bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus-Specific T Cell Immunity Is Maintained in Immunosenescent Rhesus Macaques
Authors: Čičin-Šain Luka , Sylwester Andrew W. , Hagen Shoko I. , Siess Don C. , Currier Noreen , Legasse Alfred W. , Fischer Miranda B. , Koudelka Caroline W. , Axthelm Michael K. , Nikolich-Žugich Janko , Picker Louis J. 
Published: July 2011

Abstract
Although CMV infection is largely benign in immunocompetent people, the specific T cell responses associated with control of this persistent virus are enormous and must be maintained for life. These responses may increase with advanced age and have been linked to an “immune risk profile” that is associated with poor immune responsiveness and increased mortality in aged individuals. Based on this association, it has been suggested that CMV-specific T cell responses might become dysfunctional with age and thereby contribute to the development of immune senescence by homeostatic disruption of other T cell populations, diminished control of CMV replication, and/or excess chronic inflammation. In this study, we use the rhesus macaque (RM) model of aging to ask whether the quantity and quality of CMV-specific T cell responses differ between healthy adult RMs and elderly RMs that manifest hallmarks of immune aging. We demonstrate that the size of the CD4+ and CD8+ CMV-specific T cell pools are similar in adult versus old RMs and show essentially identical phenotypic and functional characteristics, including a dominant effector memory phenotype, identical patterns of IFN-γ, TNF-α, and IL-2 production and cytotoxic degranulation, and comparable functional avidities of optimal epitope-specific CD8+ T cells. Most importantly, the response to and protection against an in vivo CMV challenge were identical in adult and aged RMs. These data indicate that CMV-specific T cell immunity is well maintained in old RMs and argue against a primary role for progressive dysfunction of these responses in the development of immune senescence.
Multiple toe transfer and sensory free flap use after a traumatic amputation of multiple digits. Surgery done in a single setting: A case study
Authors: Galpern David W , Tsai Tsu‐Min 
Published: July 2011

AbstractCrush avulsion injuries to the hand with concomitant traumatic amputation of multiple digits can be a devastating injury to the patient. These injuries have multiple issues occurring under emergency conditions. When feasible, replantation of the multiple digits is optimal, but in many cases, it is not possible. Because of the crushing force on the digits, they are not viable candidates for replantation. The usual course of treatment for these patients is a two stage procedure, usually involving a groin flap. Here, we present the case of a patient who had a left hand skin avulsion of the whole palm and P1 of index, long, ring and small fingers. The left index finger had a complete amputation at the P2 level, the long, ring and small fingers all had complete amputations at the P1 level. This injury was dealt with by a left foot second and third toe transplant, a sensory free flap from the left big toe and a fourth toe microvascular free transfer to the left hand. The remainder of the defect was managed with a 10 × 14 cm reversed radial forearm flap and a combination of full and split thickness skin grafts. The procedure was performed in a single operation, obviating the need for a second surgery. This procedure optimized the patient's outcome during a single setting, making it an ideal choice in an emergency setting. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.
Green light-emitting diodes based on a hybrid TiO2 nanoparticle-conducting polymer blend
Authors: Nguyen Phuong Hoai Nam , Nguyen Nang Dinh 
Published: July 2011

Abstract
The energy transfer in a blend of conducting polymers, poly[9-vinylcarbarzole] (PVK) and poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), was investigated. Energy transfer from PVK to MEH-PPV leads to enhanced emission of MEH-PPV. Photoluminescence (PL) of the nanocomposite of TiO
2 and the blended polymer films was enhanced as the relative content of TiO
2 was increased, and, in particular, the most improved PL was observed for the optimal ratio of TiO
2 and these films emitted green light. These results provide further insight into the photophysics of conjugated polymers and the improvement of the current–voltage (I–V) characteristics of the devices based on blended conducting polymer systems.
Transcriptomic Response of Listeria monocytogenes during the Transition to the Long-Term-Survival Phase
Authors: Wen Jia , Deng Xiangyu , Li Zengxin , Dudley Edward G. , Anantheswaran Ramaswamy C. , Knabel Stephen J. , Zhang Wei 
Published: July 2011

