bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Subinhibitory Concentrations of Antibiotics on Intrachromosomal Homologous Recombination in
Escherichia coli
Authors: López Elena , Blázquez Jesús 
Published: June 2009

ABSTRACT

Subinhibitory concentrations of some antibiotics, such as fluoroquinolones, have been reported to stimulate mutation and, consequently, bacterial adaptation to different stresses, including antibiotic pressure. In
Escherichia coli
, this stimulation is mediated by alternative DNA polymerases induced via the SOS response. Sublethal concentrations of the fluoroquinolone ciprofloxacin have been shown to stimulate recombination between divergent sequences in
E. coli
. However, the effect of ciprofloxacin on recombination between homologous sequences and its SOS dependence have not been studied. Moreover, the possible effects of other antibiotics on homologous recombination remain untested. The aim of this work was to study the effects of sublethal concentrations of ciprofloxacin and 10 additional antibiotics, including different molecular families with different molecular targets, on the rate of homologous recombination of DNA in
E. coli
. The antibiotics tested were ciprofloxacin, ampicillin, ceftazidime, imipenem, chloramphenicol, tetracycline, gentamicin, rifampin (rifampicin), trimethoprim, fosfomycin, and colistin. Our results indicate that only ciprofloxacin consistently stimulates the intrachromosomal recombinogenic capability of homologous sequences in
E. coli
. The ciprofloxacin-based stimulation occurs at concentrations and times that apparently do not dramatically compromise the viability of the whole population, and it is dependent on RecA and partially dependent on SOS induction. One of the main findings of this work is that, apart from quinolone antibiotics, none of the most used antibiotics, including trimethoprim (a known inducer of the SOS response), has a clear side effect on homologous recombination in
E. coli
. In addition to the already described effects of some antibiotics on mutagenicity, DNA transfer, and genetic transformability in naturally competent species, the effect of increasing intrachromosomal recombination of homologous DNA sequences can be uniquely ascribed to fluoroquinolones, at least for
E. coli
.
AFN-1252, a FabI Inhibitor, Demonstrates a Staphylococcus-Specific Spectrum of Activity
Authors: Karlowsky James A. , Kaplan Nachum , Hafkin Barry , Hoban Daryl J. , Zhanel George G. 
Published: June 2009

ABSTRACT

AFN-1252, a potent inhibitor of enoyl-acyl carrier protein reductase (FabI), inhibited all clinical isolates of
Staphylococcus aureus
(
n
= 502) and
Staphylococcus epidermidis
(
n
= 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of ≤0.12 μg/ml. In contrast, AFN-1252 was inactive (MIC
90
, >4 μg/ml) against clinical isolates of
Streptococcus pneumoniae
, beta-hemolytic streptococci,
Enterococcus
spp.,
Enterobacteriaceae
, nonfermentative gram-negative bacilli, and
Moraxella catarrhalis
. These data support the continued development of AFN-1252 for the treatment of patients with resistant staphylococcal infections.
The Manganese Transporter MntH Is a Critical Virulence Determinant forBrucella abortus2308 in Experimentally Infected Mice
Authors: Anderson Eric S. , Paulley James T. , Gaines Jennifer M. , Valderas Michelle W. , Martin Daniel W. , Menscher Evan , Brown Timothy D. , Burns Colin S. , Roop R. Martin 
Published: June 2009

ABSTRACTThe gene designated BAB1_1460 in theBrucella abortus2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenicmntHmutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe2+, Zn2+, Co2+, or Ni2+. Consistent with the apparent selectivity of the corresponding gene product, the expression of themntHgene inB. abortus2308 is repressed by Mn2+, but not Fe2+, and this Mn-responsive expression is mediated by a Mur-like repressor. TheB. abortus mntHmutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. TheB. abortus mntHmutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn2+transport mediated by MntH plays an important role in the physiology ofB. abortus2308, particularly during its intracellular survival and replication in the host.
Leishmania majorPhosphoglycans Influence the Host Early Immune Response by Modulating Dendritic Cell Functions
Authors: Liu Dong , Kebaier Chahnaz , Pakpour Nazzy , Capul Althea A. , Beverley Stephen M. , Scott Phillip , Uzonna Jude E. 
Published: June 2009

