bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidation of the two-phase Nb/Nb5Si3 composite: The role of energetics, thermodynamics, segregation, and interfaces
Authors: Liu Shi-Yu , Shang Jia-Xiang , Wang Fu-He , Liu Shiyang , Zhang Yue , Li Dejun , Shields Darwin , Xue Wenhua , Liu Yingdi , Dang Hongli , Wang Sanwu
Published: January 2013

Oxidation behavior of the two-phase Nb/Nb5Si3 composite is of significant importance for the potential applications of the composite at high-temperature conditions. We investigate the atomic-scale oxidation mechanism of the Nb/Nb5Si3 composite with first-principles density-functional theory and thermodynamics analysis. In particular, the effects of energetics, thermodynamics, segregation, and interfaces are identified. The clean composite surface is found to be composed of both Nb(110) and Si-terminated Nb5Si3(001). Energetics and thermodynamics calculations show that, during the oxidation process, the Nb(110) surface is oxidized first, followed by the segregation of niobium of the Nb5Si3(001) surface and subsequent oxidation of the Nb element of Nb5Si3. High coverage of oxygen results in dissolved oxygen in bulk Nb through the diffusion of oxygen in the surface and at the interface. The theoretical investigation also provides an explanation, at the atomic-scale, for the experimental observation that the oxidation layer is essentially composed of niobium oxide and almost free of silicon. Furthermore, the methodology of this work can be applied to investigations of the oxidation behavior of other two-phase and multi-phase composites.
Fluctuated atom-sized junctions in a liquid environment
Authors: Tsutsui Makusu , Taniguchi Masateru
Published: January 2013

Durability of atom-sized junctions in a liquid environment was investigated and compared with that in a vacuum. The single atom junction lifetime was measured in an organic solvent under various stretching speed vd ranging from 10 to 0.001 nm/s. We found the natural lifetime of about 1 s for Au single-atom chains formed in a non-polar organic solvent at vd ≤ 0.01 nm/s, which was an order of magnitude shorter than that in a vacuum. The decreased junction lifetime indicates contact instability induced by thermal collisions of solvent molecules that exert pressure on the nanocontacts.
High p-type conduction in high-Al content Mg-doped AlGaN
Authors: Kinoshita Toru , Obata Toshiyuki , Yanagi Hiroyuki , Inoue Shin-ichiro
Published: January 2013

We report on the successful fabrication of highly conductive p-type Mg-doped Al0.7Ga0.3N thin films grown on sapphire substrates by metal-organic chemical vapor deposition. Photoluminescence measurements show that Mg doping for growth with a high V/III ratio and moderate Mg concentration can effectively suppress self-compensation by the formation of nitrogen vacancy complexes. The lowest electrical resistivity was found to be 47 Ω cm at room temperature. Moreover, the temperature dependence of the p-type conductivity in these high-Al content AlGaN films shows the extremely small effective activation energies of 47–72 meV at temperatures below 500 K.
Bio-oil production by fast pyrolysis from agriculture residue in northeastern China
Authors: Xie Huaqing , Yu Qingbo , Qin Qin , Zhang Haitao , Fu Xinglong
Published: January 2013

In this paper, three typical agriculture residues (corn cob (CC), peanut shell (PS), and pine cone (PC)) from northeastern China were investigated for fast pyrolysis to produce bio-oil. The influences of carrier gas velocity, temperature, and particle size of biomass on bio-oil yield were studied. With the increase of carrier gas velocity, the bio-oil yield increased, but the increase rate of bio-oil yield first increased and then decreased. As temperature increased, the bio-oil yield first increased and then decreased. The variation trends of bio-oil yield with particle size for the three biomasses were different. For CC, the bio-oil yield increased with the reduction of the granularity; but it was completely opposite for PS and PC. The main components of the exhaust gas were CO2, CO, H2, and small quantities of CHx. The compounds of bio-oil were mostly with oxygen functional groups, resulting in the higher content of oxygen element, then leading to low calorific value.
Effect of self-consistent electric field on characteristics of graphene p-i-n tunneling transit-time diodes
Authors: Semenenko V. L. , Leiman V. G. , Arsenin A. V. , Mitin V. , Ryzhii M. , Otsuji T. , Ryzhii V.
Published: January 2013

We develop a device model for p-i-n tunneling transit-time diodes based on single- and multiple graphene layer structures operating at the reverse bias voltages. The model of the graphene tunneling transit-time diode (GTUNNETT) accounts for the features of the interband tunneling generation of electrons and holes and their ballistic transport in the device i-section, as well as the effect of the self-consistent electric field associated with the charges of propagating electrons and holes. Using the developed model, we calculate the dc current-voltage characteristics and the small-signal ac frequency-dependent admittance as functions of the GTUNNETT structural parameters, in particular, the number of graphene layers and the dielectric constant of the surrounding media. It is shown that the admittance real part can be negative in a certain frequency range. As revealed, if the i-section somewhat shorter than one micrometer, this range corresponds to the terahertz frequencies. Due to the effect of the self-consistent electric field, the behavior of the GTUNNETT admittance in the range of its negativity of its real part is rather sensitive to the relation between the number of graphene layers and dielectric constant. The obtained results demonstrate that GTUNNETTs with optimized structure can be used in efficient terahertz oscillators.
Effect of plasma inhomogeneity on plasma wakefield acceleration driven by long bunches
Authors: Lotov K. V. , Pukhov A. , Caldwell A.
Published: January 2013

