bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dolomitization of the Lower Ordovician Aguathuna Formation carbonates, Port au Port Peninsula, western Newfoundland, Canada: implications for a hydrocarbon reservoir
Authors: Azmy Karem , Lavoie Denis , Knight Ian , Chi Guoxiang 
Published: August 2008

The Lower Ordovician Aguathuna Formation (∼100 m thick) is formed of shallow-marine carbonates, which constitute the uppermost part of the St. George Group of western Newfoundland. Sedimentation was paused by a major subaerial exposure (St. George Unconformity), which likely developed a significant pore system in the underlying carbonates by meteoric dissolution. The sequence has been affected by multiphase dolomitization that caused complex changes in the rock porosity. The Aguathuna dolomites are classified into three main generations ranging in crystal size between ∼4 µm and 2 mm. The occurrence of fabric-retentive dolomicrites implies that dolomitization likely started during the early stages of diagenesis. Although dolomitization is pervasive in the upper part of the formation and significantly occludes the pores, some intervals in the lower part have higher porosity. The development of lower permeable layers overlain by an impermeable (seal) cap suggests a possible potential diagenetic trap. Unlike sabkha deposits, the Aguathuna carbonates do not have evaporite interlayers. Furthermore, the low Sr contents (∼96 ppm) and the δ18O values of earlier dolomites (–3.3‰ to –6.9‰ VPDB (Vienna Pee Dee Belemnite)) are also difficult to reconcile with a brine origin. The Sr/Ca molar ratios (0.0067–0.0009), calculated for the earliest dolomitizing fluid, suggest a modified seawater origin, likely mixed sea and meteoric waters. The least radiogenic 87Sr/86Sr values of the earliest dolomite are consistent with those of early Ordovician seawater, which supports an early-stage diagenesis. Petrography, geochemistry, and fluid inclusions of the late dolomites suggest precipitation at higher temperatures (∼73–95 °C) in deeper burial environments from hydrothermal solutions.
BH3-only protein mimetic obatoclax sensitizes cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis
Authors: Mott Justin L. , Bronk Steve F. , Mesa Ruben A. , Kaufmann Scott H. , Gores Gregory J. 
Published: August 2008

Abstract
Human cholangiocarcinomas evade apoptosis by overexpression of Mcl-1. The drug obatoclax (GX15-070) inhibits antiapoptotic members of the Bcl-2 family including Mcl-1. The purpose of this study is to determine if obatoclax sensitizes human cholangiocarcinoma cells to apoptosis. The human cholangiocarcinoma cell lines, KMCH, KMBC, and TFK, were employed for these studies. Protein expression was assessed by immunoblot and protein-protein interactions detected by coprecipitation of the polypeptide of interest with S-tagged Mcl-1. Activation of Bak and Bax was observed by immunocytochemistry with conformation-specific antisera. Obatoclax induced minimal apoptosis alone; however, it increased apoptosis 3- to 13-fold in all three cancer cell lines when combined with Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Obatoclax did not alter cellular expression of Bid, Bim, Puma, Noxa, Bak, Bax, Mcl-1, or cFLIP. Mcl-1 binding to Bak was readily identified in untreated cells, and this association was disrupted by treating the cells with obatoclax. Additionally, Bim binding to Mcl-1 was markedly decreased by obatoclax treatment. We also identified alterations in Bak and Bax conformation following treatment with obatoclax plus Apo2L/TRAIL but not with either Apo2L/TRAIL or obatoclax alone. In conclusion, obatoclax releases Bak and Bim from Mcl-1 and sensitizes human cholangiocarcinoma cells to Apo2L/TRAIL-induced apoptosis. Obatoclax is a potentially promising adjunctive agent for the treatment of this cancer. [Mol Cancer Ther 2008;7(8):2339–47]
Anti-CD30 diabody-drug conjugates with potent antitumor activity
Authors: Kim Kristine M. , McDonagh Charlotte F. , Westendorf Lori , Brown Lindsay L. , Sussman Django , Feist Tiffany , Lyon Robert , Alley Stephen C. , Okeley Nicole M. , Zhang Xinqun , Thompson Melissa C. , Stone Ivan , Gerber Hans-Peter , Carter Paul J. 
Published: August 2008