ABSTRACTThe precise role ofLeishmaniaglycoconjugate molecules including phosphoglycans (PGs) and lipophosphoglycan (LPG) on host cellular responses is still poorly defined. Here, we investigated the interaction ofLeishmania major LPG2null mutant (lpg2−), which lacks both PGs and LPG, with dendritic cells (DCs) and the subsequent early immune response in infected mice. Surprisingly, the absence of phosphoglycans did not influence expression pattern of major histocompatibility complex class II (MHC II), CD40, CD80, and CD86 on DCs in vitro and in vivo. However,lpg2−L. majorinduced significantly higher production of interleukin-12p40 (IL-12p40) by infected bone marrow-derived DCs (BMDCs) than wild-type (WT) parasites in vitro. Furthermore, the production of IL-12p40 by draining lymph node cells fromlpg2−mutant-infected mice was higher than those from WTL. major-infected mice. In model antigen presentation experiments, DCs fromlpg2−mutant-infected mice induced more gamma interferon (IFN-γ) and IL-2 production byLeishmania-specific T cells than those from WT-infected mice. Lymphocytes isolated from mice infected for 3 days withlpg2−parasites produce similar levels of IFN-γ, but significantly less IL-4 and IL-10 than WT controls. Decreased IL-4 production was also seen in another general PG-deficient mutant lacking the Golgi UDP-galactose transporters (lpg5A−lpg5B−), but not with thelpg1−mutant lacking only LPG, thereby implicating PGs generally in the reduction of IL-4 production. Thus,LeishmaniaPGs influence host early immune response by modulating DC functions in a way that inhibits antigen presentation and promotes early IL-4 response, and their absence may impact the balance between Th1 and Th2 responses.
Unique Roles of DosT and DosS in DosR Regulon Induction and
Mycobacterium tuberculosis
Dormancy
Authors: Honaker Ryan W. , Leistikow Rachel L. , Bartek Iona L. , Voskuil Martin I. 
Published: June 2009

ABSTRACT

In
Mycobacterium tuberculosis
, the sensor kinases DosT and DosS activate the transcriptional regulator DosR, resulting in the induction of the DosR regulon, which is important for anaerobic survival and perhaps latent infection. The individual and collective roles of these sensors have been postulated biochemically, but their roles in vivo have remained unclear. This work demonstrates distinct and additive roles for each sensor during anaerobic dormancy. Both sensors are necessary for wild-type levels of DosR regulon induction, and concomitantly, full induction of the regulon is required for wild-type anaerobic survival. In the anaerobic model, DosT plays an early role, responding to hypoxia. DosT then induces the regulon and with it DosS, which sustains and further induces the regulon. DosT then loses its functionality as oxygen becomes limited, and DosS alone maintains induction of the genes from that point forward. Thus,
M. tuberculosis
has evolved a system whereby it responds to hypoxic conditions in a stepwise fashion as it enters an anaerobic state.
Composing expressive runtime security policies
Authors: Bauer Lujo , Ligatti Jay , Walker David 
Published: June 2009

Program monitors enforce security policies by interposing themselves into the control flow of untrusted software whenever that software attempts to execute security-relevant actions. At the point of interposition, a monitor has authority to permit or deny (perhaps conditionally) the untrusted software's attempted action. Program monitors are common security enforcement mechanisms and integral parts of operating systems, virtual machines, firewalls, network auditors, and antivirus and antispyware tools.
Unfortunately, the runtime policies we require program monitors to enforce grow more complex, both as the monitored software is given new capabilities and as policies are refined in response to attacks and user feedback. We propose dealing with policy complexity by organizing policies in such a way as to make them composable, so that complex policies can be specified more simply as compositions of smaller subpolicy modules. We present a fully implemented language and system called Polymer that allows security engineers to specify and enforce composable policies on Java applications. We formalize the central workings of Polymer by defining an unambiguous semantics for our language. Using this formalization, we state and prove an uncircumventability theorem which guarantees that monitors will intercept all security-relevant actions of untrusted software.
Shared subtypes
Authors: Ahn Ki Yung , Sheard Tim 
Published: June 2009

A newtype declaration in Haskell introduces a new type renaming an existing type. The two types are viewed by the programmer as semantically different, but share the same runtime representation. When operations on the two semantic views coincide, the run-time cost of conversion between the two types is reduced to zero (in both directions) because of this common representation.
We describe a new language feature called Shared Subtypes (SSubtypes), which generalizes these properties of the newtype declaration. SSubtypes allow programmers to specify subtype rules between types and sharing rules between data constructors. A value of a type T, where T is a subtype of U, can always be cast, at no cost, to value of type U. This free up-casting allows library functions that consume the supertype to be applied without cost to subtypes. Yet any semantic interpretations desired by the programmer can be enforced by the compiler. SSubtype declarations work particularly well with GADTs. GADTs use differing type indexes to make explicit semantic differences, by using a different index for each way of viewing the data. Shared subtypes allow GADTs to share the same runtime representation as a reference type, of which the GADT is a refinement.
Language and program design for functional dependencies
Authors: Jones Mark P. , Diatchki Iavor S. 
Published: June 2009

