bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feasibility of Inpatient Geriatric Assessment for Older Adults Receiving Induction Chemotherapy for Acute Myelogenous Leukemia
Authors: Klepin Heidi D. , Geiger Ann M. , Tooze Janet A. , Kritchevsky Stephen B. , Williamson Jeff D. , Ellis Leslie R. , Levitan Denise , Pardee Timothy S. , Isom Scott , Powell Bayard L.
Published: September 2011

Objectives

To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML).

Design

Prospective observational cohort study.

Setting

Single academic institution.

Participants

Individuals aged 60 and older with newly diagnosed AML and planned chemotherapy.

Measurements

Bedside GA was performed during inpatient exmination for AML. GA measures included the modified Mini‐Mental State Examination; Center for Epidemiologic Studies Depression Scale; Distress Thermometer, Pepper Assessment Tool for Disability (includes self‐ reported activities of daily living (ADLs), instrumental ADLs, and mobility questions); Short Physical Performance Battery (includes timed 4‐m walk, chair stands, standing balance); grip strength, and Hematopoietic Cell Transplantation Comorbidity Index.

Results

Of 54 participants (mean age 70.8 ± 6.4) eligible for this analysis, 92.6% completed the entire GA battery (mean time 44.0 ± 14 minutes). The following impairments were detected: cognitive impairment, 31.5%; depression, 38.9%; distress, 53.7%; impairment in ADLs, 48.2%; impaired physical performance, 53.7%; and comorbidity, 46.3%. Most were impaired in one (92.6%) or more (63%) functional domains. For the 38 participants rated as having good performance status according to standard oncologic assessment (Eastern Cooperative Oncology Performance Scale score ≤1), impairments in individual GA measures ranged from 23.7% to 50%. Significant variability in cognitive, emotional, and physical status was detected even after stratification according to tumor biology (cytogenetic risk group classification).

Conclusion

Inpatient GA was feasible and added new information to standard oncology assessment, which may be important for stratifying therapeutic risk in older adults with AML.
How comfortable is neonatal transport?
Authors: Harrison Cath , McKechnie Liz
Published: September 2011

Aims:  Discomfort and stress have been widely studied in the newborn baby but data are lacking for the infant undergoing transport. The aim of our study was to identify infant discomfort during road transport and its pattern.

Methods:  This was a prospective cohort study on all infants transported by the Yorkshire Neonatal Transport Service over a 6‐month period. The same environmental measures were used for each baby. The premature infant pain profile was used to measure stress and discomfort at five specified times during transport. The score before any intervention was the gold standard.

Results:  Of 239 transport episodes, 140 had complete data. Twenty‐four babies were ventilated and routinely sedated with morphine, and the remaining babies had no pain relief. The same pattern of premature infant pain profile (PIPP) score was seen in all infants regardless of gestation or sedation. The raw PIPP scores (and data when ranked) peaked during road transport, and this was a significant change compared to baseline observations. This pattern was consistent across all gestational age groups. The sedated/ventilated babies showed the same pattern although it was blunted.

Conclusion:  All babies showed higher levels of discomfort during transport compared to baseline. More work is needed to develop interventions that could potentially decrease this.
Effect of roll clearance of mechanical processing of corn silage harvested at the black‐line stage of maturity on carbohydrate and protein utilization in dairy cows
Authors: TANIGAWA Tamako , OOSAKA Ikuo , KAWAMOTO Satoshi , HARA Satoshi
Published: September 2011

The experiment was conducted to evaluate the effect of roll clearance of mechanical processing of whole plant corn silage (CS) on carbohydrate and protein utilization in dairy cows. Treated CS was harvested at the black‐line stage of maturity and chopped at a theoretical length of cut (TLC) of 9.5 mm without processing or at a TLC of 19 mm with processing at a roll clearance of 1, 3 and 5 mm. Four ruminally and duodenally cannulated dry cows were assigned to a 4 × 4 Latin square design for 14‐day periods. Cows were fed diets containing 77% CS and 23% soybean meal (dry matter basis) to equalize the crude protein supply. Mechanical processing had no significant effect on dry matter intake and neutral detergent fiber digestibility. Ruminal and total tract starch digestibility and total digestible nutrients tended to be higher with processing at a roll clearance of 1 or 3 mm than at 5 mm. Microbial nitrogen efficiency in cows did not differ among all treatment groups. These results suggest that when CS is harvested at the black‐line stage of maturity, roll clearance should be 3 mm or less with a TLC of 19 mm.
Mapping QTL for fat area ratios and serum leptin concentrations in a Duroc purebred population
Authors: UEMOTO Yoshinobu , SOMA Yusuke , SATO Shuji , SHIBATA Tomoya , KADOWAKI Hiroshi , KATOH Kazuo , KOBAYASHI Eiji , SUZUKI Keiichi
Published: September 2011

The reduction of extra subcutaneous, intermuscular and abdominal fat is important to increase the carcass lean percentage of pigs. Image analyses of fat area ratios were effective for estimation of separated fat in pig carcasses. Serum concentrations of leptin are useful as physiological predictors of fat accumulation in pigs. The objectives of the present study were to perform a quantitative trait locus (QTL) analysis for fat area ratios and serum leptin concentrations in a Duroc purebred population. Pigs (n = 226 to 538) were measured for fat area ratios of carcass cross‐sections at the fifth to sixth thoracic vertebrae, half body length and last thoracic vertebra using an image analysis system, and serum leptin concentration. In total, animals were genotyped for 129 markers and used for QTL analysis. For fat area ratios, four significant and 12 suggestive QTLs were detected on chromosomes 1, 6, 7, 8, 9, 12 and 13. Significant QTLs were detected on the same region of chromosome 6, which was located near a leptin receptor gene. For serum leptin concentrations, two significant and two suggestive QTLs were detected on chromosomes 6, 9, and 16, and the QTLs on chromosome 6 were also in the same region for fat area ratios.
Identification and characterization of lactic acid bacteria isolated from mixed pasture of timothy and orchardgrass, and its badly preserved silage
Authors: TOHNO Masanori , KOBAYASHI Hisami , NOMURA Masaru , UEGAKI Ryuichi , CAI Yimin
Published: September 2011

