bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy*
Authors: Charpentier C , Karmochkine M , Laureillard D , Tisserand P , Bélec L , Weiss L , Si‐Mohamed A , Piketty C 
Published: July 2008

ObjectivesRecent data showed the selection of mutations in the integrase gene, mainly involving position 148 or 155, in patients displaying virological failure (VF) on raltegravir (RAL) therapy. Here, we describe the development of RAL resistance, in both plasmatic and cellular compartments, in three heavily pretreated HIV‐infected patients failing RAL‐containing regimens.MethodsThree of 17 patients receiving RAL displayed VF. The entire integrase gene, isolated from plasma and peripheral blood mononuclear cells (PBMC), was sequenced. A clonal analysis was performed in one patient at the time of VF.ResultsAt the time of VF, RAL‐resistance mutations were selected: (i) Q148R in patients 1 and 3; (ii) T66A and E92Q in patient 2. A gradual accumulation of new mutations was observed in all patients, including G140S, Q148H and N155H in patient 1, L74I in patient 2, and G140S in patient 3. Clonal analysis showed the coexistence, in patient 1, of the two common resistance pathways (mutations Q148R/H and N155H) found in distinct quasi‐species. In addition, RAL‐resistance mutations were detected in HIV DNA in all patients.ConclusionsHaving rapidly established, resistance to RAL evolves and diversifies, and is likely to impact the efficacy of subsequently used second‐generation integrase inhibitors. Moreover, RAL‐resistance mutations can be archived early in PBMC.
Megadontia, striae periodicity and patterns of enamel secretion in Plio‐Pleistocene fossil hominins
Authors: Lacruz Rodrigo S. , Dean M. Christopher , Ramirez‐Rozzi Fernando , Bromage Timothy G. 
Published: July 2008

AbstractEarly hominins formed large and thick‐enamelled cheek‐teeth within relatively short growth periods as compared with modern humans. To understand better the developmental basis of this process, we measured daily enamel increments, or cross striations, in 17 molars of Plio‐Pleistocene hominins representing seven different species, including specimens attributed to early Homo. Our results show considerable variation across species, although all specimens conformed to the known pattern characterised by greater values in outer than inner enamel, and greater cuspal than cervical values. We then compared our results with the megadontia index, which represents tooth size in relation to body mass, for each species to assess the effect of daily growth rates on tooth size. Our results indicate that larger toothed (megadont) taxa display higher rates or faster forming enamel than smaller toothed hominins. By forming enamel quickly, large tooth crowns were able to develop within the constraints of shorter growth periods. Besides daily increments, many animals express long‐period markings (striae of Retzius) in their enamel. We report periodicity values (number of cross striations between adjacent striae) in 14 new specimens of Australopithecus afarensis, Paranthropus aethiopicus, Paranthropus boisei, Homo habilis, Homo rudolfensis and Homo erectus, and show that long‐period striae express a strong association with male and average male–female body mass. Our results for Plio‐Pleistocene hominins show that the biological rhythms that give rise to long‐period striae are encompassed within the range of variation known for modern humans, but show a lower mean and modal value of 7 days in australopithecines. In our sample of early Homo, mean and modal periodicity values were 8 days, and therefore similar to modern humans. These new data on daily rates of enamel formation and periodicity provide a better framework to interpret surface manifestations of internal growth markings on fossil hominin tooth crowns. Importantly, our data on early hominin cross striation variation may now contribute towards solving difficult taxonomic diagnoses where much may depend on fragmentary molar remains and enamel structure.
Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer
Authors: Kreusel Klaus‐Martin , Bechrakis Nikolaos E. , Wiegel Thomas , Krause Lothar , Foerster Michael H. 
Published: July 2008

Abstract.Purpose:  To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer.Methods:  Twenty‐two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies.Results:  In eight of 22 (36%; 95% confidence interval [CI] 17–59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65–97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies.Conclusions:  Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.
Two‐year follow‐up of posterior capsule opacification after implantation of a hydrophilic or hydrophobic acrylic intraocular lens
Authors: Kugelberg Maria , Wejde Gisela , Jayaram Hari , Zetterström Charlotta 
Published: July 2008

