bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single‐walled carbon nanotubes
Authors: Shvedova A. A. , Kagan V. E. 
Published: October 2009

Abstract.Nano‐sized materials and nano‐scaled processes are widely used in many industries. They are being actively introduced as diagnostic and therapeutic in biomedicine and they are found in numerous consumer products. The small size of nanoparticles, comparable with molecular machinery of cells, may affect normal physiological functions of cells and cause cytotoxicity. Their toxic potential cannot be extrapolated from studies of larger particles due to unique physicochemical properties of nanomaterials. Therefore, the use of nanomaterials may pose unknown risks to human health and the environment. This review discusses several important issues relevant to pulmonary toxicity of nanoparticles, especially single‐walled carbon nanotubes (SWCNT), their direct cytotoxic effects, their ability to cause an inflammatory response, and induce oxidative stress upon pharyngeal aspiration or inhalation. Further, recognition and engulfment of nanotubes by macrophages as they relate to phagocytosis and bio‐distribution of nanotubes in tissues and circulation are discussed. The immunosuppressive effects of CNT and their significance in increased sensitivity of exposed individuals to microbial infections are summarized. Finally, data on biodegradation of SWCNT by oxidative enzymes of inflammatory cells are presented in lieu of their persistence and distribution in the body.
MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging
Authors: Bates David J. , Li Na , Liang Ruqiang , Sarojini Harshini , An Jin , Masternak Michal M. , Bartke Andrzej , Wang Eugenia 
Published: October 2009

SummaryThe Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the post‐transcriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA (miRNA) microarray screening to identify dwarf‐specific lead miRNAs, and investigate their roles as pivotal molecular regulators directing the long‐lived phenotype. Mapping the signature miRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveals that dwarf mice post‐transcriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3′‐untranslated region reporter constructs in co‐transfection experiments confirm that miRNA‐27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this miRNA in vivo. Moreover, the putative repressed action of this miRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as 2 months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver – glutathione metabolism, the urea cycle and polyamine biosynthesis – miRNA‐27a is a key post‐transcriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended healthspan and longevity.
The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women
Authors: Redman Leanne M. , Veldhuis Johannes D. , Rood Jennifer , Smith Steven R. , Williamson Donald , Ravussin Eric ,   for the Pennington CALERIE Team
Published: October 2009

SummaryLifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age‐associated decline in growth hormone (GH), insulin‐like growth factor (IGF)‐1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty‐three young (36.8 ± 1.0 years), overweight (BMI 27.8 ± 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00–08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: −1 ± 1%, CR: −10 ± 1%, CR + EX: −10 ± 1%, LCD: −14 ± 1%), fat mass (control: −2 ± 3%, CR: −24 ± 3%, CR + EX: −25 ± 3%, LCD: −31 ± 2%) and visceral fat (control: −2 ± 4%, CR: −28 ± 4%, CR + EX: −27 ± 3%, LCD: −36 ± 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 ± 13%, LCD: 27 ± 22%, P < 0.05) and amplitude (CR + EX: 34 ± 14%, LCD: 30 ± 20%, P < 0.05) but not to changes in secretory burst frequency or GH half‐life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF‐1 concentrations were increased only in CR + EX (10 ± 7%, P < 0.05) and LCD (19 ± 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF‐1 in nonobese men and women.
Short‐term dietary restriction and fasting precondition against ischemia reperfusion injury in mice
Authors: Mitchell James R. , Verweij Mariëlle , Brand Karl , Van De Ven Marieke , Goemaere Natascha , Van Den Engel Sandra , Chu Timothy , Forrer Flavio , Müller Cristina , De Jong Marion , Van IJcken Wilfred , IJzermans Jan N. M. , Hoeijmakers Jan H. J. , De Bruin Ron W. F. 
Published: October 2009

SummaryDietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long‐term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2–4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water‐only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short‐term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin‐like growth factor‐1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short‐term DR or fasting revealed a significant enrichment of signature genes of long‐term DR. These data demonstrate that brief periods of reduced food intake, including short‐term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.
Age‐related alterations of gene expression patterns in human CD8+ T cells
Authors: Cao Jia‐Ning , Gollapudi Sastry , Sharman Edward H. , Jia Zhenyu , Gupta Sudhir 
Published: October 2009

