bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical Sympathectomy of Interscapular Brown Adipose Tissue
Authors: Thureson‐Klein ÅSa , Lagercrantz Hugo , Barnard Tudor 
Published: February 2011

AbstractAdult non‐cold adapted rats were injected with 6‐hydroxydopamine (6‐OHDA) or saline and their interscapular brown adipose tissue (BAT) was removed after appropriate periods of time. Fluorescence histo‐chemistry of control BAT demonstrated the presence of an extensive network of varicose fibers among the adipocytes and at the blood vessels. This was confirmed by electron microscopy which a!so revealed large and small dense core vesicles sparsely distributed in axons and terminals indicating the presence of noradren‐aline (NA). After 6‐OHDA injection the fluorescence from varicosities was abolished both among the adipocytes and at the vessels. Thus, chemical sympathectomy was more effective than surgical‐ or immuno‐sympathectomy, which spare the innervation of adipocytes. Parallelling the disappearance of fluorescence was a significant decrease of measurable NA. During recovery the extractable NA increased before the reappearance of fluorescent varicosities. This could be explained by transmitter accumulation in the nerve‐trunks within the tissue, which, in general, appeared unaffected by 6‐OHDA. A large number of cells with a strong yellowish fluorescence distributed through the BAT was unaffected by 6‐OHDA. There was no evidence for the presence of intrinsic ganglia.
Influence of Moderate Vasoconstriction on the Wave Reflection Properties of the Pulmonary Arterial Bed
Authors: Piene Hroar , Hauge Anton 
Published: February 2011

AbstractIncreased transmural pressure in the pulmonary arterial bed may reduce vascular input impedance and reduce hydraulic power linked to pulsatile blood flow. Vascular impedance and pulsatile hydraulic power (Wp) levels of isolated perfused rabbit lungs were compared after similar rises of pulmonary arterial pressure (PAp), induced either by vasoconstriction or by left atrial pressure (LAp) elevation. Resulting Wp levels were significantly smaller after vasoconstriction than LAp elevation. Wp showed a minimum level at physiologic PAp (about 20 cm H2O) irrespective of the cause of PAp elevation. Pressure pulse wave reflection coefficient (Γ) was calculated for control and test situations, and was found to be approximately doubled after vasoconstriction. Only minor changes in Γ were found after LAP elevation. Accordingly, moderate vasoconstriction (resulting PAp≅20 cm H2O) caused a backward traveling pressure wave of high amplitude, appearing in counter‐phase to the forward pressure wave at the input site. The total pressure wave amplitude was thereby markedly lowered, resulting in a reduced Wp level. We assume that this effect of moderate vasoconstriction may be one reason for the existence of vascular smooth muscles in the pulmonary arteries.
The Influence of Pulmonary Blood Flow Rate on Vascular Input Impedance and Hydraulic Power in the Sympathetically and Noradrenaline Stimulated Cat Lung
Authors: Piene Hroar 
Published: February 2011

AbstractThis study was designed to evaluate the influence of sympathetic nerve stimulation (NS) and α‐adrenergic receptor stimulation (αS) on the pulmonary vascular input impedance and hydraulic power output of the right heart during variations of cardiac output (CO). An open chest cat preparation was used and pulsatile pressure and flow in the pulmonary artery were measured by high frequency response transducers. Calculations showed that vascular resistance (VR) was inversely dependent on CO, hut input impedance of the unstimulated lung was not influenced by CO variations. NS or αS increased VR and input impedance significantly, and the relation pulsatile hydraulic power/total hydraulic power (Wp/Wt) increased 40%, indicating that such stimulation has larger relative influence on impedance than on resistance. The reduction of arterial compliance during NS (maximal stimulus) was calculated to be 60%, independent of CO. Input impedance during NS or αS was reduced by CO elevations, probably because the concomitant distension of the arterial bed reduced arterial resistance and inertance. The ratio Wp/CO, which expresses the fraction of pulsatile hydraulic power lost per ml mean arterial flow, was found to be flow dependent both in control and stimulated conditions: Wp/CO was positively correlated to CO in control condition and weakly negatively correlated to CO during stimulation. At high CO the arterial vessels could he stimulated and stiffened without much extra load on the right heart.
Single nucleotide polymorphisms across a species’ range: implications for conservation studies of Pacific salmon
Authors: SEEB L. W. , TEMPLIN W. D. , SATO S. , ABE S. , WARHEIT K. , PARK J. Y. , SEEB J. E. 
Published: February 2011

