bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineation of Early Changes in Cases with Progressive Supranuclear Palsy‐Like Pathology. Astrocytes in Striatum are Primary Targets of Tau Phosphorylation and GFAP Oxidation
Authors: Santpere Gabriel , Ferrer Isidre 
Published: May 2008

AbstractProgressive supranuclear palsy (PSP) is a complex tauopathy usually confirmed at post‐mortem in advanced stages of the disease. Early PSP‐like changes that may outline the course of the disease are not known. Since PSP is not rarely associated with argyrophilic grain disease (AGD) of varible intensity, the present study was focused on AGD cases with associated PSP‐like changes in an attempt to delineate early PSP‐like pathology in this category of cases. Three were typical clinical and pathological PSP. Another case presented with cognitive impairment, abnormal behavior and two falls in the last three months. One case suffered from mild cognitive impairment, and two had no evidence of neurological abnormality. Neuropathological study revealed, in addition to AGD, increased intensity and extent of lesion in three groups of regions, striatum, pallidus/subthalamus and selected nuclei of the brain stem, correlating with neurological impairment. Biochemical studies disclosed oxidative damage in the striatum and amygdala. Together the present observations suggest (i) early PSP‐like lesions in the striatum, followed by the globus pallidus/subthalamus and selected nuclei of the brain stem; (ii) early involvement of neurons and astrocytes, but late appearance of tufted astrocytres; and (iii) oxidative damage of glial acidic protein in the striatum.
Genotoxicity of Combined Exposure to Polycyclic Aromatic Hydrocarbons and UVA—A Mechanistic Study
Authors: Douki Thierry , Ksoury Zakaria , Marie Caroline , Favier Alain , Ravanat Jean‐Luc , Maitre Anne 
Published: May 2008

AbstractSolar UV radiation and benzo[a]pyrene (BaP) are two carcinogenic agents. When combined, their deleterious properties are synergistic. In order to get insights into the underlying processes, we carried out a mechanistic study within isolated DNA photosensitized to UVA radiation by either BaP, its diol epoxide metabolite (BPDE) or the tetraol arising from the hydrolysis of this last molecule. Measurement of the level of the oxidized base 8‐oxo‐7,8‐dihydroguanine revealed that BaP is a poor sensitizer while BPDE and tetraol are more potent ones. None of these compounds was found to photosensitize formation of cyclobutane pyrimidine dimers through triplet energy transfer. On the basis of the distribution of oxidized DNA bases, we could show that photosensitization of DNA by BPDE involves electron abstraction (Type I) while tetraol acts mainly through singlet oxygen production (Type II). Under our experimental conditions, Type I was the major photosensitization process, which shows the lack of involvement of tetraol in the observed photo‐oxidation reaction. Finally, we could show that the adducts, resulting from the alkylation of DNA by BPDE, are very potent sensitizers. Indeed, they are located in the close vicinity of the double helix and thus perfectly placed to induce oxidation reactions.
Establishment of a Cell-Based Assay for Screening of Compounds Inhibiting Very Early Events in the Cytomegalovirus Replication Cycle and Characterization of a Compound Identified Using the Assay
Authors: Fukui Yoshiko , Shindoh Keiko , Yamamoto Yumiko , Koyano Shin , Kosugi Isao , Yamaguchi Toyofumi , Kurane Ichiro , Inoue Naoki 
Published: May 2008

ABSTRACT
To simplify the detection of infectious human cytomegalovirus (HCMV), we generated a cell line that produced luciferase in a dose-dependent manner upon HCMV infection. Using this cell line, we identified anti-HCMV compounds from a diverse library of 9,600 compounds. One of them, 1-(3,5-dichloro-4-pyridyl)piperidine-4-carboxamide (DPPC), was effective against HCMV (Towne strain) infection of human lung fibroblast cells at a 50% effective concentration of 2.5 μM. DPPC also inhibited the growth of clinical HCMV isolates and guinea pig and mouse cytomegaloviruses. Experiments using various time frames for treatment of the cells with DPPC demonstrated that DPPC was effective during the first 24 h after HCMV infection. DPPC treatment decreased not only viral DNA replication but also IE1 and IE2 expression at mRNA and protein levels in the HCMV-infected cells. However, DPPC did not inhibit the attachment of HCMV particles to the cell surface. DPPC is a unique compound that targets the very early phase of cytomegalovirus infection, probably by disrupting a pathway that is important after viral entry but before immediate-early gene expression.
Reduced Tissue Parasitic Load and Infectivity to Sand Flies in Dogs Naturally Infected byLeishmania(Leishmania)chagasifollowing Treatment with a Liposome Formulation of Meglumine Antimoniate
Authors: Ribeiro Raul R. , Moura Eliane P. , Pimentel Vitor M. , Sampaio Weverton M. , Silva Sydnei M. , Schettini Dante A. , Alves Cintia F. , Melo Ferdinan A. , Tafuri Wagner L. , Demicheli Cynthia , Melo Maria N. , Frézard Frédéric , Michalick Marilene S. M. 
Published: May 2008

