bluuebunny/crossref_metadata_2025 huggingface dataset:
Ga
As
∕
Al
Ox
micropillar fabrication for small mode volume photon sources
Authors: Choi John M. , Silverman Kevin L. , Stevens Martin J. , Harvey Todd L. , Mirin Richard P.
Published: January 2010

Micropillar devices have shown promise as single photon sources for applications in quantum key distribution as well as single photon metrology and fundamental science. For higher temperature operation (77K), a high quality factor (Q) cavity and a small modal volume are necessary for enhanced spontaneous emission. Although high Q’s have been demonstrated, achieving small modal volumes is difficult due to the limited index contrast available from the lattice-matched Bragg layers of GaAs and AlGaAs. However, by wet thermal oxidation of AlGaAs or AlAs layers to amorphous aluminum oxide (AlOx), very high index contrast layers can be obtained. This allows for high reflectivity mirrors with fewer Bragg pairs, resulting in reduced mode volume from reduced penetration of the optical mode within the mirror pairs. The authors apply this method in a GaAs∕Al0.95Ga0.05As material system and describe a fabrication process for such devices, utilizing a BCl3:Cl2:Ar etch. Photoluminescence measurements of micropillars with three top and five bottom layers are demonstrated. They are measured to have Q’s of 200–400 for approximately 1–3μm diameters, respectively. These results indicate that high Q devices may be possible while simultaneously reducing the modal volume.
Nanoindentation study of thin plasma enhanced chemical vapor deposition SiCOH low-k films modified in He/H2 downstream plasma
Authors: Vanstreels Kris , Urbanowicz Adam M.
Published: January 2010

The effect of He/H2 downstream plasma (DSP) on the mechanical properties of plasma enhanced chemical vapor deposition SiCOH low-k films was studied using nanoindentation (NI) with the continuous-stiffness measurement technique. Furthermore, the main requirements for reliable NI measurements on plasma-modified low-k films are discussed. The results show that the mechanical properties of these films are intimately linked with their porosity and that exposure to He/H2 DSP causes a change in both the porosity and the mechanical properties of the films. This change is related to the removal of porogen residue formed during the ultraviolet curing of the low-k film.
Vaccines with MF59 Adjuvant Expand the Antibody Repertoire to Target Protective Sites of Pandemic Avian H5N1 Influenza Virus
Authors: Khurana Surender , Chearwae Wanida , Castellino Flora , Manischewitz Jody , King Lisa R. , Honorkiewicz Agnieszka , Rock Michael T. , Edwards Kathryn M. , Del Giudice Giuseppe , Rappuoli Rino , Golding Hana
Published: January 2010

An oil-based adjuvant improves the efficacy of an H5N1 vaccine by inducing antibodies against additional sites on influenza surface proteins.
Can't Get Next to You
Authors: Minzenberg Michael
Published: January 2010

The stress-response system of infant rat brains disrupts the rats' capacity for learning to maintain close proximity to mothers who are stressed themselves.
Cracking the Code of Pseudomonas Longevity: Unveiling the PAMPs!
Authors: Ahmad Shama
Published: January 2010

Mutations that change the biochemistry of bacterial lipid metabolites may explain why the chronic lung infections of cystic fibrosis patients are so hard to treat.
Neutrophil Gelatinase-Associated Lipocalin Expresses Antimicrobial Activity by Interfering withl-Norepinephrine-Mediated Bacterial Iron Acquisition
Authors: Miethke Marcus , Skerra Arne
Published: January 2010

l-norepinephrine (NE) is a neuroendocrine catecholamine that supports bacterial growth by mobilizing iron from a primary source such as holotransferrin to increase its bioavailability for cellular uptake. Iron complexes of NE resemble those of bacterial siderophores that are scavenged by human neutrophil gelatinase-associated lipocalin (NGAL) as part of the innate immune defense. Here, we show that NGAL binds iron-complexed NE, indicating physiological relevance for both bacterial and human iron metabolism. The fluorescence titration of purified recombinant NGAL with the FeIII·(NE)3iron complex revealed high affinity for this ligand, with aKDof 50.6 nM. In contrast, the binding protein FeuA ofBacillus subtilis, which is involved in the bacterial uptake of triscatecholate iron complexes, has aKDfor FeIII·(NE)3of 1.6 μM, indicating that NGAL is an efficient competitor. Furthermore, NGAL was shown to inhibit the NE-mediated growth of bothE. coliandB. subtilisstrains that either are capable or incapable of producing their native siderophores enterobactin and bacillibactin, respectively. These experiments suggest that iron-complexed NE directly serves as an iron source for bacterial uptake systems, and that NGAL can function as an antagonist of this iron acquisition process. Interestingly, a functional FeuABC uptake system was shown to be necessary for NE-mediated growth stimulation as well as its NGAL-dependent inhibition. This study demonstrates for the first time that human NGAL not only neutralizes pathogen-derived virulence factors but also can effectively scavenge an iron-chelate complex abundant in the host.
Fasting Increases Tobramycin Oral Absorption in Mice
Authors: De Leo Luigina , Di Toro Nicola , Decorti Giuliana , Malusà Noelia , Ventura Alessandro , Not Tarcisio
Published: January 2010