ABSTRACT

Listeria monocytogenes
can change its cellular morphology from bacilli to cocci during the transition to the long-term-survival (LTS) phase. The LTS cells demonstrated increased baro- and thermotolerance compared to their vegetative counterparts. So far, the underlying mechanisms that trigger this morphological and physiological transition remain largely unknown. In this study, we compared the transcriptomic profiles of
L. monocytogenes
serotype 4b strain F2365 at different growth stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome DNA chip approach. We identified a total of 225 differentially expressed genes (≥4-fold;
P
< 0.05) during the transition to the LTS phase in TSBYE. Genes related to cell envelope structure, energy metabolism, and transport were most significantly upregulated in the LTS phase. The upregulation of compatible solute transporters may lead to the accumulation of cellular solutes, lowering intracellular water activity and thus increasing bacterial stress resistance during the transition to the LTS phase. The downregulation of genes associated with protein synthesis may indicate a status of metabolic dormancy of the LTS cells. The transcriptomic profiles of resuscitated LTS cells in fresh TSBYE resembled those of log-phase cells (
r
=0.94), as the LTS cells rapidly resume metabolic activities and transit back to log phase with decreased baro- and thermotolerance.
Scaffoldin Modules Serving as “Cargo” Domains To Promote the Secretion of Heterologous Cellulosomal Cellulases by Clostridium acetobutylicum
Authors: Chanal Angélique , Mingardon Florence , Bauzan Marielle , Tardif Chantal , Fierobe Henri-Pierre 
Published: July 2011

ABSTRACT

The secretion of large heterologous cellulases by
Clostridium acetobutylicum
was formerly shown to be deleterious. To circumvent this issue, various scaffoldins' modules were grafted at their N termini. Family 3a cellulose binding module combined with an X2 module(s) was found to trigger the secretion of
Clostridium cellulolyticum
cellulases by the solventogenic bacterium.
Potential of
pmoA
Amplicon Pyrosequencing for Methanotroph Diversity Studies
Authors: Lüke Claudia , Frenzel Peter 
Published: July 2011

ABSTRACT

We analyzed the potential of
pmoA
amplicon pyrosequencing compared to that of Sanger sequencing with paddy soils as a model environment. We defined operational taxonomic unit (OTU) cutoff values of 7% and 18%, reflecting methanotrophic species and major phylogenetic
pmoA
lineages, respectively. Major lineages were already well covered by clone libraries; nevertheless, pyrosequencing provided a higher level of diversity at the species level.
New Nystatin-Related Antifungal Polyene Macrolides with Altered Polyol Region Generated via Biosynthetic Engineering of Streptomyces noursei
Authors: Brautaset Trygve , Sletta Håvard , Degnes Kristin F. , Sekurova Olga N. , Bakke Ingrid , Volokhan Olga , Andreassen Trygve , Ellingsen Trond E. , Zotchev Sergey B. 
Published: July 2011

ABSTRACT

Polyene macrolide antibiotics, including nystatin and amphotericin B, possess fungicidal activity and are being used as antifungal agents to treat both superficial and invasive fungal infections. Due to their toxicity, however, their clinical applications are relatively limited, and new-generation polyene macrolides with an improved therapeutic index are highly desirable. We subjected the polyol region of the heptaene nystatin analogue S44HP to biosynthetic engineering designed to remove and introduce hydroxyl groups in the C-9-C-10 region. This modification strategy involved inactivation of the P450 monooxygenase NysL and the dehydratase domain in module 15 (DH15) of the nystatin polyketide synthase. Subsequently, these modifications were combined with replacement of the exocyclic C-16 carboxyl with the methyl group through inactivation of the P450 monooxygenase NysN. Four new polyene macrolides with up to three chemical modifications were generated, produced at relatively high yields (up to 0.51 g/liter), purified, structurally characterized, and subjected to
in vitro
assays for antifungal and hemolytic activities. Introduction of a C-9 hydroxyl by DH15 inactivation also blocked NysL-catalyzed C-10 hydroxylation, and these modifications caused a drastic decrease in both antifungal and hemolytic activities of the resulting analogues. In contrast, single removal of the C-10 hydroxyl group by NysL inactivation had only a marginal effect on these activities. Results from the extended antifungal assays strongly suggested that the 9-hydroxy-10-deoxy S44HP analogues became fungistatic rather than fungicidal antibiotics.
Ligand Responses of Vfr, the Virulence Factor Regulator from Pseudomonas aeruginosa
Authors: Serate Jose , Roberts Gary P. , Berg Otto , Youn Hwan 
Published: July 2011