ABSTRACTThe toxicity and antileishmanial effectiveness of a novel liposome formulation of meglumine antimoniate in mongrel dogs with visceral leishmaniasis (VL) obtained from a region where VL is endemic in Brazil have been investigated. Groups of 12 animals received by the intravenous route four doses (with 4-day intervals) of either liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg of body weight/dose), empty liposomes (GII), or isotonic saline (GIII). Evaluation of markers of hematopoietic, hepatic, and renal functions before and just after treatment showed no significant change. On the other hand, transitory adverse reactions, including prostration, defecation, tachypnea, and sialorrhea, were observed during the first 15 min after injections in GI and GII. Parasitological evaluation of sternal bone marrow 4 days after the last dose showed a significant reduction of parasite burden in GI, compared to the other groups. Immunocytochemical evaluations of the skin, bone marrow, cervical lymph nodes, livers, and spleens of dogs for parasites, 150 days after treatment, indicated significant parasite suppression (higher than 95.7%) in the lymph nodes, livers, and spleens of GI, compared to control groups. Feeding ofLutzomyia longipalpisphlebotomines on dogs from GI, 150 days after treatment, resulted in a significant reduction of sand fly infection efficiency, compared to feeding on animals from GII and GIII. This is the first report of both long-term parasite suppression and reduction of infectivity to sand flies in naturally infected dogs following treatment with a liposome-encapsulated drug. Importantly, this was achieved using a 20-fold-lower cumulative dose of Sb than is used for conventional antimonial treatment.
Identification of a Novel Multidrug Efflux Pump of
Mycobacterium tuberculosis
Authors: Danilchanka Olga , Mailaender Claudia , Niederweis Michael 
Published: May 2008

ABSTRACT

The impermeability of the outer membrane in combination with drug efflux are major determinants of the natural drug resistance of mycobacteria. β-Lactams are the most widely used antibiotics for treatment of bacterial infections. However, it is unknown how β-lactams enter
Mycobacterium tuberculosis
and whether efflux pumps exist that can export these drugs out of the cell. To identify the molecular mechanisms of
M. tuberculosis
resistance to β-lactams, a library of 7,500 transposon mutants was generated in the model organism
Mycobacterium bovis
BCG. Thirty-three unique insertion sites were determined that conferred medium or high-level (≥2,000 μg/ml) resistance to ampicillin. Three mutants in sulfolipid synthesis or transport were highly resistant to ampicillin, indicating an indirect effect of the lipid composition on the outer membrane permeability of
M. bovis
BCG to ampicillin. Mutants with insertions in genes encoding surface molecules such as PPE proteins or lipoarabinomannan were also completely resistant to ampicillin, thus suggesting a lack of transport across the outer membrane. Insertion of the transposon in front of
bcg0231
increased transcription of the gene and concomitantly the resistance of
M. bovis
BCG to ampicillin, streptomycin, and chloramphenicol by 32- to 64-fold. Resistance to vancomycin and tetracycline was increased four- to eightfold. Bcg0231 and Rv0194 are almost identical ATP-binding cassette transporters. Expression of
rv0194
significantly reduced accumulation of ethidium bromide and conferred multidrug resistance to
Mycobacterium smegmatis
. Both effects were abrogated in the presence of the efflux pump inhibitor reserpine. These results demonstrate that Rv0194 is a novel multidrug efflux pump of
M. tuberculosis
.
In Vivo Pharmacodynamic Profiling of Doripenem againstPseudomonas aeruginosaby Simulating Human Exposures
Authors: Kim Aryun , Banevicius Mary Anne , Nicolau David P. 
Published: May 2008

