bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification, Biological Activities, and Molecular Cloning of a Novel Mannose‐Binding Lectin from Bulbs of Zephyranthes candida Herb (Amaryllidaceae)
Authors: Wu Chuan‐Fang , Li Jian , An Jie , Chang Li‐Qing , Chen Fang , Bao Jin‐Ku
Published: September 2010

A novel mannose‐binding agglutinin was purified from bulbs of Zephyranthes candida Herb by extraction, precipitation with 80% (NH4)2SO4, and ion‐exchange chromatography on DEAE‐Sepharose followed by gel filtration on Sephacryl S‐100. The purified Z. candida agglutinin (ZCA) migrated as a single band of 12 kDa on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis under reducing and non‐reducing conditions. The apparent molecular mass of the lectin, as determined by gel filtration chromatography, was 48 kDa. The results indicated that ZCA was composed of four identical subunits of 12 kDa each (homotetrameric nature). The ZCA agglutinated rabbit erythrocytes, Escherichia coli and Saccharomyces cerevisiae cells at concentrations of 0.95,1.90, and 31.30 μg/mL, respectively. Bioassays indicated that ZCA has a significant effect on wheat aphid survival. Mortality after 7 d was > 90% at 0.26%. A degenerate primer was designed in accordance with the N‐terminal partial sequence of purified ZCA. The full‐length cDNA was cloned by 3′‐ and 5′‐rapid amplification of cDNA ends. The full‐length cDNA had 661 bp and the sequence encoded an open reading frame of 168 amino acids. The mature protein of ZCA includes 109 amino acid residues and the molecular weight of the protein was 12.1 kDa. The result show that the zca gene encodes a protein precursor with a signal peptide, a mature protein, and a C‐terminal cleavage amino acids sequence. Molecular modeling of ZCA indicated that its three‐dimensional structure strongly resembles that of the snowdrop agglutinin. Blocks' analysis revealed that the deduced amino acid sequence of ZCA has three functional domains specific for agglutination and three carbohydrate binding boxes (QDNY).

(Managing editor: Li‐Hui Zhao)
Effects of Climate Change and Shifts in Forest Composition on Forest Net Primary Production
Authors: Chiang Jyh‐Min , Iverson Louts R. , Prasad Anantha , Brown Kim J.
Published: September 2010

Forests are dynamic in both structure and species composition, and these dynamics are strongly influenced by climate. However, the net effects of future tree species composition on net primary production (NPP) are not well understood. The objective of this work was to model the potential range shifts of tree species (DISTRIB Model) and predict their impacts on NPP (PnET‐II Model) that will be associated with alterations in species composition. We selected four 200 × 200 km areas in Wisconsin, Maine, Arkansas, and the Ohio‐West Virginia area, representing focal areas of potential species range shifts. PnET‐II model simulations were carried out assuming that all forests achieved steady state, of which the species compositions were predicted by DISTRIB model with no migration limitation. The total NPP under the current climate ranged from 552 to 908 g C/m2 per year. The effects of potential species redistributions on NPP were moderate (−12% to +8%) compared with the influence of future climatic changes (−60% to +25%). The direction and magnitude of climate change effects on NPP were largely dependent on the degree of warming and water balance. Thus, the magnitude of future climate change can affect the feedback system between the atmosphere and biosphere.
Why are Nitrogen Concentrations in Plant Tissues Lower under Elevated CO2? A Critical Examination of the Hypotheses
Authors: Taub Daniel R. , Wang Xianzhong
Published: September 2010

Plants grown under elevated atmospheric [CO2] typically have decreased tissue concentrations of N compared with plants grown under current ambient [CO2]. The physiological mechanisms responsible for this phenomenon have not been definitely established, although a considerable number of hypotheses have been advanced to account for it. In this review we discuss and critically evaluate these hypotheses. One contributing factor to the decreases in tissue N concentrations clearly is dilution of N by increased photosynthetic assimilation of C. In addition, studies on intact plants show strong evidence for a general decrease in the specific uptake rates (uptake per unit mass or length of root) of N by roots under elevated CO2. This decreased root uptake appears likely to be the result both of decreased N demand by shoots and of decreased ability of the soil‐root system to supply N. The best‐supported mechanism for decreased N supply is a decrease in transpiration‐driven mass flow of N in soils due to decreased stomatal conductance at elevated CO2, although some evidence suggests that altered root system architecture may also play a role. There is also limited evidence suggesting that under elevated CO2, plants may exhibit increased rates of N loss through volatilization and/or root exudation, further contributing to lowering tissue N concentrations.
Metal concentrations of insects associated with the South African Ni hyperaccumulator Berkheya coddii (Asteraceae)
Authors: BOYD ROBERT S. , DAVIS MICHEAL A. , WALL MICHAEL A. , BALKWILL KEVIN
Published: September 2010

