bluuebunny/crossref_metadata_2025_split huggingface dataset:
The biochemical basis of antimicrobial responses in Manduca sexta
Authors: Jiang Haobo 
Published: September 2010

AbstractInnate immunity is essential for the wellbeing of vertebrates and invertebrates. Key components of this defense system include pattern recognition receptors that bind to infectious agents, extra–and intra–cellular proteins that relay signals, as well as molecules and cells that eliminate pathogens. We have been studying the defense mechanisms in a biochemical model insect, Manduca sexta. In this insect, hemolin, peptidoglycan recognition proteins, β‐1,3‐glucan recognition proteins and C‐type lectins detect microbial surface molecules and induce immune responses such as phagocytosis, nodulation, encapsulation, melanization and production of antimicrobial peptides. Some of these responses are mediated by extracellular serine proteinase pathways. The proteolytic activation of prophenoloxidase (proPO) yields active phenoloxidase (PO) which catalyzes the formation of quinones and melanin for wound healing and microbe killing. M. sexta hemolymph proteinase 14 (HP14) precursor interacts with peptidoglycan or β‐1,3‐glucan, autoactivates, and leads to the activation of other HPs including HP21 and proPO‐activating proteinases (PAPs). PAP‐1, ‐2 and ‐3 cut proPO to generate active PO in the presence of two serine proteinase homologs. Inhibition of the proteinases by serpins and association of the proteinase homologs with bacteria ensure a localized defense reaction. M. sexta HP1, HP6, HP8, HP17 and other proteinases may also participate in proPO activation or processing of spätzle and plasmatocyte spreading peptide.
Insect immune resistance to parasitoids
Authors: Carton Yves , Poirié Marylène , Nappi Anthony J. 
Published: September 2010

AbstractInsect host—parasitoid interactions involve complex physiological, biochemical and genetic interactions. Against endoparasitoids, immune‐competent hosts initiate a blood cell‐mediated response that quickly destroys the intruders and envelops them in a multilayered melanotic capsule. During the past decade, considerable progress has been made in identifying some of the critical components of the host response, mainly because of the use of efficient molecular tools. This review examines some of the components of the innate immune response of Drosophila, an insect that has served as an exceptionally good experimental model for studying non‐self recognition processes and immune cell signaling mechanisms. Topics considered in this review include hematopoiesis, proliferation and adhesion of hemocytes, melanogenesis and associated cytotoxic molecules, and the genetic aspects of the host‐parasitoid interaction.
Wolbachiasymbiosis and insect immune response
Authors: Siozios Stefanos , Sapountzis Panagiotis , Ioannidis Panagiotis , Bourtzis Kostas 
Published: September 2010

AbstractBacterial intracellular symbiosis is very common in insects, having significant consequences in promoting the evolution of life and biodiversity. The bacterial group that has recently attracted particular attention isWolbachia pipientiswhich probably represents the most ubiquitous endosymbiont on the planet.W. pipientisis a Gram‐negative obligatory intracellular and maternally transmitted α‐proteobacterium, that is able to establish symbiotic associations with arthropods and nematodes. In arthropods,Wolbachia pipientisinfections have been described in Arachnida, in Isopoda and mainly in Insecta. They have been reported in almost all major insect orders including Diptera, Coleoptera, Hemiptera, Hymenoptera, Orthoptera and Lepidoptera. To enhance its transmission,W. pipientiscan manipulate host reproduction by inducing parthenogenesis, feminization, male killing and cytoplasmic incompatibility. Several polymerase chain reaction surveys have indicated that up to 70% of all insect species may be infected withW. pipientis.How doesW. pipientismanage to get established in diverse insect host species? How is this intracellular bacterial symbiont species so successful in escaping the host immune response? The present review presents recent advances and ongoing scientific efforts in the field. The current body of knowledge in the field is summarized, revelations from the available genomic information are presented and as yet unanswered questions are discussed in an attempt to present a comprehensive picture of the unique ability ofW. pipientisto establish symbiosis and to manipulate reproduction while evading the host's immune system.
Therapeutic Potential of a Combination of Two Gene-Specific Small Interfering RNAs against Clinical Strains of
Acanthamoeba
Authors: Lorenzo-Morales Jacob , Martín-Navarro Carmen M. , López-Arencibia Atteneri , Santana-Morales María A. , Afonso-Lehmann Raquel N. , Maciver Sutherland K. , Valladares Basilio , Martínez-Carretero Enrique 
Published: September 2010