In order to understand the relationship between lactic acid bacteria (LAB) species and silage fermentation, a total of 65 LAB strains isolated from mixed pasture of timothy (Phleum pratense L.) and orchardgrass (Dactylis glomerata L.), and its badly preserved silages were subjected to phenotypic and genetic analysis. According to these analyses, the isolates were divided into 13 groups, including Enterococcus gallinarum, Lactobacillus acidipiscis, L. coryniformis subsp. coryniformis, L. coryniformis subsp. torquens, L. curvatus, L. paraplantarum, L. plantarum subsp. argentoratensis, L. plantarum subsp. plantarum, L. sakei subsp. carnosus, Lactococcus garvieae, Lactococcus lactis subsp. cremoris, Leuconostoc pseudomesenteroides, Pediococcus acidilactici, Pediococcus pentosaceus, Weissella hellenica, Weissella paramesenteroides and Carnobacterium divergens. This is the first report to document that C. divergens, L. acidipiscis, L. sakei subsp. carnosus, L. garvieae, phenotypically novel L. lactis subsp. cremoris, E. gallinarum and W. hellenica are present in vegetative forage crops. L. plantarum group strains were most frequently isolated from the badly preserved silages. Some isolates showed a wide range of growth preferences for carbohydrate utilization, optimal growth pH and temperature in vitro, indicating that they have a high growth potential. These results are useful in understanding the diversity of LAB associated with decayed silage of timothy and orchardgrass.
Variation in chemical composition of corn dried distillers grains with solubles in relation to in situ protein degradation profiles in the rumen
Authors: KAJIKAWA Hiroshi , MIYAZAWA Kei , YANASE Ayako , TANABE Yuki , TSUCHIDA Yu , MITSUMOTO Yukiko , KOZATO Yoshinobu , MITSUMORI Makoto
Published: September 2011

Chemical composition and in situ degradation profiles were analyzed for 27 samples of dried distillers grains with solubles (DDGS) distributed in Japan, and a wide variation was found in neutral detergent fiber (NDF) content, which had positive relationships to detergent‐insoluble crude proteins such as neutral detergent‐insoluble crude protein (NDICP) and acid detergent‐insoluble CP (ADICP). Samples with lower NDF (< 35% on dry matter (DM)) showed higher soluble fractions of protein, but the degradation rate of microbially degradable protein in the rumen was not different in comparison with the samples with higher NDF, and no difference was shown between samples with higher and lower NDF after 24 and 48 h of in situ incubation for DM and CP degradation, respectively. The NDICP content in the digestion residue decreased with time of incubation, especially for samples with higher NDF, while the ADICP content increased. These results suggest that a part of the soluble fraction of CP in DDGS would be incorporated into NDICP by the heating process in bio‐ethanol production, which is still highly degradable, whereas another part of the fraction incorporated into ADICP would proceed to the advanced steps of irreversible amino‐carbonyl reaction.
A comparative assessment of interface pressures generated by four surgical theatre heel pressure ulcer prophylactics
Authors: Malkoun Mario , Huber Jacqueline , Huber David
Published: September 2011

Current heel protection devices used in the operating room do not comply with the consensus document of the European and National (North American) Pressure Ulcer Advisory Panels. A complying prototype has been tested. Prospective cohort study comparing interface pressures. While using the prototype device, the heel interface pressure is significantly [mean 0·0 mmHg, standard deviation (SD) 0·0] less than the viscose elastic gel (VEG) mat (mean 174·8 mmHg, SD 64·5), the Action® heel block (mean 182·3 mmHg, SD 70·8) and the theatre table (mean 193·2 mmHg, SD 57·1). At the Achilles tendon, the prototype device (mean 16·2 mmHg, SD 19·0) is significantly superior to the Oasis (mean 183·7 mmHg, SD 67·4) and Action® heel blocks (mean 112·3 mmHg, SD 64·7). At the lateral malleolus, the prototype device (mean 0·0, SD 0·0) is better than the Action® (mean 24·3 mmHg, SD 53·4) and Oasis heel blocks (mean 20·9 mmHg, SD 49·2). At the calf, the prototype (mean 53·7 mmHg, SD 23·0) imposed more pressure than all other devices tested but was not statistically significant compared with the theatre table or the VEG mat. It is possible to design a device that protects the heel, lateral malleolus and Achilles tendon without causing hyperextension of the knee and consequent popliteal vein compression, thereby complying with the above guidelines.
Breaking the ice: planetesimal formation at the snowline
Authors: Aumatell Guillem , Wurm Gerhard
Published: September 2011

Recently Saito & Sirono proposed that large ice aggregates which drift inwards in protoplanetary discs breakup during sublimation, ejecting embedded silicate particles. This would lead to a concentration of small solid particles close to the snowline. In view of this model, we carried out laboratory experiments where we observed freely levitating ice aggregates sublimating. We find that frequent breakup is indeed very common. Scaled to a 10 cm aggregate, about 2 × 104 small silicate aggregates might result. This supports the idea that sublimation of drifting ice aggregates might locally increase the density of small dust (silicate) particles which might more easily be swept up by larger dust aggregates or trigger gravitational instability. Either way, this might locally boost the formation of planetesimals at the snowline.
Nutritional Characteristics of Seed Proteins in 28 Vicia Species (Fabaceae) from Southern Spain
Authors: Pastor‐Cavada Elena , Juan Rocio , Pastor Julio E. , Alaiz Manuel , Vioque Javier
Published: September 2011

