bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental constraints defining the distribution, composition, and evolution of chlorophototrophs in thermal features of Yellowstone National Park
Authors: HAMILTON T. L. , VOGL K. , BRYANT D. A. , BOYD E. S. , PETERS J. W. 
Published: September 2011

AbstractChlorophotoautotrophy, the use of chlorophylls to convert light energy into chemical energy for carbon dioxide fixation, is the primary metabolic process linking the inorganic and organic carbon pools on Earth. To understand the potential effects of various environmental constraints on the evolution of chlorophototrophy better, we studied the distribution, diversity, and abundance of chlorophylls and genes involved in their synthesis along geothermal gradients in Yellowstone National Park, Wyoming. Genes involved in chlorophyll biosynthesis were constrained to temperatures of less than ∼70 °C and were only detected at this elevated temperature when the pH was in the circumneutral to alkaline range. The upper temperature limit for the detection of chlL/bchL1 and bchY2 decreased systematically with increasingly acidic pH, an observation likely attributable to sulfide, which upon oxidation, generates acidic spring water and reduces the availability of bicarbonate the preferred source of inorganic carbon for phototrophs. Spring pH was also the best predictor of the phylogenetic diversity of chlL/bchL communities. The phylogenetic similarity of chlL/bchL genes between sites was significantly correlated with that of chlorophylls. The predominance of chlorophyll a and bacteriochlorophyll a among extracted pigments was consistent with predominance of chlL/bchL genes affiliated with the Cyanobacteria and Chloroflexiales, respectively, and might be related to the fact that the majority of these organisms are photoautotrophs. Together, these results suggest that a combination of temperature, pH, and/or sulfide influences the distribution, diversity, and evolution of chlorophotrophs and the chlorophylls that they synthesize.
The incidence of plateau at 2max is affected by a bout of prior‐priming exercise
Authors: Gordon Dan , Schaitel Kari , Pennefather Amy , Gernigon Marie , Keiller Don , Barnes Richard 
Published: September 2011

SummaryThe purpose of this study was to determine the effect of 6 min of prior‐priming exercise on the incidence of plateau at 2max. Twelve trained cyclists (age, 21 ± 3 years; height, 175·0 ± 8·0 cm; weight, 69·0 ± 10·4 kg; maximal oxygen uptake (2max), 56·3 ± 6·9 ml kg−1 min−1) completed three incremental tests to volitional exhaustion, which were classified as unprimed (UP), heavy‐primed (HP) and severe‐primed (SP), at a work rate of 1 W 2 s−1, from an initial workload of 100 W, for the determination of 2max. 2max trial in the HP and SP conditions was preceded by a period of 4‐min unloaded cycling followed by a further 6 min of constant load cycling at Δ50%2 gas exchange threshold (GET)‐ 2max (HP) and Δ75%2 GET‐2max (SP). Expired air was recorded on a breath‐by‐breath basis during all trials. The criteria adopted for a plateau in2max was a Δ2 over the final two consecutive 30‐s sampling periods ≤2·1 ml kg−1 min−1. There was a significant increase in plateau responses between the UP (50%) and HP (100%) conditions (P = 0·001) coupled with a significant change in the slope of the regression line during the final 60 s of the 2max test, UP and HP (P = 0·0299) and UP and SP (P = 0·0296). These data suggest that a bout of prior‐priming exercise promotes an increased incidence of plateau responses at VO2max. It is suggested that future studies address how such an approach can be adopted without prior knowledge of GET.
The effects of spherical aberration on static accommodative responses in emmetropes and myopes
Authors: Wu Ying , Jiang Bai‐Chuan 
Published: September 2011

