bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function
Authors: Marwick John A , Stevenson Christopher S , Chung Kian Fan , Adcock Ian M , Kirkham Paul A 
Published: July 2010

AbstractBackgroundThe key co-repressor complex components HDAC-2, Mi-2α/β and mSin3a are all critical to the regulation of gene transcription. HDAC-2 function is impaired by oxidative stress in a PI3Kδ dependant manner which may be involved in the chronic glucocorticoid insensitive inflammation in the lungs of COPD patients. However, the impact of cigarette smoke exposure on the expression of mSin3a and Mi2α/β and their role in glucocorticoid responsiveness is unknown.MethodsWild type, PI3Kγ knock-out (PI3Kγ-/-) and PI3K kinase dead knock-in (PI3KδD910/A910) transgenic mice were exposed to cigarette smoke for 3 days and the expression levels of the co-repressor complex components HDAC-2, mSin3a, Mi-2α and Mi-2β and HDAC-2 activity in the lungs were assessed.ResultsCigarette smoke exposure impaired glucocorticoid function and reduced HDAC-2 activity which was protected in the PI3KδD910/A910mice. Both mSin3a and Mi-2α protein expression was reduced in smoke-exposed mice. Budesonide alone protected mSin3a protein expression with no additional effect seen with abrogation of PI3Kγ/δ activity, however Mi-2α, but not Mi-2β, expression was protected in both PI3KδD910/A910and PI3Kγ-/-budesonide-treated smoke-exposed mice. The restoration of glucocorticoid function coincided with the protection of both HDAC activity and mSin3a and Mi-2α protein expression.ConclusionsCigarette smoke exposure induced glucocorticoid insensitivity and alters co-repressor activity and expression which is prevented by blockade of PI3K signaling with glucocorticoid treatment. Inhibition of PI3Kδ signalling in combination with glucocorticoid treatment may therefore provide a therapeutic strategy for restoring oxidant-induced glucocortiocid unresponsiveness.
Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response
Authors: Killedar Smruti , DiRosario Julianne , Divers Erin , Popovich Phillip G , McCarty Douglas M , Fu Haiyan 
Published: July 2010

AbstractBackgroundRecently, using a mouse model of mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological deterioration, we showed that MPS IIIB neuropathology is accompanied by a robust neuroinflammatory response of unknown consequence. This study was to assess whether MPS IIIB lymphocytes are pathogenic.MethodsLymphocytes from MPS IIIB mice were adoptively transferred to naïve wild-type mice. The recipient animals were then evaluated for signs of disease and inflammation in the central nervous system.ResultsOur results show for the first time, that lymphocytes isolated from MPS IIIB mice caused a mild paralytic disease when they were injected systemically into naïve wild-type mice. This disease is characterized by mild tail and lower trunk weakness with delayed weight gain. The MPS IIIB lymphocytes also trigger neuroinflammation within the CNS of recipient mice characterized by an increase in transcripts of IL2, IL4, IL5, IL17, TNFα, IFNα and Ifi30, and intraparenchymal lymphocyte infiltration.ConclusionsOur data suggest that an autoimmune response directed at CNS components contributes to MPS IIIB neuropathology independent of lysosomal storage pathology. Adoptive transfer of purified T-cells will be needed in future studies to identify specific effector T-cells in MPS IIIB neuroimmune pathogenesis.
Ultrasound guided injection of dexamethasone versus placebo for treatment of plantar fasciitis: protocol for a randomised controlled trial
Authors: McMillan Andrew M , Landorf Karl B , Gilheany Mark F , Bird Adam R , Morrow Adam D , Menz Hylton B 
Published: July 2010