Abstract
The high levels of some metals in metal hyperaccumulator plants may be transferred to insect associates. We surveyed insects collected from the South African Ni hyperaccumulator Berkheya coddii to document whole‐body metal concentrations (Co, Cr, Cu, Mg, Mn, Ni, Pb, Zn). We also documented the concentrations of these metals in leaves, stems and inflorescences, finding extremely elevated levels of Ni (4 700–16 000 ∞g/g) and high values (5–34 ∞g/g) for Co, Cr, and Pb. Of 26 insect morphotypes collected from B. coddii, seven heteropterans, one coleopteran, and one orthopteran contained relatively high concentrations of Ni (> 500 ∞g/g). The large number of high‐Ni heteropterans adds to discoveries of others (from California USA and New Caledonia) and suggests that members of this insect order may be particularly Ni tolerant. Nymphs of the orthopteran (Stenoscepa) contained 3 500 ∞g Ni/g, the greatest Ni concentration yet reported for an insect. We also found two beetles with elevated levels of Mg (> 2 800 ∞g/g), one beetle with elevated Cu (> 70 ∞g/g) and one heteropteran with an elevated level of Mn (> 200 ∞g/g). Our results show that insects feeding on a Ni hyperaccumulator can mobilize Ni into food webs, although we found no evidence of Ni biomagnification in either herbivore or carnivore insect taxa. We also conclude that some insects associated with hyperaccumulators can contain Ni levels that are high enough to be toxic to vertebrates.
Expression of two types of acetylcholinesterase gene from the silkworm, Bombyx mori, in insect cells
Authors: SHANG JIN‐YAN , SHAO YA‐MING , LANG GUO‐JUN , YUAN GAN , TANG ZHEN‐HUA , ZHANG CHUAN‐XI
Published: September 2010

Complementary DNAs encoding two types of acetylcholinesterase (AChE) were isolated from the silkworm, Bombyx mori. The type 1 (Bmace1) and type 2 (Bmace2) ORFs are 2052 and 1917 bp in length, respectively. Both the complete ORFs of the Bmaces and C‐terminal truncated forms were recombined into the Bacmid baculovirus vector under the control of the polyhedrin promoter and expressed in Trichoplusia ni (Tn‐5B1‐4) cells. The resulting products exhibited AChE activity and glycosylation of the expressed proteins. An inhibition assay indicated that the ace2‐type enzyme was more sensitive than the ace1‐type enzyme to inhibition by eserine and paraoxon.
The fatty acid compositions of predator Piocoris luridus (Heteroptera: Lygaeidae) and its host Monosteria unicostata (Heteroptera: Tingidae) reared on almond
Authors: CAKMAK OZLEM , BASHAN MEHMET , BOLU HALIL
Published: September 2010

The changes in fatty acid compositions during nutritional interaction among almond Amygdalus communis Linnaeus (Rosales: Rosaceae) (host plant), lacebug Monosteria unicostata (Mulsant and Rey) (Heteroptera: Tingidae) and its predator Piocoris luridus Fieber (Heteroptera: Lygaeidae) were determined by gas chromatography and gas chromatography‐mass spectrometry analyses. The fatty acid profiles of phospholipids and triacylglycerols were substantially different. Unlike the general observations for virtually most terrestrial insects, arachidonic and eicosapentaenoic acids were detected in high proportions of phospholipid fractions in both insects, especially in P. luridus. Also the almond tissues provide very little oleic acid to the herbivore diet, yet both insect species developed high proportions of this component. Our data reveals instances of specific accumulation of fatty acid biosynthesis, elongation/desaturation, and not incorporating selected fatty acids into cellular lipids.
The diurnal activity, movement and trypanosome infection rates of Glossina fuscipes fuscipes (Diptera: Glossinidae) in Buvuma Island, Lake Victoria, Uganda
Authors: OGWAL LONJINO M. , KALYEBI ANDREW , KADDU JOHN B.
Published: September 2010

The diurnal activity patterns, trypanosome infection rates and movement of Glossina fuscipes fuscipes (Diptera: Glossinidae) were investigated in Buvuma Island, Lake Victoria, Uganda. Hourly trapping of tsetse flies was undertaken to determine their activity rhythm while a capture‐mark‐release‐recapture method was conducted to assess the movement and dispersal of tsetse flies between lakeshore, hinterland and further inland sites along a transected area. Dissection of tsetse flies was also undertaken to determine the trypanosome infection rates in salivary glands, proboscis and mid‐gut. Results indicated a bimodal diurnal activity profile for G. f. fuscipes on the Island, both on the lakeshore and in the hinterland. Movement and dispersal of G. f. fuscipes tsetse flies occurred between lakeshore, hinterland and further inland sites with a greater tendency of flies to move to the lakeshore. Trypanosome infection rates of 4.32% for Trypasoma vivax and 1.15% for T. congolense were found in G. f. fuscipes.
Influence of host age and host deprivation on longevity, egg load dynamics and oviposition rate in Microplitis rufiventris
Authors: HEGAZI ESMAT MOHAMED , EL‐AZIZ GEHAN MOHAMED ABD , EL‐SHAZLY AHMED YOUSEF , KHAFAGI WEDAD EMAM
Published: September 2010