The pharmacokinetics of the aminoglycoside tobramycin was evaluated after oral administration to fed or fasting (15 h) mice. As expected, under normal feeding conditions, oral absorption was negligible; however, fasting induced a dramatic increase in tobramycin bioavailability. The dual-sugar test with lactulose andl-rhamnose confirmed increased small bowel permeability via the paracellular route in fasting animals. When experiments aimed at increasing the oral bioavailability of hydrophilic compounds are performed, timing of fasting should be extremely accurate.
Delineation of a Bacterial Starvation Stress Response Network Which Can Mediate Antibiotic Tolerance Development
Authors: Fung Danny K. C. , Chan Edward W. C. , Chin Miu L. , Chan Raphael C. Y.
Published: January 2010

This study aimed at elucidating the physiological basis of bacterial antibiotic tolerance. By use of a combined phenotypic and gene knockout approach, exogenous nutrient composition was identified as a crucial environmental factor which could mediate progressive development of tolerance with markedly varied drug specificity and sustainability. Deprivation of amino acids was a prerequisite for tolerance formation, conferring condition-specific phenotypes against inhibitors of cell wall synthesis and DNA replication (ampicillin and ofloxacin, respectively), according to the relative abundances of ammonium salts, phosphate, and nucleobases. Upon further depletion of glucose, this variable phase consistently evolved into a sustainable mode, along with enhanced capacity to withstand the effect of the protein synthesis inhibitor gentamicin. Nevertheless, all phenotypes produced during spontaneous nutrient depletion lacked the sustainable, multidrug-tolerant features exhibited by the stationary-phase population and were attributed to complex interaction between starvation-mediated metabolic and stress protection responses on the basis of the following reasons: (i) the nutrition-dependent tolerance characteristics observed suggested that adaptive biosynthetic mechanisms could suppress but not fully avert tolerance under transient starvation conditions; (ii) formation of specific phenotypes could be inhibited by suppressing protein synthesis prior to nutrient depletion; (iii) bacteriostatic drugs produced only weak tolerance in the absence of starvation signals; and (iv) the attenuation of the stringent and SOS responses, as well as the functionality of other putative tolerance determinants, including
rpoS
,
hipA
,
glpD
, and
phoU
, could alter the induction requirement and drug specificity of the resultant phenotypes. These data reveal the common physiological grounds characteristic of starvation responses and the onset of antibiotic tolerance in bacteria.
Pharmacokinetics of Liposomal Amphotericin B in Pleural Fluid
Authors: Moriyama Brad , Torabi-Parizi Parizad , Pratt Alexandra K. , Henning Stacey A. , Pennick Gennethel , Shea Yvonne R. , Roy Chowdhuri Sinchita , Rinaldi Michael G. , Barrett A. John , Walsh Thomas J.
Published: January 2010

We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC
pleural fluid
) to that in serum (AUC
serum
) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.12 to 4.91 μg/ml. Given the relatively low level of intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema.
Inhibition of Human Immunodeficiency Virus Type 1 by Triciribine Involves the Accessory Protein Nef
Authors: Ptak Roger G. , Gentry Brian G. , Hartman Tracy L. , Watson Karen M. , Osterling M. Clayton , Buckheit Robert W. , Townsend Leroy B. , Drach John C.
Published: January 2010

Triciribine (TCN) is a tricyclic nucleoside that inhibits human immunodeficiency virus type 1 (HIV-1) replication by a unique mechanism not involving the inhibition of enzymes directly involved in viral replication. This activity requires the phosphorylation of TCN to its 5′ monophosphate by intracellular adenosine kinase. New testing with a panel of HIV and simian immunodeficiency virus isolates, including low-passage-number clinical isolates and selected subgroups of HIV-1, multidrug resistant HIV-1, and HIV-2, has demonstrated that TCN has broad antiretroviral activity. It was active in cell lines chronically infected with HIV-1 in which the provirus was integrated into chromosomal DNA, thereby indicating that TCN inhibits a late process in virus replication. The selection of TCN-resistant HIV-1 isolates resulted in up to a 750-fold increase in the level of resistance to the drug. DNA sequence analysis of highly resistant isolate HIV-1H10found five point mutations in the HIV-1 genenef, resulting in five different amino acid changes. DNA sequencing of the other TCN-resistant isolates identified at least one and up to three of the same mutations observed in isolate HIV-1H10. Transfer of the mutations from TCN-resistant isolate HIV-1H10to wild-type virus and subsequent viral growth experiments with increasing concentrations of TCN demonstrated resistance to the drug. We conclude that TCN is a late-phase inhibitor of HIV-1 replication and that mutations innefare necessary and sufficient for TCN resistance.
Prevalence, Resistance Mechanisms, and Susceptibility of Multidrug-Resistant Bloodstream Isolates of
Pseudomonas aeruginosa
Authors: Tam Vincent H. , Chang Kai-Tai , Abdelraouf Kamilia , Brioso Cristina G. , Ameka Magdalene , McCaskey Laurie A. , Weston Jaye S. , Caeiro Juan-Pablo , Garey Kevin W.
Published: January 2010