AbstractBackgroundPlantar fasciitis is the most commonly reported cause of chronic pain beneath the heel. Management of this condition commonly involves the use of corticosteroid injection in cases where less invasive treatments have failed. However, despite widespread use, only two randomised trials have tested the effect of this treatment in comparison to placebo. These trials currently offer the best available evidence by which to guide clinical practice, though both were limited by methodological issues such as insufficient statistical power. Therefore, the aim of this randomised trial is to compare the effect of ultrasound‐guided corticosteroid injection versus placebo for treatment of plantar fasciitis.MethodsThe trial will be conducted at the La Trobe University Podiatry Clinic and will recruit 80 community‐dwelling participants. Diagnostic ultrasound will be used to diagnose plantar fasciitis and participants will be required to meet a range of selection criteria. Participants will be randomly allocated to one of two treatment arms: (i) ultrasound‐guided injection of the plantar fascia with 1 mL of 4 mg/mL dexamethasone sodium phosphate (experimental group), or (ii) ultrasound‐guided injection of the plantar fascia with 1 mL normal saline (control group). Blinding will be applied to participants and the investigator performing procedures, measuring outcomes and analysing data. Primary outcomes will be pain measured by the Foot Health Status Questionnaire and plantar fascia thickness measured by ultrasound at 4, 8 and 12 weeks. All data analyses will be conducted on an intention‐to‐treat basis.ConclusionThis will be a randomised trial investigating the effect of dexamethasone injection on pre‐specified treatment outcomes in people with plantar fasciitis. Within the parameters of this protocol, the trial findings will be used to make evidence‐based recommendations regarding the use of corticosteroid injection for treatment of this condition.Trial RegistrationAustralian New Zealand Clinical Trials Registry. ACTRN12610000239066.
Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes
Authors: Quintin Emilie , Scoazec Jean-Yves , Marotte Hubert , Miossec Pierre 
Published: July 2010

Abstract
Introduction
The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods
A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results
Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions
MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.
Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families
Authors: Arason Adalgeir , Gunnarsson Haukur , Johannesdottir Gudrun , Jonasson Kristjan , Bendahl Pär-Ola , Gillanders Elizabeth M , Agnarsson Bjarni A , Jönsson Göran , Pylkäs Katri , Mustonen Aki , Heikkinen Tuomas , Aittomäki Kristiina , Blomqvist Carl , Melin Beatrice , Johannsson Oskar TH , Møller Pål , Winqvist Robert , Nevanlinna Heli , Borg Åke , Barkardottir Rosa B 
Published: July 2010

Abstract
Introduction:
A significant proportion of high-risk breast cancer families are not explained by mutations in known genes. Recent genome-wide searches (GWS) have not revealed any single major locus reminiscent of BRCA1 and BRCA2, indicating that still unidentified genes may explain relatively few families each or interact in a way obscure to linkage analyses. This has drawn attention to possible benefits of studying populations where genetic heterogeneity might be reduced. We thus performed a GWS for linkage on nine Icelandic multiple-case non-BRCA1/2 families of desirable size for mapping highly penetrant loci. To follow up suggestive loci, an additional 13 families from other Nordic countries were genotyped for selected markers.

Methods:
GWS was performed using 811 microsatellite markers providing about five centiMorgan (cM) resolution. Multipoint logarithm of odds (LOD) scores were calculated using parametric and nonparametric methods. For selected markers and cases, tumour tissue was compared to normal tissue to look for allelic loss indicative of a tumour suppressor gene.

Results:
The three highest signals were located at chromosomes 6q, 2p and 14q. One family contributed suggestive LOD scores (LOD 2.63 to 3.03, dominant model) at all these regions, without consistent evidence of a tumour suppressor gene. Haplotypes in nine affected family members mapped the loci to 2p23.2 to p21, 6q14.2 to q23.2 and 14q21.3 to q24.3. No evidence of a highly penetrant locus was found among the remaining families. The heterogeneity LOD (HLOD) at the 6q, 2p and 14q loci in all families was 3.27, 1.66 and 1.24, respectively. The subset of 13 Nordic families showed supportive HLODs at chromosome 6q (ranging from 0.34 to 1.37 by country subset). The 2p and 14q loci overlap with regions indicated by large families in previous GWS studies of breast cancer.

Conclusions:
Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.
Human CD34+ cells mobilized by granulocyte colony-stimulating factor ameliorate radiation-induced liver damage in mice
Authors: Li Ning , Zhang Li , Li Huixiang , Fang Baijun 
Published: July 2010

Abstract
Introduction
On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34+ HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation.