ABSTRACTDoripenem is a new broad-spectrum carbapenem with activity against a range of gram-negative pathogens, including nonfermenting bacteria such asPseudomonas aeruginosa. The objective of this study was to evaluate simulated human exposures to doripenem using a neutropenic murine thigh infection model against 24 clinicalP. aeruginosaisolates with a wide range of MICs. Dosing regimens in mice were designed to approximate the free time above MIC (fT>MIC) observed with 500 mg doripenem every 8 h given as either a 1-h or 4-h intravenous infusion in humans. Maximal antibacterial killing was associated with doripenem exposures of ≥40%fT>MIC; bacteriostatic effects were noted at ≈20%fT>MIC. The simulated 1-h infusion provided bactericidal effects for isolates with MICs of ≤2 μg/ml, while variable killing was noted for isolates with MICs of 4 to 8 μg/ml and regrowth for isolates with an MIC of 16 μg/ml. The 4-h infusion regimen displayed similar killing for isolates with MICs of ≤2 μg/ml and enhanced activity for two of the four isolates with an MIC of 4 μg/ml. Given that the 4-h regimen yields negligiblefT>MIC for MICs of ≥8 μg/ml, regrowth was generally observed. Simulated doses of 500 mg doripenem every 8 h infused over 1 h demonstrated antibacterial killing forP. aeruginosaisolates with MICs of 0.125 to 8 μg/ml. Exposures of ≥40%fT>MIC resulted in the most pronounced bactericidal effects, while killing was variable for 20 to 30%fT>MIC. Infusing doses over 4 h enhanced efficacy against selected pseudomonal isolates with an MIC of 4 μg/ml.
Impact of the RNA Chaperone Hfq on the Fitness and Virulence Potential of Uropathogenic
Escherichia coli
Authors: Kulesus Richard R. , Diaz-Perez Karen , Slechta E. Susan , Eto Danelle S. , Mulvey Matthew A. 
Published: May 2008

ABSTRACT

Hfq is a bacterial RNA chaperone involved in the posttranscriptional regulation of many stress-inducible genes via small noncoding RNAs. Here, we show that Hfq is critical for the uropathogenic
Escherichia coli
(UPEC) isolate UTI89 to effectively colonize the bladder and kidneys in a murine urinary tract infection model system. The disruption of
hfq
did not affect bacterial adherence to or invasion of host cells but did limit the development of intracellular microcolonies by UTI89 within the terminally differentiated epithelial cells that line the lumen of the bladder. In vitro, the
hfq
mutant was significantly impaired in its abilities to handle the antibacterial cationic peptide polymyxin B and reactive nitrogen and oxygen radicals and to grow in acidic medium (pH 5.0). Relative to the wild-type strain, the
hfq
mutant also had a substantially reduced migration rate on motility agar and was less prone to form biofilms. Hfq activities are known to impact the regulation of both the stationary-phase sigma factor RpoS (σ
S
) and the envelope stress response sigma factor RpoE (σ
E
). Although we saw similarities among
hfq
,
rpoS
, and
rpoE
deletion mutants in our assays, the
rpoE
and
hfq
mutants were phenotypically the most alike. Cumulatively, our data indicate that Hfq likely affects UPEC virulence-related phenotypes primarily by modulating membrane homeostasis and envelope stress response pathways.
Expression of CD1d and Ligand-Induced Cytokine Production Are Tissue Specific in Mucosal Epithelia of the Human Lower Reproductive Tract
Authors: Kawana Kei , Matsumoto Junko , Miura Shiho , Shen Li , Kawana Yukiko , Nagamatsu Takeshi , Yasugi Toshiharu , Fujii Tomoyuki , Yang Huixia , Quayle Alison J. , Taketani Yuji , Schust Danny J. 
Published: May 2008

ABSTRACTMucosal epithelia of the human lower reproductive tract (vagina, cervix, and penile urethra) are exposed to sexually transmitted microbes, includingChlamydia trachomatis. The in vivo susceptibility of each tissue type to infection withC. trachomatisis quite distinct. CD1d is expressed on the surface of antigen-presenting cells, including mucosal epithelial cells, and interacts specifically with invariant NKT cells. Invariant NKT cells play a role in both innate and adaptive immune responses to microbes. Here we assessed CD1d expression in normal reproductive tissues by using immunohistochemistry. Immortalized epithelial cell lines from the human lower reproductive tract (vagina, endocervix, and penile urethra) were examined for CD1d expression and for ligand-induced cytokine production induced by CD1d cross-linking. CD1d expression in normal tissue was strong in the vagina but weak in the endocervix and penile urethra. Gamma interferon exposure induced CD1d transcription in all of the cell types studied, with the strongest induction in vaginal cells. Flow cytometry revealed cell surface expression of CD1d in vaginal and penile urethral epithelial cells but not in endocervical cells. Ligation of surface-expressed CD1d by monoclonal antibody cross-linking promoted interleukin-12 (IL-12) and IL-15, but not IL-10, production in vaginal and penile urethral cells. No induction was demonstrated in endocervical cells. CD1d-mediated cytokine production in penile urethral cells was abrogated byC. trachomatisinfection. Basal deficiency in CD1d-mediated immune responsiveness may result in susceptibility to sexually transmitted agents. Decreased CD1d-mediated signaling may helpC. trachomatisevade detection by innate immune cells.
Do high-altitude natives have enhanced exercise performance at altitude?
Authors: Brutsaert Tom D. 
Published: May 2008