Pseudomonas aeruginosa
is an important pathogen commonly implicated in nosocomial infections. The occurrence of multidrug-resistant (MDR)
P. aeruginosa
strains is increasing worldwide and limiting our therapeutic options. The MDR phenotype can be mediated by a variety of resistance mechanisms, and the corresponding relative biofitness is not well established. We examined the prevalence, resistance mechanisms, and susceptibility of MDR
P. aeruginosa
isolates (resistant to ≥3 classes of antipseudomonal agents [penicillins/cephalosporins, carbapenems, quinolones, and aminoglycosides]) obtained from a large, university-affiliated hospital. Among 235 nonrepeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from 20 unique patients) were found to be MDR (crude prevalence rate, 14%). All isolates were resistant to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins, and 21% were resistant to the aminoglycosides. By using the first available isolate for each bacteremia episode (
n
= 18), 13 distinct clones were revealed by repetitive-element-based PCR. Western blotting revealed eight isolates (44%) to have MexB overexpression. Production of a carbapenemase (VIM-2) was found in one isolate, and mutations in
gyrA
(T83I) and
parC
(S87L) were commonly found. Growth rates of most MDR isolates were similar to that of the wild type, and two isolates (11%) were found to be hypermutable. All available isolates were susceptible to polymyxin B, and only one isolate was nonsusceptible to colistin (MIC, 3 mg/liter), but all isolates were nonsusceptible to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring of the prevalence and resistance mechanisms of MDR
P. aeruginosa
would enable us to formulate rational treatment strategies to combat nosocomial infections.
Dry Powder PA-824 Aerosols for Treatment of Tuberculosis in Guinea Pigs
Authors: Garcia-Contreras Lucila , Sung Jean C. , Muttil Pavan , Padilla Danielle , Telko Martin , VerBerkmoes Jarod L. , Elbert Katharina J. , Hickey Anthony J. , Edwards David A.
Published: January 2010

Novel treatments for multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB), or latent TB are needed urgently. Recently, we reported the formulation and characterization of the nitroimidazo-oxazine PA-824 for efficient aerosol delivery as dry powder porous particles and the subsequent disposition in guinea pigs after pulmonary administration. The objective of the present study was to evaluate the effects of these PA-824 therapeutic aerosols on the extent of TB infection in the low-inoculum aerosol infection guinea pig model. Four weeks after infection by the pulmonary route, animals received daily treatment for 4 weeks of either a high or a low dose of PA-824 dry powder aerosol. Animals received PA-824 cyclodextrin/lecithin suspensions orally as positive controls, and those receiving placebo particles or no treatment were negative controls. The lungs and spleens of animals receiving the high dose of inhaled PA-824 particles exhibited a lower degree of inflammation (indicated by wet tissue weights), bacterial burden, and tissue damage (indicated by histopathology) than those of untreated or placebo animals. Treatment with oral PA-824 cyclodextrin/lecithin suspension resulted in a more significant reduction in the bacterial burden of lungs and spleen, consistent with a dose that was larger than inhaled doses (eight times the inhaled low dose and four times the inhaled high dose). However, histopathological analysis revealed that the extent of tissue damage was comparable in groups receiving the oral or either inhaled dose. The present studies indicate the potential use of PA-824 dry powder aerosols in the treatment of TB.
The Extreme C Terminus of
Shigella flexneri
IpaB Is Required for Regulation of Type III Secretion, Needle Tip Composition, and Binding
Authors: Roehrich A. Dorothea , Martinez-Argudo Isabel , Johnson Steven , Blocker Ariel J. , Veenendaal Andreas K. J.
Published: January 2010

Type III secretion systems (T3SSs) are widely distributed virulence determinants of Gram-negative bacteria. They translocate bacterial proteins into host cells to manipulate them during infection. The
Shigella
T3SS consists of a cytoplasmic bulb, a transmembrane region, and a hollow needle protruding from the bacterial surface. The distal tip of mature, quiescent needles is composed of IpaD, which is topped by IpaB. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which other virulence effector proteins may be translocated. IpaB is required for regulation of secretion and may be the host cell sensor. However, its mode of needle association is unknown. Here, we show that deletion of 3 or 9 residues at the C terminus of IpaB leads to fast constitutive secretion of late effectors, as observed in a Δ
ipaB
strain. Like the Δ
ipaB
mutant, mutants with C-terminal mutations also display hyperadhesion. However, unlike the Δ
ipaB
mutant, they are still invasive and able to lyse the internalization vacuole with nearly wild-type efficiency. Finally, the mutant proteins show decreased association with needles and increased recruitment of IpaC. Taken together, these data support the notion that the state of the tip complex regulates secretion. We propose a model where the quiescent needle tip has an “off” conformation that turns “on” upon host cell contact. Our mutants may adopt a partially “on” conformation that activates secretion and is capable of recruiting some IpaC to insert pores into host cell membranes and allow invasion.
Burkholderia cenocepaciaCreates an Intramacrophage Replication Niche in Zebrafish Embryos, Followed by Bacterial Dissemination and Establishment of Systemic Infection
Authors: Vergunst Annette C. , Meijer Annemarie H. , Renshaw Stephen A. , O'Callaghan David
Published: January 2010