SummaryAging is associated with progressive T‐cell deficiency and increased incidence of infections, cancer and autoimmunity. In this comprehensive study, we have compared the gene expression profiles in CD8+ T cells from aged and young healthy subjects using Affymetrix microarray Human Genome U133A‐2 GeneChips. A total of 5.2% (754) of the genes analyzed had known functions and displayed statistically significant age‐associated expression changes. These genes were involved in a broad array of complex biological processes, mainly in nucleic acid and protein metabolism. Functional groups, in which down‐regulated genes were overrepresented, were the following: RNA transcription regulation, RNA and DNA metabolism, intracellular (Golgi, endoplasmic reticulum and nuclear) transportation, signaling transduction pathways (T‐cell receptor, Ras/MAPK, JNK/Stat, PI3/AKT, Wnt, TGFβ, insulin‐like growth factor and insulin), and the ubiquitin cycle. In contrast, the following functional groups contained more up‐regulated genes than expected: response to oxidative stress and cytokines, apoptosis, and the MAPKK signaling cascade. These age‐associated gene expression changes may be responsible for impaired DNA replication, RNA transcription, and signal transduction, possibly resulting in instability of cellular and genomic integrity, and alterations of growth, differentiation, apoptosis and anergy in human aged CD8+ T cells.
Multilocus Variable-Number Tandem-Repeat Analysis and Plasmid Profiling To Study the Occurrence of
bla
CMY-2
within a Pulsed-Field Gel Electrophoresis-Defined Clade of
Salmonella enterica
Serovar Typhimurium
Authors: Adhikari B. , Besser T. E. , Gay J. M. , Fox L. K. , Hancock D. D. , Davis M. A. 
Published: October 2009

ABSTRACT

Salmonella enterica
serovar Typhimurium circulating in food animal populations and carrying resistance to antimicrobial agents represents a human health risk. Recently, a new clade of
S
. Typhimurium, WA-TYP035/187, was reported in cattle and humans in the Pacific Northwest, United States of America. The objective of this study was to describe a possible mechanism of acquisition of expanded-spectrum cephalosporin resistance in this clade. Ceftazidime resistance increased steadily among WA-TYP035/187 isolates, from 0% (0/2) in 1999 to 77.8% (28/36) in 2006 (χ
2
for linear trend,
P
value of <0.001). Among 112 bovine-source and 18 human-source isolates, 49 (43.8%) and 12 (66.7%) were resistant to ceftazidime, respectively. Multiple-locus variable-number tandem-repeat analysis (MLVA) and plasmid profiling suggested that resistance was acquired by multiple independent genetic events within the WA-TYP035/187 clade. Given the lack of an obvious reservoir in species other than cattle and a parallel rise in ceftiofur resistance in the bovine-specific serovar
S
almonella enterica
serovar Dublin in the same time frame and region, selection pressure due to the use of the expanded-spectrum cephalosporin drug ceftiofur in cattle is a likely factor driving the increasing cephalosporin resistance of WA-TYP035/187.
Benthic Bacterial Diversity in Submerged Sinkhole Ecosystems
Authors: Nold Stephen C. , Pangborn Joseph B. , Zajack Heidi A. , Kendall Scott T. , Rediske Richard R. , Biddanda Bopaiah A. 
Published: October 2009

ABSTRACT

Physicochemical characterization, automated ribosomal intergenic spacer analysis (ARISA) community profiling, and 16S rRNA gene sequencing approaches were used to study bacterial communities inhabiting submerged Lake Huron sinkholes inundated with hypoxic, sulfate-rich groundwater. Photosynthetic cyanobacterial mats on the sediment surface were dominated by
Phormidium autumnale
, while deeper, organically rich sediments contained diverse and active bacterial communities.
In Vivo Bioluminescence Imaging for the Study of Intestinal Colonization by
Escherichia coli
in Mice
Authors: Foucault M.-L. , Thomas L. , Goussard S. , Branchini B. R. , Grillot-Courvalin C. 
Published: October 2009

ABSTRACT

Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of
Escherichia coli
harboring the genes for either the bacterial luciferase from
Photorhabdus luminescens
or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of
Photinus pyralis
(red and green thermostable
P. pyralis
luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (
R
2
= 0.98) or transcutaneously in the abdominal region of whole animals (
R
2
= 0.99) and the CFU counts in the feces of bacteria harboring the
luxABCDE
operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2Ω

P
ami
luxABCDE

), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of
E. coli
could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization.
Mechanisms of Hop Inhibition Include the Transmembrane Redox Reaction
Authors: Behr Jürgen , Vogel Rudi F. 
Published: October 2009