Abstract:  The study of local plants could provide useful data for the possible development of future crops with good nutritional and functional properties. The nutritional characteristics of the seed proteins of 28 Vicia species (31 taxa) (Fabaceae) from Spain were studied. Protein contents in studied Vicia ranged from 20.1% in V. articulata to 32% in V. pyrenaica. V. altissima, which is only deficient in Trp, showed the most balanced amino acid composition, while the remaining taxa were limiting in Met, Cys, and Trp. In vitro protein digestibility (IVPD) ranged from 78% in V. incana to 86.3% in V. hirsuta. In addition to the amino acid composition and IVPD, other nutritional parameters, such as amino acid score, biological value, protein efficiency ratio, or protein digestibility corrected amino acid score, were studied. Results confirm the interest of studying wild populations of cultivated and non cultivated Vicia species as potentially interesting sources of seeds with good nutritional characteristics.
Laparoscopically assisted resections of small bowel stromal tumors are safe and effective
Authors: CAI Wei , WANG Zheng Ting , WU Liang , ZHONG Jie , ZHENG Min Hua
Published: September 2011

OBJECTIVE:  To compare the efficacy of laparoscopically assisted and open resections in treatment of small bowel stromal tumors (SBST).

METHODS:  A retrospective study of 85 patients who underwent curative resections for SBST (38 by laparoscopically assisted procedures and 47 by open procedures) was performed.

RESULTS:  There were no differences between open and laparoscopically assisted approaches in terms of patients' age, gender, presenting symptoms, histological risk or extent of resection (P > 0.05). The median tumor size for laparoscopically assisted resections was 4.0 cm (range 1.2–7.0 cm), which was the same as that for the open resections (range 2.0–10.0 cm). There were fewer complications in the laparoscopic group than those in the open resection group (7.9% vs 17.0%), but no significant difference was observed (P > 0.05). The 2‐year survival of the two patient groups was almost the same (86.8% vs 89.4%). Laparoscopically assisted procedures required on average 22.5 min less of operating time (87.5 min vs 110.0 min, P = 0.006), 1.0 day less of bowel recovery time (3.0 days vs 4.0 days, P = 0.001) and 5.0 days less in hospital stay (8.0 days vs 13.0 days, P < 0.001).

CONCLUSION:  Laparoscopically assisted resection of SBST is a safe alternative to open resection.
Accuracy of Blood Pressure Measurements Reported in an Electronic Medical Record During Routine Primary Care Visits
Authors: Fishman Paul A. , Anderson Melissa L. , Cook Andrea J. , Ralston James D. , Catz Sheryl L. , Carlson Jim , Larson Eric B. , Green Beverly B.
Published: September 2011

J Clin Hypertens (Greenwich). 2011;13:821–828. ©2011 Wiley Periodicals, Inc.

Electronic medical records (EMRs) allow for real‐time access to blood pressure (BP) information on a population basis and improve identification and treatment of individuals with hypertension. Despite the potential uses of the data available from EMRs, relatively little research has examined the reliability of this data. To address this gap, the authors examined the reliability of BP taken at primary care visits and recorded in an EMR with those taken at a research study visit at which standard protocols were used to measure BP among all adults as well as by sex and age. Systolic BP (SBP) averaged 3.7 (17.3) points and diastolic BP (DBP) was 2.8 (10.6) points lower in the EMR than in the study visit across age and sex groups, with all differences statistically significant. For this cohort of patients with a diagnosis of hypertension, there was moderate correlation between BP measurements taken in clinic and at research. However, BP control for individuals, as defined by an SBP <140 mm Hg and DBP 90 mm Hg, differed by almost 25%. Known variability of BP and clinic procedures for measuring and recording BP may account for these differences.
Resveratrol blocks diabetes‐induced early vascular lesions and vascular endothelial growth factor induction in mouse retinas
Authors: Kim Young Hee , Kim Yoon Sook , Roh Gu Seob , Choi Wan Sung , Cho Gyeong Jae
Published: September 2011

Purpose:  Vessel leakage and loss of pericytes are early signs of diabetic retinopathy (DR), which leads to vision loss. Upregulation of the vascular endothelial growth factor (VEGF) during diabetes plays a key role in mediating these vascular lesions. The aim of this study is to investigate the effects of resveratrol, a natural plant‐derived phytoalexin, on vascular damage and VEGF induction in mouse retinas of early diabetes.

Methods:  Diabetes was induced in C57BL/6 mice by five consecutive‐intraperitoneal injections of 55 mg/kg of streptozotocin (STZ). Animals injected with buffer only were used as controls. Beginning 1 month after the fifth injection of STZ or buffer, 20 mg/kg of resveratrol was administered by oral gavage daily for 4 weeks to diabetic and control mice, and all mice were killed 2 months after the injections. We assessed vessel leakage, pericyte loss and VEGF protein expression in mouse retinas of 2‐month diabetes compared with controls with or without resveratrol treatment.

Results:  Diabetes led to increase vessel leakage, pericyte loss and VEGF protein level in the mouse retinas compared with controls; however, these changes were effectively blocked by resveratrol treatment.