Bacteria belonging to the “Burkholderia cepaciacomplex” (Bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. These Gram-negative bacteria can adopt an intracellular lifestyle, although their ability to replicate intracellularly has been difficult to demonstrate. Here we show that Bcc bacteria survive and multiply in macrophages of zebrafish embryos. Local dissemination by nonlytic release from infected cells was followed by bacteremia and extracellular replication.Burkholderia cenocepaciaisolates belonging to the epidemic electrophoretic type 12 (ET12) lineage were highly virulent for the embryos; intravenous injection of <10 bacteria of strain K56-2 killed embryos within 3 days. However, small but significant differences between the clonal ET12 isolates K56-2, J2315, and BC7 were evident. In addition, the innate immune response in young embryos was sufficiently developed to control infection with other less virulent Bcc strains, such asBurkholderia vietnamiensisFC441 andBurkholderia stabilisLMG14294. A K56-2cepRquorum-sensing regulator mutant was highly attenuated, and its ability to replicate and spread to neighboring cells was greatly reduced. Our data indicate that the zebrafish embryo is an excellent vertebrate model to dissect the molecular basis of intracellular replication and the early innate immune responses in this intricate host-pathogen interaction.
Polysaccharide Capsule and Sialic Acid-Mediated Regulation Promote Biofilm-Like Intracellular Bacterial Communities during Cystitis
Authors: Anderson Gregory G. , Goller Carlos C. , Justice Sheryl , Hultgren Scott J. , Seed Patrick C.
Published: January 2010

UropathogenicEscherichia coli(UPEC) is the leading cause of urinary tract infections (UTIs). A murine UTI model has revealed an infection cascade whereby UPEC undergoes cycles of invasion of the bladder epithelium, intracellular proliferation in polysaccharide-containing biofilm-like masses called intracellular bacterial communities (IBC), and then dispersal into the bladder lumen to initiate further rounds of epithelial colonization and invasion. We predicted that the UPEC K1 polysaccharide capsule is a key constituent of the IBC matrix. Compared to prototypicE. coliK1 strain UTI89, a capsule assembly mutant had a fitness defect in functionally TLR4+and TLR4−mice, suggesting a protective role of capsule in inflamed and noninflamed hosts. K1 capsule assembly and synthesis mutants had dramatically reduced IBC formation, demonstrating the common requirement for K1 polysaccharide in IBC development. The capsule assembly mutant appeared dispersed in the cytoplasm of the bladder epithelial cells and failed to undergo high-density intracellular replication during later stages of infection, when the wild-type strain continued to form serial generations of IBC. Deletion of the sialic acid regulator genenanRpartially restored IBC formation in the capsule assembly mutant. These data suggest that capsule is necessary for efficient IBC formation and that aberrant sialic acid accumulation, resulting from disruption of K1 capsule assembly, produces a NanR-mediated defect in intracellular proliferation and IBC development. Together, these data demonstrate the complex but important roles of UPEC polysaccharide encapsulation and sialic acid signaling in multiple stages of UTI pathogenesis.
Haemophilus ducreyiSapA Contributes to Cathelicidin Resistance and Virulence in Humans
Authors: Mount Kristy L. B. , Townsend Carisa A. , Rinker Sherri D. , Gu Xiaoping , Fortney Kate R. , Zwickl Beth W. , Janowicz Diane M. , Spinola Stanley M. , Katz Barry P. , Bauer Margaret E.
Published: January 2010

Haemophilus ducreyiis an extracellular pathogen of human epithelial surfaces that resists human antimicrobial peptides (APs). The organism's genome contains homologs of genessensitive toantimicrobialpeptides (sapoperon) in nontypeableHaemophilus influenzae. In this study, we characterized thesap-containing loci ofH. ducreyi35000HP and demonstrated thatsapAis expressed in broth cultures andH. ducreyi-infected tissue;sapAis also conserved among both class I and class IIH. ducreyistrains. We constructed a nonpolarsapAmutant ofH. ducreyi35000HP, designated 35000HPsapA, and compared the percent survival of wild-type 35000HP and 35000HPsapAexposed to several human APs, including α-defensins, β-defensins, and the cathelicidin LL-37. Unlike anH. influenzae sapAmutant, strain 35000HPsapAwas not more susceptible to defensins than strain 35000HP was. However, we observed a significant decrease in the survival of strain 35000HPsapAafter exposure to LL-37, which was complemented by introducingsapAintrans. Thus, the Sap transporter plays a role in resistance ofH. ducreyito LL-37. We next compared mutant strain 35000HPsapAwith strain 35000HP for their ability to cause disease in human volunteers. Although both strains caused papules to form at similar rates, the pustule formation rate at sites inoculated with 35000HPsapAwas significantly lower than that of sites inoculated with 35000HP (33.3% versus 66.7%;P= 0.007). Together, these data establish that SapA acts as a virulence factor and as one mechanism forH. ducreyito resist killing by antimicrobial peptides. To our knowledge, this is the first demonstration that an antimicrobial peptide resistance mechanism contributes to bacterial virulence in humans.
Assessment of the Duration of Protection in
Campylobacter jejuni
Experimental Infection in Humans
Authors: Tribble David R. , Baqar Shahida , Scott Daniel A. , Oplinger Michael L. , Trespalacios Fernando , Rollins David , Walker Richard I. , Clements John D. , Walz Steven , Gibbs Paul , Burg Edward F. , Moran Anthony P. , Applebee Lisa , Bourgeois A. Louis
Published: January 2010