ABSTRACT

Vfr, a transcription factor homologous to the
Escherichia coli
cyclic AMP (cAMP) receptor protein (CRP), regulates many aspects of virulence in
Pseudomonas aeruginosa
. Vfr, like CRP, binds to cAMP and then recognizes its target DNA and activates transcription. Here we report that Vfr has important functional differences from CRP in terms of ligand sensing and response. First, Vfr has a significantly higher cAMP affinity than does CRP, which might explain the mysteriously unidirectional functional complementation between the two proteins (S. E. H. West et al., J. Bacteriol. 176:7532–7542, 1994). Second, Vfr is activated by both cAMP and cGMP, while CRP is specific to cAMP. Mutagenic analyses show that Thr133 (analogous to Ser128 of CRP) is the key residue for both of these distinct Vfr properties. On the other hand, substitutions that cause cAMP-independent activity in Vfr are similar to those seen in CRP, suggesting that a common cAMP activation mechanism is present. In the course of these analyses, we found a remarkable class of Vfr variants that have completely reversed the regulatory logic of the protein: they are active in DNA binding without cAMP and are strongly inhibited by cAMP. The physiological impact of Vfr's ligand sensing and response is discussed, as is a plausible basis for the fundamental change in protein allostery in the novel group of Vfr variants.
Staphylococcus lugdunensis IsdG Liberates Iron from Host Heme
Authors: Haley Kathryn P. , Janson Eric M. , Heilbronner Simon , Foster Timothy J. , Skaar Eric P. 
Published: July 2011

ABSTRACTStaphylococcus lugdunensisis often found as part of the normal flora of human skin but has the potential to cause serious infections even in healthy individuals. It remains unclear what factors enableS. lugdunensisto transition from a skin commensal to an invasive pathogen. Analysis of the complete genome reveals a putative iron-regulated surface determinant (Isd) system encoded withinS. lugdunensis. In other bacteria, the Isd system permits the utilization of host heme as a source of nutrient iron to facilitate bacterial growth during infection. In this study, we establish thatS. lugdunensisexpresses an iron-regulated IsdG-family heme oxygenase that binds and degrades heme. Heme degradation by IsdG results in the release of free iron and the production of the chromophore staphylobilin. IsdG-mediated heme catabolism enables the use of heme as a sole source of iron, establishing IsdG as a pathophysiologically relevant heme oxygenase inS. lugdunensis. Together these findings offer insight into howS. lugdunensisfulfills its nutritional requirements while invading host tissues and establish theS. lugdunensisIsd system as being involved in heme-iron utilization.
Role of pagL and lpxO in Bordetella bronchiseptica Lipid A Biosynthesis
Authors: MacArthur I. , Jones J. W. , Goodlett D. R. , Ernst R. K. , Preston A. 
Published: July 2011

ABSTRACTPagL and LpxO are enzymes that modify lipid A. PagL is a 3-O deacylase that removes the primary acyl chain from the 3 position, and LpxO is an oxygenase that 2-hydroxylates specific acyl chains in the lipid A.pagLandlpxOhomologues have been identified in the genome ofBordetella bronchiseptica, but in the current structure forB. bronchisepticalipid A the 3 position is acylated and 2-OH acylation is not reported. We have investigated the role ofB. bronchiseptica pagLandlpxOin lipid A biosynthesis. We report a different structure for wild-type (WT)B. bronchisepticalipid A, including the presence of 2-OH-myristate, the presence of which is dependent onlpxO. We also demonstrate that the 3 position is not acylated in the major WT lipid A structures but that mutation ofpagLresults in the presence of 3-OH-decanoic acid at this position, suggesting that lipid A containing this acylation is synthesized but that PagL removes most of it from the mature lipid A. These data refine the structure ofB. bronchisepticalipid A and demonstrate thatpagLandlpxOare involved in its biosynthesis.
The Residue Threonine 82 of DevR (DosR) Is Essential for DevR Activation and Function in Mycobacterium tuberculosis Despite Its Atypical Location
Authors: Gautam Uma Shankar , Sikri Kriti , Tyagi Jaya Sivaswami 
Published: July 2011

