bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment
Authors: Li Li-Fu , Liao Shuen-Kuei , Huang Chung-Chi , Hung Ming-Jui , Quinn Deborah A 
Published: August 2008

Abstract
Introduction
Lung fibrosis, reduced lung compliance, and severe hypoxemia found in patients with acute lung injury often result in a need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and fibrogeneic activity but the mechanisms regulating the interaction between high tidal volume and lung fibrosis are unclear. We hypothesized that high-tidal-volume ventilation increased pulmonary fibrosis in acute lung injury via the serine/threonine kinase-protein kinase B (Akt) and mitogen-activated protein kinase pathways.

Methods
After 5 days of bleomycin administration to simulate acute lung injury, male C57BL/6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume mechanical ventilation (30 ml/kg) or low-tidal-volume mechanical ventilation (6 ml/kg) with room air for 1 to 5 hours.

Results
High-tidal-volume ventilation induced type I and type III procollagen mRNA expression, microvascular permeability, hydroxyproline content, Masson's trichrome staining, S100A4/fibroblast specific protein-1 staining, activation of Akt and extracellular signal-regulated kinase (ERK) 1/2, and production of macrophage inflammatory protein-2 and 10 kDa IFNγ-inducible protein in a dose-dependent manner. High-tidal-volume ventilation-induced lung fibrosis was attenuated in Akt-deficient mice and in mice with pharmacologic inhibition of ERK1/2 activity by PD98059.

Conclusion
We conclude that high-tidal-volume ventilation-induced microvascular permeability, lung fibrosis, and chemokine production were dependent, in part, on activation of the Akt and ERK1/2 pathways.
Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-α regulation
Authors: Mandrekar Pranoti , Catalano Donna , Jeliazkova Valentina , Kodys Karen 
Published: August 2008

AbstractImmunomodulatory effects of alcohol use involve regulation of innate immune cell function leading to liver disease. Alteration of inflammatory responses by alcohol is linked to dysregulated TNF-α production. Alcohol-induced oxidative stress also contributes to alterations in inflammatory cell activity. Heat shock proteins (hsps) and the heat shock transcription factor-1 (HSF-1) induced by oxidative stress regulate NF-κB activation and TNF-α gene expression in monocytes and macrophages. Here, we report that in vitro alcohol treatment induced and augmented LPS-induced HSF-1 nuclear translocation and DNA-binding activity in monocytes and macrophages. Supershift analysis revealed that alcohol regulated HSF-1- and not HSF-2-binding activity. Hsp70, a target gene induced by HSF-1, was transiently increased within 24 h by alcohol, but extended alcohol exposure decreased hsp70 in macrophages. The alcohol-induced alteration of hsp70 correlated with a concomitant change in hsp70 promoter activity. Hsp90, another HSF-1 target gene, was decreased during short-term alcohol but increased after prolonged alcohol exposure. Decreased hsp90-HSF-1 complexes after short-term alcohol indicated dissociation of HSF-1 from hsp90. On the other hand, hsp90 interacted with client protein IκB kinase β, a signaling intermediate of the LPS pathway, followed by IκBα degradation and increased NF-κB activity after chronic alcohol exposure, indicating that hsp90 plays an important role in supporting inflammatory cytokine production. Inhibition of hsp90 using geldanamycin prevented prolonged alcohol-induced elevation in LPS-induced NF-κB and TNF-α production. These results suggest that alcohol exposure differentially regulates hsp70 and hsp90 via HSF-1 activation. Further, hsp90 regulates TNF-α production in macrophages contributing to alcohol-induced inflammation.
Strategic Inventories in Vertical Contracts
Authors: Anand Krishnan , Anupindi Ravi , Bassok Yehuda 
Published: August 2008