AbstractStudies of the oceanic and near‐shore distributions of Pacific salmon, whose migrations typically span thousands of kilometres, have become increasingly valuable in the presence of climate change, increasing hatchery production and potentially high rates of bycatch in offshore fisheries. Genetics data offer considerable insights into both the migratory routes as well as the evolutionary histories of the species. However, these types of studies require extensive data sets from spawning populations originating from across the species’ range. Single nucleotide polymorphisms (SNPs) have been particularly amenable for multinational applications because they are easily shared, require little interlaboratory standardization and can be assayed through increasingly efficient technologies. Here, we discuss the development of a data set for 114 populations of chum salmon through a collaboration among North American and Asian researchers, termed PacSNP. PacSNP is focused on developing the database and applying it to problems of international interest. A data set spanning the entire range of species provides a unique opportunity to examine patterns of variability, and we review issues associated with SNP development. We found evidence of ascertainment bias within the data set, variable linkage relationships between SNPs associated with ancestral groupings and outlier loci with alleles associated with latitude.
Outcomes of pseudophakic retinal detachment
Authors: Tuft Stephen J. , Gore Daniel M. , Bunce Catey , Sullivan Paul M. , Minassian Darwin C. 
Published: February 2011

Abstract.Purpose:  To provide data on the outcome of pseudophakic retinal detachment (PRD).Methods:  In a retrospective case–control study, we identified a consecutive series of 63 298 cataract extractions (45 520 patients) performed in a single institution between 1994 and 2003. We included 249 cases with PRD and 845 controls that had cataract surgery on the same day as cases but without PRD. Outcome measures were the risk of impaired vision (6/18–6/60) or blindness (<6/60). A multinomial logistic regression model evaluated risk factors for impaired vision or blindness, while multivariable regression models measured the relative risk of poor visual outcome for posterior capsule tear (PCT) and PRD.Results:  Primary pars plana vitrectomy was performed on 207 (84.5%) of the 245 cases treated with surgery, of which 175 (71.4%) needed one procedure. The final acuity was <6/60 in 62 cases (24.9%) and 34 controls (4.0%). After PRD, the relative risk for a final visual outcome <6/60 was 6.8 [95% confidence interval (CI) 4.3–10.6; p < 0.001], and we estimated that the proportion of blindness attributable to PRD was 1.1% (CI 0.7–1.9%). A PCT prior to a PRD was not associated with an increased risk of macular detachment (p = 0.165), but it did carry an increased risk of blindness [odds ratio 4.8 (CI 2.2–10.2; p < 0.001].Conclusion:  Although a PCT has an adverse effect on visual outcome after cataract surgery, a PRD is the foremost surgery‐related risk for a poor visual outcome. Patient education of symptoms and prompt treatment may limit the visual consequences.
Amelioration of Amyloid β‐Induced Cognitive Deficits by Zataria multiflora Boiss. Essential Oil in a Rat Model of Alzheimer's Disease
Authors: Majlessi Nahid , Choopani Samira , Kamalinejad Mohammad , Azizi Zahra 
Published: February 2011

SUMMARYIntroduction: The limitations of current Alzheimer's disease (AD) therapeutics have prompted investigation into innovative therapeutics focused on antiinflammatory, antioxidant, and neuroprotective agents including those from medicinal plants. Numerous plants have been tested for their potential for alleviating symptoms of AD. Aims:Zataria multiflora Boiss. (ZM) a member of Lamiaceae family has been used in Iranian traditional medicine for its beneficial effects on mental abilities. Therefore, the effect of its essential oil was evaluated in a rat model of AD. Methods: Amyloid β‐protein (Aβ) fragment 25–35 was injected bilaterally in the CA1 region of rats hippocampus and the effect of different doses of ZM essential oil (50, 100, or 200 μL/kg) on cognitive function was investigated in the Morris water maze. Acute toxicity of the essential oil was also studied. Results: The results showed increases in escape latency, traveled distance, heading angle, and decreases in target quadrant entries in Aβ‐received groups as compared to the control group. This impairment was reversed by ZM essential oil. The results of acute toxicity testing revealed that the calculated LD50 (1264.9 μL/kg) is much higher than the therapeutic dose (100 μL/kg). Conclusions: It seems that antioxidant, antiinflammatory, and anticholinesterase activities of ZM or its main constituents might contribute to its beneficial effects in this model. Our findings suggest that ZM may be a potentially valuable source of natural therapeutic agents for the treatment of AD. However, further investigations are necessary to establish its clinical efficacy and potential toxicity, before any recommendations concerning its use as a medication in the treatment of AD.
Screening of Therapeutic Strategies for Huntington's Disease in YAC128 Transgenic Mice
Authors: Gil‐Mohapel Joana M. 
Published: February 2011

