bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a modified Respiration Activity Monitoring System for accurate and highly resolved measurement of respiration activity in shake flask fermentations
Authors: Hansen Sven , Hariskos Ioanna , Luchterhand Bettina , Büchs Jochen 
Published: August 2012

Abstract

Background
The Respiration Activity Monitoring System (RAMOS) is an established device to measure on-line the oxygen transfer rate (OTR), thereby, yielding relevant information about metabolic activities of microorganisms and cells during shake flask fermentations. For very fast-growing microbes, however, the RAMOS technique provides too few data points for the OTR. Thus, this current study presents a new model based evaluation method for generating much more data points to enhance the information content and the precision of OTR measurements.

Results
In cultivations with E.coli BL21 pRSET eYFP-IL6, short diauxic and even triauxic metabolic activities were detected with much more detail compared to the conventional evaluation method. The decline of the OTR during the stop phases during oxygen limitations, which occur when the inlet and outlet valves of the RAMOS flask were closed for calibrating the oxygen sensor, were also detected. These declines reflected a reduced oxygen transfer due to the stop phases. In contrast to the conventional calculation method the new method was almost independent from the number of stop phases chosen in the experiments.

Conclusions
This new model based evaluation method unveils new peaks of metabolic activity which otherwise would not have been resolved by the conventional RAMOS evaluation method. The new method yields substantially more OTR data points, thereby, enhancing the information content and the precision of the OTR measurements. Furthermore, oxygen limitations can be detected by a decrease of the OTR during the stop phases.
Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis
Authors: Kim Jeong Yeon , Lee Eun Young , Lee Eun Bong , Lee Yun Jong , Yoo Hyun Jung , Choi Jiyong , Song Yeong Wook 
Published: August 2012

Abstract
Introduction
Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis.

Methods
FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.

Results
Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14+ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.

Conclusion
These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.
Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement
Authors: Valentini Gabriele , Vettori Serena , Cuomo Giovanna , Iudici Michele , D'Abrosca Virginia , Capocotta Domenico , Del Genio Gianmattia , Santoriello Carlo , Cozzolino Domenico 
Published: August 2012

Abstract
Introduction
We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.

Methods
Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.

Results
At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X
2
= 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04).

Conclusion
Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.
Early menopause and severity of rheumatoid arthritis in women older than 45 years
Authors: Pikwer Mitra , Nilsson Jan-Åke , Bergström Ulf , Jacobsson Lennart TH , Turesson Carl 
Published: August 2012

Abstract
Introduction
We aimed to investigate whether recognized hormonal predictors of rheumatoid arthritis (RA) also influence the severity of RA.

Methods
One hundred thirty-four incident RA cases identified by four different local and national registers, who had participated in a community-based health survey between 1991 and 1996, were included. By a retrospective structured review of the medical records, information on the use of disease-modifying antirheumatic drugs (DMARDs), erosions on radiographs, rheumatoid factor (RF) status, and disability measured by using the health assessment questionnaire (HAQ) were collected. The variables were added to the SPSS TwoStep Cluster Analysis to reveal natural groupings of RA severity. Known hormonal predictors analyzed were breastfeeding history, history of oral contraceptive (OC) use, and menopausal age.

Results
The mean age at RA diagnosis was 63.4 years; 72% were RF positive, and 28% had received biological treatment. Three clusters were identified, one with severe RA, one with mild/moderate RF-positive RA, and one with mild/moderate RF-negative RA. A significant difference (P = 0.005) was found in the distribution of clusters between patients with a history of early menopause compared with those with menopause after 45 years, with a higher proportion with mild/moderate RF-negative RA in the early-menopause subset. No major difference in severity of the disease was noted depending on OC use or history of breastfeeding.

Conclusions
Early menopause was associated with a milder form of RA. Hormonal changes may influence pathways that are distinct from those leading to severe, progressive disease.
Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study
Authors: Bragadottir Gudrun , Redfors Bengt , Ricksten Sven-Erik 
Published: August 2012

Abstract
Introduction
Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery.

Methods
Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods.

Results
Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P < 0.001). This was accompanied by a 12% increase in RBF (P < 0.05) and a 13% decrease in renal vascular resistance (P < 0.05). Mannitol increased the RBF/cardiac output (CO) relation (P = 0.040). Mannitol caused no significant changes in RO2Ext or renal FF.