Eight years ago, functional dependencies, a concept from the theory of relational databases, were proposed as a mechanism for avoiding common problems with multiple parameter type classes in Haskell. In this context, functional dependencies give programmers a means to specify the semantics of a type class more precisely, and to obtain more accurate inferred types as a result. As time passed, however, several issues were uncovered - both in the design of a language to support functional dependencies, and in the ways that programmers use them - that led some to search for new, better alternatives.
This paper focusses on two related aspects of design for functional dependencies: (i) the design of language/type system extensions that implement them; and (ii) the design of programs that use them. Our goal is to clarify the issues of what functional dependencies are, how they should be used, and how the problems encountered with initial proposals and implementations can be addressed.
Convectively Induced Transverse Band Signatures in Satellite Imagery
Authors: Lenz A. , Bedka K. M. , Feltz W. F. , Ackerman S. A. 
Published: June 2009

Abstract
Transverse cirrus bands have commonly been observed in the outflow of thunderstorms, though little literature exists on the subject. The primary objective of this paper is to characterize the transverse band signature in satellite imagery with references to storm location, movement, and life cycle. The transverse band signature was observed in nearly half of all convective systems analyzed between May and August 2006, commonly in the mature and decay stages of the system. Storm size and propagation did not appear to influence transverse bands, though the bands did appear to be associated with negative 300-hPa relative vorticity and positive divergence. Transverse bands lasted an average duration of 9 h and generally occurred during the nighttime hours. The satellite analysis was combined with eddy dissipation rate (EDR) atmospheric turbulence observations collected by commercial aircraft. At least one observation of light (moderate) turbulence was found within transverse bands for 93% (44%) of events, indicating that the presence of transverse bands in satellite imagery is a strong indicator for aviation turbulence.
Neutrophil morphology and migration are affected by substrate elasticity
Authors: Oakes Patrick W. , Patel Dipan C. , Morin Nicole A. , Zitterbart Daniel P. , Fabry Ben , Reichner Jonathan S. , Tang Jay X. 
Published: June 2009

Abstract
To reach sites of inflammation, neutrophils execute a series of adhesion and migration events that include transmigration through the vascular endothelium and chemotaxis through the vicinal extracellular matrix until contact is made with the point of injury or infection. These in vivo microenvironments differ in their mechanical properties. Using polyacrylamide gels of physiologically relevant elasticity in the range of 5 to 100 kPa and coated with fibronectin, we tested how neutrophil adhesion, spreading, and migration were affected by substrate stiffness. Neutrophils on the softest gels showed only small changes in spread area, whereas on the stiffest gels they showed a 3-fold increase. During adhesion and migration, the magnitudes of the distortions induced in the gel substrate were independent of substrate stiffness, corresponding to the generation of significantly larger traction stresses on the stiffer gels. Cells migrated more slowly but more persistently on stiffer substrates, which resulted in neutrophils moving greater distances over time despite their slower speeds. The largest tractions were localized to the posterior of migrating neutrophils and were independent of substrate stiffness. Finally, the phosphatidylinositol 3-kinase inhibitor LY294002 obviated the ability to sense substrate stiffness, suggesting that phosphatidylinositol 3-kinase plays a mechanistic role in neutrophil mechanosensing.
Fpocket: An open source platform for ligand pocket detection
Authors: Le Guilloux Vincent , Schmidtke Peter , Tuffery Pierre 
Published: June 2009

Abstract

Background
Virtual screening methods start to be well established as effective approaches to identify hits, candidates and leads for drug discovery research. Among those, structure based virtual screening (SBVS) approaches aim at docking collections of small compounds in the target structure to identify potent compounds. For SBVS, the identification of candidate pockets in protein structures is a key feature, and the recent years have seen increasing interest in developing methods for pocket and cavity detection on protein surfaces.

Results
Fpocket is an open source pocket detection package based on Voronoi tessellation and alpha spheres built on top of the publicly available package Qhull. The modular source code is organised around a central library of functions, a basis for three main programs: (i) Fpocket, to perform pocket identification, (ii) Tpocket, to organise pocket detection benchmarking on a set of known protein-ligand complexes, and (iii) Dpocket, to collect pocket descriptor values on a set of proteins. Fpocket is written in the C programming language, which makes it a platform well suited for the scientific community willing to develop new scoring functions and extract various pocket descriptors on a large scale level. Fpocket 1.0, relying on a simple scoring function, is able to detect 94% and 92% of the pockets within the best three ranked pockets from the holo and apo proteins respectively, outperforming the standards of the field, while being faster.