Natives of high altitude (HA) may have enhanced physical work capacity in hypoxia due to growth and development at altitude or, in the case of indigenous Andean and Himalayan residents, due to population genetic factors that determine higher limits to exercise performance. There is a growing scientific literature in support of both hypotheses, although the specific developmental vs. genetic origins of putative population trait differences remain obscure. Considering whole-body measures of exercise performance, a review of the literature suggests that indigenous HA natives have higher mean maximal oxygen consumption (VO2 max) in hypoxia and smaller VO2 maxdecrement with increasing hypoxia. At present, there is insufficient information to conclude that HA natives have enhanced work economy or greater endurance capacity, although for the former a number of studies indicate that this may be the case for Tibetans. At the physiological level, supporting the hypothesis of enhanced pulmonary gas exchange efficiency, HA natives have smaller alveolar–arterial oxygen partial pressure difference ((A–a)DO2), lower pulmonary ventilation (VE), and likely higher arterial O2saturation (SaO2) during exercise. At the muscle level, a handful of studies show no differences in fiber-type distributions, capillarity, oxidative enzymes, or the muscle response to training. At the metabolic level, a few studies suggest differences in lactate production/removal and (or) lactate buffering capacity, but more work is needed in this area.
Effects of carbohydrate ingestion 15 min before exercise on endurance running capacity
Authors: Tokmakidis Savvas P. , Karamanolis Ioannis A. 
Published: May 2008

This study examined the effects of pre-exercise carbohydrate ingestion on exercise metabolism and endurance running capacity. Eleven active subjects (VO2 max 49.0 ± 1.7 mL·kg–1·min–1, mean ± SE) performed two exercise trials 15 min after ingesting glucose (G; 1 g·kg body mass–1) and placebo (CON). Each subject ran on a level treadmill for 5 min at 60%, 45 min at 70%, and then at 80% of VO2 max until exhaustion. Serum glucose and plasma insulin reached their peak concentrations (p < 0.01) 15 min after glucose ingestion and declined at the onset of exercise. Serum glycerol concentrations were lower (p < 0.01) in the G trial than in the CON trial after 30 min of exercise to exhaustion. In addition, after 45 min of exercise to exhaustion, the levels of free fatty acids were lower in G than in CON (p < 0.05). No differences were observed in carbohydrate oxidation rates during exercise between treatments (G, 2.53 ± 0.08 g·min–1; CON, 2.40 ± 0.09 g·min–1). Time to exhaustion was 12.8% longer in G (p < 0.01) than in CON. These results suggest that glucose ingestion 15 min before prolonged exercise provides an additional carbohydrate source to the exercising muscle, thus improving endurance running capacity.
A walking intervention improves capillary glucose control in women with gestational diabetes mellitus: a pilot study
Authors: Davenport Margie H. , Mottola Michelle F. , McManus Ruth , Gratton Rob 
Published: May 2008

Exercise prescriptions that can be translated into clinical recommendations are clearly needed for women with gestational diabetes mellitus (GDM). A pilot project was developed to document the effectiveness of a structured low-intensity walking protocol on capillary glucose control in GDM women. Ten GDM women followed conventional management of diet and insulin therapy, plus a low-intensity walking program (W) from diagnosis to delivery. Capillary glucose concentrations, insulin requirements, and pregnancy outcomes were compared with a matched cohort by body mass index (BMI), age, and insulin usage (20 GDM women who followed conventional management alone (C)). Baseline capillary glucose concentrations were not significantly different between the W and C groups. The W group had an average acute drop in capillary glucose concentration from pre- to post-exercise of 2.0 mmol·L–1. In addition, the W group had significantly lower mean glucose concentrations in the fasted state and 1 h after meals than the C group in the week prior to delivery. These lower glucose concentrations were achieved while requiring fewer units of insulin per day (C, 0.50 ± 0.37 U·kg–1; W, 0.16 ± 0.13 U·kg–1; p < 0.05), injected less frequently. These results suggest an effective role in glucose regulation for this structured walking program.
Effects of weight lifting training combined with plyometric exercises on physical fitness, body composition, and knee extension velocity during kicking in football
Authors: Perez-Gomez Jorge , Olmedillas Hugo , Delgado-Guerra Safira , Royo Ignacio Ara , Vicente-Rodriguez German , Ortiz Rafael Arteaga , Chavarren Javier , Calbet Jose A.L. 
Published: May 2008