Conclusions
Mannitol treatment of postoperative AKI induces a renal vasodilation and redistributes systemic blood flow to the kidneys. Mannitol does not affect filtration fraction or renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply.
Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase
Authors: Raiber Eun-Ang , Beraldi Dario , Ficz Gabriella , Burgess Heather E , Branco Miguel R , Murat Pierre , Oxley David , Booth Michael J , Reik Wolf , Balasubramanian Shankar 
Published: August 2012

Abstract
Background
Methylation of cytosine in DNA (5mC) is an important epigenetic mark that is involved in the regulation of genome function. During early embryonic development in mammals, the methylation landscape is dynamically reprogrammed in part through active demethylation. Recent advances have identified key players involved in active demethylation pathways, including oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) by the TET enzymes, and excision of 5fC by the base excision repair enzyme thymine DNA glycosylase (TDG). Here, we provide the first genome-wide map of 5fC in mouse embryonic stem (ES) cells and evaluate potential roles for 5fC in differentiation.

Results
Our method exploits the unique reactivity of 5fC for pulldown and high-throughput sequencing. Genome-wide mapping revealed 5fC enrichment in CpG islands (CGIs) of promoters and exons. CGI promoters in which 5fC was relatively more enriched than 5mC or 5hmC corresponded to transcriptionally active genes. Accordingly, 5fC-rich promoters had elevated H3K4me3 levels, associated with active transcription, and were frequently bound by RNA polymerase II. TDG down-regulation led to 5fC accumulation in CGIs in ES cells, which correlates with increased methylation in these genomic regions during differentiation of ES cells in wild-type and TDG knockout contexts.

Conclusions
Collectively, our data suggest that 5fC plays a role in epigenetic reprogramming within specific genomic regions, which is controlled in part by TDG-mediated excision. Notably, 5fC excision in ES cells is necessary for the correct establishment of CGI methylation patterns during differentiation and hence for appropriate patterns of gene expression during development.
A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation
Authors: Chu Jaime , Mir Alexander , Gao Ningguo , Rosa Sabrina , Monson Christopher , Sharma Vandana , Steet Richard , Freeze Hudson H. , Lehrman Mark A. , Sadler Kirsten C. 
Published: August 2012

Summary
Individuals with congenital disorders of glycosylation (CDG) have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO), which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI) enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf), which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy and the broader molecular and developmental abnormalities that contribute to disorders associated with defective protein glycosylation.
Serotonin has early, cilia-independent roles inXenopusleft-right patterning
Authors: Vandenberg Laura N. , Lemire Joan M. , Levin Michael 
Published: August 2012

SummaryConsistent left-right (LR) patterning of the heart and viscera is a crucial part of normal embryogenesis. Because errors of laterality form a common class of birth defects, it is important to understand the molecular mechanisms and stage at which LR asymmetry is initiated. Frog embryos are a system uniquely suited to analysis of the mechanisms involved in orientation of the LR axis because of the many genetic and pharmacological tools available for use and the fate-map and accessibility of early blastomeres. Two major models exist for the origin of LR asymmetry and both implicate pre-nervous serotonergic signaling. In the first, the charged serotonin molecule is instructive for LR patterning; it is redistributed asymmetrically along the LR axis and signals intracellularly on the right side at cleavage stages. A second model suggests that serotonin is a permissive factor required to specify the dorsal region of the embryo containing chiral cilia that generate asymmetric fluid flow during neurulation, a much later process. We performed theory-neutral experiments designed to distinguish between these models. The results uniformly support a role for serotonin in the cleavage-stage embryo, long before the appearance of cilia, in ventral right blastomeres that do not contribute to the ciliated organ.
Atlantic cod (Gadus morhua L.) in situ cardiac performance at cold temperatures: long-term acclimation, acute thermal challenge and the role of adrenaline
Authors: Lurman Glenn J. , Petersen Lene H. , Gamperl A. Kurt 
Published: August 2012