Effects of plasma inhomogeneity on self-modulating proton bunches and accelerated electrons were studied numerically. The main effect is the change of the wakefield wavelength which results in phase shifts and loss of accelerated particles. This effect imposes severe constraints on density uniformity in plasma wakefield accelerators driven by long particle bunches. The transverse two stream instability that transforms the long bunch into a train of micro-bunches is less sensitive to density inhomogeneity than are the accelerated particles. The bunch freely passes through increased density regions and interacts with reduced density regions.
Small molecule solution-processed bulk heterojunction solar cells with inverted structure using porphyrin donor
Authors: Yamamoto Takaki , Hatano Junichi , Nakagawa Takafumi , Yamaguchi Shigeru , Matsuo Yutaka
Published: January 2013

Utilizing tetraethynyl porphyrin derivative (TE-Por) as a small molecule donor material, we fabricated a small molecule solution-processed bulk heterojunction (BHJ) solar cell with inverted structure, which exhibited 1.6% power conversion efficiency (JSC (short-circuit current) = 4.6 mA/cm2, VOC (open-circuit voltage) = 0.90 V, and FF (fill factor) = 0.39) in the device configuration indium tin oxide/TiOx (titanium sub-oxide)/[6,6]-phenyl-C61-butyric acid methyl ester:TE-Por (5:1)/MoOx (molybdenum sub-oxide)/Au under AM1.5 G illumination at 100 mW/cm2. Without encapsulation, the small molecule solution-processed inverted BHJ solar cell also showed remarkable durability to air, where it kept over 73% of its initial power conversion efficiency after storage for 28 days under ambient atmosphere in the dark.
Tunable Fano resonances based on two-beam interference in microring resonator
Authors: Hu Ting , Yu Ping , Qiu Chen , Qiu Huiye , Wang Fan , Yang Mei , Jiang Xiaoqing , Yu Hui , Yang Jianyi
Published: January 2013

In this paper, a resonant system is demonstrated on silicon-on-insulator wafer to achieve tunable Fano resonances. In this system, the Fano resonance originates from the interference of two beams resonant in the microring resonator. The shapes of the Fano resonances are tunable through controlling the phase difference of the two beams. Both large slope and high extinction ratio (ER) are obtained when the phase difference is 0.5π or 1.5π. Experimental results show that Fano resonances with steep slope and ER over 20 dB are achieved in the whole free spectral range by controlling the microheaters to meet the phase condition.
Chemical sensing by differential thermal analysis with a digitally controlled fiber optic interferometer
Authors: Gonçalves L. C. , González-Aguilar G. , Frazão O. , Baptista J. M. , Jorge P. A. S.
Published: January 2013

In this work the implementation of an optical fiber interferometric system for differential thermal analysis enabling the identification of chemical species is described. The system is based on a white light Mach-Zehnder configuration using pseudo-heterodyne demodulation to interrogate two identical fiber Bragg gratings (FBG) in a differential scheme. System performance is compared using either standard hardware or low cost virtual instrumentation for operation control and signal processing. The operation with the virtual system enabled temperature measurements with a ±0.023 °C resolution nearly matching the performance of the standard hardware. The system ability to discriminate chemical species by differential thermal analysis was demonstrated. Mixed samples of acetone and methanol could be successfully identified, indicating the suitability of the system for high precision measurements using low cost instrumentation.
Size-based hydrodynamic rare tumor cell separation in curved microfluidic channels
Authors: Sun Jiashu , Liu Chao , Li Mengmeng , Wang Jidong , Xianyu Yunlei , Hu Guoqing , Jiang Xingyu
Published: January 2013

In this work, we propose a rapid and continuous rare tumor cell separation based on hydrodynamic effects in a label-free manner. The competition between the inertial lift force and Dean drag force inside a double spiral microchannel results in the size-based cell separation of large tumor cells and small blood cells. The mechanism of hydrodynamic separation in curved microchannel was investigated by a numerical model. Experiments with binary mixture of 5- and 15-μm-diameter polystyrene particles using the double spiral channel showed a separation purity of more than 95% at the flow rate above 30 ml/h. High throughput (2.5 × 108 cells/min) and efficient cell separation (more than 90%) of spiked HeLa cells and 20 × diluted blood cells was also achieved by the double spiral channel.
Fabrication of hexagonally packed cell culture substrates using droplet formation in a T-shaped microfluidic junction
Authors: Peng Lee Chiun , Hsin Chen Yi , Hang Wei Zung
Published: January 2013

A method is here proposed to fabricate ordered hexagonally packed cell culture substrates with hexagonally arranged cell patterning areas. We generated photo-sensitive polymeric microdroplets in a T-shaped microfluidic junction by an immiscible liquid, and then solidified the collective self-assembled hexagonal droplet array to obtain the cell culture substrate, on which we took the grooves formed between the solidified droplets as the hexagonally arranged cell patterning areas. The most promising advantage of our method is that we can actively tune the droplet size by simply adopting different volumetric flow rates of the two immiscible fluids to form cell culture substrates with differently sized cell patterning areas. Besides, the examination results of the cell culture substrate's characteristics validate whether our method is capable of creating substrates with high spatial uniformity. To verify the cell patterning function of our cell culture substrates, we used the semi-adherent RAW cells to demonstrate the effectiveness of patterning of suspended/adherent cells before/after adhesion. Over 90% cell viability and cell patterning rate suggest that our method may be a promising approach for future applications of cell patterning on biochips.
Application of zero-index metamaterials for surface plasmon guiding
Authors: Zhu Weiren , Rukhlenko Ivan D. , Premaratne Malin
Published: January 2013