ABSTRACT

Pathogenic strains of the genus
Acanthamoeba
are causative agents of severe infections, such as fatal encephalitis and a sight-threatening amoebic keratitis. Antimicrobial therapy for these infections is generally empirical, and patient recovery is often problematic, due to the existence of a highly resistant cyst stage in these amoebae. In previous studies, small interfering RNAs (siRNAs) against the catalytic domains of extracellular serine proteases and glycogen phosphorylase from
Acanthamoeba
were designed and evaluated for future therapeutic use. The silencing of proteases resulted in
Acanthamoeba
failing to degrade human corneal cells, and silencing of glycogen phosphorylase caused amoebae to be unable to form mature cysts. After the siRNA design and concentration were optimized in order to avoid toxicity problems, cultures of
Acanthamoeba
were treated with a combination of both siRNAs, and cells were evaluated under an inverted microscope. This siRNA-based treatment dramatically affected the growth rate and cellular survival of the amoebae. These results were observed less than 48 h after the initiation of the treatment. In order to check possible toxic effects of the siRNA combination, three eukaryotic cell lines (HeLa, murine macrophages, and osteosarcoma cells) were treated with the same molecules, and cytotoxicity was examined by measuring lactate dehydrogenase release. The future use of the combination of these siRNAs is proposed as a potential therapeutic approach against pathogenic strains of
Acanthamoeba
.
In VitroActivities of Several Antimicrobial Agents against Recently Isolated and GenotypedChlamydia trachomatisUrogenital Serovars D through K
Authors: Donati Manuela , Di Francesco Antonietta , D'Antuono Antonietta , Delucca Federica , Shurdhi Alisa , Moroni Alessandra , Baldelli Raffaella , Cevenini Roberto 
Published: September 2010

ABSTRACTA systematic evaluation of the susceptibility of allChlamydia trachomatisurogenital serovars (D through K) to levofloxacin, erythromycin, doxycycline, clarithromycin, and azithromycin was performed. AllC. trachomatisserovars had comparable susceptibilities with respect to the various antimicrobials tested, thus confirming the homogeneous data so far obtained regarding the susceptibility ofC. trachomatisto antimicrobial agents.
DifferentialAspergillus lentulusEchinocandin Susceptibilities Are Fksp Independent
Authors: Staab Janet F. , Kahn Jennifer Nielsen , Marr Kieren A. 
Published: September 2010

ABSTRACTThe recently described speciesAspergillus lentulusexhibits differential and reduced susceptibilities to echinocandins and other antifungal drugsin vitro. A. lentulusisolates overall are less susceptible to caspofungin, although they maintain susceptibility to anidulafungin and micafungin. Mutations or polymorphisms infks, the gene encoding the catalytic subunit of β-1,3-glucan synthase, are known to confer decreased susceptibility to echinocandins inCandidaspp. andAspergillus fumigatus. The analysis of theA. lentulus fkssequence did not reveal a polymorphism at any of the known hot-spot regions of the gene. Caspofungin and micafungin kinetic inhibition profiles of theA. lentulusglucan synthase were comparable to those from susceptibleA. fumigatusenzymes. Although the basal cell wall chitin levels inA. lentulusaveraged 60% of those inA. fumigatus, echinocandin treatment promoted the increase of cell wall chitin in both organisms, indicating thatA. lentulusdisplays a compensatory chitin response similar to that ofA. fumigatus. The data suggest that differential echinocandin susceptibilities inA. lentulusare independent of the echinocandin target, Fksp, and they emphasize the potential that the drugs' capacity to inhibit the target enzyme is unequal at the cellular level.
Molecular Characterization of Off-Target Activities of Telithromycin: a Potential Role for Nicotinic Acetylcholine Receptors
Authors: Bertrand Daniel , Bertrand Sonia , Neveu Estelle , Fernandes Prabhavathi 
Published: September 2010