A human
Campylobacter jejuni
infection model provided controlled exposure to assess vaccine efficacy and investigate protective immunity for this important diarrheal pathogen. A well-characterized outbreak strain,
C. jejuni
81-176, was investigated using a volunteer experimental infection model to evaluate the dose range and duration of protection. Healthy
Campylobacter
-seronegative adults received
C. jejuni
strain 81-176 via oral inoculation of 10
5
, 10
7
, or 10
9
CFU (5 adults/dose), which was followed by clinical and immunological monitoring. Based on dose range clinical outcomes, the 10
9
-CFU dose (
n
= 31) was used to assess homologous protection at 28 to 49 days (short-term veterans [STV];
n
= 8) or 1 year (long-term veterans [LTV];
n
= 7) after primary infection. An illness dose effect was observed for naïve subjects (with lower doses, 40 to 60% of the subjects were ill; with the 10
9
-CFU dose, 92% of the subjects were ill) along with complete protection for the STV group and attenuated illness for the LTV group (57%). Partial resistance to colonization was seen in STV (25% of the subjects were not infected; 3-log-lower maximum excretion level). Systemic and mucosal immune responses were robust in naïve subjects irrespective of the dose or the severity of illness. In contrast, in STV there was a lack of circulating antibody-secreting cells (ASC), reflecting the local mucosal effector responses. LTV exhibited comparable ASC responses to primary infection, and anamnestic fecal IgA responses likely contributed to self-resolving illness prior to antibiotic treatment.
Campylobacter
antigen-dependent production of gamma interferon by peripheral blood mononuclear cells was strongly associated with protection from illness, supporting the hypothesis that TH1 polarization has a primary role in acquired immunity to
C. jejuni
. This study revealed a
C. jejuni
dose-related increase in campylobacteriosis rates, evidence of complete short-term protection that waned with time, and immune response patterns associated with protection.
Screening of Predicted Secreted Antigens fromMycobacterium bovisReveals the Immunodominance of the ESAT-6 Protein Family
Authors: Jones Gareth J. , Gordon Stephen V. , Hewinson R. Glyn , Vordermeier H. Martin
Published: January 2010

Results of previous studies utilizing bioinformatic approaches in antigen-mining experiments revealed that secreted proteins are among the most frequently recognized antigens fromMycobacterium bovis. Thus, we hypothesized that the analysis of secreted proteins is likely to reveal additional immunogenic antigens that can be used to increase the specificity of diagnostic tests or be suitable vaccination candidates for mycobacterial infections. To test this hypothesis, 382 pools of overlapping peptides spanning 119M. bovissecreted and potentially secreted proteins were screened for the ability to stimulate a gamma interferon responsein vitrousing whole blood from tuberculin-positive reactor (TB reactor) cattle. Of the 119 proteins screened, 70 (59%) induced positive responses in the TB reactor animals to various degrees. Strikingly, all but one of the 15 ESAT-6 proteins tested were recognized by at least 30% of the TB reactor animals, with 12 of the 22 most commonly recognized antigens belonging to this protein family. Further analysis of these data demonstrated that there was no significant difference in immunogenicity between the ESAT-6 proteins that were components of potentially intact ESX secretory systems and those corresponding to additional partialesxloci. Importantly for vaccine design, antigenic epitopes in some highly conserved regions shared by numerous ESAT-6 proteins were identified. However, despite this considerable homology, peptide-mapping experiments also revealed that immunodominant peptides were located in regions of amino acid variability.
Early ovule development in Papaver rhoeas
Authors: Cass David D. , Fabi George C.
Published: January 2010

Adjacent placentae in the youngest floral buds that were studied were seen to be in contact, possessing axial procambial cells in a mass of ground tissue and two layers of anticlinally dividing cells at their surfaces. Nucelli are initiated by periclinal divisions in the second layer; normally two or three adjacent cells are involved. Initiation sites are four to six cells apart. Nucelli develop into spheres with single protoderm layers and ground tissue. At this time localized divisions in placental procambium and adjacent ground tissue produce procambial strands, each strand representing an incipient ovule trace. Such strands propagate acropetally from the placental procambium. Primary xylem and phloem within these strands appear to differentiate acropetally. Ovular integuments are produced by the nucellar protoderm in which the division planes are variable but periclinal divisions predominate. The megasporocyte differentiates interior to the protoderm at the apex of the nucellus. Based on the time of appearance of ovule trace procambial strands and their spatial relationship to individual nucelli, it appears that each nucellus induces the development of its prospective ovule trace.
Changes in metabolism induced in Helianthus leaves by sudden hypoxia or chilling stress
Authors: McIntosh S. , Andrews D. , Moorby Jonathan , Thompson R. G. , Fensom D. S.
Published: January 2010

Exposure of a sunflower leaf to hypoxia or chilling stress interrupts translocation from the leaf and also alters the distribution of 14C-assimilates into sugars and amino acids. As translocation from the leaf recovers, there are changes in the distribution of label in the sugars and amino acids that coincide with this recovery. These observations lend support to the idea that certain concentrations of sugars and amino acids are necessary to support translocation out of the leaf.
Ultrastructural observations on Helvellaceae (Pezizales, Ascomycetes). IV. Ascospore ontogeny in selected species of Gyromitra subgenus Discina
Authors: Kimbrough James W. , Wu Chi-Guang , Gibson Jack L.
Published: January 2010