Citation information: Wu Y & Jiang B‐C. The effects of spherical aberration on static accommodative responses in emmetropes and myopes. Ophthalmic Physiol Opt 2011, 31, 595–602. doi: 10.1111/j.1475‐1313.2011.00870.xAbstractPurpose:  To compare the effects of spherical aberration (SA) on accommodative responses between emmetropes (EMs), stable myopes (SMs), and progressing myopes (PMs).Methods:  The accommodative responses (AR) induced by negative lenses from 0 to −5 D in 1 D steps were measured with a Complete Ophthalmic Analysis System (COAS) for 10 emmetropes (EMs), 13 stable myopes (SMs), and 9 progressing myopes (PMs). Three types of AR were calculated from wavefront aberration data based on ocular foci within a paraxial area, natural pupil area, and a 3.5 mm‐diameter annular pupil area. The accommodative stimulus response curves (ASRCs) were compared between the three groups and between the three AR conditions.Results:  The difference in the slope of ASRC was significant between the three AR conditions (p < 0.0001) but it was not significant between the three refractive groups. In each group, the slope of ASRC for the accommodative response measured within the paraxial area of the pupil (paraxial AR) was significantly steeper than that measured for the natural pupil (total AR) and also for that estimated for the 3.5 mm‐diameter annular pupil (p < 0.01). The difference in the y‐intercept of ASRC between the three AR conditions was also significant (p = 0.02) but not between the three refractive groups. The y‐intercept of ASRC for paraxial AR was more positive than that for total AR in SMs (p < 0.01) and in PMs (p < 0.05); the y‐intercept of ASRC for the 3.5 mm peripheral AR was more positive than that for total AR in SMs (p < 0.05).Conclusions:  The spherical aberration of the eye has a significant effect on the slope of ASRC and is less in PMs than in EMs and SMs.
Does Decreased Access to Emergency Departments Affect Patient Outcomes? Analysis of Acute Myocardial Infarction Population 1996–2005
Authors: Shen Yu‐Chu , Hsia Renee Y. 
Published: September 2011

ObjectiveWe analyze whether decreased emergency department (ED) access results in adverse patient outcomes or changes in the patient health profile for patients with acute myocardial infarction (AMI).DataWe merge Medicare claims, American Hospital Association annual surveys, Medicare hospital cost reports, and location information for 1995–2005.Study DesignWe define four ED access change categories and estimate a ZIP Code fixed‐effects regression models on the following AMI outcomes: mortality rates, age, and probability of percutaneous transluminal coronary angioplasty (PTCA) on day of admission.Principal FindingsWe find a small increase in 30‐day to 1‐year mortality rates among patients in communities that experience a <10‐minute increase in driving time. Among patients in communities with >30‐minute increases, we find a substantial increase in long‐term mortality rates, a shift to younger ages (suggesting that older patients die en route), and a higher probability of immediate PTCA. Most of the adverse effects disappear after the transition years.ConclusionsDeterioration in geographic access to ED affects a small segment of the population, and most adverse effects are transitory. Policy planners can minimize the adverse effects by providing assistance to ensure adequate capacity of remaining EDs, and facilitating the realignment of health care resources during the critical transition periods.
A Comparison of Health Care Use for Physician‐Referred and Self‐Referred Episodes of Outpatient Physical Therapy
Authors: Pendergast Jane , Kliethermes Stephanie A. , Freburger Janet K. , Duffy Pamela A. 
Published: September 2011

ObjectiveTo compare patient profiles and health care use for physician‐referred and self‐referred episodes of outpatient physical therapy (PT).Data SourceFive years (2003–2007) of private health insurance claims data, from a Midwest insurer, on beneficiaries aged 18–64.Study DesignRetrospective analyses of health care use of physician‐referred (N = 45,210) and self‐referred (N = 17,497) ambulatory PT episodes of care was conducted, adjusting for age, gender, diagnosis, case mix, and year.Data Collection/ExtractionPhysical therapy episodes began with the physical therapist initial evaluation and ended on the last date of service before 60 days of no further visits. Episodes were classified as physician‐referred if the patient had a physician claim from a reasonable referral source in the 30 days before the start of PT.Principal FindingsThe self‐referred group was slightly younger, but the two groups were very similar in regard to diagnosis and case mix. Self‐referred episodes had fewer PT visits (86 percent of physician‐referred) and lower allowable amounts ($0.87 for every $1.00), after covariate adjustment, but did not differ in related health care utilization after PT.ConclusionsHealth care use during PT episodes was lower for those who self‐referred, after adjusting for key variables, but did not differ after the PT episode.
The Health Care Cost Implications of Overweight and Obesity during Childhood
Authors: Au Nicole 
Published: September 2011