Adult size, longevity, egg load dynamics and oviposition of Microplitis rufiventris Kok. which began their development in the first, second, third (preferred hosts) or fourth (non‐preferred hosts) instar larvae of Spodoptera littoralis (Boisd.) were studied. The parasitoid size was largely determined by the initial host size at parasitism. Non‐ovipositing females derived from older hosts lived for longer periods than those derived from younger ones. However, the ovipositing females, irrespective of their size, lived for almost the same periods. At emergence, the oviducts of adult females contain a significant amount of mature eggs available for oviposition for a few hours on eclosion day. Egg load increases during the early phase of adult life. The amount of additional mature eggs and rate of egg maturation per hour was greater for wasps derived from preferred hosts compared with those in females derived from non‐preferred hosts. The pattern of egg production in M. rufiventris females depended on the availability of hosts for parasitization. Host‐deprived females depleted the egg complement with aging; the longer the host deprivation, the lower the oviduct egg load. Marked reduction in both realized or potential fecundity of host‐deprived females was observed following host availability. Host privation for more than 3 days induced a marked deficit fecundity pattern through the female's life. The realized fecundity was determined by the interaction among host availability, the number of eggs that are matured over the female's life span, oviposition rate and host size from which the female was derived. These results suggest that: (i) M. rufiventris wasp is a weak synovigenic species; (ii) the maturation of additional eggs is inhibited once the maximum oviduct egg load is reached; (iii) the egg load of the newly emerged female is significantly less than the realized fecundity; and (iv) because M.rufiventris females oviposit fewer eggs when they begin depleting their egg supply at 3 days, augmentative releases will require release immediately following emergence to ensure the highest parasitization rate in the field.
Energy budgets of the Chinese green lacewing (Neuroptera: Chrysopidae) and its potential for biological control of the cotton aphid (Homoptera: Aphididae)
Authors: GAO FENG , LIU XIANG‐HUI , GE FENG
Published: September 2010

Energy budgets of larval stages of the Chinese green lacewing, Chrysopa sinica (Tjeder) (Neuroptera: Chrysopidae) were determined under laboratory conditions at photo‐period of 14:10 L:D, 27 ± 1°C and 75%± 2% RH. The energy used as ingestion, assimilation, respiration, productivity and feces was constructed for each developmental stage. In addition, under these experimental conditions, the potential of C. sinica as a biological control agent was evaluated according to the ingestion by this predator and the energy content of cotton aphid, Aphis gossypii (Glover) (Homoptera: Aphididae). The larval stage of C. sinica was able to consume 1281.4 1‐day‐old aphids, 1018.7 2‐day‐old aphids, 626.9 3‐day‐old aphids, 393.5 4‐day‐old aphids, 312.1 5‐day‐old aphids or 203.5 9‐day‐old aphids, respectively. No significant difference was detected between the estimated number of aphids consumed by the lacewings using energetic methods and the actual number of aphids consumed by the lacewings in this experiment. Our results showed that C. sinica is an important natural enemy of the cotton aphid, and energetic methods are very useful to quantify biological control efficacy of natural enemies.
Survival of boll weevil (Coleoptera: Curculionidae) adults after feeding on pollens from various sources
Authors: GREENBERG SHOIL M. , JONES GRETCHEN D. , EISCHEN FRANK , COLEMAN RANDY J. , ADAMCZYK JOHN J. , LIU TONG‐XIAN , SETAMOU MAMOUDOU
Published: September 2010

The survival of overwintering boll weevil, Anthonomus grandis grandis (Boheman), adults on non‐cotton hosts in the Lower Rio Grande Valley (LRGV) of Texas was examined from 2001 to 2006. The success of the Boll Weevil Eradication Program, which was re‐introduced into the LRGV in 2005, depends on controlling overwintering boll weevil populations. Laboratory studies were conducted using boll weevil adults that were captured in pheromone traps from September through March. The number of adults captured per trap declined significantly in the field from fall to the beginning of spring (3.5‐7.0‐fold). The proportion of trapped males and females did not differ significantly. The mean weight of boll weevil adults captured in September was 13.3 mg, while those of captured adults from November to February were significantly lower and ranged from 6.7 to 7.8 mg. Our results show that boll weevil adults can feed on different plant pollens. The highest longevity occurred when adults were fed almond pollen or mixed pollens (72.6 days and 69.2 days, respectively) and the lowest when they fed on citrus pollen or a non‐food source (9.7 days or 7.4 days, respectively). The highest adult survival occurred on almond and mixed pollens [88.0%‐97. 6% after 1st feeding period (10 days), 78.0%‐90.8% after 3rd feeding period (10 days), 55. 0%‐83.6% after 5th feeding period (10 days), and 15.2%‐32.4% after 10th feeding period (10 days)]. The lowest adult survival occurred on citrus pollen [52.0%‐56.0% after 1st feeding period (10 days), 13.3% after 3rd and 5th feeding periods (10 days), and 0 after 6th feeding period (10 days)]. Pollen feeding is not a behavior restricted to adult boll weevils of a specific sex or physiological state. Understanding how boll weevil adults survive in the absence of cotton is important to ensure ultimate success of eradicating this pest in the subtropics.
Tunnel geometry of the subterranean termite Reticulitermes grassei (Isoptera: Rhinotermitidae) in response to sand bulk density and the presence of food
Authors: NOBRE TÂNIA , NUNES LINA , BIGNELL DAVID E.
Published: September 2010

The cryptic habits of subterranean termites restricts detailed analysis of their foraging patterns in situ, but the process is evidently dominated by tunnel constructions connecting the nest with woody resources discovered within the territory of each colony. In this study, tunnel formation and orientation were studied experimentally in the termite Reticulitermes grassei (Clément), using 2‐dimensional laboratory foraging arenas containing fine sand as the substratum. The building of exploratory tunnels over a 10‐day period and the geometry of the resulting network are described. Fractal analysis showed that tunnel geometry had a fractal dimension, regardless of the total length tunnelled whether foragers encountered the food source or not. The bulk density of the sand in the arenas affected the distances tunnelled, with higher density reducing construction, but did not affect tunnel geometry. Tunnels were not discernibly orientated with respect to the positioning of the food source, even in a situation where termites had failed to find the food source at a distance of less than 50 mm, suggesting that volatiles from wood are not attractants.
Biology and control of the fruit borer, Conopomorpha sinensis Bradley on litchi (Litchi chinensis Sonn.) in northern Thailand
Authors: SCHULTE MARIE JOY , MARTIN KONRAD , SAUERBORN JOACHIM
Published: September 2010