The ultrastructure of ascospore ontogeny and spore wall microchemistry are described in three sessile, discoid species of Gyromitra previously placed in Discina. Silver proteinate and barium permanganate were used as poststains to enhance the definition of various wall layers and spore organelles. Early stages of ascosporogenesis and primary wall formation are similar to those described in other species of Pezizales. Secondary wall formation, which results in characteristic spore ornamentation, is similar in Gyromitra brunnea, Gyromitra leucoxantha, and Gyromitra perlata. Mature spores of these species differ in the size and shape of translucent lacunae within the secondary wall, and in the morphology of apiculi. The lacunae originate through blebbing of primary wall material through the epispore into the secondary wall, resulting in the isolation of electron-translucent primary wall clumps within the electron-dense secondary wall. These and other ultrastructural observations of apothecial tissues support the maintenance of the Helvellaceae (sensu lato) to include taxa of the tribes Helvelleae, Discineae, and Rhizineae. Phylogenetic linkages of these taxa to other families of Pezizales are suggested. Key words: ascosporogenesis, ascospore wall structure and microchemistry, discomycete systematics and phylogeny.
Distribution of plant macroremains in surface sediments of Marion Lake, southwestern British Columbia
Authors: Wainman Newton , Mathewes Rolf W.
Published: January 2010

Thirty surface sediment samples were collected from Marion Lake to establish the present-day distribution patterns of potential plant macrofossils, with emphasis on remains derived from upland species. Sample sites could be separated into three distinct groups on the basis of their macrofossil representation: offshore sites, west shore sites, and east shore sites. Significantly fewer macrofossils were found in offshore sites than in nearshore sites. East shore sites had fewer forest macrofossils because of the presumed filtering effect of a bordering sedge marsh. Conifer needles were always more abundant that their seeds, whereas for most other taxa, reproductive structures were more common than vegetative ones. Thuja plicata and Tsuga heterophylla were well represented by vegetative remains reflecting their shared dominance (ca. 90%) within 100 m of the lakeshore. The highest frequencies and concentrations of macroremains were scale leaves and branchlets of Thuja, indicating that western red cedar should be readily detectable in older fossil deposits. A proportional relationship exists between macrofossil concentrations and site frequency, indicating mixing and dispersal before deposition in the lake. A major inlet stream (Jacob's Creek) brings in many macroremains and appears to be the major source of Alnus rubra seeds and foliage of Abies amabilis and Pinus monticola. Seeds of the aquatic macrophyte Najas flexilis and oospores of the alga Nitella were frequently encountered in surface samples, although neither taxon was reported as growing in Marion Lake. This surface sediment study provided insights valuable to the interpretation of a postglacial macrofossil record in a companion study (N. W. Wainman and R. W. Mathewes 1987. Can. J. Bot. 65: 2179–2187).
The arrangement of scales and bristles on Mallomonas (Chrysophyceae): a proposed mechanism for the formation of the cell covering
Authors: Siver Peter A. , Glew John R.
Published: January 2010

The siliceous cell covering of Mallomonas consists of a series of imbricated scales and bristles arranged in a very precise pattern. Scales on a given cell are aligned in spiral rows with their longitudinal axes parallel, perpendicular, or at an oblique angle to the longitudinal axis of the cell. The scales within each spiral row are overlapped in a posterior to anterior manner, whereas the spiral rows themselves are overlapped in an anterior to posterior fashion. The result is that an individual scale is overlapped by the scale positioned posterior to it in the same spiral row and by the scale(s) in the spiral row anterior to it. A mechanism is proposed to explain the formation of the cell covering whereby the scales and bristles are released from the cell sequentially at a given site and simultaneously moved over the outside of the cell membrane to their final positions. The force used to release a scale is coupled with that needed to slide the scales into place. The V-rib and (or) proximal rim provide a means by which each scale is properly spaced and ultimately guided into position. The proposed mechanism is contrasted with an alternative model where the siliceous components are moved around and orientated within the cell before being released into their final positions.
The relationship between time of pollination, pollination efficiency, and cone size in western red cedar (Thuja plicata)
Authors: Colangeli Anna M. , Owens John N.
Published: January 2010

The pollination mechanism in western red cedar (Thuja plicata Donn) is described for container-grown clones. The seed cones ended dormancy at the end of February 1986, opened exposing the ovules, and soon after secreted pollination drops. Unpollinated cones remained open and secreted pollination drops for 15 to 20 days, before the expansion of the bract scales completely covered the ovules. The presence of pollen hastened cone closure so that it occurred within 4 or 5 days of pollination. Pollen in the micropyle was essential for ovule maturation and subsequent cone development. The developmental stage of the seed cones at pollination influenced the proportion of ovules per cone containing pollen (pollination efficiency). Each cone bore between 13 and 16 ovules. The proportion of ovules per cone that received pollen in the micropyles was highest when pollinations were conducted after cone opening but before bract scale expansion. A positive relationship was found between pollination efficiency and the length of mature seed cones.
Fonctionnement des stomates de Cocotier (Cocos nucifera) au champ
Authors: Passos Edson Eduardo Melo , Silva Jorge Vieira Da
Published: January 2010