Methods
G-CSF-mobilized CD34+ HSCs (1 × 105 cells per mouse) were injected via tail vein in the irradiated femal nonobese diabetic/severe combined immunodeficient mice. Irradiated control animals received only saline infusion.

Results
The mobilized CD34+ HSCs significantly ameliorated radiation-induced liver damage. In the liver of recipient mice killed 21 days after irradiation, human albumin+ Y-chromosome+ hepatocyte-like cells, or human cytokeratin+ Y-chromosome+ hepatocyte-like cells formed cords of hepatocytes, occupied ~30% of the 4-μm section surrounding portal tracts. Furthermore, human-specific albumin mRNA expressed in the liver and human albumin was detected in the serum only in the CD34+ HSC-treated mice.

Conclusions
Treatment with G-CSF-mobilized CD34+ HSCs from bone marrow into peripheral blood could significantly promote tissue reparation after acute liver injury by radiation in mice, possibly by the ability of CD34+ HSCs to generate hepatocytes. So mobilization of CD34+ HSCs might offer a novel therapeutic approach for the treatment of radiation-induced complications after radiotherapy or other acute liver diseases in humans.
Acid–base responses to feeding and intestinal Cl– uptake in freshwater- and seawater-acclimated killifish,Fundulus heteroclitus, an agastric euryhaline teleost
Authors: Wood Chris M. , Bucking Carol , Grosell Martin 
Published: July 2010

SUMMARYMarine teleosts generally secrete basic equivalents (HCO3–) and take up Na+ and Cl– in the intestine so as to promote absorption of H2O. However, neither the integration of these functions with feeding nor the potential role of the gut in ionoregulation and acid–base balance in freshwater have been well studied. The euryhaline killifish (Fundulus heteroclitus) is unusual in lacking both an acid-secreting stomach and a mechanism for Cl– uptake at the gills in freshwater. Responses to a satiation meal were evaluated in both freshwater- and seawater-acclimated killifish. In intact animals, there was no change in acid or base flux to the external water after the meal, in accord with the absence of any post-prandial alkaline tide in the blood. Indeed, freshwater animals exhibited a post-prandial metabolic acidosis (‘acidic tide’), whereas seawater animals showed no change in blood acid–base status. In vitro gut sac experiments revealed a substantially higher rate of Cl– absorption by the intestine in freshwater killifish, which was greatest at 1–3 h after feeding. The Cl– concentration of the absorbate was higher in preparations from freshwater animals than from seawater killifish and increased with fasting. Surprisingly, net basic equivalent secretion rates were also much higher in preparations from freshwater animals, in accord with the ‘acidic tide’; in seawater preparations, they were lowest after feeding and increased with fasting. Bafilomycin (1 μmol l–1) promoted an 80% increase in net base secretion rates, as well as in Cl– and fluid absorption, at 1–3 h post-feeding in seawater preparations only, explaining the difference between freshwater and seawater fish. Preparations from seawater animals at 1–3 h post-feeding also acidified the mucosal saline, and this effect was associated with a marked rise in PCO2, which was attenuated by bafilomycin. Measurements of chyme pH from intact animals confirmed that intestinal fluid (chyme) pH and basic equivalent concentration were lowest after feeding in seawater killifish, whereas PCO2 was greatly elevated (80–95 Torr) in chyme from both seawater and freshwater animals but declined to lower levels (13 Torr) after 1–2 weeks fasting. There were no differences in pH, PCO2 or the concentrations of basic equivalents in intestinal fluid from seawater versus freshwater animals at 12–24 h or 1–2 weeks post-feeding. The results are interpreted in terms of the absence of gastric HCl secretion, the limitations of the gills for acid–base balance and Cl– transport, and therefore the need for intestinal Cl– uptake in freshwater killifish, and the potential for O2 release from the mucosal blood flow by the high PCO2 in the intestinal fluids. At least in seawater killifish, H+-ATPase running in parallel to HCO3–:Cl– exchange in the apical membranes of teleost enterocytes might reduce net base secretion and explain the high PCO2 in the chyme after feeding.
Serotonin and its metabolism in basal deuterostomes: insights fromStrongylocentrotus purpuratusandXenoturbella bocki
Authors: Squires Leah N. , Rubakhin Stanislav S. , Wadhams Andinet Amare , Talbot Kristen N. , Nakano Hiroaki , Moroz Leonid L. , Sweedler Jonathan V. 
Published: July 2010