Abstract.Purpose:  To evaluate posterior capsule opacification (PCO) 2 years after cataract surgery following implantation of a hydrophilic or a hydrophobic single‐piece acrylic intraocular lens (IOL) with a sharp edge.Methods:  Phacoemulsification cataract surgery was performed in one eye of 120 patients with senile cataract in this prospective study. They were randomized to implantation of either a hydrophilic acrylic IOL (BL27; Bausch & Lomb, Rochester, NY, USA) or a hydrophobic acrylic IOL (AcrySof® SA60AT; Alcon Laboratories, Fort Worth, TX, USA). Two years after surgery, retroillumination images were obtained and PCO area and severity were evaluated using pocoman software. Best corrected visual acuity (VA) (both high‐contrast [100%] and low‐contrast [2.5%]), glare, laser flare and intraocular pressure were measured. Capsulotomy rates were recorded.Results:  Patients implanted with the hydrophilic IOL had a greater percentage area and severity of PCO compared with patients with the hydrophobic IOL (p < 0.001). There was no difference in PCO between men and women in the hydrophilic group. However, in the hydrophobic group, women had significantly more PCO than men (p < 0.05). Patients with the hydrophobic acrylic IOL had better high‐ and low‐contrast visual activity (VA) (p < 0.01) and less glare (p < 0.001) than those with a hydrophilic acrylic IOL. Of the patients with the hydrophilic IOL, 42% underwent capsulotomy, compared with 10% in the hydrophobic group (p < 0.001).Conclusions:  Two years after surgery, patients with the SA60AT hydrophobic acrylic IOL had less PCO and better high‐ and low‐contrast VA than patients with the BL27 hydrophilic acrylic IOL.
Parameter-test-ideals of Cohen–Macaulay rings
Authors: Katzman Mordechai 
Published: July 2008

AbstractWe describe an algorithm for computing parameter-test-ideals in certain local Cohen–Macaulay rings. The algorithm is based on the study of a Frobenius map on the injective hull of the residue field of the ring and on the application of Sharp’s notion of ‘special ideals’. Our techniques also provide an algorithm for computing indices of nilpotency of Frobenius actions on top local cohomology modules of the ring and on the injective hull of its residue field. The study of nilpotent elements on injective hulls of residue fields also yields a great simplification of the proof of the celebrated result in the article Generators of D-modules in positive characteristic (J. Alvarez-Montaner, M. Blickle and G. Lyubeznik, Math. Res. Lett. 12 (2005), 459–473).
Differential equations on complex projective hypersurfaces of low dimension
Authors: Diverio Simone 
Published: July 2008

AbstractLet n=2,3,4,5 and let X be a smooth complex projective hypersurface of $\mathbb {P}^{n+1}$. In this paper we find an effective lower bound for the degree of X, such that every holomorphic entire curve in X must satisfy an algebraic differential equation of order k=n=dim X, and also similar bounds for order k>n. Moreover, for every integer n≥2, we show that there are no such algebraic differential equations of order k<n for a smooth hypersurface in $\mathbb {P}^{n+1}$.
Global divisibility of Heegner points and Tamagawa numbers
Authors: Jetchev Dimitar 
Published: July 2008

AbstractWe improve Kolyvagin’s upper bound on the order of the p-primary part of the Shafarevich–Tate group of an elliptic curve of rank one over a quadratic imaginary field. In many cases, our bound is precisely that predicted by the Birch and Swinnerton-Dyer conjectural formula.
Plurigenera of general type surfaces in mixed characteristic
Authors: Suh Junecue 
Published: July 2008

AbstractWe construct general type surfaces in mixed characteristic whose geometric genera can be made to jump by an arbitrarily prescribed positive amount under specialization. We then show that this phenomenon of jumping geometric genus presents itself in some compact Shimura surfaces. Finally, we find a set of conditions, met by the latter Shimura surfaces, that forces the higher plurigenera to remain constant in reduction modulo p.
Characterization of the New Metallo-β-Lactamase VIM-13 and Its Integron-Borne Gene from a
Pseudomonas aeruginosa
Clinical Isolate in Spain
Authors: Juan Carlos , Beceiro Alejandro , Gutiérrez Olivia , Albertí Sebastián , Garau Margalida , Pérez José L. , Bou Germán , Oliver Antonio 
Published: July 2008

ABSTRACT

During a survey conducted to evaluate the incidence of class B carbapenemase (metallo-β-lactamase [MBL])-producing
Pseudomonas aeruginosa
strains from hospitals in Majorca, Spain, five clinical isolates showed a positive Etest MBL screening test result. In one of them, strain PA-SL2, the presence of a new
bla
VIM
derivative (
bla
VIM-13
) was detected by PCR amplification with
bla
VIM-1
-specific primers followed by sequencing. The
bla
VIM-13
-producing isolate showed resistance to all β-lactams (except aztreonam), gentamicin, tobramycin, and ciprofloxacin. VIM-13 exhibited 93% and 88% amino acid sequence identities with VIM-1 and VIM-2, respectively.
bla
VIM-13
was cloned in parallel with
bla
VIM-1
, and the resistance profile conferred was analyzed both in
Escherichia coli
and in
P. aeruginosa
backgrounds. Compared to VIM-1, VIM-13 conferred slightly higher levels of resistance to piperacillin and lower levels of resistance to ceftazidime and cefepime. VIM-13 and VIM-1 were purified in parallel as well, and their kinetic parameters were compared. The
k
cat
/
K