ObjectiveTo investigate whether childhood overweight at age 4–5 increases publicly funded health care costs during childhood, and to explore the role of timing and duration of overweight on health costs.Data SourcesThe Longitudinal Study of Australian Children (2004–2008) and linked records from Medicare, Australia's public health insurance provider (2004–2009).Study DesignThe influence of overweight status on non‐hospital Medicare costs incurred by children over a 5‐year period was estimated using two‐part models and one‐part generalized linear models (GLM). All models controlled for demographic, socioeconomic, and parental characteristics.Principal FindingsBeing overweight at age 4–5 is associated with significantly higher pharmaceutical and medical care costs. The results imply that for all children aged 4 and 5 in 2004–2005, those who were overweight had a combined 5‐year Medicare bill that was AUD$9.8 million higher than that of normal weight children. Results from dynamic analyses show that costs of childhood overweight occur contemporaneously, and the duration of overweight is positively associated with medical costs for children who became overweight after age 5.ConclusionsThis study reveals that the financial burden to the public health system of childhood overweight and obesity occurs even during the first 5 years of primary school.
Ursolic acid induces apoptosis in human leukaemia cells and exhibits anti‐leukaemic activity in nude mice through the PKB pathway
Authors: Gao Ning , Cheng Senping , Budhraja Amit , Gao Ziyi , Chen Jieping , Liu E‐Hu , Huang Cheng , Chen Deying , Yang Zailin , Liu Qun , Li Ping , Shi Xianglin , Zhang Zhuo 
Published: September 2011

BACKGROUND AND PURPOSE Ursolic acid (UA) has been extensively used as an anti‐leukaemic agent in traditional Chinese medicine. In the present study, we investigated the ability of UA to induce apoptosis in human leukaemia cells in relation to its effects on caspase activation, Mcl‐1 down‐regulation and perturbations in stress‐induced signalling pathways such as PKB and JNK.EXPERIMENTAL APPROACH Leukaemia cells were treated with UA after which apoptosis, caspase activation, PKB and JNK signalling pathways were evaluated. The anti‐tumour activity of UA was evaluated using xenograft mouse model.KEY RESULTS UA induced apoptosis in human leukaemia cells in a dose‐ and time‐dependent manner; this was associated with caspase activation, down‐regulation of Mcl‐1 and inactivation of PKB accompanied by activation of JNK. Enforced activation of PKB by a constitutively active PKB construct prevented UA‐mediated JNK activation, Mcl‐1 down‐regulation, caspase activation and apoptosis. Conversely, UA lethality was potentiated by the PI3‐kinase inhibitor LY294002. Interruption of the JNK pathway by pharmacological or genetic (e.g. siRNA) attenuated UA‐induced apoptosis. Furthermore, UA‐mediated inhibition of tumour growth in vivo was associated with induction of apoptosis, inactivation of PKB as well as activation of JNK.CONCLUSIONS AND IMPLICATIONS Collectively, these findings suggest a hierarchical model of UA‐induced apoptosis in human leukaemia cells in which UA induces PKB inactivation, leading to JNK activation and culminating in Mcl‐1 down‐regulation, caspase activation and apoptosis. These findings indicate that interruption of PKB/JNK pathways may represent a novel therapeutic strategy in haematological malignancies.
The structure and function of the glucagon‐like peptide‐1 receptor and its ligands
Authors: Donnelly Dan 
Published: September 2011