Abstract
Anti-CD30 diabodies were engineered with two cysteine mutations for site-specific drug conjugation in each chain of these homodimeric antibody fragments. Diabodies were conjugated with ∼4 equivalents of the anti-tubulin drugs, monomethyl auristatin E or F, via a protease-cleavable dipeptide linker, to create the conjugates, diabody-vcE4 and diabody-vcF4, respectively. Diabody conjugation had only minor (&lt;3-fold) effects on antigen binding. Diabody-vcF4 was potently cytotoxic against the antigen-positive cell lines, Karpas-299 (34 pmol/L IC50) and L540cy (22 pmol/L IC50), and was 8- and 21-fold more active than diabody-vcE4 against these cell lines, respectively. Clearance of diabody-vcF4 (99-134 mL/d/kg) was 5-fold slower than for the nonconjugated diabody in naive severe combined immunodeficient mice. Diabody-vcF4 had potent and dose-dependent antitumor activity against established Karpas-299 xenografts and gave durable complete responses at well-tolerated doses. Biodistribution experiments with diabody-[3H]-vcF4 (0.72-7.2 mg/kg) in tumor-bearing mice showed a dose-dependent increase in total auristatin accumulation in tumors (≤520 nmol/L) and decrease in relative auristatin accumulation (≤8.1 %ID/g), with peak localization at 4 to 24 h after dosing. Diabody-vcF4 had ∼4-fold lower cytotoxic activity than the corresponding IgG1-vcF4 conjugate in vitro. A similar potency difference was observed in vivo despite 25- to 34-fold faster clearance of diabody-vcF4 than IgG1-vcF4. This may reflect that dose-escalated diabody-vcF4 can surpass IgG1-vcF4 in auristatin delivery to tumors, albeit with higher auristatin exposure to some organs including kidney and liver. Diabody-drug conjugates can have potent antitumor activity at well-tolerated doses and warrant further optimization for cancer therapy. [Mol Cancer Ther 2008;7(8):2486–97]
Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users
Authors: Ramaekers JG , Kauert G , Theunissen EL , Toennes SW , Moeller MR 
Published: August 2008

AbstractPerformance impairment during Δ9-tetrahydrocannabinol (THC) intoxication has been well described in occasional cannabis users. It is less clear whether tolerance develops to the impairing effects of THC in heavy users of cannabis. The aim of the present study was to assess neurocognitive performance during acute THC intoxication in occasional and heavy users. Twenty-four subjects (12 occasional cannabis users and 12 heavy cannabis users) participated in a double-blind, placebo-controlled, two-way mixed model design. Both groups received single doses of THC placebo and 500 μg/kg THC by smoking. Performance tests were conducted at regular intervals between 0 and 8 h after smoking, and included measures of perceptual motor control (critical tracking task), dual task processing (divided attention task), motor inhibition (stop signal task) and cognition (Tower of London). THC significantly impaired performance of occasional cannabis users on critical tracking, divided attention and the stop signal task. THC did not affect the performance of heavy cannabis users except in the stop signal task, i.e. stop reaction time increased, particularly at high THC concentrations. Group comparisons of overall performance in occasional and heavy users did not reveal any persistent performance differences due to residual THC in heavy users. These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC.
Suppression of Basal Spontaneous Gonadotropin-Releasing Hormone Neuronal Activity during Lactation: Role of Inhibitory Effects of Neuropeptide Y
Authors: Xu Jing , Kirigiti Melissa A. , Cowley Michael A. , Grove Kevin L. , Smith M. Susan 
Published: August 2008