ABSTRACT

In this work, a novel mechanistic model of hop inhibition beyond the proton ionophore action toward (beer spoiling) bacteria was developed. Investigations were performed with model systems using cyclic voltammetry for the determination of redox processes/conditions in connection with growth challenges with hop-sensitive and -resistant
Lactobacillus brevis
strains in the presence of oxidants. Cyclic voltammetry identified a transmembrane redox reaction of hop compounds at low pH (common in beer) and in the presence of manganese (present in millimolar levels in lactic acid bacteria). The antibacterial action of hop compounds could be extended from the described proton ionophore activity, lowering the intracellular pH, to pronounced redox reactivity, causing cellular oxidative damage. Accordingly, a correlation between the resistance of
L. brevis
strains to a sole oxidant to their resistance to hop could not be expected and was not detected. However, in connection with our recent study concerning hop ionophore properties and the resistance of hop-sensitive and -tolerant
L. brevis
strains toward proton ionophores (J. Behr and R. F. Vogel, J. Agric. Food Chem. 57:6074-6081, 2009), we suggest that both ionophore and oxidant resistance are required for survival under hop stress conditions and confirmed this correlation according to the novel mechanistic model. In consequence, the expression of several published hop resistance mechanisms involved in manganese binding/transport and intracellular redox balance, as well as that of proteins involved in oxidative stress under “highly reducing” conditions (cf. anaerobic cultivation and “antioxidative” hop compounds in the growth medium), is now comprehensible. Accordingly, hop resistance as a multifactorial dynamic property at least implies distinct resistance levels against two different mechanisms of hop inhibition, namely, proton ionophore-induced and oxidative stress-induced mechanisms. Beyond this specific model of hop inhibition, these investigations provide general insight on the role of electrophysiology and ion homeostasis in bacterial stress responses to membrane-active drugs.
Abundance of Novel and Diverse
tfdA
-Like Genes, Encoding Putative Phenoxyalkanoic Acid Herbicide-Degrading Dioxygenases, in Soil
Authors: Zaprasis Adrienne , Liu Ya-Jun , Liu Shuang-Jiang , Drake Harold L. , Horn Marcus A. 
Published: October 2009

ABSTRACT

Phenoxyalkanoic acid (PAA) herbicides are widely used in agriculture. Biotic degradation of such herbicides occurs in soils and is initiated by α-ketoglutarate- and Fe
2+
-dependent dioxygenases encoded by
tfdA
-like genes (i.e.,
tfdA
and
tfdA
α). Novel primers and quantitative kinetic PCR (qPCR) assays were developed to analyze the diversity and abundance of
tfdA
-like genes in soil. Five primer sets targeting
tfdA
-like genes were designed and evaluated. Primer sets 3 to 5 specifically amplified
tfdA
-like genes from soil, and a total of 437 sequences were retrieved. Coverages of gene libraries were 62 to 100%, up to 122 genotypes were detected, and up to 389 genotypes were predicted to occur in the gene libraries as indicated by the richness estimator Chao1. Phylogenetic analysis of in silico-translated
tfdA
-like genes indicated that soil
tfdA
-like genes were related to those of group 2 and 3
Bradyrhizobium
spp.,
Sphingomonas
spp., and uncultured soil bacteria. Soil-derived
tfdA
-like genes were assigned to 11 clusters, 4 of which were composed of novel sequences from this study, indicating that soil harbors novel and diverse
tfdA
-like genes. Correlation analysis of 16S rRNA and
tfdA
-like gene similarity indicated that any two bacteria with
D
> 20% of group 2
tfdA
-like gene-derived protein sequences belong to different species. Thus, data indicate that the soil analyzed harbors at least 48 novel bacterial species containing group 2
tfdA
-like genes. Novel qPCR assays were established to quantify such new
tfdA
-like genes. Copy numbers of
tfdA
-like genes were 1.0 × 10
6
to 65 × 10
6
per gram (dry weight) soil in four different soils, indicating that hitherto-unknown, diverse
tfdA
-like genes are abundant in soils.
Aromatic Hydroxylation of Indan by
o
-Xylene-Degrading
Rhodococcus
sp. Strain DK17
Authors: Kim Dockyu , Lee Choong Hwan , Choi Jung Nam , Choi Ki Young , Zylstra Gerben J. , Kim Eungbin 
Published: October 2009

ABSTRACT

The metabolically versatile
Rhodococcus
sp. strain DK17 utilizes indan as a growth substrate via the
o
-xylene pathway. Metabolite and reverse transcription-PCR analyses indicate that
o
-xylene dioxygenase hydroxylates indan at the 4,5 position of the aromatic moiety to form
cis
-indan-4,5-dihydrodiol, which is dehydrogenated to 4,5-indandiol by a dehydrogenase. 4,5-Indandiol undergoes ring cleavage by a
meta
-cleavage dioxygenase.
Crucial Role for Insertion Sequence Elements in
Lactobacillus helveticus
Evolution as Revealed by Interstrain Genomic Comparison
Authors: Kaleta Pawel , O'Callaghan John , Fitzgerald Gerald F. , Beresford Thomas P. , Ross R. Paul 
Published: October 2009