The behavior of coconut (Cocos nucifera L.) stomata was studied under field conditions in adult plants. Hourly determination of relative stomatal opening and of stomatal conductance values revealed that coconut stomata were opened maximally between 0800 and 1600; by the end of this period, the stomata closed rapidly as solar radiation decreased. Changes in temperature and relative humidity of the air did not affect stomatal behavior. The maximum relative stomatal opening occurred at midday, when the water potential of the leaf is at its lowest point, showing that stomatal behavior depends mostly on solar radiation and does not control water loss efficiently under conditions of water stress.
INFLATION TARGETING IN INDONESIA: SEARCHING FOR A THRESHOLD
Authors: CHOWDHURY ANIS , HAM ROGER
Published: January 2010

It could be argued that for some developing countries, low to moderate inflation is beneficially related to economic growth and that it is only after a certain threshold level that inflation becomes deleterious to growth. This has implications for macroeconomic policy requirements placed on developing countries by international loan bodies. This paper, using data from Indonesia, examines the relationship between growth and inflation. Particularly, a threshold VAR model is used to test for changes in the relationship between inflation and growth. The results so far are exploratory and limited by a small data sample. The results are consistent with a threshold level between 8.5% and 11% producing structural shifts in the relationship between inflation and growth.
The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent
Authors: Janovská Alena , Hatzinikolas George , Mano Mark , Wittert Gary A.
Published: January 2010

A high-saturated-fat diet (HFD) induces obesity and insulin resistance (IR). IR has been linked to alterations and increased saturation in the phospholipid composition of skeletal muscles. We aimed to determine whether HFD feeding affects fatty acid (FA) membrane profile in a muscle fiber type-specific manner. We measured phospholipid FAs and expression of FA synthesis genes in oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles from rats fed either standard chow (standard laboratory diet, SLD) or a HFD. The HFD increased fat mass, plasma insulin, and leptin levels. Compared with EDL, SOL muscles preferentially accumulated C18 over C16 FAs and n-6 over n-3 polyunsaturated FAs (PUFAs) on either diet. With the HFD, SOL muscles contained more n-9 monounsaturated FAs (MUFAs) and n-6 PUFAs and less n-7 MUFAs and n-3 PUFAs than EDL muscles and had lower unsaturation index, a pattern known to be associated with IR. Stearoyl-CoA desaturase-1 expression was ∼13-fold greater in EDL than in SOL muscles but did not change with the HFD in either muscle. The expression of Elongase-5 was higher, and that of Elongase-6 (Elovl6) was lower in EDL compared with SOL muscles with both diets. In EDL muscles, the expression of Elovl6 was lower in the HFD than in the SLD. The pattern of FA uptake, expression, and diet-induced changes in FA desaturating and elongating enzymes maintained higher FA unsaturation in EDL muscles. Accordingly, the fiber type composition of skeletal muscles and their distribution may be important in the development and progression of obesity and IR.
Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction
Authors: Leos Rafael A. , Anderson Miranda J. , Chen Xiaochuan , Pugmire Juliana , Anderson K. Arbor , Limesand Sean W.
Published: January 2010

In this study, we examined chronic norepinephrine suppression of insulin secretion in sheep fetuses with placental insufficiency-induced intrauterine growth restriction (IUGR). Glucose-stimulated insulin secretion (GSIS) was measured with a square-wave hyperglycemic clamp in the presence or absence of adrenergic receptor antagonists phentolamine (α) and propranolol (β). IUGR fetuses were hypoglycemic and hypoxemic and had lower GSIS responsiveness ( P ≤ 0.05) than control fetuses. IUGR fetuses also had elevated plasma norepinephrine (3,264 ± 614 vs. 570 ± 86 pg/ml; P ≤ 0.05) and epinephrine (164 ± 32 vs. 60 ± 12 pg/ml; P ≤ 0.05) concentrations. In control fetuses, adrenergic inhibition increased baseline plasma insulin concentrations (1.7-fold, P ≤ 0.05), whereas during hyperglycemia insulin was not different. A greater ( P ≤ 0.05) response to adrenergic inhibition was found in IUGR fetuses, and the average plasma insulin concentrations increased 4.9-fold at baseline and 7.1-fold with hyperglycemia. Unlike controls, basal plasma glucose concentrations fell ( P ≤ 0.05) with adrenergic antagonists. GSIS responsiveness, measured by the change in insulin, was higher (8.9-fold, P ≤ 0.05) in IUGR fetuses with adrenergic inhibition than controls (1.8-fold, not significant), showing that norepinephrine suppresses insulin secretion in IUGR fetuses. Strikingly, in IUGR fetuses, adrenergic inhibition resulted in a greater GSIS responsiveness, because β-cell mass was 56% lower and the maximal stimulatory insulin response tended ( P < 0.1) to be higher than controls. This persistent norepinephrine suppression appears to be partially explained by higher mRNA concentrations of adrenergic receptors α1D, α2A, and α2Bin a cohort of fetuses that were naïve to the antagonists. Therefore, norepinephrine suppression of insulin secretion was maintained, in part, by upregulating adrenergic receptor expression, but the β-cells also appeared to compensate with enhanced GSIS. These findings may begin to explain why IUGR infants have a propensity for increased glucose requirements if norepinephrine is suddenly decreased after birth.
Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study
Authors: Christiansen Tore , Paulsen Søren K. , Bruun Jens M. , Pedersen Steen B. , Richelsen Bjørn
Published: January 2010