SUMMARYHuntington's disease (HD) is a hereditary neurodegenerative disorder caused by an unstable expansion of cytosine‐adenine‐guanine (CAG) repeats in the HD gene. The symptoms include cognitive dysfunction and severe motor impairment with loss of voluntary movement coordination that is later replaced by bradykinesia and rigidity. The neuropathology is characterized by neuronal loss mainly in the striatum and cortex, and the appearance of neuronal intranuclear inclusions of mutant huntingtin. The mechanisms responsible for neurodegeneration are still not fully understood although excitotoxicity and a consequent increase in intracellular calcium concentration as well as the activation of caspases and calapins are known to play a key role. There is currently no satisfactory treatment or cure for this disease. The YAC128 transgenic mice express the full‐length human HD gene with 128 CAG repeats and constitute a unique model for the study of HD as they replicate the slow and biphasic progression of behavioral deficits characteristic of the human condition and show striatal neuronal loss. As such, these transgenic mice have been an invaluable model not only for the elucidation of the neurodegenerative pathways in HD, but also for the screening and development of new therapeutic approaches. Here, I will review the unique characteristics of this transgenic HD model and will provide a summary of the therapies that have been tested in these mice, namely: potentiation of the protective roles of wild‐type huntingtin and mutant huntingtin aggregation, transglutaminase inhibition, inhibition of glutamate‐ and dopamine‐induced toxicity, apoptosis inhibition, use of essential fatty acids, and the novel approach of intrabody gene therapy. The insights obtained from these and future studies will help identify potential candidates for clinical trials and will ultimately contribute to the discovery of a successful treatment for this devastating neurodegenerative disorder.
Reversible Signal Binding by the Pseudomonas aeruginosa Quorum-Sensing Signal Receptor LasR
Authors: Sappington Kaia J. , Dandekar Ajai A. , Oinuma Ken-Ichi , Greenberg E. Peter 
Published: February 2011

ABSTRACT

Many members of the LuxR family of acyl-homoserine lactone (acyl-HSL)-dependent quorum-sensing transcriptional activators are thought to have the unusual characteristics of requiring the signal ligand during polypeptide synthesis to fold into an active conformation and of binding signal extraordinarily tightly. This is the case for the
N
-3-oxo-dodecanoyl-HSL-dependent
Pseudomonas aeruginosa
virulence regulator LasR. We present evidence that LasR can fold into an active conformation
in vivo
in the absence of the acyl-HSL ligand. We also present evidence indicating that in the cellular environment, LasR and
N
-3-oxo-dodecanoyl-HSL readily dissociate. After dissociation, LasR can remain in a properly folded conformation capable of reassociating with signal. We present a new model for the folding and signal binding of LasR and other members of the family of transcription factors to which LasR belongs. Our findings have important implications concerning the cellular responses to decreased environmental concentrations of signals and have implications about potential quorum-sensing inhibition strategies.

IMPORTANCE
The opportunistic pathogen
Pseudomonas aeruginosa
causes difficult to treat and incurable diseases. Quorum sensing controls expression of many virulence factors in this bacterium, and the quorum-sensing signal receptor LasR has been targeted for anti-quorum-sensing therapeutic development. The work described here changes the current view about how LasR interacts with the quorum-sensing signal to which it responds. This is of importance for therapeutic development. The experiments also address a poorly studied aspect of quorum sensing: the response to decreases in quorum-sensing signals. This has importance with respect to understanding the ecology and evolution of quorum sensing.
Comparison of oral versus parenteral iron supplementation on the health and productivity of piglets
Authors: Maes D. , Steyaert M. , Vanderhaeghe C. , López Rodríguez A. , de Jong E. , del Pozo Sacristán R. , Vangroenweghe F. , Dewulf J. 
Published: February 2011