Conclusion
Fpocket provides a rapid, open source and stable basis for further developments related to protein pocket detection, efficient pocket descriptor extraction, or drugablity prediction purposes. Fpocket is freely available under the GNU GPL license at http://fpocket.sourceforge.net.
A core-attachment based method to detect protein complexes in PPI networks
Authors: Wu Min , Li Xiaoli , Kwoh Chee-Keong , Ng See-Kiong 
Published: June 2009

Abstract

Background
How to detect protein complexes is an important and challenging task in post genomic era. As the increasing amount of protein-protein interaction (PPI) data are available, we are able to identify protein complexes from PPI networks. However, most of current studies detect protein complexes based solely on the observation that dense regions in PPI networks may correspond to protein complexes, but fail to consider the inherent organization within protein complexes.

Results
To provide insights into the organization of protein complexes, this paper presents a novel core-attachment based method (COACH) which detects protein complexes in two stages. It first detects protein-complex cores as the "hearts" of protein complexes and then includes attachments into these cores to form biologically meaningful structures. We evaluate and analyze our predicted protein complexes from two aspects. First, we perform a comprehensive comparison between our proposed method and existing techniques by comparing the predicted complexes against benchmark complexes. Second, we also validate the core-attachment structures using various biological evidence and knowledge.

Conclusion
Our proposed COACH method has been applied on two different yeast PPI networks and the experimental results show that COACH performs significantly better than the state-of-the-art techniques. In addition, the identified complexes with core-attachment structures are demonstrated to match very well with existing biological knowledge and thus provide more insights for future biological study.
The histone methyltransferase SUV420H2 and Heterochromatin Proteins HP1 interact but show different dynamic behaviours
Authors: Souza Patricia P , Völkel Pamela , Trinel Dave , Vandamme Julien , Rosnoblet Claire , Héliot Laurent , Angrand Pierre-Olivier 
Published: June 2009

Abstract

Background
Histone lysine methylation plays a fundamental role in chromatin organization and marks distinct chromatin regions. In particular, trimethylation at lysine 9 of histone H3 (H3K9) and at lysine 20 of histone H4 (H4K20) governed by the histone methyltransferases SUV39H1/2 and SUV420H1/2 respectively, have emerged as a hallmark of pericentric heterochromatin. Controlled chromatin organization is crucial for gene expression regulation and genome stability. Therefore, it is essential to analyze mechanisms responsible for high order chromatin packing and in particular the interplay between enzymes involved in histone modifications, such as histone methyltransferases and proteins that recognize these epigenetic marks.

Results
To gain insights into the mechanisms of SUV420H2 recruitment at heterochromatin, we applied a tandem affinity purification approach coupled to mass spectrometry. We identified heterochromatin proteins HP1 as main interacting partners. The regions responsible for the binding were mapped to the heterochromatic targeting module of SUV420H2 and HP1 chromoshadow domain. We studied the dynamic properties of SUV420H2 and the HP1 in living cells using fluorescence recovery after photobleaching. Our results showed that HP1 proteins are highly mobile with different dynamics during the cell cycle, whereas SUV420H2 remains strongly bound to pericentric heterochromatin. An 88 amino-acids region of SUV420H2, the heterochromatic targeting module, recapitulates both, HP1 binding and strong association to heterochromatin.

Conclusion
FRAP experiments reveal that in contrast to HP1, SUV420H2 is strongly associated to pericentric heterochromatin. Then, the fraction of SUV420H2 captured and characterized by TAP/MS is a soluble fraction which may be in a stable association with HP1. Consequently, SUV420H2 may be recruited to heterochromatin in association with HP1, and stably maintained at its heterochromatin sites in an HP1-independent fashion.
A complex selection signature at the human AVPR1B gene
Authors: Cagliani Rachele , Fumagalli Matteo , Pozzoli Uberto , Riva Stefania , Cereda Matteo , Comi Giacomo P , Pattini Linda , Bresolin Nereo , Sironi Manuela 
Published: June 2009

AbstractBackgroundThe vasopressin receptor type 1b (AVPR1B) is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; commonAVPR1Bhaplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses.ResultsHere we have analyzed the two exons of the gene and the data we present suggest thatAVPR1Bhas been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg) in this region has been subjected to directional selection.ConclusionAlthough the underlying selective pressure(s) remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.