ABSTRACT

The DevR (DosR) response regulator initiates the bacterial adaptive response to a variety of signals, including hypoxia in
in vitro
models of dormancy. Its receiver domain works as a phosphorylation-mediated switch to activate the DNA binding property of its output domain. Receiver domains are characterized by the presence of several highly conserved residues, and these sequence features correlate with structure and hence function. In response regulators, interaction of phosphorylated aspartic acid at the active site with the conserved threonine is believed to be crucial for phosphorylation-mediated conformational change. DevR contains all the conserved residues, but the structure of its receiver domain in the unphosphorylated protein is strikingly different, and key threonine (T82), tyrosine (Y101), and lysine (K104) residues are placed uncharacteristically far from the D54 phosphorylation site. In view of the atypical location of T82 in DevR, the present study aimed to examine the importance of this residue in the activation mechanism.
Mycobacterium tuberculosis
expressing a DevR T82A mutant protein is defective in autoregulation and supports hypoxic induction of the DevR regulon only very weakly. These defects are ascribed to slow and partial phosphorylation and the failure of T82A mutant protein to bind cooperatively with DNA. Our results indicate that the T82 residue is crucial in implementing conformational changes in DevR that are essential for cooperative binding and for subsequent gene activation. We propose that the function of the T82 residue in the activation mechanism of DevR is conserved in spite of the unusual architecture of its receiver domain.
The 5.5 Protein of Phage T7 Inhibits H-NS through Interactions with the Central Oligomerization Domain
Authors: Ali Sabrina S. , Beckett Emily , Bae Sandy Jeehoon , Navarre William Wiley 
Published: July 2011

ABSTRACT

The 5.5 protein (T7p32) of coliphage T7 (5.5
T7
) was shown to bind and inhibit gene silencing by the nucleoid-associated protein H-NS, but the mechanism by which it acts was not understood. The 5.5
T7
protein is insoluble when expressed in
Escherichia coli
, but we find that 5.5
T7
can be isolated in a soluble form when coexpressed with a truncated version of H-NS followed by subsequent disruption of the complex during anion-exchange chromatography. Association studies reveal that 5.5
T7
binds a region of H-NS (residues 60 to 80) recently found to contain a distinct domain necessary for higher-order H-NS oligomerization. Accordingly, we find that purified 5.5
T7
can disrupt higher-order H-NS-DNA complexes
in vitro
but does not abolish DNA binding by H-NS
per se
. Homologues of the 5.5
T7
protein are found exclusively among members of the
Autographivirinae
that infect enteric bacteria, and despite fairly low sequence conservation, the H-NS binding properties of these proteins are largely conserved. Unexpectedly, we find that the 5.5
T7
protein copurifies with heterogeneous low-molecular-weight RNA, likely tRNA, through several chromatography steps and that this interaction does not require the DNA binding domain of H-NS. The 5.5 proteins utilize a previously undescribed mechanism of H-NS antagonism that further highlights the critical importance that higher-order oligomerization plays in H-NS-mediated gene repression.
Ectoine and Hydroxyectoine as Protectants against Osmotic and Cold Stress: Uptake through the SigB-Controlled Betaine-Choline- Carnitine Transporter-Type Carrier EctT from Virgibacillus pantothenticus
Authors: Kuhlmann Anne U. , Hoffmann Tamara , Bursy Jan , Jebbar Mohamed , Bremer Erhard 
Published: July 2011

ABSTRACTVirgibacillus pantothenticushas been shown to synthesize the compatible solute ectoine in response to high salinity or low growth temperature. We found that exogenously provided ectoine and hydroxyectoine also serve as protectants against these challenges. Transport studies with [14C]ectoine revealed that both types of stress induced a high-affinity ectoine uptake activity inV. pantothenticus. By using anEscherichia colimutant defective in osmoprotectant uptake systems, a functional complementation approach for osmostress resistance in the presence of ectoine was employed to retrieve a gene encoding an ectoine transporter fromV. pantothenticus.The cloned gene (ectT) encodes a protein (EctT) that is a member of the BCCT (betaine-choline-carnitine-transporter) family of carriers. Osmoprotection assays demonstrated that the EctT carrier mediates the preferential import of ectoine and hydroxyectoine but also possesses minor uptake activities for the compatible solutes proline and glycine betaine. Northern blot analysis with RNA isolated fromV. pantothenticusrevealed that a rise in the external osmolality or a reduction in growth temperature strongly increased the transcription of theectTgene. Primer extension analysis demonstrated thatectTwas transcribed under these conditions from a SigB-type promoter. SigB is the master regulator of the general stress regulon of bacilli and provides protection to cells against various challenges, including high salinity and low temperature. Both the synthesis of ectoine and the EctT-mediated uptake of ectoine and hydroxyectoine are triggered by the same environmental cues, high salinity and cold stress, and thereby provide, in a concerted fashion, the protection ofV. pantothenticusagainst these challenges.
Transformation Frequency of a mariner-Based Transposon in Rickettsia rickettsii
Authors: Clark Tina R. , Lackey Amanda M. , Kleba Betsy , Driskell Lonnie O. , Lutter Erika I. , Martens Craig , Wood David O. , Hackstadt Ted 
Published: July 2011