Increased neuropeptide Y (NPY) activity drives the chronic hyperphagia of lactation and may contribute to the suppression of GnRH activity. The majority of GnRH neurons are contacted by NPY fibers, and GnRH cells express NPY Y5 receptor (Y5R). Therefore, NPY provides a neurocircuitry for information about food intake/energy balance to be directly transmitted to GnRH neurons. To investigate the effects of lactation on GnRH neuronal activity, hypothalamic slices were prepared from green fluorescent protein-GnRH transgenic rats. Extracellular loose-patch recordings determined basal GnRH neuronal activity from slices of ovariectomized control and lactating rats. Compared with controls, hypothalamic slices from lactating rats had double the number of quiescent GnRH neurons (14.51 ± 2.86 vs. 7.04 ± 2.84%) and significantly lower firing rates of active GnRH neurons (0.25 ± 0.02 vs. 0.37 ± 0.03 Hz). To study the NPY-postsynaptic Y5R system, whole-cell current-clamp recordings were performed in hypothalamic slices from control rats to examine NPY/Y5R antagonist effects on GnRH neuronal resting membrane potential. Under tetrodotoxin treatment, NPY hyperpolarized GnRH neurons from −56.7 ± 1.94 to −62.1 ± 1.83 mV; NPY’s effects were blocked by Y5R antagonist. To determine whether increased endogenous NPY tone contributes to GnRH neuronal suppression during lactation, hypothalamic slices were treated with Y5R antagonist. A significantly greater percentage of GnRH cells were activated in slices from lactating rats (52%) compared with controls (28%). These results suggest that: 1) basal GnRH neuronal activity is suppressed during lactation; 2) NPY can hyperpolarize GnRH neurons via postsynaptic Y5R; and 3) increased inhibitory NPY tone during lactation is a component of the mechanisms responsible for suppression of GnRH neuronal activity.
Neuropeptide Y (NPY) directly hyperpolarizes GnRH neurons via postsynaptic NPY Y5 receptor. Increased inhibitory NPY tone during lactation is an important component of the suppression of GnRH neuronal activity.
The effects of short-term antioxidant supplementation on oxidative stress and flight performance in adult budgerigars Melopsittacus undulatus
Authors: Larcombe S. D. , Tregaskes C. A. , Coffey J. S. , Stevenson A. E. , Alexander L. , Arnold K. E. 
Published: August 2008

SUMMARY
Antioxidants are known to play an important role in quenching reactive oxygen species (ROS), thus ameliorating oxidative stress. Since increased metabolism associated with exercise can increase oxidative stress, dietary antioxidants may be a limiting factor in determining aspects of physical performance. Here we tested whether oxidative stress associated with flight exercise of captive adult budgerigars, Melopsittacus undulatusdiffered after they received a diet containing either enhanced (EQ) or reduced levels (RQ) of a nutritional supplement (Nutrivit®) rich in antioxidants for 4 weeks. We also assessed differences in take-off escape time, a potential fitness-determining physiological capability. Oxidative stress was measured in two ways: comet assay to measure DNA damage; and analysis of malondialdehyde(MDA), a by-product of lipid peroxidation. Flight exercise appeared to increase oxidative stress. Moreover, birds had a higher percentage of intact DNA (fewer alkali labile sites) in one comet measure and lower levels of MDA after an EQ diet than after an RQ diet. We found no difference in flight performance between the two diets. Our results suggested that birds exerted maximum effort in escape flights, regardless of diet. However, this was at a cost of increased oxidative stress post-flight when on a reduced quality diet,but not when on an enhanced, antioxidant-rich diet. We suggest that dietary antioxidants may prove important in reducing exercise-related costs through multiple physiological pathways. Further work is necessary to fully understand the effects of antioxidants and oxidative stress on exercise performance in the longer term.
Bile salts are effective taste stimuli in channel catfish
Authors: Rolen S. H. , Caprio J. 
Published: August 2008

SUMMARY
Bile salts are known olfactory stimuli for teleosts, but only a single report has indicated that the taste system of a fish was sensitive to this class of stimuli. Here, gustatory responses of the channel catfish, Ictalurus punctatus, to four bile salts that included taurine-,glycine- and non-conjugated compounds along with three stimulatory amino acids as a comparison were investigated using extracellular electrophysiological techniques. Integrated multiunit responses were obtained from the branch of the facial nerve innervating taste buds on the maxillary barbel. Bile salts were shown to be highly effective facial taste stimuli, with estimated electrophysiological thresholds for three of the four tested bile salts of approximately 10–11 mol l–1 to 10–10 mol l–1, slightly lower by 1–2 log units than those to amino acids in the same species. Although the sensitivity of the facial taste system of the channel catfish to bile salts is high, the relative magnitude of the response to suprathreshold concentrations of bile salts was significantly less than that to amino acids. Multiunit cross-adaptation experiments indicate that bile salts and amino acids bind to relatively independent receptor sites; however, nerve-twig data and single-fiber recordings suggest that both independent and shared neural pathways exist for the transmission of bile salt and amino acid information to the primary gustatory nucleus of the medulla.
The physiology of the midgut ofLutzomyia longipalpis(Lutz and Neiva 1912): pH in different physiological conditions and mechanisms involved in its control
Authors: Santos Vânia C. , Araujo Ricardo N. , Machado Luciane A. D. , Pereira Marcos H. , Gontijo Nelder F. 
Published: August 2008