Although zero-index metamaterials (ZIMs) have been extensively studied in electromagnetics, their applications in plasmonics have not been investigated so far. In this Letter, we propose strategies for efficient manipulation of surface plasmon polariton (SPP) flow using anisotropic ZIMs. Through rigorous theoretical analysis backed up by full-wave simulations, we suggest two applications of anisotropic ZIMs in plasmonics, namely, adjusting the phase delay of SPPs and guiding SPPs about a rounded metal corner. The proposed applications of ZIMs may prove useful for plasmonic interconnects in integrated ultra-high speed circuitry.
Diet supplementation with clinoptilolite improves energy status, reproductive efficiency and increases milk yield in dairy heifers
Authors: Karatzia Maria A. , Katsoulos Panagiotis D. , Karatzias Harilaos
Published: January 2013

The objective of this study was to investigate the effect of long-term dietary inclusion of clinoptilolite on the energy status, reproductive parameters and milk yield of dairy heifers. Eighty Holstein pregnant heifers were equally divided to two groups: treatment group heifers were fed the ration supplemented with 200 g clinoptilolite per day; control group heifers were fed the basal ration and served as controls. The experiment started on Day 210 of gestation and lasted until the end of the first lactation period. Blood samples were collected from each animal at the start of the experiment, 30 days later on the day of calving and then on a monthly basis and were analysed for serum glucose and ketone bodies. On the same days, all animals were monitored for body condition score. Cows were observed for heat every day and were inseminated at first heat after the 60th day postpartum. Calving to first heat interval, calving to first service interval, number of services per conception and calving interval were calculated for both groups. Milk yield for each cow was recorded monthly and 305-day milk yield was calculated. Clinoptilolite supplementation significantly increased body condition score and blood serum concentration of glucose and significantly decreased blood serum concentration of ketone bodies. Clinoptilolite also improved significantly the reproductive parameters evaluated and significantly increased milk production. These results indicate that daily dietary administration of 200 g of clinoptilolite can be used for the improvement of animal performance in dairy herds.
A review of potential contaminants in Australian livestock feeds and proposed guidance levels for feed
Authors: MacLachlan D. J. , Blaney B. J. , Cook L. G. , Klim E. , Scholl R. , Sexton M. , Spragg J. , Watts R.
Published: January 2013

Contaminants of man-made and natural origin need to be managed in livestock feeds to protect the health of livestock and that of human consumers of livestock products. This requires access to information on the transfer from feed to food to inform risk profiles and assessments, and to guide management interventions such as regulation or Hazard Analysis Critical Control Point approaches. This paper reviews contaminants of known and potential concern in the production of livestock feeds in Australia and compares existing but differing state and national regulatory standards with international standards. The contaminants considered include man-made organic chemical contaminants (e.g. legacy pesticides), elemental contaminants (e.g. arsenic, cadmium, lead), phytotoxins (e.g. gossypol) and mycotoxins (e.g. aflatoxins). Reference is made to scientific literature and evaluations by regulators to propose maximum levels that can be used for guidance by those involved in managing contamination incidents or developing feed safety programs.
Evolution of natural and social science interactions in global change research programs
Authors: Mooney Harold A. , Duraiappah Anantha , Larigauderie Anne
Published: January 2013

Efforts to develop a global understanding of the functioning of the Earth as a system began in the mid-1980s. This effort necessitated linking knowledge from both the physical and biological realms. A motivation for this development was the growing impact of humans on the Earth system and need to provide solutions, but the study of the social drivers and their consequences for the changes that were occurring was not incorporated into the Earth System Science movement, despite early attempts to do so. The impediments to integration were many, but they are gradually being overcome, which can be seen in many trends for assessments, such as the Intergovernmental Platform on Biodiversity and Ecosystem Services, as well as both basic and applied science programs. In this development, particular people and events have shaped the trajectories that have occurred. The lessons learned should be considered in such emerging research programs as
Future Earth
, the new global program for sustainability research. The transitioning process to this new program will take time as scientists adjust to new colleagues with different ideologies, methods, and tools and a new way of doing science.
Complex dynamics in learning complicated games
Authors: Galla Tobias , Farmer J. Doyne
Published: January 2013