ABSTRACT
Adverse effects have limited the clinical use of telithromycin. Preferential inhibition of the nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (α3β2 and NMJ), the ciliary ganglion of the eye (α3β4 and α7), and the vagus nerve innervating the liver (α7) could account for the exacerbation of myasthenia gravis, the visual disturbance, and the liver failure seen with telithromycin use. The studies presented here enable the prediction of expected side effects of macrolides in development, such as solithromycin (CEM-101).
Mitochondrial Electron Transport Inhibition and Viability of Intraerythrocytic
Plasmodium falciparum
Authors: Painter Heather J. , Morrisey Joanne M. , Vaidya Akhil B. 
Published: September 2010

ABSTRACT

Although mitochondrial electron transport is a validated target of the antimalarial drug atovaquone, the molecular details underlying parasite demise are unclear. We have shown that a critical function of mitochondrial electron transport in blood-stage
Plasmodium falciparum
is to support pyrimidine biosynthesis. Here, we explore the effects of atovaquone, alone and in combination with proguanil, on
P. falciparum
viability. Our results suggest that the effects of inhibition depend upon the erythrocytic stage of the parasites and the duration of exposure. Ring- and schizont-stage parasites are most resilient to drug treatment and can survive for 48 h, with a fraction remaining viable even after 96 h. Survival of parasites does not appear to require nutrient uptake. Thus, intraerythrocytic parasites with inhibited mitochondrial electron transport and collapsed mitochondrial membrane potential do not undergo apoptosis but enter an apparent static state. These results have significant implications for desirable properties of antimalarials under development that target mitochondrial functions.
In Vitro
Sensitivity and Resistance of 46
Leptospira
Strains Isolated from Rats in the Philippines to 14 Antimicrobial Agents
Authors: Chakraborty Antara , Miyahara Satoshi , Villanueva Sharon Y. A. M. , Gloriani Nina G. , Yoshida Shin-ichi 
Published: September 2010

ABSTRACT

The
in vitro
susceptibilities of 46
Leptospira
isolates from rats to 14 antimicrobial agents were tested. All of the strains were found to be sensitive to ampicillin, cefotaxime, ciprofloxacin, norfloxacin, doxycycline, erythromycin, and streptomycin. In contrast, the tested isolates showed resistance to amphotericin B, 5-fluorouracil, fosfomycin, trimethoprim, sulfamethoxazole, neomycin, and vancomycin. These findings will help in selecting effective and ineffective antimicrobials for treatment of leptospirosis and for the development of new selective media, respectively.
Effect of N-1/C-8 Ring Fusion and C-7 Ring Structure on Fluoroquinolone Lethality
Authors: Malik Muhammad , Marks Kevin R. , Schwanz Heidi A. , German Nadezhda , Drlica Karl , Kerns Robert J. 
Published: September 2010

ABSTRACT

Quinolones rapidly kill bacteria by two mechanisms, one that requires protein synthesis and one that does not. The latter, which is measured as lethal action in the presence of the protein synthesis inhibitor chloramphenicol, is enhanced by N-1 cyclopropyl and C-8 methoxy substituents, as seen with the highly lethal compound PD161144. In some compounds, such as levofloxacin, the N-1 and C-8 substituents are fused. To assess the effect of ring fusion on killing, structural derivatives of levofloxacin and PD161144 differing at C-7 were synthesized and examined with
Escherichia coli
. A fused-ring derivative of PD161144 exhibited a striking absence of lethal activity in the presence of chloramphenicol. In general, ring fusion had little effect on lethal activity when protein synthesis was allowed, but fusion reduced lethal activity in the absence of protein synthesis to extents that depended on the C-7 ring structure. Additional fused-ring fluoroquinolones, pazufloxacin, marbofloxacin, and rufloxacin, also exhibited reduced activity in the presence of chloramphenicol. Energy minimization modeling revealed that steric interactions of the
trans
-oriented N-1 cyclopropyl and C-8 methoxy moieties skew the quinolone core, rigidly orient these groups perpendicular to core rings, and restrict the rotational freedom of C-7 rings. These features were not observed with fused-ring derivatives. Remarkably, structural effects on quinolone lethality were not explained by the recently described X-ray crystal structures of fluoroquinolone-topoisomerase IV-DNA complexes, suggesting the existence of an additional drug-binding state.
Inhibition of T Cells Provides Protection against Early Invasive Pneumococcal Disease
Authors: LeMessurier Kim , Häcker Hans , Tuomanen Elaine , Redecke Vanessa 
Published: September 2010