SUMMARYNutrient digestion and absorption after blood feeding are important events for Lutzomyia longipalpis, which uses these nutrients to produce eggs. In this context, the pH inside the digestive tract is an important physiological feature as it can markedly influence the digestive process as well as interfere with Leishmania development in infected phlebotomines. It was described previously that unfed females have an acidic midgut (pH 6). In this study, the pH inside the midgut of blood-fed females was measured. The abdominal midgut (AM) pH varied from 8.15±0.31 in the first 10 h post-blood meal to 7.7±0.17 after 24 h. While the AM was alkaline during blood digestion, the pH in the thoracic midgut (TM) remained acidic (5.5–6.0). In agreement with these findings, the enzymeα-glucosidase, which has an optimum pH of 5.8, is mainly encountered in the acidic TM. The capacity of unfed females to maintain the acidic intestinal pH was also evaluated. Our results showed the presence of an efficient mechanism that maintains the pH almost constant at about 6 in the midgut, but not in the crop. This mechanism is promptly interrupted in the AM by blood ingestion. RT-PCR results indicated the presence of carbonic anhydrase in the midgut cells, which apparently is required to maintain the pH at 6 in the midgut of unfed females. Investigations on the phenomenon of alkalization observed after blood ingestion indicated that two mechanisms are involved: in addition to the alkalization promoted by CO2 volatilization there is a minor contribution from a second mechanism not yet characterized. Some inferences concerning Leishmania development and pH in the digestive tube are presented.
Effects of Spatially Varying Selection on Nucleotide Diversity and Linkage Disequilibrium: Insights From Deer Mouse Globin Genes
Authors: Storz Jay F , Kelly John K 
Published: August 2008

Abstract
An important goal of population genetics is to elucidate the effects of natural selection on patterns of DNA sequence variation. Here we report results of a study to assess the joint effects of selection, recombination, and gene flow in shaping patterns of nucleotide variation at genes involved in local adaptation. We first describe a new summary statistic, Zg, that measures the between-sample component of linkage disequilibrium (LD). We then report results of a multilocus survey of nucleotide diversity and LD between high- and low-altitude populations of deer mice, Peromyscus maniculatus. The multilocus survey included two closely linked α-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to different elevational zones. The primary goals were to assess whether the α-globin genes exhibit the hallmarks of spatially varying selection that are predicted by theory (i.e., sharply defined peaks in the between-population components of nucleotide diversity and LD) and to assess whether peaks in diversity and LD may be useful for identifying specific sites that distinguish selectively maintained alleles. Consistent with theoretical expectations, HBA-T1 and HBA-T2 were characterized by highly elevated levels of diversity between populations and between allele classes. Simulation and empirical results indicate that sliding-window analyses of Zg between allele classes may provide an effective means of pinpointing causal substitutions.
Quantitative Trait Loci Affecting Phenotypic Plasticity and the Allometric Relationship of Ovariole Number and Thorax Length in Drosophila melanogaster
Authors: Bergland Alan O , Genissel Anne , Nuzhdin Sergey V , Tatar Marc 
Published: August 2008

Abstract
Environmental factors during juvenile growth such as temperature and nutrition have major effects on adult morphology and life-history traits. In Drosophila melanogaster, ovary size, measured as ovariole number, and body size, measured as thorax length, are developmentally plastic traits with respect to larval nutrition. Herein we investigated the genetic basis for plasticity of ovariole number and body size, as well the genetic basis for their allometric relationship using recombinant inbred lines (RILs) derived from a natural population in Winters, California. We reared 196 RILs in four yeast concentrations and measured ovariole number and body size. The genetic correlation between ovariole number and thorax length was positive, but the strength of this correlation decreased with increasing yeast concentration. Genetic variation and genotype-by-environment (G × E) interactions were observed for both traits. We identified quantitative trait loci (QTL), epistatic, QTL-by-environment, and epistatic-by-environment interactions for both traits and their scaling relationships. The results are discussed in the context of multivariate trait evolution.
A Male-Specific Fatty Acid ω-Hydroxylase, SXE1, Is Necessary for Efficient Male Mating in Drosophila melanogaster
Authors: Fujii Shinsuke , Toyama Akemi , Amrein Hubert 
Published: August 2008