Game theory is the standard tool used to model strategic interactions in evolutionary biology and social science. Traditionally, game theory studies the equilibria of simple games. However, is this useful if the game is complicated, and if not, what is? We define a complicated game as one with many possible moves, and therefore many possible payoffs conditional on those moves. We investigate two-person games in which the players learn based on a type of reinforcement learning called experience-weighted attraction (EWA). By generating games at random, we characterize the learning dynamics under EWA and show that there are three clearly separated regimes: (
i
) convergence to a unique fixed point, (
ii
) a huge multiplicity of stable fixed points, and (
iii
) chaotic behavior. In case (
iii
), the dimension of the chaotic attractors can be very high, implying that the learning dynamics are effectively random. In the chaotic regime, the total payoffs fluctuate intermittently, showing bursts of rapid change punctuated by periods of quiescence, with heavy tails similar to what is observed in fluid turbulence and financial markets. Our results suggest that, at least for some learning algorithms, there is a large parameter regime for which complicated strategic interactions generate inherently unpredictable behavior that is best described in the language of dynamical systems theory.
Ciliary contact interactions dominate surface scattering of swimming eukaryotes
Authors: Kantsler Vasily , Dunkel Jörn , Polin Marco , Goldstein Raymond E.
Published: January 2013

Interactions between swimming cells and surfaces are essential to many microbiological processes, from bacterial biofilm formation to human fertilization. However, despite their fundamental importance, relatively little is known about the physical mechanisms that govern the scattering of flagellated or ciliated cells from solid surfaces. A more detailed understanding of these interactions promises not only new biological insights into structure and dynamics of flagella and cilia but may also lead to new microfluidic techniques for controlling cell motility and microbial locomotion, with potential applications ranging from diagnostic tools to therapeutic protein synthesis and photosynthetic biofuel production. Due to fundamental differences in physiology and swimming strategies, it is an open question of whether microfluidic transport and rectification schemes that have recently been demonstrated for pusher-type microswimmers such as bacteria and sperm cells, can be transferred to puller-type algae and other motile eukaryotes, because it is not known whether long-range hydrodynamic or short-range mechanical forces dominate the surface interactions of these microorganisms. Here, using high-speed microscopic imaging, we present direct experimental evidence that the surface scattering of both mammalian sperm cells and unicellular green algae is primarily governed by direct ciliary contact interactions. Building on this insight, we predict and experimentally verify the existence of optimal microfluidic ratchets that maximize rectification of initially uniform
Chlamydomonas reinhardtii
suspensions. Because mechano-elastic properties of cilia are conserved across eukaryotic species, we expect that our results apply to a wide range of swimming microorganisms.
Coiled-coil protein Scy is a key component of a multiprotein assembly controlling polarized growth inStreptomyces
Authors: Holmes Neil A. , Walshaw John , Leggett Richard M. , Thibessard Annabelle , Dalton Kate A. , Gillespie Michael D. , Hemmings Andrew M. , Gust Bertolt , Kelemen Gabriella H.
Published: January 2013

Polarized growth in eukaryotes requires polar multiprotein complexes. Here, we establish that selection and maintenance of cell polarity for growth also requires a dedicated multiprotein assembly in the filamentous bacterium,Streptomyces coelicolor. We present evidence for a tip organizing center and confirm two of its main components: Scy (Streptomycescytoskeletal element), a unique bacterial coiled-coil protein with an unusual repeat periodicity, and the known polarity determinant DivIVA. We also establish a link between the tip organizing center and the filament-forming protein FilP. Interestingly, both deletion and overproduction of Scy generated multiple polarity centers, suggesting a mechanism wherein Scy can both promote and limit the number of emerging polarity centers via the organization of the Scy-DivIVA assemblies. We propose that Scy is a molecular “assembler,” which, by sequestering DivIVA, promotes the establishment of new polarity centers for de novo tip formation during branching, as well as supporting polarized growth at existing hyphal tips.
Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo
Authors: Ilyushin Denis G. , Smirnov Ivan V. , Belogurov Alexey A. , Dyachenko Igor A. , Zharmukhamedova Tatiana Iu. , Novozhilova Tatjana I. , Bychikhin Eugene A. , Serebryakova Marina V. , Kharybin Oleg N. , Murashev Arkadii N. , Anikienko Konstantin A. , Nikolaev Eugene N. , Ponomarenko Natalia A. , Genkin Dmitry D. , Blackburn G. Michael , Masson Patrick , Gabibov Alexander G.
Published: January 2013

The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD
50
of
S
-(2-(diethylamino)ethyl)
O
-isobutyl methanephosphonothioate without perturbation of long-term behavior.
Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons
Authors: Schaeffer Marie , Langlet Fanny , Lafont Chrystel , Molino François , Hodson David J. , Roux Thomas , Lamarque Laurent , Verdié Pascal , Bourrier Emmanuel , Dehouck Bénédicte , Banères Jean-Louis , Martinez Jean , Méry Pierre-François , Marie Jacky , Trinquet Eric , Fehrentz Jean-Alain , Prévot Vincent , Mollard Patrice
Published: January 2013

To maintain homeostasis, hypothalamic neurons in the arcuate nucleus must dynamically sense and integrate a multitude of peripheral signals. Blood-borne molecules must therefore be able to circumvent the tightly sealed vasculature of the blood–brain barrier to rapidly access their target neurons. However, how information encoded by circulating appetite-modifying hormones is conveyed to central hypothalamic neurons remains largely unexplored. Using in vivo multiphoton microscopy together with fluorescently labeled ligands, we demonstrate that circulating ghrelin, a versatile regulator of energy expenditure and feeding behavior, rapidly binds neurons in the vicinity of fenestrated capillaries, and that the number of labeled cell bodies varies with feeding status. Thus, by virtue of its vascular connections, the hypothalamus is able to directly sense peripheral signals, modifying energy status accordingly.
Complementary hemispheric specialization for language production and visuospatial attention
Authors: Cai Qing , Van der Haegen Lise , Brysbaert Marc
Published: January 2013