The effects of a training program consisting of weight lifting combined with plyometric exercises on kicking performance, myosin heavy-chain composition (vastus lateralis), physical fitness, and body composition (using dual-energy X-ray absorptiometry (DXA)) was examined in 37 male physical education students divided randomly into a training group (TG: 16 subjects) and a control group (CG: 21 subjects). The TG followed 6 weeks of combined weight lifting and plyometric exercises. In all subjects, tests were performed to measure their maximal angular speed of the knee during instep kicks on a stationary ball. Additional tests for muscle power (vertical jump), running speed (30 m running test), anaerobic capacity (Wingate and 300 m running tests), and aerobic power (20 m shuttle run tests) were also performed. Training resulted in muscle hypertrophy (+4.3%), increased peak angular velocity of the knee during kicking (+13.6%), increased percentage of myosin heavy-chain (MHC) type IIa (+8.4%), increased 1 repetition maximum (1 RM) of inclined leg press (ILP) (+61.4%), leg extension (LE) (+20.2%), leg curl (+15.9%), and half squat (HQ) (+45.1%), and enhanced performance in vertical jump (all p ≤ 0.05). In contrast, MHC type I was reduced (–5.2%, p ≤ 0.05) after training. In the control group, these variables remained unchanged. In conclusion, 6 weeks of strength training combining weight lifting and plyometric exercises results in significant improvement of kicking performance, as well as other physical capacities related to success in football (soccer).
A single protein meal increases recovery of muscle function following an acute eccentric exercise bout
Authors: Etheridge Timothy , Philp Andrew , Watt Peter W. 
Published: May 2008

The purpose of this study was to examine the effects of acute protein ingestion on the recovery of muscle function and markers of muscle damage in the 72 h post eccentric-exercise. Nine recreationally active males recorded quadriceps maximum isometric voluntary contraction (MVC), peak 5 s power output (PPO), and perceived muscle soreness. Plasma creatine kinase (CK) and protein carbonyl (PC) content were measured prior to exercise. Delayed-onset muscle soreness (DOMS) was induced by a 30 min downhill run (–10°) at a target intensity of 75% age-predicted heart rate maximum, immediately followed by ingestion of 100 g protein (containing 40 g essential amino acids; PRO) or placebo (CON) solution. The pre-exercise measures were re-taken in the subsequent 24, 48, and 72 h. CK, PC, and perceived muscle soreness increased significantly following exercise and with each supplement at 24 h. PC and muscle soreness remained elevated at 48 and 72 h (p < 0.05), whereas CK returned to baseline values. No difference between conditions was observed for these measures. Peak MVC significantly declined in CON to –7.9% at 24 h, reaching a nadir of –10% at 48 h (p < 0.05). In the PRO group, MVC remained within pre-exercise values at all time points. PPO followed a similar trend, reaching its nadir of –8.7% at 48 h in CON (p < 0.05), but had recovered in the PRO trial. Ingestion of a single post-exercise protein mixture increases the rate of force and power restoration at 48 h, suggesting potential for protein as an ergogenic aid during the DOMS period.
Effective typestate verification in the presence of aliasing
Authors: Fink Stephen J. , Yahav Eran , Dor Nurit , Ramalingam G. , Geay Emmanuel 
Published: May 2008

This article addresses the challenge of sound typestate verification, with acceptable precision, for real-world Java programs. We present a novel framework for verification of typestate properties, including several new techniques to precisely treat aliases without undue performance costs. In particular, we present a flow-sensitive, context-sensitive, integrated verifier that utilizes a parametric abstract domain combining typestate and aliasing information. To scale to real programs without compromising precision, we present a staged verification system in which faster verifiers run as early stages which reduce the workload for later, more precise, stages.
We have evaluated our framework on a number of real Java programs, checking correct API usage for various Java standard libraries. The results show that our approach scales to hundreds of thousands of lines of code, and verifies correctness for 93% of the potential points of failure.