Conclusion:  Our data suggest that resveratrol is effective to decrease vascular lesions and VEGF induction in mouse retinas of early diabetes.
Role of CCR2 in immunobiology and neurobiology
Authors: Yamasaki Ryo , Liu LiPing , Lin Jessica , Ransohoff Richard M.
Published: September 2011

Chemokines and their receptors play crucial roles in the trafficking of leukocytes and are of particular interest in the context of the unique inflammatory responses elicited in the central nervous system (CNS). The chemokine receptor CCR2 and its ligand CCL2 have been implicated in a wide range of immunobiological processes and neuropathologies, including recruitment of monocytes and regulation of bone marrow homeostasis, as well as multiple sclerosis, HIV‐associated dementia, Alzheimer’s disease and neuropathic pain. Recently, powerful biological tools (CCR2‐red fluorescent protein [RFP] knock‐in mice) have been developed to analyze the functions of CCR2 in different cell populations, and intriguing results have emerged from those mice. The present review emphasizes CCR2/CCL2 as a key chemokine/chemokine receptor pair that controls the recruitment or retention of a key subset of mononuclear phagocytes in inflammation associated with host defense or disease. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2011.00024.x, January 2012)
Sensitivity and Specificity of Canine Pancreas‐Specific Lipase (cPL) and Other Markers for Pancreatitis in 70 Dogs with and without Histopathologic Evidence of Pancreatitis
Authors: Trivedi S. , Marks S.L. , Kass P.H. , Luff J.A. , Keller S.M. , Johnson E.G. , Murphy B.
Published: September 2011

Background

Pancreatitis is a common disorder in dogs for which the antemortem diagnosis remains challenging.

Objectives

To compare the sensitivity and specificity of serum markers for pancreatitis in dogs with histopathologic evidence of pancreatitis or lack thereof.

Animals

Seventy dogs necropsied for a variety of reasons in which the pancreas was removed within 4 hours of euthanasia and serological markers were evaluated within 24 hours of death.

Methods

Prospective study: Serum was analyzed for amylase and lipase activities, and concentrations of canine trypsin‐like immunoreactivity (cTLI) and canine pancreas‐specific lipase (cPL). Serial transverse sections of the pancreas were made every 2 cm throughout the entire pancreas and reviewed using a semiquantitative histopathologic grading scheme.

Results

The sensitivity for the SpeccPL(cutoff value 400 μg/L) was 21 and 71% in dogs with mild (n = 56) or moderate‐severe pancreatitis (n = 7), and 43 and 71% (cutoff value 200 μg/L), respectively. The sensitivity for thecTLI, serum amylase, and lipase in dogs with mild or moderate‐severe pancreatitis was 30 and 29%; 7 and 14%; and 54 and 71%, respectively. The specificity for the SpeccPLbased on 7 normal pancreata was 100 and 86% (cutoff value 400 and 200 μg/L, respectively), whereas the specificity for thecTLI, serum amylase, and lipase activity was 100, 100, and 43%, respectively.

Conclusion and Clinical Importance

The SpeccPLdemonstrated the best overall performance characteristics (sensitivity and specificity) compared to other serum markers for diagnosing histopathologic lesions of pancreatitis in dogs.
Cross‐reactivity of acid‐sensing ion channel and Na+–H+ exchanger antagonists with nicotinic acetylcholine receptors
Authors: Santos‐Torres Julio , Ślimak Marta A. , Auer Sebastian , Ibañez‐Tallon Inés
Published: September 2011

Non‐Technical Summary  Cardiovascular disease and high blood pressure (hypertension) are frequent in the human population. Amiloride is commonly given as a diuretic to reduce hypertension without eliminating potassium, while zoniporide is used to aid in recovery after cardiac failure. We show here that high concentrations of these drugs have additional effects on nicotinic receptors that are present in the brain and body. The possibility that these drugs could affect nicotinic receptors when given as medications should be further investigated.
Postnatal loss of brainstem serotonin neurones compromises the ability of neonatal rats to survive episodic severe hypoxia
Authors: Cummings Kevin J. , Hewitt Julie C. , Li Aihua , Daubenspeck John A. , Nattie Eugene E.
Published: September 2011

Non‐Technical Summary  Failure to withstand severe hypoxia (failed autoresuscitation) has been documented in sudden infant death syndrome (SIDS) cases, and SIDS is associated with a constellation of defects within the brainstem serotonin system, including reduced serotonin content. Neonatal mice with reduced numbers of serotonergic neurones beginning in utero also have major defects in autoresuscitation at the beginning of the second postnatal week. Here we injected a neurotoxin into the brainstems of 2‐ to 3‐day‐old rat pups, reducing serotonin content by ∼80%, and at P7–10 tested their ability to autoresuscitate when challenged with repeated episodes of environmental anoxia. Pups with reduced serotonin content have delayed gasping in response to each challenge, as well as a significantly higher mortality by the last episode. These new data imply that a postnatal loss of brainstem serotonin in infants could increase the risk of SIDS during severely hypoxic conditions.
Motion Cueing Algorithm Online Parameter Switching in a Blink of an Eye—A Time-Variant Approach
Authors: Lorenz Tobias , Jaschke Klaus , Köster Frank
Published: September 2011

The development and evaluation of human centered driver assistance systems is one major research focus within the automotive domain of the Institute of Transportation Systems (TS) at the German Aerospace Center (DLR). To investigate the impact of new driver assistance systems on driver behavior different research facilities from simulations to real car environments are used. One research facility at TS is the dynamic driving simulator with a hexapod structure. Using dynamic driving simulators to reproduce real car motion is a major challenge as the workspace is limited. Within this paper a method of state adaption is presented. This method enables a discrete switching of high-pass filter corner frequencies within one single simulation time step. Thereby discontinuities of the filter output signal as well as in the derivatives of the output signal are avoidable. Thus, it is possible to adapt corner frequencies of high-pass filters of a Motion Cueing Algorithm (MCA), according to the current driving situation. The paper starts with a description of the MCA currently used for the motion rendering at TS. Afterward the state adaption method is described including the challenges for adapting this method to the current MCA structure. In the end of the new structure for the time-variant MCA as well as the boundary conditions for corner frequency switching and the test results of the new time-variant approach using the state adaption method are outlined.
Numerical Evaluation of Single Fiber Motion for Short-Fiber-Reinforced Composite Materials Processing
Authors: Zhang Dongdong , E. Smith Douglas , A. Jack David , Montgomery-Smith Stephen
Published: September 2011