Fruit and leaf shoot of litchi (Litchi chinensis) infestation by naturally occurring populations of the fruit borer, Conopomorpha sinensis larvae and C. sinensis parasitization rates were determined in litchi orchards in northern Thailand at high (ca. 1 400 m ASL) and low (ca. 800 m ASL) elevations with different, non‐over‐lapping fruiting seasons. In addition, spray applications of Bacillus thuringiensis var. aizawai, the natural compound spinosad and the chemical pesticide imidacloprid were conducted in the field to test the effects of these agents on C. sinensis fruit infestation rate. Fruit infestation rate and fruit growth, studied in a low elevation orchard, were sigmoidal and showed a highly significant positive correlation (P· 0.01). Leaf shoot infestation rate in the low elevation orchard decreased in the course of the fruiting season (March until May), but increased in the high elevation orchard, where no fruits were present within the same period of time. Together, these results indicate that females of C. sinensis clearly prefer fruits over shoots for oviposition. If no fruits are available, which was the case in the high elevation orchard during that time, they are constrained to lay their eggs on shoots. The parasitization rate of C. sinensis larvae in untreated fruits was 54.3%. The parasitoid species were Chelonus chailini (90.8%) and Phanerotoma sp. (9.2%). In the leaf shoots, C. sinensis was found to be parasitized by Phanerotoma sp. and Apanteles briareus. The applications of the different active agents had no significant effect on C. sinensis fruit infestation compared to the untreated control. Besides the cryptic life of the larvae, this is most probably explained by the fact that C. sinensis has several generations during the fruiting season. Because of the high parasitization rates recorded, an alternative and more effective control measure than the application of pesticides might be the augmentative release of parasitoids.
The insect cellular immune response
Authors: Strand Michael R.
Published: September 2010

The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.
Innate immunity in Drosophila: Pathogens and pathways
Authors: Govind Shubha
Published: September 2010

Following in the footsteps of traditional developmental genetics, research over the last 15 years has shown that innate immunity against bacteria and fungi is governed largely by two NF‐κB signal transduction pathways, Toll and IMD. Antiviral immunity appears to stem from RNA interference, whereas resistance against parasitoids is conferred by Toll signaling. The identification of these post‐transcriptional regulatory mechanisms and the annotation of most Drosophila immunity genes have derived from functional genomic studies using “model” pathogens, intact animals and cell lines. The D. melanogaster host has thus provided the core information that can be used to study responses to natural microbial and metazoan pathogens as they become identified, as well as to test ideas of selection and evolutionary change. These analyses are of general importance to understanding mechanisms of other insect host‐pathogen interactions and determinants of variation in host resistance.
Fatigue preconditioning increases fatigue resistance in mouse flexor digitorum brevis muscles with non‐functioning KATPchannels
Authors: Boudreault Louise , Cifelli Carlo , Bourassa François , Scott Kyle , Renaud Jean‐Marc
Published: September 2010

The objective of this study was to determine how an initial fatigue bout (FAT1 at 37°C) affects free myoplasmic Ca2+concentration and force ([Ca2+]i/force) during a subsequent fatigue bout (FAT2) in mouse flexor digitorum brevis (FDB). During FAT1, both tetanic [Ca2+]i/force decreased; however, they decreased to significantly lower levels when FAT1 was carried out in the presence of glibenclamide, a sarcolemmal KATP(sKATP) channel blocker. Glibenclamide also elicited greater increases in unstimulated [Ca2+]i/force, which occurred when fibres failed to fully relax between contractions during FAT1. Finally, glibenclamide impaired force recovery after FAT1. The decreases in tetanic [Ca2+]i/force and increases in unstimulated [Ca2+]i/force were slower during FAT2 elicited 60 min after FAT1. Under control conditions, the effects were small with very few significant differences. In the presence of glibenclamide, on the other hand, the differences between FAT1 and FAT2 were very large. Unexpectedly, the differences in unstimulated and tetanic [Ca2+]i/force between control and glibenclamide conditions observed during FAT1 were no longer observed during FAT2. The lack of differences was not related to a failure of glibenclamide to block KATPchannels during FAT2 because the effects of FAT1 on FAT2 were also observed using Kir6.2−/−mouse FDB, which lack sKATPchannel activity. The differences in [Ca2+]i/force between FAT1 and FAT2 could be observed with FAT1 duration of just 30 s and a FAT1–FAT2 interval of at least 30 min. A modulation of factors involved in ischaemic pre‐conditioning, i.e. A1‐adenosine receptors, sKATPand mitochondrial KATP(mKATP) channels, PKC and reactive oxygen species, during FAT1 had no effect on FAT2 fatigue kinetics. It is concluded that a preceding fatigue bout triggers an acute physiological process that prevents the contractile dysfunction induced by non‐functioning KATPchannels.
Head direction cell firing properties and behavioural performance in 3‐D space
Authors: Taube Jeffrey S.
Published: September 2010