Language production and spatial attention are the most salient lateralized cerebral functions, and their complementary specialization has been observed in the majority of the population. To investigate whether the complementary specialization has a causal origin (the lateralization of one function causes the opposite lateralization of the other) or rather is a statistical phenomenon (different functions lateralize independently), we determined the lateralization for spatial attention in a group of individuals with known atypical right hemispheric (RH) lateralization for speech production, based on a previous large-scale screening of left-handers. We show that all 13 participants with RH language dominance have left-hemispheric dominance for spatial attention, and all but one of 16 participants with left-hemispheric language dominance are RH dominant for spatial attention. Activity was observed in the dorsal fronto-parietal pathway of attention, including the inferior parietal sulcus and superior parietal lobule, the frontal eye-movement field, and the inferior frontal sulcus/gyrus, and these regions functionally colateralized in the hemisphere dominant for attention, independently of the side of lateralization. Our results clearly support the Causal hypothesis about the complementary specialization, and we speculate that it derives from a longstanding evolutionary origin. We also suggest that the conclusions about lateralization based on an unselected sample of the population and laterality assessment using coarse functional transcranial Doppler sonography should be interpreted with more caution.
Extracellular transmission of a DNA mycovirus and its use as a natural fungicide
Authors: Yu Xiao , Li Bo , Fu Yanping , Xie Jiatao , Cheng Jiasen , Ghabrial Said A. , Li Guoqing , Yi Xianhong , Jiang Daohong
Published: January 2013

Mycoviruses are thought not to be infectious as free particles and to lack an extracellular phase in their life cycles, limiting the broad use of hypovirulence-associated mycoviruses in controlling fungal disease. Here, we demonstrate that purified particles of a DNA mycovirus,
Sclerotinia sclerotiorum
hypovirulence-associated DNA virus 1 (SsHADV-1), are infectious when applied extracellularly to its host
Sclerotinia sclerotiorum
. Virus particles isolated from an infected host can infect the hyphae of virus-free
S. sclerotiorum
directly when applied to hyphae grown on potato dextrose agar or sprayed on leaves of
Arabidopsis thaliana
and
Brassica napus
, regardless of vegetative compatibility affiliation. When applied to leaves, the virus can suppress the development of lesions. SsHADV-1 can also reduce disease severity and enhance rapeseed yield significantly under field conditions. SsHADV-1 has a narrow host range; it can infect
Sclerotinia minor
and
Sclerotinia nivalis
, sister species of
S. sclerotiorum
, and cause debilitation of these two fungi, but cannot infect or transfect other tested fungi, such as
Botrytis cinerea
, which shares the same family with
S. sclerotiorum
. Virus particles are likely to be very stable on the leaves of
A. thaliana
plants because viral DNA could be detected at 15 d postinoculation on unwounded leaves and at 10 d postinoculation on wounded leaves, respectively; however, this virus could not infect and move in plant cells. Our findings may prompt a reconsideration of the generalization that mycoviruses lack an extracellular phase in their life cycles and stimulate the search for other DNA mycoviruses with potential use as natural fungicides.
Ingredients of a 2,000-y-old medicine revealed by chemical, mineralogical, and botanical investigations
Authors: Giachi Gianna , Pallecchi Pasquino , Romualdi Antonella , Ribechini Erika , Lucejko Jeannette Jacqueline , Colombini Maria Perla , Mariotti Lippi Marta
Published: January 2013

In archaeology, the discovery of ancient medicines is very rare, as is knowledge of their chemical composition. In this paper we present results combining chemical, mineralogical, and botanical investigations on the well-preserved contents of a tin
pyxis
discovered onboard the Pozzino shipwreck (second century B.C.). The contents consist of six flat, gray, discoid tablets that represent direct evidence of an ancient medicinal preparation. The data revealed extraordinary information on the composition of the tablets and on their possible therapeutic use. Hydrozincite and smithsonite were by far the most abundant ingredients of the Pozzino tablets, along with starch, animal and plant lipids, and pine resin. The composition and the form of the Pozzino tablets seem to indicate that they were used for ophthalmic purposes: the Latin name
collyrium
(eyewash) comes from the Greek name
κoλλυ´ρα
, which means “small round loaves.” This study provided valuable information on ancient medical and pharmaceutical practices and on the development of pharmacology and medicine over the centuries. In addition, given the current focus on natural compounds, our data could lead to new investigations and research for therapeutic care.
ABHD12 controls brain lysophosphatidylserine pathways that are deregulated in a murine model of the neurodegenerative disease PHARC
Authors: Blankman Jacqueline L. , Long Jonathan Z. , Trauger Sunia A. , Siuzdak Gary , Cravatt Benjamin F.
Published: January 2013