This paper presents a computational approach for simulating the motion of a single fiber suspended within a viscous fluid. We develop a finite element method (FEM) for modeling the dynamics of a single rigid fiber suspended in a moving fluid. Our approach seeks solutions using the Newton–Raphson method for the fiber’s linear and angular velocities such that the net hydrodynamic forces and torques acting on the fiber are zero. Fiber motion is then computed with a Runge-Kutta method to update the fiber position and orientation as a function of time. Low-Reynolds-number viscous flows are considered since these best represent the flow conditions for a polymer melt within a mold cavity. This approach is first used to verify Jeffery’s orbit (1922) and addresses such issues as the role of a fiber’s geometry on the dynamics of a single fiber, which were not addressed in Jeffery’s original work. The method is quite general and allows for fiber shapes that include, but are not limited to, ellipsoidal fibers (such as that studied in Jeffery’s original work), cylindrical fibers, and bead-chain fibers. The relationships between equivalent aspect ratio and geometric aspect ratio of cylindrical and other axisymmetric fibers are derived in this paper.
Enhancing Basal Transmission
Authors: Foley John F.
Published: September 2011

Astrocytes respond to single axon potentials and then enhance synaptic transmission in a calcium- and purinergic signaling–dependent mechanism.
Antitrypanosomal Activity of Fexinidazole, a New Oral Nitroimidazole Drug Candidate for Treatment of Sleeping Sickness
Authors: Kaiser Marcel , Bray Michael A. , Cal Monica , Bourdin Trunz Bernadette , Torreele Els , Brun Reto
Published: September 2011

Fexinidazole is a 5-nitroimidazole drug currently in clinical development for the treatment of human sleeping sickness (human African trypanosomiasis [HAT]), caused by infection with species of the protozoan parasite
Trypanosoma brucei
. The compound and its two principal metabolites, sulfoxide and sulfone, have been assessed for their ability to kill a range of
T. brucei
parasite strains
in vitro
and to cure both acute and chronic HAT disease models in the mouse. The parent molecule and both metabolites have shown trypanocidal activity
in vitro
in the 0.7-to-3.3 μM (0.2-to-0.9 μg/ml) range against all parasite strains tested.
In vivo
, fexinidazole is orally effective in curing both acute and chronic diseases in the mouse at doses of 100 mg/kg of body weight/day for 4 days and 200 mg/kg/day for 5 days, respectively. Pharmacokinetic data indicate that it is likely that the sulfoxide and sulfone metabolites provide most, if not all, of the
in vivo
killing activity. Fexinidazole and its metabolites require up to 48 h exposure in order to induce maximal trypanocidal efficacy
in vitro
. The parent drug and its metabolites show no
in vitro
cross-reactivity in terms of trypanocidal activity with either themselves or other known trypanocidal drugs in use in humans. The
in vitro
and
in vivo
antitrypanosomal activities of fexinidazole and its two principal metabolites provide evidence that the compound has the potential to be an effective oral treatment for both the
T. b. gambiense
and
T. b. rhodesiense
forms of human sleeping sickness and both stages of the disease.
Impact of Granulocytes on the Antimicrobial Effect of Tedizolid in a Mouse Thigh Infection Model
Authors: Drusano G. L. , Liu Weiguo , Kulawy Robert , Louie Arnold
Published: September 2011

Tedizolid (TR-700, formerly torezolid) is the active component of the new oxazolidinone prodrug tedizolid phosphate (TR-701). We had previously demonstrated that tedizolid possessed potent antistaphylococcal activity superior to that of linezolid in a neutropenic mouse thigh infection model (A. Louie, W. Liu, R. Kulawy, and G. L. Drusano, Antimicrob. Agents Chemother. 55:3453-3460, 2011). In the current investigation, we used a mouse thigh infection model to delineate the effect of an interaction of TR-700 and granulocytes on staphylococcal cell killing. We compared the antistaphylococcal killing effect of doses of TR-701 equivalent to human exposures ranging from 200 to 3,200 mg/day in both granulocytopenic and normal mice. The mice were evaluated at 24, 48, and 72 h after therapy initiation. In granulocytopenic mice, a clear exposure response in which, depending on the time point of evaluation, stasis was achieved at “human-equivalent” doses of slightly below 2,300 mg/day (at 24 h) to slightly below 2,000 mg/day (at 72 h) was observed. In immune-normal animals, stasis was achieved at human-equivalent doses of slightly greater than 100 mg/day or less. The variance in bacterial cell killing results was attributable to the presence of granulocytes (without drug), the direct effect of TR-700 on
Staphylococcus aureus
, and the effect of the drug on
Staphylococcus aureus
mediated through granulocytes. The majority of the bacterial cell killing in normal animals was attributable to the effect of TR-700 mediated through granulocytes. Additional studies need to be undertaken to elucidate the mechanism underlying this observation.
Synergistic Killing of Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula by Colistin Combined with Doripenem in an In Vitro Pharmacokinetic/Pharmacodynamic Model
Authors: Bergen Phillip J. , Tsuji Brian T. , Bulitta Jurgen B. , Forrest Alan , Jacob Jovan , Sidjabat Hanna E. , Paterson David L. , Nation Roger L. , Li Jian
Published: September 2011