Previous studies have identified a population of neurons in the rat brain that discharge as a function of the animal's directional heading in the horizontal plane, independent of their location and on‐going behaviour. Most studies on head direction (HD) cells have explored how they respond in two‐dimensional environments within the horizontal plane. Many animals, however, live and locomote in a three‐dimensional world. This paper reviews how HD cells respond when the animal locomotes on a vertical surface or inverted on a ceiling. We found that HD cells fire in a normal, direction‐dependent manner when the rat is in the vertical plane, but not when the animal is inverted. Recent behavioural studies reported that rats are capable of accurately performing a navigational task when inverted, but only when the task was simple and started from not more than one or two entry points. Probe trials found that they did not have a flexible, map‐like representation of space when inverted. The loss of the directional signal when the animal is in an inverted orientation may account for the absence of the map‐like representation. Taken together, these findings indicate that a normal otolith signal contributes an important role to HD cell discharge.
Anisotropic Hydraulic Permeability Under Finite Deformation
Authors: Ateshian Gerard A. , Weiss Jeffrey A.
Published: September 2010

The structural organization of biological tissues and cells often produces anisotropic transport properties. These tissues may also undergo large deformations under normal function, potentially inducing further anisotropy. A general framework for formulating constitutive relations for anisotropic transport properties under finite deformation is lacking in the literature. This study presents an approach based on representation theorems for symmetric tensor-valued functions and provides conditions to enforce positive semidefiniteness of the permeability or diffusivity tensor. Formulations are presented, which describe materials that are orthotropic, transversely isotropic, or isotropic in the reference state, and where large strains induce greater anisotropy. Strain-induced anisotropy of the permeability of a solid-fluid mixture is illustrated for finite torsion of a cylinder subjected to axial permeation. It is shown that, in general, torsion can produce a helical flow pattern, rather than the rectilinear pattern observed when adopting a more specialized, unconditionally isotropic spatial permeability tensor commonly used in biomechanics. The general formulation presented in this study can produce both affine and nonaffine reorientations of the preferred directions of material symmetry with strain, depending on the choice of material functions. This study addresses a need in the biomechanics literature by providing guidelines and formulations for anisotropic strain-dependent transport properties in porous-deformable media undergoing large deformations.
Modified postannealing of the Ge condensation process for better-strained Si material and devices
Authors: Liu Xuyan , Ma Xiaobo , Du Xiaofeng , Liu Weili , Song Zhitang , Lin Chenglu
Published: September 2010

A modified postannealing at 1000 °C in N2 ambient has been carried out to improve the Ge distribution in the SiGe layer fabricated by the Ge condensation process, which is a potential technique for strained Si fabrication. Three kinds of SiGe-on-insulator samples have been fabricated by so-called Ge condensation, which is the oxidation of the SiGe layer on an insulator to enhance the Ge fraction. After different postannealing processes and the necessary cleaning steps, 20-nm-thick strained Si films are epitaxially grown on them. Though the differences of surface topography among the three samples are not great, the one with the modified postannealing process has the most uniform Ge element distribution and the least misfit dislocations. Meanwhile, the strain values obtained by Raman spectra are coherent with the Ge fraction in SiGe near the Si/SiGe interface and the sample with the modified postannealing process has a larger strain value than the one with a conventional postannealing. The performance of metal-oxide-semiconductor field-effect transistors, based on the strained Si samples here, shows a significant enhancement, compared to those based on Si and Si on insulator samples.
Synthetic Lethal Screen of an EGFR-Centered Network to Improve Targeted Therapies
Authors: Astsaturov Igor , Ratushny Vladimir , Sukhanova Anna , Einarson Margret B. , Bagnyukova Tetyana , Zhou Yan , Devarajan Karthik , Silverman Joshua S. , Tikhmyanova Nadezhda , Skobeleva Natalya , Pecherskaya Anna , Nasto Rochelle E. , Sharma Catherine , Jablonski Sandra A. , Serebriiskii Ilya G. , Weiner Louis M. , Golemis Erica A.
Published: September 2010

A targeted RNAi screen reveals potential targets for combination approaches to cancer treatment.
Making Modifications
Authors: Hurtley Stella M.
Published: September 2010

The translational speed of proteins influences whether they are cotranslationally degraded after arginylation.
Complement for Inflammation Resolution
Authors: Gough Nancy R.
Published: September 2010

Compromised T cell response to the complement system may contribute to chronic inflammatory diseases, such as rheumatoid arthritis.
Location Matters
Authors: Mueller Kristen L.
Published: September 2010

Compartmentalization of signaling components allows induction of distinct pathways downstream of a pathogen receptor.
The Myelin Brake: When Enough Is Enough
Authors: Macklin Wendy B.
Published: September 2010

The lipid phosphatase PTEN and the scaffold protein Dlg1 restrict myelination in the peripheral nervous system.
Strong
In Vitro
Activities of Two New Rifabutin Analogs against Multidrug-Resistant
Mycobacterium tuberculosis
Authors: García Ana-Belén , Palacios Juan J. , Ruiz María-Jesús , Barluenga José , Aznar Fernando , Cabal María-Paz , García José María , Díaz Natalia
Published: September 2010

Two new rifabutin analogs, RFA-1 and RFA-2, show high
in vitro
antimycobacterial activities against
Mycobacterium tuberculosis
. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins.
In Vivo
Pharmacodynamics of New Lipopeptide MX-2401
Authors: Craig W. A. , Andes D. R. , Stamstad T.
Published: September 2010