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. V̇o2max was increased by 14–18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1α, IL-15, and IL-18 were decreased, and adiponectin was increased ( P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% ( P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers ( P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin ( P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups ( P < 0.05). In conclusion, rather large weight losses (>5–7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased V̇o2max, was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation.
The Decerebrate Cat Generates the Essential Features of the Force Constraint Strategy
Authors: Honeycutt Claire F. , Nichols T. Richard
Published: January 2010

Cats actively respond to horizontal perturbations of the supporting surface according to the force constraint strategy. In this strategy, the force responses fall into two groups oriented in either rostral and medial directions or caudal and lateral directions, rather than in strict opposition to the direction of perturbation. When the distance between forelimbs and hindlimbs is decreased, the responses are less constrained and directed more in line with the perturbation. We have recently shown that electromyographic responses from limb muscles of the decerebrate cat resemble those obtained in the intact animal. Our objectives here were to determine whether the decerebrate cat preparation would also exhibit the force constraint strategy and whether that strategy would exhibit the characteristic dependence on limb position on the strategy. Horizontal support surface perturbations were delivered and three-dimensional exerted forces were recorded from all four limbs. Clustered force responses were generated by all four limbs and were found to be statistically indistinguishable between animals decerebrated using two different levels of transection. The directionality of the force responses was preserved throughout successive time epochs during the perturbations. In addition, the clustering of force responses increased with distance between forelimbs and hindlimbs. These results indicate that the force constraint strategy used by terrestrial animals to maintain stability can be generated without the assistance of the cerebral cortices and without prior training. This suggests an important role for the lower brain stem and spinal cord in generating an appropriate strategy to maintain stability.
Interleukin-15 and Its Receptor Augment Dendritic Cell Vaccination against theneuOncogene through the Induction of Antibodies Partially Independent of CD4 Help
Authors: Steel Jason C. , Ramlogan Charmaine A. , Yu Ping , Sakai Yoshio , Forni Guido , Waldmann Thomas A. , Morris John C.
Published: January 2010

Interleukin-15 (IL-15) stimulates the diffrentiation and proliferation of T, B, and natural killer cells; enhances CD8+ cytolytic T-ceII activity; helps maintain CD44hiCD8+ memory T cells; and stimulates immunoglobulin synthesis by B cells. IL-15 is trans-presented to effector cells by its receptor, IL-15Rα, expressed on dendritic cells (DC) and monocytes. We examined the antitumor effect of adenoviral-mediated gene transfer of IL-15 and IL-15Rα to augment a DC vaccine directed against the NEU (ErbB2) oncoprotein. Transgenic BALB-neuT mice vaccinated in late-stage tumor development with a DC vaccine expressing a truncated NEU antigen, IL-I5, and its receptor (DCAd.Neu+Ad_mIL-15+Ad.mlL-15Rα) were protected from mammary carcinomas, with 70% of animals tumor-free at 30 weeks compared with none of the animals vaccinated with NEU alone (DCAd.Neu). The combination of neu, IL-15, and IL-15Rα gene transfer leads to a significaintly greater anti-NEU antibody response compared with mice treated with DCAd.Neu or DCAd.Neu combined with either IL-15 (DCAd.Neu+Ad.mlL-15) or lL-15Rα (DCAd.Neu+Ad.mlL-15Rα). The antitumor effect was antibody mediated and involved modulation of NEU expression and signaIing. Depletion of CD4+ cells did not abrogate the antitumor effect of the vaccine, nor did it inhibit the induction of anti-NEU aritibodies. Coexpression of IL-15 and IL-15Rα in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4+ T-helper function. Cancer Res; 70(3); 1072–81
The EphB6 Receptor Cooperates with c-Cbl to Regulate the Behavior of Breast Cancer Cells
Authors: Truitt Luke , Freywald Tanya , DeCoteau John , Sharfe Nigel , Freywald Andrew
Published: January 2010

Cancer invasiveness plays a major role in the mortality of patients with solid tumors, and deregulated cell adhesion and migration are suspected to drive invasive behavior. Since Eph receptor tyrosine kinases control both cell attachment and migration, they may act to define the level of cancer invasiveness. EphB6 is an unusual Eph receptor, lacking catalytic capacity due to alterations in its kinase domain. Interestingly, increased metastatic activity is associated with reduced EphB6 receptor expression in several tumor types, including breast cancer. This emphasizes the potential of EphB6 to act as a suppressor of cancer aggressiveness; however, the mechanism of its action is not well understood. We show that restoration of EphB6 expression in invasive breast cancer cells supports actin-dependent spreading and attachment and blocks invasiveness. EphB6 stimulation induces its tyrosine phosphorylation, which is crucial for its function and is mediated by the EphB4 receptor. This is accompanied by EphB6–c-Cbl interaction and phosphorylation of c-Cbl partner, the Abl kinase. Cbl silencing suppresses Abl phosphorylation, cell adhesion, and morphologic changes and blocks the ability of EphB6 to inhibit invasiveness, confirming its importance for EphB6 activity. Despite its crucial role in EphB6 responses, EphB4 also acts in an EphB6-independent manner to enhance invasive activity, suggesting that cancer invasiveness may be defined by the balance in the EphB6-EphB4 system. Overall, our observations suggest a new role for EphB6 in suppressing cancer invasiveness through c-Cbl–dependent signaling, morphologic changes, and cell attachment and indicate that EphB6 may represent a useful prognostic marker and a promising target for therapeutic approaches. Cancer Res; 70(3); 1141–53