The aim of this study was to compare oral iron supplementation in feed with a standard iron injection and assess the impact on the health and productivity of pigs. The reliability of a quick test (HemoCue) for the measurement of blood haemoglobin concentration was also investigated. Three pig herds, with a total of 88 sows and their piglets, were included in the study. Piglets in treatment group O were fed a special iron‐rich feed on days 2 to 4, 5 to 7 and 8 to 12 of lactation using a specially designed feeding device. Piglets in group IM received 200 mg of an iron dextran complex intramuscularly at three days of age. Haemoglobin concentrations and performance of the piglets were compared between groups. The mean haemoglobin concentrations in pigs at weaning were 131.4 and 116.4 g/l for pigs in groups O and IM, respectively (P<0.01). Daily weight gain (253.9 v 248.8 g/day) and piglet mortality (11.4 v 12.2 per cent) were slightly better in group O than in group IM (P>0.05).
Results of the struggle at ancient Ephesus: natural processes 1, human intervention 0
Authors: Kraft John C. , Rapp George , Brükner Helmut , Kayan İlhan 
Published: February 2011

Abstract
Coastal areas have been prime locations for habitation and commerce. Early authors such as Pausanias (second century CE), and Strabo (64 or 63 BCE–24 CE) noted the impacts of shoreline changes. Geomorphological and subsurface geological data, combined with archaeological excavation and ancient texts, indicate a long interplay between natural processes of estuarine infilling by sediments from the Küçük Menderes River (ancient Cayster River) and multiple attempts of human intervention to preserve the harbours of Ephesus. Strabo noted that harbour engineering efforts there, such as the construction of a mole to prevent siltation, instead created a sediment trap that made things worse. The pre-Holocene river valley was inundated by Holocene sea-level rise that formed the ancient Gulf of Ephesus. Extensive palaeogeographical studies, based on sediment coring, geomorphology, archaeology and history, have provided details of the problems the inhabitants faced in keeping vital harbours in operation. Dating and analysis of sedimentary deposits has allowed the description of shifting river courses, floodplain changes, human intervention, and anthropogenic deposits at Ephesus. During and following Classical times sediment deposition rapidly began to fill in the embayment, requiring the inhabitants to regularly shift the harbours westward. Ultimately, it was to no avail.
Geoarchaeology and the value of multidisciplinary palaeoenvironmental approaches: a case study from the Tehran Plain, Iran
Authors: Gillmore G. K. , Stevens T. , Buylaert J. P. , Coningham R. A. E. , Batt C. , Fazeli H. , Young R. , Maghsoudi M. 
Published: February 2011

Abstract

Tepe Pardis, a significant Neolithic–Chalcolithic site on the Tehran Plain in Iran, is, like many sites in the area, under threat from development. The site contains detailed evidence of (1) the Neolithic–Chalcolithic transition, (2) an Iron Age cemetery and (3) how the inhabitants adapted to an unstable fan environment through resource exploitation (of clay deposits for relatively large-scale ceramic production by
c
. 5000 BC, and importantly, possible cutting of artificial water channels). Given this significance, models have been produced to better understand settlement distribution and change in the region. However, these models must be tied into a greater understanding of the impact of the geosphere on human development over this period. Forming part of a larger project focusing on the transformation of simple, egalitarian Neolithic communities into more hierarchical Chalcolithic ones, the site has become the focus of a multidisciplinary project to address this issue. Through the combined use of sedimentary and limited pollen analysis, radiocarbon and optically stimulated luminescence dating (the application of the last still rare in Iran), a greater understanding of the impact of alluvial fan development on human settlement through alluviation and the development of river channel sequences is possible. Notably, the findings presented here suggest that artificial irrigation was occurring at the site as early as 6.7±0.4 ka (4300–5100 BC).
Early Neolithic sands at West Voe, Shetland Islands: implications for human settlement
Authors: Gillmore G. K. , Melton N. 
Published: February 2011