Combination therapy may be required for multidrug-resistant (MDR)
Pseudomonas aeruginosa
. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR
P. aeruginosa
. Studies were conducted in a one-compartment
in vitro
pharmacokinetic/pharmacodynamic model for 96 h at two inocula (∼10
6
and ∼10
8
CFU/ml) against a colistin-heteroresistant reference strain (ATCC 27853) and a colistin-resistant MDR clinical isolate (19147 n/m). Four combinations utilizing clinically achievable concentrations were investigated. Microbiological response was examined by log changes and population analysis profiles. Colistin (constant concentrations of 0.5 or 2 mg/liter) plus doripenem (peaks of 2.5 or 25 mg/liter every 8 h; half-life, 1.5 h) substantially increased bacterial killing against both strains at the low inoculum, while combinations containing colistin at 2 mg/liter increased activity against ATCC 27853 at the high inoculum; only colistin at 0.5 mg/liter plus doripenem at 2.5 mg/liter failed to improve activity against 19147 n/m at the high inoculum. Combinations were additive or synergistic against ATCC 27853 in 16 and 11 of 20 cases (4 combinations across 5 sample points) at the 10
6
- and 10
8
-CFU/ml inocula, respectively; the corresponding values for 19147 n/m were 16 and 9. Combinations containing doripenem at 25 mg/liter resulted in eradication of 19147 n/m at the low inoculum and substantial reductions in regrowth (including to below the limit of detection at ∼50 h) at the high inoculum. Emergence of colistin-resistant subpopulations of ATCC 27853 was substantially reduced and delayed with combination therapy. This investigation provides important information for optimization of colistin-doripenem combinations.
Mouse Monoclonal Antibodies to Anthrax Edema Factor Protect against Infection
Authors: Leysath Clinton E. , Chen Kuang-Hua , Moayeri Mahtab , Crown Devorah , Fattah Rasem , Chen Zhaochun , Das Suman R. , Purcell Robert H. , Leppla Stephen H.
Published: September 2011

Bacillus anthracis
is the causative agent of anthrax, and the tripartite anthrax toxin is an essential element of its pathogenesis. Edema factor (EF), a potent adenylyl cyclase, is one of the toxin components. In this work, anti-EF monoclonal antibodies (MAb) were produced following immunization of mice, and four of the antibodies were fully characterized. MAb 3F2 has an affinity of 388 pM, was most effective for EF detection, and appears to be the first antibody reported to neutralize EF by binding to the catalytic C
B
domain. MAb 7F10 shows potent neutralization of edema toxin activity
in vitro
and
in vivo
; it targets the N-terminal protective antigen binding domain. The four MAb react with three different domains of edema factor, and all were able to detect purified edema factor in Western blot analysis. None of the four MAb cross-reacted with the lethal factor toxin component. Three of the four MAb protected mice in both a systemic edema toxin challenge model and a subcutaneous spore-induced foreleg edema model. A combination of three of the MAb also significantly delayed the time to death in a third subcutaneous spore challenge model. This appears to be the first direct evidence that monoclonal antibody-mediated neutralization of EF alone is sufficient to delay anthrax disease progression.
Immunization with Apoptotic Phagocytes Containing Histoplasma capsulatum Activates Functional CD8+T Cells To Protect against Histoplasmosis
Authors: Hsieh Shih-Hung , Lin Jr-Shiuan , Huang Juin-Hua , Wu Shang-Yang , Chu Ching-Liang , Kung John T. , Wu-Hsieh Betty A.
Published: September 2011

We have previously revealed the protective role of CD8+T cells in host defense againstHistoplasma capsulatumin animals with CD4+T cell deficiency and demonstrated that sensitized CD8+T cells are restimulatedin vitroby dendritic cells that have ingested apoptotic macrophage-associatedHistoplasmaantigen. Here we show that immunization with apoptotic phagocytes containing heat-killedHistoplasmaefficiently activated functional CD8+T cells whose contribution was equal to that of CD4+T cells in protection againstHistoplasmachallenge. Inhibition of macrophage apoptosis due to inducible nitric oxide synthase (iNOS) deficiency or by caspase inhibitor treatment dampened the CD8+T cell but not the CD4+T cell response to pulmonaryHistoplasmainfection. In mice subcutaneously immunized with viableHistoplasmayeasts whose CD8+T cells are protective againstHistoplasmachallenge, there was heavy granulocyte and macrophage infiltration and the infiltrating cells became apoptotic. In mice subcutaneously immunized with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled apoptotic macrophages containing heat-killedHistoplasma, the CFSE-labeled macrophage material was found to localize within dendritic cells in the draining lymph node. Moreover, depleting dendritic cells in immunized CD11c-DTR mice significantly reduced CD8+T cell activation. Taken together, our results revealed that phagocyte apoptosis in theHistoplasma-infected host is associated with CD8+T cell activation and that immunization with apoptotic phagocytes containing heat-killedHistoplasmaefficiently evokes a protective CD8+T cell response. These results suggest that employing apoptotic phagocytes as antigen donor cells is a viable approach for the development of efficacious vaccines to elicit strong CD8+T cell as well as CD4+T cell responses toHistoplasmainfection.
Toxoplasma gondii Induces B7-2 Expression through Activation of JNK Signal Transduction
Authors: Morgado Pedro , Ong Yi-Ching , Boothroyd John C. , Lodoen Melissa B.
Published: September 2011