ABSTRACT

Transformation frequencies of a
mariner
-based transposon system in
Rickettsia rickettsii
were determined using a plaque assay system for enumeration and isolation of mutants. Sequence analysis of insertion sites in both
R. rickettsii
and
R. prowazekii
indicated that insertions were random. Transposon mutagenesis provides a useful tool for rickettsial research.
Characterization of Components of the Staphylococcus aureus mRNA Degradosome Holoenzyme-Like Complex
Authors: Roux Christelle M. , DeMuth Jonathon P. , Dunman Paul M. 
Published: July 2011

ABSTRACTBacterial two-hybrid analysis identified theStaphylococcus aureusRNA degradosome-like complex to include RNase J1, RNase J2, RNase Y, polynucleotide phosphorylase (PNPase), enolase, phosphofructokinase, and a DEAD box RNA helicase. Results also revealed that the recently recognized RNase RnpA interacts with theS. aureusdegradosome and that this interaction is conserved in other Gram-positive organisms.
Optimizing Chemotherapy-Free Survival for the ER/HER2-Positive Metastatic Breast Cancer Patient
Authors: Glück Stefan , Arteaga Carlos L. , Osborne C. Kent 
Published: July 2011

Abstract
The recent incremental advances made in the treatment of metastatic breast cancer have elicited potential for survival extension in this treatable, yet incurable, population of breast cancer patients. Clinicians have focused on targeted therapies, which aim at signaling receptors such as the human epidermal receptor superfamily, the estrogen receptor, VEGF, the insulin-like growth factor receptor, the hepatocyte growth factor receptor (cMET), phosphoinositide 3-kinase, mTOR, and many others. Clin Cancer Res; 17(17); 5559–61. ©2011 AACR.
Exon 11 Skipping of E-Cadherin RNA Downregulates Its Expression in Head and Neck Cancer Cells
Authors: Sharma Sanjai , Liao Wei , Zhou Xiaofeng , Wong David T.W. , Lichtenstein Alan 
Published: July 2011

Abstract
E-cadherin is an important tumor suppressor gene whose expression is lost when cells acquire a metastatic phenotype. We analyzed the role of E-cadherin missplicing as a mechanism of its downregulation by analyzing a misspliced E-cadherin transcript that lacks exon 11 of this gene. This results in a frameshift and a premature termination codon that targets this transcript for degradation. Tumor tissues, including breast (20%, n = 9), prostate (30%, n = 9) and head and neck (75%, n = 8) cancer, express the exon 11-skipped transcripts (vs. nonmalignant controls) and its levels inversely correlate with E-cadherin expression. This is a novel mechanism of E-cadherin downregulation by missplicing in tumor cells, which is observed in highly prevalent human tumors. In the head and neck cancer model, nontumorigenic keratinocytes express exon 11–skipped splice product two- to sixfold lower than the head and neck tumor cell lines. Mechanistic studies reveal that SFRS2 (SC35), a splicing factor, as one of the regulators that increases missplicing and downregulates E-cadherin expression. Furthermore, this splicing factor was found to be overexpressed in 5 of 7 head and neck cell lines and primary head and neck tumors. Also, methylation of E-cadherin gene acts as a regulator of this aberrant splicing process. In 2 head and neck cell lines, wild-type transcript expression increased 16- to 25-folds, whereas the percentage of exon 11-skipped transcripts in both the cell lines decreased five- to 30-folds when cells were treated with a hypomethylating agent, azacytidine. Our findings reveal that promoter methylation and an upregulated splicing factor (SFRS2) are involved in the E-cadherin missplicing in tumors. Mol Cancer Ther; 10(9); 1751–9. ©2011 AACR.