on N. tabacum in Guizhou Province of China and the disease must be considered in existing disease management practices.

References: (1) W. Brian et al. Mol. Plant Pathol. 8:561, 2007. (2) A. G. Mcleod et al. N. Z. J. Crop Hortic. Sci/Exp. Agric. 12:866, 1958. (3) Z. Y. Zhang. Page 37 in: Flora Fungorum Sinicorum. Vol. 26. Science Press, Beijing, 2006.