MX-2401 is a novel lipopeptide (amphomycin analog) with a broad-spectrum bactericidal activity against Gram-positive organisms. We used murine thigh and lung infection models in neutropenic and normal mice to characterize the
in vivo
pharmacokinetic/pharmacodynamic (PK/PD) activities of MX-2401. The compound (2.5 to 40 mg/kg of body weight) demonstrated linear PK characterized by an area under the concentration-time curve (AUC) of 228 to 3,265 μg·h/ml and half-lives of 5.7 to 8.8 h. MICs ranged from 0.25 to 2 μg/ml. The
in vivo
postantibiotic effect was prolonged (8.5 h with
Staphylococcus aureu
s and 10.3 to 12.3 with
Streptococcus pneumonia
e). MX-2401 exhibited dose-dependent
in vivo
activity against various strains of
S. pneumoniae
and
S. aureus
; penicillin and macrolide resistance in the pneumococci and methicillin resistance in the staphylococci had no impact on the antimicrobial activity of the drug. To determine which PK/PD index correlated best with MX-2401 activity, dose fractionation studies over a 72-hour period were performed. The maximum concentration of drug in serum divided by the MIC (
C
max
/MIC) correlated best with the efficacy for both
S
.
aureu
s and
S
.
pneumonia
e. Static doses required free-drug
C
max
/MIC values of 0.683 to 1.06. Free-drug 72-h AUC/MIC values for the static dose were in the range of 7.49 to 32.3 and were less than expected. The drug showed modest enhancement in activity in the presence of white blood cells (1.7- to 3.4-fold). The potency of the drug in the lung was only marginally lower than in the thigh (1.3- to 1.9-fold). Based on its PK/PD profile, MX-2401 appears to be a promising new lipopeptide agent for treatment of infections by Gram-positive bacteria, including those induced by antibiotic-resistant pathogens.
Aziridine-2,3-Dicarboxylate-Based Cysteine Cathepsin Inhibitors Induce Cell Death inLeishmania majorAssociated with Accumulation of Debris in Autophagy-Related Lysosome-Like Vacuoles
Authors: Schurigt Uta , Schad Caroline , Glowa Christin , Baum Ulrike , Thomale Katja , Schnitzer Johannes K. , Schultheis Martina , Schaschke Norbert , Schirmeister Tanja , Moll Heidrun
Published: September 2010

The papain-like cysteine cathepsins expressed byLeishmaniaplay a key role in the life cycle of these parasites, turning them into attractive targets for the development of new drugs. We previously demonstrated that two compounds of a series of peptidomimetic aziridine-2,3-dicarboxylate [Azi(OBn)2]-based inhibitors, Boc-(S)-Leu-(R)-Pro-(S,S)-Azi(OBn)2(compound 13b) and Boc-(R)-Leu-(S)-Pro-(S,S)-Azi(OBn)2(compound 13e), reduced the growth and viability ofLeishmania majorand the infection rate of macrophages while not showing cytotoxicity against host cells. In the present study, we characterized the mode of action of inhibitors 13b and 13e inL. major. Both compounds targeted leishmanial cathepsin B-like cysteine cathepsin cysteine proteinase C, as shown by fluorescence proteinase activity assays and active-site labeling with biotin-tagged inhibitors. Furthermore, compounds 13b and 13e were potent inducers of cell death in promastigotes, characterized by cell shrinkage, reduction of mitochondrial transmembrane potential, and increased DNA fragmentation. Transmission electron microscopic studies revealed the enrichment of undigested debris in lysosome-like organelles participating in micro- and macroautophagy-like processes. The release of digestive enzymes into the cytoplasm after rupture of membranes of lysosome-like vacuoles resulted in the significant digestion of intracellular compartments. However, the plasma membrane integrity of compound-treated promastigotes was maintained for several hours. Taken together, our results suggest that the induction of cell death inLeishmaniaby cysteine cathepsin inhibitors 13b and 13e is different from mammalian apoptosis and is caused by incomplete digestion in autophagy-related lysosome-like vacuoles.
Fusidic Acid Resistance Determinants in
Staphylococcus aureus
Clinical Isolates
Authors: Chen Hsiao-Jan , Hung Wei-Chun , Tseng Sung-Pin , Tsai Jui-Chang , Hsueh Po-Ren , Teng Lee-Jene
Published: September 2010

A total of 71 fusidic acid-resistant
Staphylococcus aureus
(45 methicillin-resistant and 26 methicillin-susceptible) isolates were examined for the presence of resistance determinants. Among 45 fusidic acid-resistant methicillin-resistant
S. aureus
(MRSA), isolates, 38 (84%) had
fusA
mutations conferring high-level resistance to fusidic acid (the MIC was ≥128 μg/ml for 22/38), none had
fusB
, and 7 (16%) had
fusC
. For 26 fusidic acid-resistant methicillin-susceptible
S. aureus
(MSSA), only 3 possessed
fusA
mutations, but 15 (58%) had
fusB
and 8 (31%) had
fusC
. Low-level resistance to fusidic acid (MICs ≤ 32 μg/ml) was found in most
fusB
- or
fusC
-positive isolates. For 41 isolates (38 MRSA and 3 MSSA), with
fusA
mutations, a total of 21 amino acid substitutions in EF-G (
fusA
gene) were detected, of which R76C, E444K, E444V, C473S, P478S, and M651I were identified for the first time. The nucleotide sequencing of
fusB
and flanking regions in an MSSA isolate revealed the structure of partial IS
257
-
aj1
-LP-
fusB
-
aj2
-
aj3
-IS
257
-partial
blaZ
, which is identical to the corresponding region in pUB101, and the rest of
fusB
-carrying MSSA isolates also show similar structures. On the basis of
spa
and staphylococcal cassette chromosome
mec
element (SCC
mec
) typing, two major genotypes,
spa
type t037-SCC
mec
type III (t037-III; 28/45; 62%) and t002-II (13/45; 29%), were predominant among 45 MRSA isolates. By pulsed-field gel electrophoresis analysis, 45 MRSA isolates were divided into 12 clusters, while 26 MSSA isolates were divided into 15 clusters. Taken together, the distribution of fusidic acid resistance determinants (
fusA
mutations,
fusB
, and
fusC
) was quite different between MRSA and MSSA groups.
In Vitro
and
In Vivo
Activities of LCB01-0371, a New Oxazolidinone
Authors: Jeong Ji-Woong , Jung Sung-Ji , Lee Hyun-Hee , Kim Yong-Zu , Park Tae-Kyo , Cho Young-Lag , Chae Sang-Eun , Baek Sung-Yoon , Woo Sung-Ho , Lee Hyang-Sook , Kwak Jin-Hwan
Published: September 2010