Abstract

In 2002 and 2004–2005 archaeological investigations were undertaken on middens exposed by coastal erosion at West Voe in the south of Mainland Shetland, UK. This work established that the site dated from
c
. 4000 cal BC to
c
. 3250 cal BC and was of major importance for two reasons: (1) as the first of Mesolithic date to be found on Shetland; (2) as the first site to be found in the Northern Isles that spanned the Mesolithic–Neolithic transition. This paper describes investigations into the origin of sands deposited around 3500 cal BC and their potential effect on human settlement. The sands in question lie between two midden deposits, the lower of which accumulated over the period 4000–3500 cal BC and the upper 3500–3250 cal BC. The sands, therefore, dated to the period shortly after the adoption of agriculture on the archipelago, represented in the lower midden by the appearance of domesticated species and ceramics at around 3700–3600 cal BC, and represented a disruption in human occupation at a critical point in the development of a changing use of the landscape.
Trastuzumab Has Preferential Activity against Breast Cancers Driven by HER2 Homodimers
Authors: Ghosh Ritwik , Narasanna Archana , Wang Shizhen Emily , Liu Shuying , Chakrabarty Anindita , Balko Justin M. , González-Angulo Ana María , Mills Gordon B. , Penuel Elicia , Winslow John , Sperinde Jeff , Dua Rajiv , Pidaparthi Sailaja , Mukherjee Ali , Leitzel Kim , Kostler Wolfgang J. , Lipton Allan , Bates Michael , Arteaga Carlos L. 
Published: February 2011

Abstract
In breast cancer cells with HER2 gene amplification, HER2 receptors exist on the cell surface as monomers, homodimers, and heterodimers with EGFR/HER3. The therapeutic antibody trastuzumab, an approved therapy for HER2+ breast cancer, cannot block ligand-induced HER2 heterodimers, suggesting it cannot effectively inhibit HER2 signaling. Hence, HER2 oligomeric states may predict the odds of a clinical response to trastuzumab in HER2-driven tumors. To test this hypothesis, we generated nontransformed human MCF10A mammary epithelial cells stably expressing a chimeric HER2–FKBP molecule that could be conditionally induced to homodimerize by adding the FKBP ligand AP1510, or instead induced to heterodimerize with EGFR or HER3 by adding the heterodimer ligands EGF/TGFα or heregulin. AP1510, EGF, and heregulin each induced growth of MCF10A cells expressing HER2–FKBP. Trastuzumab inhibited homodimer-mediated but not heterodimer-mediated cell growth. In contrast, the HER2 antibody pertuzumab, which blocks HER2 heterodimerization, inhibited growth induced by heregulin but not AP1510. Lastly, the HER2/EGFR tyrosine kinase inhibitor lapatinib blocked both homodimer- and heterodimer-induced growth. AP1510 triggered phosphorylation of Erk1/2 but not AKT, whereas trastuzumab inhibited AP1510-induced Erk1/2 phosphorylation and Shc-HER2 homodimer binding, but not TGFα-induced AKT phosphorylation. Consistent with these observations, high levels of HER2 homodimers correlated with longer time to progression following trastuzumab therapy in a cohort of patients with HER2-overexpressing breast cancer. Together, our findings confirm the notion that HER2 oligomeric states regulate HER2 signaling, also arguing that trastuzumab sensitivity of homodimers may reflect their inability to activate the PI3K (phosphoinositide 3-kinase)/AKT pathway. A clinical implication of our results is that high levels of HER2 homodimers may predict a positive response to trastuzumab. Cancer Res; 71(5); 1871–82. ©2011 AACR.
Integration of Genotypic and Phenotypic Screening Reveals Molecular Mediators of Melanoma–Stromal Interaction
Authors: Stine Megan J. , Wang C. Joanne , Moriarty Whei F. , Ryu Byungwoo , Cheong Raymond , Westra William H. , Levchenko Andre , Alani Rhoda M. 
Published: February 2011

Abstract
Tumor–endothelium interactions are critical for tumor survival and metastasis. Melanomas can rapidly metastasize early in tumor progression, but the dependence of this aggressive behavior on tumor–stromal interaction is poorly understood. To probe the mechanisms involved, we developed a heterotypic coculture methodology, allowing simultaneous tracking of genomic and phenotypic changes in interacting tumor and endothelial cells in vitro. We found a dramatic rearrangement of endothelial cell networks into patterns reminiscent of vascular beds, even on plastic and glass. Multiple genes were upregulated in the process, many coding for cell surface and secreted proteins, including Neuropilin-2 (NRP2). A critical role of NRP2 in coordinated cell patterning and growth was confirmed using the coculture system. We conclude that NRP2 represents an important mediator of melanoma–endothelial interactions. Furthermore, the described methodology represents a powerful yet simple system to elucidate heterotypic intercellular interactions mediating diverse physiological and pathological processes. Cancer Res; 71(7); 2433–44. ©2011 AACR.