Summary
The resting and maximum in situ cardiac performance of Newfoundland Atlantic cod (Gadus morhua L.) acclimated to 10, 4 and 0°C were measured at their respective acclimation temperatures, and when acutely exposed to temperature changes: i.e. hearts from 10°C fish cooled to 4°C, and hearts from 4°C fish measured at 10°C and 0°C. Intrinsic heart rate (fH) decreased from 41 beats min-1 (bpm) at 10°C to 33 bpm at 4°C and to 25 bpm at 0°C. However, this degree of thermal dependency was not reflected in maximal cardiac output. Qmax values were ~44, ~37 and ~34 ml min-1 kg-1 at 10, 4 and 0°C, respectively. Further, cardiac scope showed a slight positive compensation between 4 and 0°C (Q10 = 1.7), and full, if not a slight over compensation between 10 and 4°C (Q10 = 0.9). The maximal performance of hearts exposed to an acute decrease in temperature (i.e. from 10°C to 4°C and 4°C to 0°C) was comparable to that measured for hearts from 4 and 0°C acclimated fish, respectively. In contrast, 4°C acclimated hearts significantly out-performed 10°C acclimated hearts when tested at a common temperature of 10°C (in terms of both Qmax and power output). Only minimal differences in cardiac function were seen between hearts stimulated with basal (5 nM) vs. maximal (200 nM) levels of adrenaline, the effects of which were not temperature dependant. These results: 1) show that maximum performance of the isolated cod heart is not compromised by exposure to cold temperatures; and 2) support data from other studies which show that, in contrast to salmonids, cod cardiac performance/myocardial contractility is not dependent upon humoral adrenergic stimulation.
Comparative intralimb coordination in avian bipedal locomotion
Authors: Stößel Alexander , Fischer Martin S. 
Published: August 2012

SummaryAnalyses of how intralimb coordination during locomotion varies within and across different taxa are necessary for understanding the morphological and neurological basis for locomotion in general. Previous findings suggest that intralimb proportions are the major source of kinematic variation that governs intralimb coordination across taxa. Also, independence of kinematics from habitat preference and phylogenetic position has been suggested for mammals. This leads to the hypothesis that among equally-sized bird species exhibiting equal limb proportions similar kinematics can be observed. To test this hypothesis, the bipedal locomotion of two distantly related ground-dwelling bird species (Eudromia elegans and Coturnix coturnix) and of a less terrestrial species (Corvus monedula) was investigated by means of a biplanar high-speed x-ray videographic analysis. Birds were exhibiting similar intralimb proportions and were filmed over a broad range of speed while moving on a treadmill. Joint- and limb element angles, as well as pelvic rotations, were quantified. Regarding fore-aft motions of the limb joints and elements, a congruent pattern of intralimb coordination was observed among all experimental species. The sample of species suggests that it is largely independent of their habitat preference and systematic position and it seems to be related to demands for coping with an irregular terrain with a minimum of necessary control. Hence, the initial hypothesis was confirmed. However, this congruence is not found when looking at medio-lateral limb motions and pelvic rotations, showing distinct differences between ground-dwellers (e.g., largely restricted to a parasagittal plane) and Corvus (e.g., an increased mobility of the hip joint).
Nocturnal light environments and species ecology: implications for nocturnal color vision in forests
Authors: Veilleux Carrie C , Cummings Molly E 
Published: August 2012

Summary
While variation in the color of light in terrestrial diurnal and twilight environments has been well documented, relatively little work has examined the color of light in nocturnal habitats. Understanding the range and sources of variation in nocturnal light environments has important implications for nocturnal vision, particularly following recent discoveries of nocturnal color vision. In this study, we measured nocturnal irradiance in a dry forest/woodland and a rainforest in Madagascar over 34 nights. We found that a simple linear model including additive effects of lunar altitude, lunar phase and canopy openness successfully predicted total irradiance flux measurements across 242 clear sky measurements (r=0.85; p&lt;0.0001). However, the relationship between these variables and spectral irradiance was more complex, as interactions between lunar altitude, lunar phase and canopy openness were also important predictors of spectral variation. Further, in contrast to diurnal conditions, nocturnal forests and woodlands share a yellow-green-dominant light environment with peak flux at 560 nm. To explore how nocturnal light environments influence nocturnal vision, we compared photoreceptor spectral tuning, habitat preference and diet in 32 nocturnal mammals. In many species, long-wavelength-sensitive cone spectral sensitivity matched the peak flux present in nocturnal forests and woodlands, suggesting a possible adaptation to maximize photon absorption at night. Further, controlling for phylogeny, we found that fruit/flower consumption significantly predicted short-wavelength-sensitive cone spectral tuning in nocturnal mammals (p=0.002). These results suggest that variation in nocturnal light environments and species ecology together influence cone spectral tuning and color vision in nocturnal mammals.