m

ratios for the antibiotics mentioned above were in good agreement with the MIC data. Furthermore, EDTA inhibited the activity of VIM-13 approximately 25 times less than it inhibited the activity of VIM-1. VIM-13 was harbored in a class 1 integron, along with a new variant (Ala108Thr) of the aminoglycoside-modifying enzyme encoding gene
aacA4
, which confers resistance to gentamicin and tobramycin. Finally, the VIM-13 integron was apparently located in the chromosome, since transformation and conjugation experiments consistently yielded negative results and the
bla
VIM-13
probe hybridized only with the genomic DNA.
Impact of the Interaction of R207910 with Rifampin on the Treatment of Tuberculosis Studied in the Mouse Model
Authors: Lounis Nacer , Gevers Tom , Van Den Berg Joke , Andries Koen 
Published: July 2008

ABSTRACT

New drugs are needed to shorten the duration of tuberculosis treatment. R207910, a diarylquinoline, is very active against
Mycobacterium tuberculosis
both in vitro and in mice. In healthy volunteers, the coadministration of R207910 and rifampin induced the increased metabolism of R207910, resulting in a 50% reduction in the level of R207910 exposure. We assessed the impact of reducing the dose of R207910 on its efficacy when R207910 was combined with a background regimen of isoniazid, rifampin, and pyrazinamide. Addition of 25 mg/kg of body weight or 12.5 mg/kg R207910 to the background regimen resulted in faster bacterial clearance and culture negativity. The difference in efficacy between the two doses was not statistically significant. The minimal bactericidal dose of R207910 when it was tested as part of the combination was identical to that when it was tested as monotherapy. Because of the drug-drug interaction in humans, the activity of R207910 in humans could be less than that expected from studies with mice. Our data from the mouse model demonstrate that R207910 has significant activity, even when its exposure is reduced by 50% and when it is added to a strong background regimen of isoniazid, rifampin, and pyrazinamide. In killing kinetic studies, the bactericidal effect of R207910 in mice was modest during the first week of treatment, but it increased in the following 3 weeks, while the bactericidal activity of isoniazid was limited to the first week of treatment.
Detection of Macrolide Resistance inMycoplasma pneumoniaeby Real-Time PCR and High-Resolution Melt Analysis
Authors: Wolff Bernard J. , Thacker W. Lanier , Schwartz Stephanie B. , Winchell Jonas M. 
Published: July 2008

ABSTRACTMycoplasma pneumoniaeis a significant cause of community-acquired pneumonia, which is often empirically treated with macrolides or azalides such as erythromycin or azithromycin. Recent studies have discovered the existence of macrolide-resistant strains within the population that have been mapped to mutations within the domain V region of the 23S rRNA gene. Currently, identification of these resistant strains relies on time-consuming and labor-intensive procedures such as restriction fragment length polymorphism, MIC studies, and sequence analysis. The current study reports two distinct real-time PCR assays that can detect the A2063G or A2064G base mutation (A2058G or A2059G byEscherichia colinumbering) conferring macrolide resistance. By subjecting the amplicon of the targeted domain V region of the 23S rRNA gene to a high-resolution melt curve analysis, macrolide-resistant strains can quickly be separated from susceptible strains. Utilizing this method, we screened 100 clinical isolates and found 5 strains to possess mutations conferring resistance. These findings were concordant with both sequencing and MIC data. This procedure was also used successfully to identify both susceptible and resistant genotypes in 23 patient specimens. These patient specimens tested positive for the presence ofM. pneumoniaeby a separate real-time PCR assay, although the bacteria could not be isolated by culture. This is the first report of a real-time PCR assay capable of detecting the dominant mutations that confer macrolide resistance onM. pneumoniae, and these assays may have utility in detecting resistant strains of other infectious agents. These assays may also allow for clinicians to select appropriate treatment options more rapidly and may provide a convenient method to conduct surveillance for genetic mutations conferring antibiotic resistance.
Characterization of an ABCG-Like Transporter from the Protozoan Parasite
Leishmania
with a Role in Drug Resistance and Transbilayer Lipid Movement
Authors: Castanys-Muñoz Esther , Pérez-Victoria José María , Gamarro Francisco , Castanys Santiago 
Published: July 2008