ABSTRACTInfections caused byStreptococcus pneumoniaeare major causes of morbidity and mortality, which are in part mediated by immune cell-dependent mechanisms. Yet, the specific contributions of individual cell types to immunopathology are only partially understood. T cells are well characterized with respect to their function in protective humoral immune responses; however, their roles during early stages of infection and invasive pneumococcal disease (IPD) are less well defined. Using a mouse model of pneumococcal sepsis, we found that CD4+T cells were recruited to the lung as early as 12 h after intranasal infection. Recruitment was accompanied by upregulation of CD69 and B7-H1, reflecting T-cell activation. Unexpectedly, major histocompatibility complex (MHC) class II-deficient mice, which lack CD4+T cells, displayed an increased survival despite comparable bacterial titers in the blood, spleen, and lung. The higher survival correlated with a lower cytokine and chemokine response uponS. pneumoniaechallenge in MHC class II-deficient mice, suggesting that inflammation may contribute to the mortality of IPD. Comparable to the case for MHC class II-deficient mice, antibody-mediated depletion of CD4+T cells and drug-induced inhibition of T-cell function with cyclosporine, or interference with T-cell activation using CTLA4-immunoglobulin (Abatacept), led to significant increases in survival during IPD. Our results reveal an important and adverse role of CD4+T cells in the pathogenesis of IPD and suggest that modulation of T-cell activation during early phases ofS. pneumoniaeinvasive infection may provide a therapeutic option.
Petrology and tectonic setting of some Ordovician volcanic rocks from the Southern Uplands of Scotland
Authors: Lambert R.St J. , Holland J.G. , Leggett J.K. 
Published: September 2010

Abstract:
SUMMARY: Within the Ordovician sequence of the Southern Uplands of Scotland numerous basaltic units occur, forming local basement to sequences of chert, graptolitic mudstone and greywacke. The basalts are fault-bounded at their base. Although they have suffered secondary alteration to varying degrees, the least mobile elements, Ti, Zr, Y and Nb, show a correlation between relative chemical abundances and supposed tectonic level. The most northern tectonic slice contains alkali basalts; the central slice contains 11 examples of what are apparently ocean-floor tholeiites and 4 mildly alkaline basalts; a third slice, found at one locality only, also contains tholeiites whose chemistry is comparable with the most primitive basalts. Samples of Ordovician extrusives from Bail Hill have calc-alkaline to alkaline affinities, while extrusives from Wrae Hill are quartz-keratophyres. The geochemical pattern is consistent with a model of an opening Iapetus Ocean in which rifting pre-dated spreading such that the basement to the Lower Palaeozoic sequence of the Southern Uplands was oceanic.
Deformed stones of varied lithology in Late Precambrian tillites, western Spitzbergen
Authors: Hambrey M.J. , Waddams P. 
Published: September 2010

Abstract:
SUMMARY: Late Precambrian tillites in western Spitzbergen, which were metamorphosed and strongly deformed during mid-Palaeozoic and mid-Cenozoic orogenies, contain stones up to 1 m or more in diameter, generally set in a fine-grained psammitic and pelitic matrix. The stones are lithologically varied, and include dolostone, limestone, quartzite, granite, granite-gneiss, volcanic rocks and sandstones. The tillites illustrate the varied rheological behaviour of different rock types under the same TP conditions. Where stones are dispersed through the matrix the degree of deformation appears to follow the pattern: granite (unfoliated) < dolostone < quartzite < metavolcanic rocks < granite-gneiss < limestone, with axial ratios for granite being around 2: 1 and for limestone over 20: 1. Matrix composition has a marked influence on the degree of deformation undergone by the stones. For example, stones in a sandy matrix are more deformed than those in finer-grained matrix of an adjacent horizon, suggesting that the latter is more capable of taking up the regional strain. Similarly, the deformation of stones is greater in rocks bearing only a small amount of matrix.
Competing deformation mechanisms and slaty cleavage in deformed, quartzose meta-sediments
Authors: Morris A.P. 
Published: September 2010