Toxoplasma gondiiis a globally distributed parasite pathogen that infects virtually all warm-blooded animals. A hallmark of immunity to acute infection is the production of gamma interferon (IFN-γ) and interleukin-12 (IL-12), followed by a protective T cell response that is critical for parasite control. Naïve T cell activation requires both T-cell receptor (TCR) stimulation and the engagement of costimulatory receptors. Because of their important function in activating T cells, the expression of costimulatory ligands is believed to be under tight control. The molecular mechanisms governing their induction during microbial stimulation, however, are not well understood. We found that all three strains ofT. gondii(types I, II, and III) upregulated the expression of B7-2, but not B7-1, on the surface of mouse bone marrow-derived macrophages. Additionally, intraperitoneal infection of mice with green fluorescent protein (GFP)-expressing parasites resulted in enhanced B7-2 levels specifically on infected, GFP+CD11b+cells. B7-2 induction occurred at the transcript level, required active parasite invasion, and was not dependent on MyD88 or TRIF. Functional assays demonstrated thatT. gondii-infected macrophages stimulated naïve T cell proliferation in a B7-2-dependent manner. Genome-wide transcriptional analysis comparing infected and uninfected macrophages revealed the activation of mitogen-activated protein kinase (MAPK) signaling in infected cells. Using specific inhibitors against MAPKs, we determined that parasite-induced B7-2 is dependent on Jun N-terminal protein kinase (JNK) but not extracellular signal-regulated kinase (ERK) or p38 signaling. We also observed thatT. gondii-induced B7-2 expression on human peripheral blood monocytes is dependent on JNK signaling, indicating that a common mechanism of B7-2 regulation byT. gondiimay exist in both humans and mice.
Complete Genome Analysis of Sulfobacillus acidophilus Strain TPY, Isolated from a Hydrothermal Vent in the Pacific Ocean
Authors: Li Bo , Chen Yaping , Liu Qian , Hu Songnian , Chen Xinhua
Published: September 2011

Sulfobacillus acidophilus
strain TPY is a moderately thermoacidophilic bacterium originally isolated from a hydrothermal vent in the Pacific Ocean. Ferrous iron and sulfur oxidation in acidic environments in strain TPY have been confirmed. Here we report the genome sequence and annotation of the strain TPY, which is the first complete genome of
Sulfobacillus acidophilus
.
Genome Sequence of Lactobacillus versmoldensis KCTC 3814
Authors: Kim Dae-Soo , Choi Sang-Haeng , Kim Dong-Wook , Kim Ryong Nam , Nam Seong-Hyeuk , Kang Aram , Kim Aeri , Park Hong-Seog
Published: September 2011

Lactobacillus versmoldensis
KCTC 3814 was isolated from raw fermented poultry salami. The species was present in high numbers and frequently dominated the lactic acid bacteria (LAB) populations of the products. Here, we announce the draft genome sequence of
Lactobacillus versmoldensis
KCTC 3814, isolated from poultry salami, and describe major findings from its annotation.
Genome Sequence of Lactobacillus pentosus IG1, a Strain Isolated from Spanish-Style Green Olive Fermentations
Authors: Maldonado-Barragán Antonio , Caballero-Guerrero Belén , Lucena-Padrós Helena , Ruiz-Barba José Luis
Published: September 2011

Lactobacillus pentosus
is the most prevalent lactic acid bacterium in Spanish-style green olive fermentations. Here we present the draft genome sequence of
L. pentosus
IG1, a bacteriocin-producing strain with biotechnological and probiotic properties isolated from this food fermentations.
Whole Genome Sequence of the Rifamycin B-Producing Strain Amycolatopsis mediterranei S699
Authors: Verma Mansi , Kaur Jaspreet , Kumar Mukesh , Kumari Kirti , Saxena Anjali , Anand Shailly , Nigam Aeshna , Ravi Vydianathan , Raghuvanshi Saurabh , Khurana Paramjit , Tyagi Akhilesh K. , Khurana Jitendra P. , Lal Rup
Published: September 2011

Amycolatopsis mediterranei
S699 is an actinomycete that produces an important antibiotic, rifamycin B. Semisynthetic derivatives of rifamycin B are used for the treatment of tuberculosis, leprosy, and AIDS-related mycobacterial infections. Here, we report the complete genome sequence (10.2 Mb) of
A. mediterranei
S699, with 9,575 predicted coding sequences.
Genome Sequence of Kosmotoga olearia Strain TBF 19.5.1, a Thermophilic Bacterium with a Wide Growth Temperature Range, Isolated from the Troll B Oil Platform in the North Sea
Authors: Swithers Kristen S. , DiPippo Jonathan L. , Bruce David C. , Detter Christopher , Tapia Roxanne , Han Shunsheng , Goodwin Lynne A. , Han James , Woyke Tanja , Pitluck Sam , Pennacchio Len , Nolan Matthew , Mikhailova Natalia , Land Miriam L. , Nesbø Camilla L. , Gogarten J. Peter , Noll Kenneth M.
Published: September 2011

Kosmotoga olearia
strain TBF 19.5.1 is a member of the
Thermotogales
that grows best at 65°C and very well even at 37°C. Information about this organism is important for understanding the evolution of mesophiles from thermophiles. Its genome sequence reveals extensive gene gains and a large content of mobile genetic elements. It also contains putative hydrogenase genes that have no homologs in the other member of the
Thermotogales
.
Complete Genome Sequence of the Dog Commensal and Human Pathogen Capnocytophaga canimorsus Strain 5
Authors: Manfredi Pablo , Pagni Marco , Cornelis Guy R.
Published: September 2011