ABSTRACT

Lactobacillus helveticus
is a versatile dairy bacterium found to possess heterogeneous genotypes depending on the ecosystem from which it was isolated. The recently published genome sequence showed the remarkable flexibility of its structure, demonstrated by a substantial level of insertion sequence (IS) element expansion in association with massive gene decay. To assess this diversity and examine the level of genome plasticity within the
L. helveticus
species, an array-based comparative genome hybridization (aCGH) experiment was designed in which 10 strains were analyzed. The aCGH experiment revealed 16 clusters of open reading frames (ORFs) flanked by IS elements. Four of these ORFs are associated with restriction/modification which may have played a role in accelerated evolution of strains in a commercially intensive ecosystem undoubtedly challenged through successive phage attack. Furthermore, analysis of the IS-flanked clusters demonstrated that the most frequently encountered ISs were also those most abundant in the genome (IS
1201
, ISL
2
, ISLhe
1
, ISLhe
2
, ISLhe
65
, and ISLhe
63
). These findings contribute to the overall viewpoint of the versatile character of IS elements and the role they may play in bacterial genome plasticity.
CLM1ofFusarium graminearumEncodes a Longiborneol Synthase Required for Culmorin Production
Authors: McCormick S. P. , Alexander N. J. , Harris L. J. 
Published: October 2009

ABSTRACTFusarium graminearumis a fungal pathogen of cereal crops (e.g., wheat, barley, maize) and produces a number of mycotoxins, including 15-acetyldeoxynivalenol, butenolide, zearalenone, and culmorin. To identify a biosynthetic gene for the culmorin pathway, an expressed-sequence-tag database was examined for terpene cyclase genes. A gene designatedCLM1was expressed under trichothecene-inducing conditions. Expression ofCLM1in yeast (Saccharomyces cerevisiae) resulted in the production of a sesquiterpene alcohol, longiborneol, which has the same ring structure as culmorin. Gene disruption and add-back experiments inF. graminearumshowed thatCLM1was required for culmorin biosynthesis.CLM1gene disruptants were able to convert exogenously added longiborneol to culmorin. Longiborneol accumulated transiently in culmorin-producing strains. The results indicate thatCLM1encodes a longiborneol synthase and is required for culmorin biosynthesis inF. graminearum.
“CandidatusCurculioniphilus buchneri,” a Novel Clade of Bacterial Endocellular Symbionts from Weevils of the GenusCurculio
Authors: Toju Hirokazu , Hosokawa Takahiro , Koga Ryuichi , Nikoh Naruo , Meng Xian Ying , Kimura Nobutada , Fukatsu Takema 
Published: October 2009

ABSTRACTHere we investigated the bacterial endosymbionts of weevils of the genusCurculio. From all four species ofCurculioweevils examined, a novel group of bacterial gene sequences were consistently identified. Molecular phylogenetic analyses demonstrated that the sequences formed a distinct clade in theGammaproteobacteria, which was not related to previously known groups of weevil endosymbionts such asNardonellaspp. andSodalis-allied symbionts. In situ hybridization revealed that the bacterium was intracellularly harbored in a bacteriome associated with larval midgut. In adult females, the bacterium was localized in the germalia at the tip of each overiole, suggesting vertical transmission via ovarial passage. Diagnostic PCR surveys detected high prevalence of the bacterial infection in natural host populations. Electron microscopy identified the reduced cell wall of the bacterial cells, and the bacterial genes exhibited AT-biased nucleotide composition and accelerated molecular evolution, which are suggestive of a long-lasting endosymbiotic association. On the basis of these results, we conclude that the novel endocellular bacteria represent the primary symbiont ofCurculioweevils and proposed the designation “CandidatusCurculioniphilus buchneri.” In addition to “Ca.Curculioniphilus,” we identifiedSodalis-allied gammaproteobacterial endosymbionts from the chestnut weevil,Curculio sikkimensis, which exhibited partial infection frequencies in host insect populations and neither AT-biased nucleotide composition nor accelerated molecular evolution. We suggest that suchSodalis-allied secondary symbionts in weevils might provide a potential source for symbiont replacements, as has occurred in an ancestor ofSitophilusgrain weevils.