ABSTRACT

Leishmaniasis treatment is hampered by the increased appearance of treatment failure. ATP-binding cassette (ABC) transporters are usually involved in drug resistance both in tumor cells and in microorganisms. Here we report the characterization of an ABCG-like transporter, LiABCG6, localized mainly at the plasma membrane in
Leishmania
protozoan parasites. When overexpressed, this half-transporter confers significant resistance to the leishmanicidal agents miltefosine and sitamaquine. This resistance phenotype is mediated by a reduction in intracellular drug accumulation. LiABCG6 also reduces the accumulation of short-chain fluorescent phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. As a whole, these results suggest that LiABCG6 could be implicated in phospholipid trafficking and drug resistance.
Effects of Antibiotics on Quorum Sensing in
Pseudomonas aeruginosa
Authors: Skindersoe Mette E. , Alhede Morten , Phipps Richard , Yang Liang , Jensen Peter O. , Rasmussen Thomas B. , Bjarnsholt Thomas , Tolker-Nielsen Tim , Høiby Niels , Givskov Michael 
Published: July 2008

ABSTRACT

During infection,
Pseudomonas aeruginosa
employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of
P. aeruginosa
, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with
P. aeruginosa
with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of
P. aeruginosa.
This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in
P. aeruginosa
. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of
N
-3-oxo-dodecanoyl-
l
-homoserine lactone.
Edelfosine Induces an Apoptotic Process in
Leishmania infantum
That Is Regulated by the Ectopic Expression of Bcl-X
L
and Hrk
Authors: Alzate Juan Fernando , Arias Andrés , Mollinedo Faustino , Rico Eva , de la Iglesia-Vicente Janis , Jiménez-Ruiz Antonio 
Published: July 2008

ABSTRACT

The alkyl-lysophospholipids edelfosine and miltefosine induce apoptosis in
Leishmania infantum
promastigotes. The finding that edelfosine-induced cell death can be regulated by the ectopic expression of the antiapoptotic and proapoptotic members of the Bcl-2 family of proteins Bcl-X
L
and Hrk suggests that this process is similar to apoptosis in eukaryotic cells.
β-1,2 Oligomannose Adhesin Epitopes Are Widely Distributed over the Different Families of
Candida albicans
Cell Wall Mannoproteins and Are Associated through both N- and O-Glycosylation Processes
Authors: Fradin Chantal , Slomianny Marie Christine , Mille Céline , Masset Annick , Robert Raymond , Sendid Boualem , Ernst Joachim F. , Michalski Jean Claude , Poulain Daniel 
Published: July 2008

ABSTRACT

β-1,2-Linked mannosides (β-Mans) are believed to contribute to
Candida albicans
virulence. The presence of β-Mans has been chemically established for two molecules (phosphopeptidomannan [PPM] and phospholipomannan) that are noncovalently linked to the cell wall, where they correspond to specific epitopes. However, a large number of cell wall mannoproteins (CWMPs) also express β-Man epitopes, although their nature and mode of β-mannosylation are unknown. We therefore used Western blotting to map β-Man epitopes for the different families of mannoproteins gradually released from the cell wall according to their mode of anchorage (soluble, released by dithiothreitol, β-1,3 glucan linked, and β-1,6 glucan linked). Reduction of β-Man epitope expression occurred after chemical and enzymatic deglycosylation of the different cell wall fractions, as well as in a secreted form of Hwp1, a representative of the CWMPs linked by glycosylphosphatidylinositol remnants. Enzyme-linked immunosorbent assay inhibition tests were performed to assess the presence of β-Man epitopes in released oligomannosides. A comparison of the results obtained with CWMPs to the results obtained with PPM and the use of mutants with mutations affecting O and N glycosylation demonstrated that both O glycosylation and N glycosylation participate in the association of β-Mans with the protein moieties of CWMPs. This process, which can alter the function of cell wall molecules and their recognition by the host, is therefore more important and more complex than originally thought, since it differs from the model established previously with PPM.
Algorithm 877
Authors: Kodama Masao 
Published: July 2008

The algorithm presented provides a package of subroutines for calculating the cylindrical functions
J
ν
(
x
),
N
ν
(
x
),
H
ν
(1)
(
x
),
H
ν
(2)
(
x
) where the order
ν
is complex and the real argument
x
is nonnegative. The algorithm is written in Fortran 95 and calculates the functions using single, double, or quadruple precision according to the value of a parameter defined in the algorithm. The methods of calculating the functions are based on a series expansion, Debye's asymptotic expansions, Olver's asymptotic expansions, and recurrence methods (Miller's algorithms). The relative errors of the functional values computed by this algorithm using double precision are less than 2.4×10
− 13
in the region 0 ≤ Re
ν
≤ 64, 0 ≤ Im
ν
≤ 63, 0.024 ≤
x
≤ 97.