Capnocytophaga canimorsusis a commensal Gram-negative bacterium, originally isolated from a dog's mouth, that causes septicemia in humans.C. canimorsushas the unusual ability to feed on host cells, including phagocytes. This capacity depends on surface-exposed glycan-foraging systems. Here we present the first complete genome sequence of aC. canimorsusstrain (Cc5).
Sequence context for transcription and translation of the ArabidopsisRPL23aAandRPL23aBparalogs
Authors: McIntosh Kerri B. , Degenhardt Rory F. , Bonham-Smith Peta C.
Published: September 2011

The 80S cytoplasmic ribosome is responsible for translating the transcriptome into the proteome. Demand for ribosome production depends on growth rate, and both the ribosomal RNA (rRNA) and ribosomal protein (RP) components must respond coordinately and rapidly to positive and negative growth stimuli to prevent deleterious effects of excess or insufficient subunits. The 81 RPs of the Arabidopsis 80S ribosome are encoded by multigene families that often exhibit overlapping patterns of transcript accumulation; however, only one isoform of each RP family (with the exception of a small number of acidic RPs) assembles into a single ribosome. Here we dissected the regulatory regions (RRs) of both members of the RPL23a family (RPL23aA and RPL23aB) to identify salient cis-acting elements involved in transcriptional, posttranscriptional, and translational regulation of expression. Full length and truncated RRs of RPL23a paralogs were cloned upstream of a GUS reporter gene and expressed in Arabidopsis transgenic plants. High level expression in mitotically active tissues, driven by RPL23aA and RPL23aB RRs, required TATA-box, telo-box, and site II motif elements. First and second introns were found to play a minor role in posttranscriptional regulation of paralogs, and conserved transcript features (e.g., UTR base composition) may be involved in enhancing translational efficiency. Overall, our results indicate that RPL23a expression is governed by a complex network of multiple regulatory layers.
Heterochromatin patterns and ribosomal DNA loci distribution in diploid and polyploid Crotalaria species (Leguminosae, Papilionoideae), and inferences on karyotype evolution
Authors: Mondin Mateus , Aguiar-Perecin Margarida L.R.
Published: September 2011

Most Crotalaria species display a symmetric karyotype with 2n = 16, but 2n = 14 is found in Chrysocalycinae subsection Incanae and 2n = 32 in American species of the section Calycinae. Seven species of the sections Chrysocalycinae, Calycinae, and Crotalaria were analyzed for the identification of heterochromatin types with GC- and AT-specific fluorochromes and chromosomal location of ribosomal DNA loci using fluorescent in situ hybridization (FISH). A major 45S rDNA locus was observed on chromosome 1 in all the species, and a variable number of minor ones were revealed. Only one 5S rDNA locus was observed in the species investigated. Chromomycin A3 (CMA) revealed CMA+ bands colocalized with most rDNA loci, small bands unrelated to ribosomal DNA on two chromosome pairs in Crotalaria incana, and CMA+ centromeric bands that were quenched by distamycin A were detected in species of Calycinae and Crotalaria sections. DAPI+ bands were detected in C. incana. The results support the species relationships based on flower specialization and were useful for providing insight into mechanisms of karyotype evolution. The heterochromatin types revealed by fluorochromes suggest the occurrence of rearrangements in repetitive DNA families in these heterochromatic blocks during species diversification. This DNA sequence turnover and the variability in number/position of rDNA sites could be interpreted as resulting from unequal crossing over and (or) transposition events. The occurrence of only one 5S rDNA locus and the smaller chromosome size in the polyploids suggest that DNA sequence losses took place following polyploidization events.
Automatic Treebank Conversion via Informed Decoding - A Case Study on Chinese Treebanks
Authors: Zhu Muhua , Zhu Jingbo , Xiao Tong
Published: September 2011

Treebanks are valuable resources for syntactic parsing. For some languages such as Chinese, we can obtain multiple constituency treebanks which are developed by different organizations. However, due to discrepancies of underlying annotation standards, such treebanks in general cannot be used together through direct data combination. To enlarge training data for syntactic parsing, we focus in this article on the challenge of unifying standards of disparate treebanks by automatically converting one treebank (source treebank) to fit a different standard which is exhibited by another treebank (target treebank).

We propose to convert a treebank in two sequential steps which correspond to the part-of-speech level and syntactic structure level (including tree structures and grammar labels), respectively. Approaches used in both levels can be unified as an
informed decoding
procedure, where information derived from original annotation in a source treebank is used to guide the conversion conducted by a POS tagger (or a parser in the syntactic structure level) trained on a target treebank. We take two Chinese treebanks as a case study, and experiments on these two treebanks show significant improvements in conversion accuracy over baseline systems, especially in situations where a target treebank is small in size.
Macrophage Autophagy and Oxidative Stress: An Ultrastructural and Immunoelectron Microscopical Study
Authors: Perrotta Ida , Carito Valentina , Russo Emilio , Tripepi Sandro , Aquila Saveria , Donato Giuseppe
Published: September 2011

The word autophagy broadly refers to the cellular catabolic processes that lead to the removal of damaged cytosolic proteins or cell organelles through lysosomes. Although autophagy is often observed during programmed cell death, it may also serve as a cell survival mechanism. Accumulation of reactive oxygen species within tissues and cells induces various defense mechanisms or programmed cell death. It has been shown that, besides inducing apoptosis, oxidative stress can also induce autophagy. To date, however, the regulation of autophagy in response to oxidative stress remains largely elusive and poorly understood. Therefore, the present study was designed to examine the ratio between oxidative stress and autophagy in macrophages after oxidant exposure (AAPH) and to investigate the ultrastructural localization of beclin-1, a protein essential for autophagy, under basal and stressful conditions. Our data provide evidence that oxidative stress induces autophagy in macrophages. We demonstrate, for the first time by immunoelectron microscopy, the subcellular localization of beclin-1 in autophagic cells.