Glucagon‐like peptide‐1(7‐36)amide (GLP‐1) is a 30‐residue peptide hormone released from intestinal L cells following nutrient consumption. It potentiates the glucose‐induced secretion of insulin from pancreatic beta cells, increases insulin expression, inhibits beta‐cell apoptosis, promotes beta‐cell neogenesis, reduces glucagon secretion, delays gastric emptying, promotes satiety and increases peripheral glucose disposal. These multiple effects have generated a great deal of interest in the discovery of long‐lasting agonists of the GLP‐1 receptor (GLP‐1R) in order to treat type 2 diabetes. This review article summarizes the literature regarding the discovery of GLP‐1 and its physiological functions. The structure, function and sequence–activity relationships of the hormone and its natural analogue exendin‐4 (Ex4) are reviewed in detail. The current knowledge of the structure of GLP‐1R, a Family B GPCR, is summarized and discussed, before its known interactions with the principle peptide ligands are described and summarized. Finally, progress in discovering non‐peptide ligands of GLP‐1R is reviewed. GLP‐1 is clearly an important hormone linking nutrient consumption with blood sugar control, and therefore knowledge of its structure, function and mechanism of action is of great importance.LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein‐Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐1
L‐Tryptophan ethyl ester dilates small mesenteric arteries by inhibition of voltage‐operated calcium channels in smooth muscle
Authors: Jadhav Ashok , Liang Wenbin , Balsevich John , Bastin Guillaume , Kroetsch Jeff , Heximer Scott , Backx Peter H , Gopalakrishnan Venkat 
Published: September 2011

BACKGROUND AND PURPOSE L‐tryptophan (L‐W) is a precursor of the vasoconstrictor, 5‐HT. However, acute administration of L‐W ethyl ester (L‐Wee) lowered blood pressure. The mechanism of action is unknown. This study compares the vascular effects of L‐W and L‐Wee in intact animals, isolated aortic rings, small mesenteric arteries (MA) and explores possible mechanisms by studies in vascular smooth muscle cells (VSMC) of MA.EXPERIMENTAL APPROACH Effects of L‐W or L‐Wee (5–50 mg kg−1, i.v.) on mean arterial pressure (MAP) and heart rate (HR) were determined in male Sprague‐Dawley rats. The effects of L‐W and L‐Wee on basal tone and of phenylephrine‐ or KCl‐induced contractions of aortic and MA rings were assessed. Effects of L‐Wee and L‐W on voltage‐operated calcium channels (VOCC) of VSMC of MA were also examined in patch‐clamp studies.KEY RESULTS Administration of L‐Wee, but not L‐W, evoked a rapid and transient dose‐dependent decrease in MAP and HR. While both agents failed to affect basal tone, L‐Wee decreased, concentration‐dependently, (Imax > 98%) tension responses to phenylephrine and KCl in an endothelium‐independent manner in aorta (IC50 2 mM) and MA (IC50 17 µM). L‐Wee evoked concentration‐dependent inhibition of VOCC currents (IC50 12 µM; Imax 90%) in VSMC of MA.CONCLUSIONS AND IMPLICATIONS Esterified L‐W (L‐Wee), but not L‐W, preferentially relaxed resistance vessels rather than conduit vessels. These effects were associated with blockade of VOCC by L‐Wee. Our findings suggest that the falls in MAP and HR induced by L‐Wee were due to blockade of VOCC by L‐Wee.
Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cruciferous vegetables (Brassicaceae): evidence for TRPA1‐independent effects
Authors: Capasso Raffaele , Aviello Gabriella , Romano Barbara , Borrelli Francesca , De Petrocellis Luciano , Di Marzo Vincenzo , Izzo Angelo A 
Published: September 2011

BACKGROUND AND PURPOSE Allyl isothiocyanate (AITC, mustard oil), a constituent of many common cruciferous vegetables (Brassicaceae), activates transient receptor potential of ankyrin type‐1 (TRPA1) channels, claimed to regulate gastrointestinal contractility. In this study, we have investigated the effect of AITC on intestinal motility.EXPERIMENTAL APPROACH Effects of AITC were investigated in vivo on upper gastrointestinal transit in mice and in mouse isolated ileum [contractions induced by electrical field stimulation (EFS), acetylcholine and spontaneous contractility]. The contractor activity of AITC was studied in mouse isolated colon. The ability of TRPA1 channel antagonists to block AITC‐induced elevation of intracellular Ca2+[Ca2+]i was assessed in HEK293 cells transfected with rat TRPA1 channels.KEY RESULTS AITC increased [Ca2+]i in HEK293 cells, reduced ileal contractility (acetylcholine‐, EFS‐induced contractions and spontaneous contractility), but contracted the isolated colon. Gentamicin and camphor (non‐selective TRPA1 channel antagonists), HC‐030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC‐induced effects in HEK293 cells but not in the ileum or colon. AITC‐induced contractions were reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased (following intragastric administration) upper gastrointestinal transit in mice These effects were not affected by HC‐030031.CONCLUSION AND IMPLICATIONS AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised.
Hydrogen sulphide‐releasing diclofenac derivatives inhibit breast cancer‐induced osteoclastogenesis in vitro and prevent osteolysis ex vivo
Authors: Frantzias J , Logan JG , Mollat P , Sparatore A , Del Soldato P , Ralston SH , Idris AI 
Published: September 2011