Advances in human genetics are leading to the discovery of new disease-causing mutations at a remarkable rate. Many such mutations, however, occur in genes that encode for proteins of unknown function, which limits our molecular understanding of, and ability to devise treatments for, human disease. Here, we use untargeted metabolomics combined with a genetic mouse model to determine that the poorly characterized serine hydrolase α/β-hydrolase domain-containing (ABHD)12, mutations in which cause the human neurodegenerative disorder PHARC (polyneuropathy, hearing loss, ataxia, retinosis pigmentosa, and cataract), is a principal lysophosphatidylserine (LPS) lipase in the mammalian brain. ABHD12
−/−
mice display massive increases in a rare set of very long chain LPS lipids that have been previously reported as Toll-like receptor 2 activators. We confirm that recombinant ABHD12 protein exhibits robust LPS lipase activity, which is also substantially reduced in ABHD12
−/−
brain tissue. Notably, elevations in brain LPS lipids in ABHD12
−/−
mice occur early in life (2–6 mo) and are followed by age-dependent increases in microglial activation and auditory and motor defects that resemble the behavioral phenotypes of human PHARC patients. Taken together, our data provide a molecular model for PHARC, where disruption of ABHD12 causes deregulated LPS metabolism and the accumulation of proinflammatory lipids that promote microglial and neurobehavioral abnormalities.
Nascent-Seq analysis of
Drosophila
cycling gene expression
Authors: Rodriguez Joseph , Tang Chih-Hang Anthony , Khodor Yevgenia L. , Vodala Sadanand , Menet Jerome S. , Rosbash Michael
Published: January 2013

Significance Statement

Rhythmic mRNA expression is a hallmark of circadian rhythms. To address this regulation in
Drosophila
, we used high throughput sequencing to compare nascent RNA and mRNA levels in fly heads at different times of day. This indicated that some genes undergo rhythmic transcription with no impact on mRNA, whereas a few strongly rhythmic mRNAs have weak transcriptional oscillations. A substantial number of rhythmic genes manifest more robust mRNA cycling than transcriptional cycling, indicating that post-transcriptional regulation plays a widespread role in boosting circadian gene expression amplitude. Our study highlights the importance of directly assaying transcription to understand gene regulation.
GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons
Authors: Schneider Hans-Peter , Alt Marco D. , Klier Michael , Spiess Alena , Andes Fabian T. , Waheed Abdul , Sly William S. , Becker Holger M. , Deitmer Joachim W.
Published: January 2013

Soluble cytosolic carbonic anhydrases (CAs) are well known to participate in pH regulation of the cytoplasm of mammalian cells. Membrane-bound CA isoforms—such as isoforms IV, IX, XII, XIV, and XV—also catalyze the reversible conversion of carbon dioxide to protons and bicarbonate, but at the extracellular face of the cell membrane. When human CA isoform IV was heterologously expressed in
Xenopus
oocytes, we observed, by measuring H
+
at the outer face of the cell membrane and in the cytosol with ion-selective microelectrodes, not only extracellular catalytic CA activity but also robust intracellular activity. CA IV expression in oocytes was confirmed by immunocytochemistry, and CA IV activity measured by mass spectrometry. Extra- and intracellular catalytic activity of CA IV could be pharmacologically dissected using benzolamide, the CA inhibitor, which is relatively slowly membrane-permeable. In acute cerebellar slices of mutant mice lacking CA IV, cytosolic H
+
shifts of granule cells following CO
2
removal/addition were significantly slower than in wild-type mice. Our results suggest that membrane-associated CA IV contributes robust catalytic activity intracellularly, and that this activity participates in regulating H
+
dynamics in the cytosol, both in injected oocytes and in mouse neurons.
Lymphocyte-derived ACh regulates local innate but not adaptive immunity
Authors: Reardon Colin , Duncan Gordon S. , Brüstle Anne , Brenner Dirk , Tusche Michael W. , Olofsson Peder S. , Rosas-Ballina Mauricio , Tracey Kevin J. , Mak Tak W.
Published: January 2013

Appropriate control of immune responses is a critical determinant of health. Here, we show that choline acetyltransferase (ChAT) is expressed and ACh is produced by B cells and other immune cells that have an impact on innate immunity. ChAT expression occurs in mucosal-associated lymph tissue, subsequent to microbial colonization, and is reduced by antibiotic treatment. MyD88-dependent Toll-like receptor up-regulates ChAT in a transient manner. Unlike the previously described CD4
+
T-cell population that is stimulated by norepinephrine to release ACh, ChAT
+
B cells release ACh after stimulation with sulfated cholecystokinin but not norepinephrine. ACh-producing B-cells reduce peritoneal neutrophil recruitment during sterile endotoxemia independent of the vagus nerve, without affecting innate immune cell activation. Endothelial cells treated with ACh in vitro reduced endothelial cell adhesion molecule expression in a muscarinic receptor-dependent manner. Despite this ability, ChAT
+
B cells were unable to suppress effector T-cell function in vivo. Therefore, ACh produced by lymphocytes has specific functions, with ChAT
+
B cells controlling the local recruitment of neutrophils.
Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival
Authors: Luo Jian , Elwood Fiona , Britschgi Markus , Villeda Saul , Zhang Hui , Ding Zhaoqing , Zhu Liyin , Alabsi Haitham , Getachew Ruth , Narasimhan Ramya , Wabl Rafael , Fainberg Nina , James Michelle L. , Wong Gordon , Relton Jane , Gambhir Sanjiv S. , Pollard Jeffrey W. , Wyss-Coray Tony
Published: January 2013