LCB01-0371 is a new oxazolidinone with cyclic amidrazone.
In vitro
activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens.
In vivo
activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against
Staphylococcus aureus.
In Vitro
Antifungal Susceptibilities and Amplified Fragment Length Polymorphism Genotyping of a Worldwide Collection of 350 Clinical, Veterinary, and Environmental
Cryptococcus gattii
Isolates
Authors: Hagen Ferry , Illnait-Zaragozi Maria-Teresa , Bartlett Karen H. , Swinne Daniëlle , Geertsen Erik , Klaassen Corné H. W. , Boekhout Teun , Meis Jacques F.
Published: September 2010

The
in vitro
susceptibilities of a worldwide collection of 350
Cryptococcus gattii
isolates to seven antifungal drugs, including the new triazole isavuconazole, were tested. With amplified fragment length polymorphism (AFLP) fingerprinting, human, veterinary, and environmental
C. gattii
isolates were subdivided into seven AFLP genotypes, including the interspecies hybrids AFLP8 and AFLP9. The majority of clinical isolates (
n
= 215) comprised genotypes AFLP4 (
n
= 76) and AFLP6 (
n
= 103). The clinical AFLP6 isolates had significantly higher geometric mean MICs for flucytosine and fluconazole than the clinical AFLP4 isolates. Of the seven antifungal compounds examined in this study, isavuconazole had the lowest MIC
90
(0.125 μg/ml) for all
C. gattii
isolates, followed by a 1 log
2
dilution step increase (MIC
90
, 0.25 μg/ml) for itraconazole, voriconazole, and posaconazole. Amphotericin B had an acceptable MIC
90
of 0.5 μg/ml, but fluconazole and flucytosine had relatively high MIC
90
s of 8 μg/ml.
Susceptibility of Treatment-Naive Hepatitis C Virus (HCV) Clinical Isolates to HCV Protease Inhibitors
Authors: Bae Andrew , Sun Siu-Chi , Qi Xiaoping , Chen Xiaowu , Ku Karin , Worth Angela , Wong Kelly A. , Harris Jeanette , Miller Michael D. , Mo Hongmei
Published: September 2010

In order to assess the natural variation in susceptibility to hepatitis C virus (HCV) NS3 protease inhibitors (PIs) among untreated HCV patient samples, the susceptibilities of 39 baseline clinical isolates were determined using a transient-replication assay on a panel of HCV PIs, including two α-ketoamides (VX-950 and SCH-503034) and three macrocyclic inhibitors (MK-7009, ITMN-191, and TMC-435350). Some natural variation in susceptibility to all HCV PIs tested was observed among the baseline clinical isolates. The susceptibility to VX-950 correlated strongly with the susceptibility to SCH-503034. A moderate correlation was observed between the susceptibilities to ITMN-191 and MK-7009. In contrast, the phenotypic correlations between the α-ketoamides and macrocyclic inhibitors were significantly lower. This difference is partly attributable to reduced susceptibility of the HCV variants containing the NS3 polymorphism Q80K (existing in 47% of genotype 1a isolates) to the macrocyclic compounds but no change in the sensitivity of the same variants to the α-ketoamides tested. Our results suggest that the natural variation in baseline susceptibility may contribute to different degrees of antiviral response among patients
in vivo
, particularly at lower doses.
Impact of Silver-Containing Wound Dressings on Bacterial Biofilm Viability and Susceptibility to Antibiotics during Prolonged Treatment
Authors: Kostenko Victoria , Lyczak Jeffrey , Turner Katherine , Martinuzzi Robert John
Published: September 2010

The long-term antimicrobial efficacy of silver dressings against bacterial biofilms was investigated in a 7-day treatment
in vitro
model where the protein-rich medium was refreshed daily in order to mimic the conditions found in a wound bed. The use of plate-to-plate transfer assays demonstrated measurable differences in the effectivenesses of several silver dressings on the viability of biofilm bacteria and their susceptibility to antibiotics. Whereas after the first day of treatment, all dressings used resulted in a significant reduction in the number of viable cells in the biofilms and disruption of the biofilm colonies, during prolonged treatment, the efficacy of dressings with hydrophilic base materials diminished with daily transfers, and bacterial populations recovered. For dressings with hydrophobic base materials, the level of efficacy correlated with the silver species loaded. Biofilm bacteria, which survived the initial silver treatment, were susceptible to tobramycin, ciprofloxacin, and trimethoprim-sulfamethoxazole, in contrast to untreated biofilms, which were highly tolerant to the same antibiotics. This acquired susceptibility was unaffected by the longevity of pretreatment with the silver dressings but depended on the dressing used. The antimicrobial efficacy of the dressings correlated with the type of the dressing base material and silver species loaded.
Binding and Action of CEM-101, a New Fluoroketolide Antibiotic That Inhibits Protein Synthesis
Authors: Llano-Sotelo Beatriz , Dunkle Jack , Klepacki Dorota , Zhang Wen , Fernandes Prabhavathi , Cate Jamie H. D. , Mankin Alexander S.
Published: September 2010