Abstract:
SUMMARY: Quartzose sediments from the Lower Palaeozoic orogen of Svalbard have suffered metamorphism to low grade (6 kb and a maximum of 500°C). Studies of the deformed micro-structures of these rocks reveal that pressure solution and intracrystalline deformation mechanisms are the major processes by which deformation occurs. The dominant mechanism for any given lithology (at approximately the above conditions of pressure and temperature) appears to depend on the rock composition. Quartzose rocks containing micaceous and other ‘impurities’ tend to deform by pressure solution, those containing little or no other material apart from quartz tend to deform by intracrystalline deformation mechanisms.
Scattered palaeomagnetic directions acquired during dioritization and stoping of the diorite-metagabbro complex, Jersey, C.I.
Authors: Duff B.A. 
Published: September 2010

Abstract:
SUMMARY: Scattered, but stable NRM (natural remanent magnetization) in the Jersey diorite-metagabbro complex, probably acquired during the formation of the complex, can be ascribed to 2 main geological processes: (i) stoping of the late Precambrian or early Cambrian diorites and metagabbros by the Jersey granites, which caused pre-stoping NRM to be dispersed by block rotation and subsidence in the granite melt; this was the largest contributor to palaeomagnetic.scatter; (ii) hybridization of the parent gabbro during granite intrusion, which added a dioritic generation of magnetite and its NRM to the NRM carried by the gabbro, and probably also caused variable, partial remagnetization of the gabbroic NRM before stoping.
A Counterexample on a Theorem by Khojasteh, Goodarzi, and Razani
Authors: Arandelović IvanD , Kečkić DragoljubJ 
Published: September 2010

AbstractIn the paper by Khojasteh et al. (2010), the authors tried to generalize Branciari's theorem, introducing the new integral type contraction mappings. In this note we give a counterexample on their main statement (Theorem 2.9). Also we give a comment explaining what the mistake in the proof is, and suggesting what conditions might be appropriate in generalizing fixed point results to cone spaces, where the cone is taken from the infinite dimensional space.
Single-Nucleotide Polymorphisms in p53 Pathway and Aggressiveness of Prostate Cancer in a Caucasian Population
Authors: Sun Tong , Lee Gwo-Shu Mary , Oh William K. , Pomerantz Mark , Yang Ming , Xie Wanling , Freedman Matthew L. , Kantoff Philip W. 
Published: September 2010

Abstract
Purpose: The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Mdm2, Mdm4, and Hausp are all critical regulators of the p53 protein. Despite the importance of the p53 pathway in prostate cancer development and progression, little is known about the association of functional single-nucleotide polymorphisms (SNP) in the p53 pathway genes and prostate cancer aggressiveness.
Experimental Design: In this study, we analyze the association of SNPs in p53, Mdm2, Mdm4, and Hausp genes with prostate cancer clinicopathologic variables in a large hospital-based Caucasian prostate cancer cohort (N = 4,073).
Results: We found that the Mdm2 SNP309 T allele was associated with earlier onset prostate cancer (P = 0.004), higher Gleason scores (P = 0.004), and higher stages in men undergoing a radical prostatectomy (P = 0.011). Both the Mdm4 and Hausp SNPs (rs1380576 and rs1529916) were found to be associated with higher D'Amico risk prostate cancer category at the time of diagnosis (P = 0.023 and P = 0.046, respectively). Mdm4 SNP was also found to be associated with higher Gleason score at radical prostatectomy (P = 0.047). We did not observe any statistically significant association between the p53 Arg72Pro polymorphism and prostate cancer aggressiveness or pathologic variables.
Conculsions: These results suggested the importance of these p53 regulators in prostate cancer development and progression. Clin Cancer Res; 16(21); 5244–51. ©2010 AACR.