Colony-stimulating factor 1 (CSF1) and interleukin-34 (IL-34) are functional ligands of the CSF1 receptor (CSF1R) and thus are key regulators of the monocyte/macrophage lineage. We discovered that systemic administration of human recombinant CSF1 ameliorates memory deficits in a transgenic mouse model of Alzheimer’s disease. CSF1 and IL-34 strongly reduced excitotoxin-induced neuronal cell loss and gliosis in wild-type mice when administered systemically before or up to 6 h after injury. These effects were accompanied by maintenance of cAMP responsive element–binding protein (CREB) signaling in neurons rather than in microglia. Using lineage-tracing experiments, we discovered that a small number of neurons in the hippocampus and cortex express CSF1R under physiological conditions and that kainic acid–induced excitotoxic injury results in a profound increase in neuronal receptor expression. Selective deletion of CSF1R in forebrain neurons in mice exacerbated excitotoxin-induced death and neurodegeneration. We conclude that CSF1 and IL-34 provide powerful neuroprotective and survival signals in brain injury and neurodegeneration involving CSF1R expression on neurons.
CD98hc (SLC3A2) regulation of skin homeostasis wanes with age
Authors: Boulter Etienne , Estrach Soline , Errante Aurélia , Pons Catherine , Cailleteau Laurence , Tissot Floriane , Meneguzzi Guerrino , Féral Chloé C.
Published: January 2013

Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report that CD98hc invalidation has no appreciable effect on cell adhesion, clearly showing that CD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.
A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi
Authors: Hoogeboom Robbert , van Kessel Kok P.M. , Hochstenbach Frans , Wormhoudt Thera A. , Reinten Roy J.A. , Wagner Koen , Kater Arnon P. , Guikema Jeroen E.J. , Bende Richard J. , van Noesel Carel J.M.
Published: January 2013

B cell chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is a clonal expansion of CD5+CD19+ B lymphocytes. Two types of CLLs are being distinguished as carrying either unmutated or somatically mutated immunoglobulins (Igs), which are associated with unfavorable and favorable prognoses, respectively. More than 30% of CLLs can be grouped based on their expression of stereotypic B cell receptors (BCRs), strongly suggesting that distinctive antigens are involved in the development of CLL. Unmutated CLLs, carrying Ig heavy chain variable (IGHV) genes in germline configuration, express low-affinity, poly-, and self-reactive BCRs. However, the antigenic specificity of CLLs with mutated IGHV-genes (M-CLL) remained elusive. In this study, we describe a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi. β-(1,6)-glucan binding depended on both the stereotypic Ig heavy and light chains, as well as on a distinct amino acid in the IGHV-CDR3. Reversion of IGHV mutations to germline configuration reduced the affinity for β-(1,6)-glucan, indicating that these BCRs are indeed affinity-selected for their cognate antigen. Moreover, CLL cells expressing these stereotypic receptors proliferate in response to β-(1,6)-glucan. This study establishes a class of common pathogens as functional ligands for a subset of somatically mutated human B cell lymphomas.
On the stability of the localized single-valued extension property under commuting perturbations
Authors: Aiena Pietro , Neumann Michael
Published: January 2013

This article concerns the permanence of the single-valued extension property at a point under suitable perturbations. While this property is, in general, not preserved under sums and products of commuting operators, we obtain positive results in the case of commuting perturbations that are quasi-nilpotent, algebraic, or Riesz operators.
BETAWARE: a machine-learning tool to detect and predict transmembrane beta-barrel proteins in prokaryotes
Authors: Savojardo Castrense , Fariselli Piero , Casadio Rita
Published: January 2013

Summary: The annotation of membrane proteins in proteomes is an important problem of Computational Biology, especially after the development of high-throughput techniques that allow fast and efficient genome sequencing. Among membrane proteins, transmembrane β-barrels (TMBBs) are poorly represented in the database of protein structures (PDB) and difficult to identify with experimental approaches. They are, however, extremely important, playing key roles in several cell functions and bacterial pathogenicity. TMBBs are included in the lipid bilayer with a β-barrel structure and are presently found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. Recently, we developed two top-performing methods based on machine-learning approaches to tackle both the detection of TMBBs in sets of proteins and the prediction of their topology. Here, we present our BETAWARE program that includes both approaches and can run as a standalone program on a linux-based computer to easily address in-home massive protein annotation or filtering.

Availability and implementation:  http://www.biocomp.unibo.it/∼savojard/betawarecl

Contact:  piero.fariselli@unibo.it

Supplementary information: Supplementary data are available at Bioinformatics online.
Use of Phosphite Salts in Laboratory and Semicommercial Tests to Control Citrus Postharvest Decay
Authors: Cerioni L. , Rapisarda V. A. , Doctor J. , Fikkert S. , Ruiz T. , Fassel R. , Smilanick J. L.
Published: January 2013