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non‐steroidal anti‐inflammatory drugs (NSAIDs) and H2S donors exhibit anti‐inflammatory and anti‐tumour properties. H2S‐releasing diclofenac (S‐DCF) derivatives are a novel class of NSAIDs combining the properties of a H2S donor with those of a conventional NSAID.EXPERIMENTAL APPROACH We studied the effects of the S‐DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo.KEY RESULTS The S‐diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA‐MB‐231 and MCF‐7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA‐MB‐231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand‐induced osteoclast formation and resorption, and caused caspase‐3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA‐MB‐231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32.CONCLUSIONS AND IMPLICATIONS S‐diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H2S‐releasing diclofenac derivatives exhibit anti‐resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease.
Friendship and religion in the Republic of Letters; the return of Justus Lipsius to Catholicism (1591)
Authors: MACHIELSEN JAN 
Published: September 2011

jan machielsen, Friendship and religion in the Republic of Letters; The return of Justus Lipsius to Catholicism (1591)The return of the Flemish humanist Justus Lipsius (1547–1606) to the Spanish Netherlands and his reconciliation with Catholicism (1591) have defined his image for posterity. Debates about the sincerity of Lipsius' religious beliefs have continued to the present day. Scholars have presented Lipsius' departure from Leiden as the result of external pressure, as effortless, and conducted in secret. By contrast, this article shows that Lipsius' public engagement in the Republic of Letters was instrumental in enabling his reconciliation with Catholicism. Lipsius employed both published and private letters and the rhetoric of friendship to win support for his return to the Southern Netherlands. After his arrival, Lipsius' correspondence and friendship with the Flemish‐Spanish Jesuit Martin Delrio (1551–1608) served as a public platform on which the humanist acted out his reconciliation. The article concludes with a discussion as to why Lipsius only published a fraction of his letters to Delrio.
A possible involvement of p62/sequestosome‐1 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis
Authors: Sasaki Motoko , Miyakoshi Masami , Sato Yasunori , Nakanuma Yasuni 
Published: September 2011

AbstractBackground and AimsGiven autophagy is involved in the pathogenesis in primary biliary cirrhosis (PBC), we examined an involvement of p62 sequestosome‐1 (p62), a specific cargo for autophagy, in the process of autophagy and cellular senescence in PBC.MethodsWe examined immunohistochemically the expression of p62 in livers taken from patients with PBC (n = 46) and control livers (n = 78) and its colocalization with microtubule‐associated proteins‐light chain 3β (LC3), lysosome‐associated membrane protein‐1 (LAMP‐1) and senescent markers (p16INK4a and p21WAF1/Cip1). We examined the expression of p62 and LC3 in cultured biliary epithelial cells (BECs) treated with various stress. The effect of p62 knockdown with siRNA on stress‐induced autophagy and cellular senescence was also assessed.ResultsThe expression of p62 was specifically seen in cytoplasmic aggregates in BECs in the inflamed and damaged small bile ducts (SBDs) in PBC, when compared with non‐inflamed ones in PBC and in control livers (P < 0.01). The co‐expression of p62 with LC3, LAMP‐1 and senescent markers was seen in the inflamed SBDs in PBC, but the intracytoplasmic localization was different. The expression of p62 and LC3 was significantly upregulated in BECs treated with various stress (P < 0.01) and pretreatment with bafilomycin A1 enhanced the accumulation of p62‐positive aggregates in BECs with serum deprivation. The knockdown of p62 decreased stress‐induced autophagy and cellular senescence.ConclusionThe aggregation of p62 is specifically increased in the damage bile ducts in PBC and may reflect dysfunctional autophagy, followed by cellular senescence in the pathogenesis of bile duct lesions in PBC.