Abstract
In Drosophila, sexual differentiation, physiology, and behavior are thought to be mediated by numerous male- and female-specific effector genes whose expression is controlled by sex-specifically expressed transcriptional regulators. One such downstream effector gene, sex-specific enzyme 1 (sxe1, cyp4d21), has been identified in a screen for genes with sex-biased expression in the head. Sxe1 was also identified in another screen as a circadian regulated gene. Here, we analyzed the spatial and temporal regulation of sxe1 and identified a function for this gene in male courtship. We show that male-specific transcriptional regulator DSXM and the clock genes are necessary for cycling of sxe1 mRNA during the diurnal cycle. Similar to sxe1 mRNA, expression of SXE1 protein oscillates in a diurnal fashion, with highest protein levels occurring around midnight. SXE1 protein expression is restricted to nonneuronal cells associated with diverse sensory bristles of both the chemo- and mechanosensory systems. Suppression or knockout of sxe1 significantly reduces mating success throughout the diurnal cycle. Finally, the metabolomic profile of wild-type and sxe1 mutant males revealed that sxe1 likely functions as a fatty acid ω-hydroxylase, suggesting that male courtship and mating success is mediated by small compounds generated by this enzyme.
Maintenance of Mitochondrial DNA by the Caenorhabditis elegans ATR Checkpoint Protein ATL-1
Authors: Mori Chihiro , Takanami Takako , Higashitani Atsushi 
Published: August 2008

Abstract
Here we show that inactivation of the ATR-related kinase ATL-1 results in a significant reduction in mitochondrial DNA (mtDNA) copy numbers in Caenorhabditis elegans. Although ribonucleotide reductase (RNR) expression and the ATP/dATP ratio remained unaltered in atl-1 deletion mutants, inhibition of RNR by RNAi or hydroxyurea treatment caused further reductions in mtDNA copy number. These results suggest that ATL-1 functions to maintain mtDNA independently of RNR.
Second-Order Moments of Segregating Sites Under Variable Population Size
Authors: Živković Daniel , Wiehe Thomas 
Published: August 2008

Abstract
The identification of genomic regions that have been exposed to positive selection is a major challenge in population genetics. Since selective sweeps are expected to occur during environmental changes or when populations are colonizing a new habitat, statistical tests constructed on the assumption of constant population size are biased by the co-occurrence of population size changes and selection. To delimit this problem and gain better insights into demographic factors, theoretical results regarding the second-order moments of segregating sites, such as the variance of segregating sites, have been derived. Driven by emerging genomewide surveys, which allow the estimation of demographic parameters, a generalized version of Tajima's D has been derived that takes into account a previously estimated demographic scenario to test single loci for traces of selection against the null hypothesis of neutral evolution under variable population size.
Human Amniotic Fluid Stem Cells Can Integrate and Differentiate into Epithelial Lung Lineages
Authors: Carraro Gianni , Perin Laura , Sedrakyan Sargis , Giuliani Stefano , Tiozzo Caterina , Lee Jooeun , Turcatel Gianluca , De Langhe Stijn P. , Driscoll Barbara , Bellusci Saverio , Minoo Parviz , Atala Anthony , De Filippo Roger Edward , Warburton David 
Published: August 2008

Abstract
A new source of stem cells has recently been isolated from amniotic fluid; these amniotic fluid stem cells have significant potential for regenerative medicine. These cells are multipotent, showing the ability to differentiate into cell types from each embryonic germ layer. We investigated the ability of human amniotic fluid stem cells (hAFSC) to integrate into murine lung and to differentiate into pulmonary lineages after injury. Using microinjection into cultured mouse embryonic lungs, hAFSC can integrate into the epithelium and express the early human differentiation marker thyroid transcription factor 1 (TTF1). In adult nude mice, following hyperoxia injury, tail vein-injected hAFSC localized in the distal lung and expressed both TTF1 and the type II pneumocyte marker surfactant protein C. Specific damage of Clara cells through naphthalene injury produced integration and differentiation of hAFSC at the bronchioalveolar and bronchial positions with expression of the specific Clara cell 10-kDa protein. These results illustrate the plasticity of hAFSC to respond in different ways to different types of lung damage by expressing specific alveolar versus bronchiolar epithelial cell lineage markers, depending on the type of injury to recipient lung.
Disclosure of potential conflicts of interest is found at the end of this article.