Potassium phosphite (KP) concentrations that inhibited the germination of 50% of Penicillium digitatum conidia were 229, 334, 360, 469, 498, or 580 mg/liter at pH 3, 4, 5, 6, 7, or 8, respectively. Increasing phosphate content in media reduced phosphite toxicity. To control green or blue mold, fruit were inoculated with P. digitatum or P. italicum, then immersed 24 h later in KP, calcium phosphite (CaP), sodium carbonate, sodium bicarbonate, or potassium sorbate for 1 min at 20 g/liter for each at 25 or 50°C. Mold incidence was lowest after potassium sorbate, CaP, or KP treatments at 50°C. CaP was often more effective than KP but left a white residue on fruit. KP was significantly more effective when fruit were stored at 10 or 15°C after treatment compared with 20°C. Acceptable levels of control were achieved only when KP was used in heated solutions or with fungicides. KP was compatible with imazalil (IMZ) and other fungicides and improved their effectiveness. KP increased thiabendazole or IMZ residues slightly. Phosphite residues did not change during storage for 3 weeks, except they declined when KP was applied with IMZ. KP caused no visible injuries or alteration in the rate of color change of citrus fruit in air or ethylene at 5 μl/liter.
First Report of Damping-off Caused by Pythium aphanidermatum on Leaf Beet (Beta vulgaris subsp. vulgaris) in Italy
Authors: Garibaldi A. , Gilardi G. , Ortu G. , Gullino M. L.
Published: January 2013

During July 2010, symptoms of crown and root rot were observed on leaf beet (Beta vulgaris L. subsp. vulgaris) grown in a commercial field near Torino (northern Italy). The first symptoms developed 25 days after sowing with temperatures ranging from 25 to 30°C, and 20% of plants were affected. Affected plants were stunted and leaves showed chlorosis and suddenly wilted. The collar and young stems were affected first and appeared brown, water-soaked, and were characterized by a soft rot. Eventually, all affected plants collapsed. Thin aerial mycelia were visible on the surface of the infected plants if maintained at a high relative humidity. Tissue fragments of 1 mm2 were excised from the margins of the lesions, dipped in a solution containing 1% sodium hypochlorite, and plated on potato dextrose agar (PDA) and on a medium selective for oomycetes (2). Plates were incubated under constant fluorescent light at 22 ± 1°C for 5 days. Five isolates, grown on V8 medium (vegetable mix 300 g; agar 15 g; CaCO3 1.5 g; distilled water 1 liter) and observed under light microscope showed the morphological characters of Pythium aphanidermatum (3). This result was confirmed by PCR and sequence analysis. The internal transcribed spacer (ITS) region of rDNA of a single isolate (Py 7/10) was amplified using the primers ITS1/ITS4 and sequenced. BLAST analysis (1) of the 815 bp segment showed a 99% homology with the sequence of P. aphanidermatum (GenBank Accession JN695786). The nucleotide sequence has been assigned to the GenBank Accession JX462954. Pathogenicity tests were performed twice on B. vulgaris subsp. vulgaris grown in 2-liter pots, containing a steam disinfested organic peat substrate (70% black peat, 30% white peat, pH 5.5 to 6, N 110 to 190 mg L–1, P2O5 140 to 230 mg L–1, K2O 170 to 280 mg L–1), infested with wheat and hemp kernels colonized with a strain of P. aphanidermatum at a rate of 1 g L–1. Ten seeds per pot were sown in four pots filled with the infested medium, while the same number of seeds were sown in non-infested substrate. Plants were kept in two growth chambers, at 20 and 27°C. The first symptoms developed 7 days after the artificial inoculation. After 20 days, 70% of plants were infected at 27°C, while 10% were affected at 20°C. Control plants remained healthy at both temperatures. P. aphanidermatum was consistently reisolated from the lesions. To our knowledge, this is the first report of damping off of B. vulgaris subsp. vulgaris caused by P. aphanidermatum in Italy. The importance of the disease, at present limited, could increase in areas where leaf beet is intensively grown.

References: (1) S. F. Altschul et al. Nucleic Acids Res. 25:3389, 1997. (2) H. Masago et al. Phytopathology 67:425, 1977. (3) T. Watanabe. Pictorial Atlas of Soil and Seed Fungi. CRC Press, Florida, 2002.
The 8D05 Parasitism Gene of Meloidogyne incognita Is Required for Successful Infection of Host Roots
Authors: Xue Bingye , Hamamouch Noureddine , Li Chunying , Huang Guozhong , Hussey Richard S. , Baum Thomas J. , Davis Eric L.
Published: January 2013

Parasitism genes encode effector proteins that are secreted through the stylet of root-knot nematodes to dramatically modify selected plant cells into giant-cells for feeding. The Mi8D05 parasitism gene previously identified was confirmed to encode a novel protein of 382 amino acids that had only one database homolog identified on contig 2374 within the Meloidogyne hapla genome. Mi8D05 expression peaked in M. incognita parasitic second-stage juveniles within host roots and its encoded protein was limited to the subventral esophageal gland cells that produce proteins secreted from the stylet. Constitutive expression of Mi8D05 in transformed Arabidopsis thaliana plants induced accelerated shoot growth and early flowering but had no visible effects on root growth. Independent lines of transgenic Arabidopsis that expressed a double-stranded RNA complementary to Mi8D05 in host-derived RNA interference (RNAi) tests had up to 90% reduction in infection by M. incognita compared with wild-type control plants, suggesting that Mi8D05 plays a critical role in parasitism by the root-knot nematode. Yeast two-hybrid experiments confirmed the specific interaction of the Mi8D05 protein with plant aquaporin tonoplast intrinsic protein 2 (TIP2) and provided evidence that the Mi8D05 effector may help regulate solute and water transport within giant-cells to promote the parasitic interaction.