SUMMARYSerotonin (5-HT), an important molecule in metazoans, is involved in a range of biological processes including neurotransmission and neuromodulation. Both its creation and release are tightly regulated, as is its removal. Multiple neurochemical pathways are responsible for the catabolism of 5-HT and are phyla specific; therefore, by elucidating these catabolic pathways we glean greater understanding of the relationships and origins of various transmitter systems. Here, 5-HT catabolic pathways were studied in Strongylocentrotus purpuratus and Xenoturbella bocki, two organisms occupying distinct positions in deuterostomes. The 5-HT-related compounds detected in these organisms were compared with those reported in other phyla. In S. purpuratus, 5-HT-related metabolites include N-acetyl serotonin, γ-glutamyl-serotonin and 5-hydroxyindole acetic acid; the quantity and type were found to vary based on the specific tissues analyzed. In addition to these compounds, varying levels of tryptamine were also seen. Upon addition of a 5-HT precursor and a monoamine oxidase inhibitor, 5-HT itself was detected. In similar experiments using X. bocki tissues, the 5-HT-related compounds found included 5-HT sulfate, γ-glutamyl-serotonin and 5-hydroxyindole acetic acid, as well as 5-HT and tryptamine. The sea urchin metabolizes 5-HT in a manner similar to both gastropod mollusks, as evidenced by the detection of γ-glutamyl-serotonin, and vertebrates, as indicated by the presence of 5-hydroxyindole acetic acid and N-acetyl serotonin. In contrast, 5-HT metabolism in X. bocki appears more similar to common protostome 5-HT catabolic pathways.
Balance responses to lateral perturbations in human treadmill walking
Authors: Hof A. L. , Vermerris S. M. , Gjaltema W. A. 
Published: July 2010

SUMMARY
During walking on a treadmill 10 human subjects (mean age 20 years) were perturbed by 100 ms pushes or pulls to the left or the right, of various magnitudes and in various phases of the gait cycle. Balance was maintained by (1) a stepping strategy (synergy), in which the foot at the next step is positioned a fixed distance outward of the ‘extrapolated centre of mass’, and (2) a lateral ankle strategy, which comprises a medial or lateral movement of the centre of pressure under the foot sole. The extrapolated centre of mass is defined as the centre of mass position plus the centre of mass velocity multiplied by a parameter related to the subject's leg length. The ankle strategy is the fastest, with a mechanical delay of about 200 ms (20% of a stride), but it can displace the centre of pressure no more than 2 cm. The stepping strategy needs at least 300 ms (30% of a stride) before foot placement, but has a range of 20 cm. When reaction time is sufficient, the magnitude of the total response is in good agreement with our hypothesis: mean centre of pressure (foot) position is a constant distance outward of the extrapolated centre of mass. If the reaction time falls short, a further correction is applied in the next step. In the healthy subjects studied here, no further corrections were necessary, so balance was recovered within two steps (one stride).
Predation or scavenging? Thoracic muscle pH and rates of water loss reveal cause of death in arthropods
Authors: Wilson Erin E. , Young Christine V. , Holway David A. 
Published: July 2010