We characterized the mechanism of action and the drug-binding site of a novel ketolide, CEM-101, which belongs to the latest class of macrolide antibiotics. CEM-101 shows high affinity for the ribosomes of Gram-negative (
Escherichia coli
) and Gram-positive (
Staphylococcus aureus
) bacteria. The ketolide shows high selectivity in its inhibitory action and readily interferes with synthesis of a reporter protein in the bacterial but not eukaryotic cell-free translation system. Binding of CEM-101 to its ribosomal target site was characterized biochemically and by X-ray crystallography. The X-ray structure of CEM-101 in complex with the
E. coli
ribosome shows that the drug binds in the major macrolide site in the upper part of the ribosomal exit tunnel. The lactone ring of the drug forms hydrophobic interactions with the walls of the tunnel, the desosamine sugar projects toward the peptidyl transferase center and interacts with the A2058/A2509 cleft, and the extended alkyl-aryl arm of the drug is oriented down the tunnel and makes contact with a base pair formed by A752 and U2609 of the 23S rRNA. The position of the CEM-101 alkyl-aryl extended arm differs from that reported for the side chain of the ketolide telithromycin complexed with either bacterial (
Deinococcus radiodurans
) or archaeal (
Haloarcula marismortui
) large ribosomal subunits but closely matches the position of the side chain of telithromycin complexed to the
E. coli
ribosome. A difference in the chemical structure of the side chain of CEM-101 in comparison with the side chain of telithromycin and the presence of the fluorine atom at position 2 of the lactone ring likely account for the superior activity of CEM-101. The results of chemical probing suggest that the orientation of the CEM-101 extended side chain observed in the
E. coli
ribosome closely resembles its placement in
Staphylococcus aureus
ribosomes and thus likely accurately reflects interaction of CEM-101 with the ribosomes of the pathogenic bacterial targets of the drug. Chemical probing further demonstrated weak binding of CEM-101, but not of erythromycin, to the ribosome dimethylated at A2058 by the action of Erm methyltransferase.
Ethidium Bromide MIC Screening for Enhanced Efflux Pump Gene Expression or Efflux Activity in
Staphylococcus aureus
Authors: Patel Diixa , Kosmidis Christos , Seo Susan M. , Kaatz Glenn W.
Published: September 2010

Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in
Staphylococcus aureus
. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed. Ethidium bromide is a substrate for all but one of the characterized
S. aureus
multidrug-resistant (MDR) efflux pumps (NorC), leading us to examine the utility of simple broth microtiter MIC determinations using this compound in identifying efflux-proficient strains. Quantitative reverse transcription-PCR identified the increased expression of one or more MDR efflux pump genes in 151/309 clinical strains (49%). Ethidium bromide MIC testing was insensitive (48%) but specific (92%) in identifying strains with gene overexpression, but it was highly sensitive (95%) and specific (99%) in identifying strains capable of ethidium efflux. The increased expression of
norA
with or without other genes was most commonly associated with efflux, and in the majority of cases that efflux was inhibited by reserpine. Ethidium bromide MIC testing is a simple and straightforward method to identify effluxing strains and can provide accurate predictions of efflux prevalence in large strain sets in a short period of time.
Cadaverine Suppresses Persistence to Carboxypenicillins in
Pseudomonas aeruginosa
PAO1
Authors: Manuel Jerrylynn , Zhanel George G. , de Kievit Teresa
Published: September 2010

The refractory nature of
Pseudomonas aeruginosa
infections is due in part to the presence of specialized cells, termed persisters, within the population. To identify genes involved in
P. aeruginosa
persister formation, a PAO1 transposon (Tn) library was challenged
en masse
with 1,000 μg/ml of carbenicillin and was enriched for mutants that were able to survive in the presence of this antibiotic. For one mutant that was further characterized, the carbenicillin MIC was equal to that of PAO1, but persister formation exhibited a 20-fold increase after exposure to the antibiotic. Sequence analysis revealed that the Tn had inserted into PA4115, a gene encoding a putative lysine decarboxylase. A PA4115 mutant that produced 48-fold and 20-fold more survivors than PAO1 after 10-h exposures to carbenicillin and ticarcillin, respectively, was generated by allelic exchange. Furthermore, the rate of carboxypenicillin-induced lysis was reduced in the PA4115 mutant. Under certain pH conditions, lysine decarboxylase converts lysine to cadaverine. By measuring cadaverine production, we discovered that the PA4115 mutant had significantly reduced lysine decarboxylase activity. To determine if reduced cadaverine levels are responsible for the increase in carbenicillin and ticarcillin persistence, viability and lysis assays were performed in the presence of exogenous cadaverine. Cadaverine increased the rate of killing and lysis of the PA4115 mutant in the presence of both antibiotics. These findings suggest that cadaverine may be able to enhance the effectiveness of carboxypenicillins against
P. aeruginosa
by reducing persister formation.