SUMMARY
The difficulty of directly observing predatory events hinders a complete understanding of how predation structures food webs. Indirect approaches such as PCR-based and isotopic analyses clarify patterns of resource consumption but fail to distinguish predation from scavenging. Given that facultative scavenging is a ubiquitous and phylogenetically widespread foraging strategy, an improved ability to discriminate prey from carrion is needed to enhance an understanding of the demographic effects of consumption and the true nature of trophic interactions. Using physiological properties of muscle tissue – specifically pH and rate of water loss – we develop a novel method to discriminate prey from carrion collected by scavenging hymenopteran predators. Our focal system is the western yellowjacket (Vespula pensylvanica), a common scavenging predator in Hawaii and western North America. Prior to consumption, the physical properties of hymenopteran muscle tissue change in a quantifiable and deterministic manner post mortem and can be used to estimate the time and putative cause of death of diet items. Applying this method in laboratory and field situations resulted in the correct identification of prey and carrion in 49 out of 56 cases (88%). Although further investigation is needed to determine how post-mortem physiology of diet items changes in the guts of consumers, the approaches developed in this study can be used to distinguish predation from scavenging by central-place foragers (particularly arthropods). Such information will provide a more definitive characterization of species interactions and food webs.
Fruit bats (Pteropodidae) fuel their metabolism rapidly and directly with exogenous sugars
Authors: Amitai O. , Holtze S. , Barkan S. , Amichai E. , Korine C. , Pinshow B. , Voigt C. C. 
Published: July 2010

SUMMARYPrevious studies reported that fed bats and birds mostly use recently acquired exogenous nutrients as fuel for flight, rather than endogenous fuels, such as lipids or glycogen. However, this pattern of fuel use may be a simple size-related phenomenon because, to date, only small birds and bats have been studied with respect to the origin of metabolized fuel, and because small animals carry relatively small energy reserves, considering their high mass-specific metabolic rate. We hypothesized that ∼150 g Egyptian fruit bats (Rousettus aegyptiacus Pteropodidae), which are more than an order of magnitude heavier than previously studied bats, also catabolize dietary sugars directly and exclusively to fuel both rest and flight metabolism. We based our expectation on the observation that these animals rapidly transport ingested dietary sugars, which are absorbed via passive paracellular pathways in the intestine, to organs of high energy demand. We used the stable carbon isotope ratio in exhaled CO2 (δ13Cbreath) to assess the origin of metabolized substrates in 16 Egyptian fruit bats that were maintained on a diet of C3 plants before experiments. First, we predicted that in resting bats δ13Cbreath remains constant when bats ingest C3 sucrose, but increases and converges on the dietary isotopic signature when C4 sucrose and C4 glucose are ingested. Second, if flying fruit bats use exogenous nutrients exclusively to fuel flight, we predicted that δ13Cbreath of flying bats would converge on the isotopic signature of the C4 sucrose they were fed. Both resting and flying Egyptian fruit bats, indeed, directly fuelled their metabolism with freshly ingested exogenous substrates. The rate at which the fruit bats oxidized dietary sugars was as fast as in 10 g nectar-feeding bats and 5 g hummingbirds. Our results support the notion that flying bats, irrespective of their size, catabolize dietary sugars directly, and possibly exclusively, to fuel flight.
Sparse but specific temporal coding by spikes in an insect sensory-motor ocellar pathway
Authors: Simmons Peter J. , de Ruyter van Steveninck Rob R. 
Published: July 2010

SUMMARYWe investigate coding in a locust brain neuron, DNI, which transforms graded synaptic input from ocellar L-neurons into axonal spikes that travel to excite particular thoracic flight neurons. Ocellar neurons are naturally stimulated by fluctuations in light collected from a wide field of view, for example when the visual horizon moves up and down. We used two types of stimuli: fluctuating light from a light-emitting diode (LED), and a visual horizon displayed on an electrostatic monitor. In response to randomly fluctuating light stimuli delivered from the LED, individual spikes in DNI occur sparsely but are timed to sub-millisecond precision, carrying substantial information: 4.5–7 bits per spike in our experiments. In response to these light stimuli, the graded potential signal in DNI carries considerably less information than in presynaptic L-neurons. DNI is excited in phase with either sinusoidal light from an LED or a visual horizon oscillating up and down at 20 Hz, and changes in mean light level or mean horizon level alter the timing of excitation for each cycle. DNI is a multimodal interneuron, but its ability to time spikes precisely in response to ocellar stimulation is not degraded by additional excitation. We suggest that DNI is part of an optical proprioceptor system, responding to the optical signal induced in the ocelli by nodding movements of the locust head during each wing-beat.