Classical reasons for carrying inventory include fixed (nonlinear) production or procurement costs, lead times, nonstationary or uncertain supply/demand, and capacity constraints. The last decade has seen active research in supply chain coordination focusing on the role of incentive contracts to achieve first-best levels of inventory. An extensive literature in industrial organization that studies incentives for vertical controls largely ignores the effect of inventories. Does the ability to carry inventory influence the problem of vertical control? Conversely, can inventories arise purely due to incentive effects? This paper explicitly considers both incentives and inventories, and their interplay, in a dynamic model of an upstream firm (supplier) and a downstream firm (buyer) who can carry inventories. In our model, none of the classical reasons for carrying inventory exists. However, as we prove, the buyer's optimal strategy in equilibrium is to carry inventories, and the supplier is unable to prevent this. These inventories arise out of purely strategic considerations not yet identified in the literature, and have a significant impact on the equilibrium solution as well as supplier, buyer, and channel profits. We prove that strategic inventories play a pivotal role under arbitrary contractual structures, general (arbitrary) demand functions and general (finite or infinite) horizon lengths. As one example, two-part tariff contracts do not lead to optimal channel performance, nor can the supplier extract away all of the channel profits, in our dynamic model. Our results imply that firms can and must carry inventories strategically, and that optimal vertical contracts must take the possibility of inventories into account.
Population Bottlenecks Increase Additive Genetic Variance But Do Not Break a Selection Limit in Rain Forest Drosophila
Authors: van Heerwaarden Belinda , Willi Yvonne , Kristensen Torsten N , Hoffmann Ary A 
Published: August 2008

Abstract
According to neutral quantitative genetic theory, population bottlenecks are expected to decrease standing levels of additive genetic variance of quantitative traits. However, some empirical and theoretical results suggest that, if nonadditive genetic effects influence the trait, bottlenecks may actually increase additive genetic variance. This has been an important issue in conservation genetics where it has been suggested that small population size might actually experience an increase rather than a decrease in the rate of adaptation. Here we test if bottlenecks can break a selection limit for desiccation resistance in the rain forest-restricted fly Drosophila bunnanda. After one generation of single-pair mating, additive genetic variance for desiccation resistance increased to a significant level, on average higher than for the control lines. Line crosses revealed that both dominance and epistatic effects were responsible for the divergence in desiccation resistance between the original control and a bottlenecked line exhibiting increased additive genetic variance for desiccation resistance. However, when bottlenecked lines were selected for increased desiccation resistance, there was only a small shift in resistance, much less than predicted by the released additive genetic variance. The small selection response in the bottlenecked lines was no greater than that observed in the control lines. Thus bottlenecks might produce a statistically detectable change in additive genetic variance but this change has no impact on the response to selection.
Segregation Models for Disomic, Tetrasomic and Intermediate Inheritance in Tetraploids: A General Procedure Applied to Rorippa (Yellow Cress) Microsatellite Data
Authors: Stift Marc , Berenos Camillo , Kuperus Peter , van Tienderen Peter H 
Published: August 2008

Abstract
Tetraploid inheritance has two extremes: disomic in allotetraploids and tetrasomic in autotetraploids. The possibility of mixed, or intermediate, inheritance models has generally been neglected. These could well apply to newly formed hybrids or to diploidizing (auto)tetraploids. We present a simple likelihood-based approach that is able to incorporate disomic, tetrasomic, and intermediate inheritance models and estimates the double-reduction rate. Our model shows that inheritance of microsatellite markers in natural tetraploids of Rorippa amphibia and R. sylvestris is tetrasomic, confirming their autotetraploid origin. However, in F1 hybrids inheritance was intermediate to disomic and tetrasomic inheritance. Apparently, in meiosis, chromosomes paired preferentially with the homolog from the same parental species, but not strictly so. Detected double-reduction rates were low. We tested the general applicability of our model, using published segregation data. In two cases, an intermediate inheritance model gave a better fit to the data than the tetrasomic model advocated by the authors. The existence of inheritance intermediate to disomic and tetrasomic has important implications for linkage mapping and population genetics and hence breeding programs of tetraploids. Methods that have been developed for either disomic or tetrasomic tetraploids may not be generally applicable, particularly in systems where hybridization is common.
Canine Polydactyl Mutations With Heterogeneous Origin in the Conserved Intronic Sequence of LMBR1
Authors: Park Kiyun , Kang Joohyun , Subedi Krishna Pd , Ha Ji-Hong , Park Chankyu 
Published: August 2008

Abstract
Canine preaxial polydactyly (PPD) in the hind limb is a developmental trait that restores the first digit lost during canine evolution. Using a linkage analysis, we previously demonstrated that the affected gene in a Korean breed is located on canine chromosome 16. The candidate locus was further limited to a linkage disequilibrium (LD) block of &lt;213 kb composing the single gene, LMBR1, by LD mapping with single nucleotide polymorphisms (SNPs) for affected individuals from both Korean and Western breeds. The ZPA regulatory sequence (ZRS) in intron 5 of LMBR1 was implicated in mammalian polydactyly. An analysis of the LD haplotypes around the ZRS for various dog breeds revealed that only a subset is assigned to Western breeds. Furthermore, two distinct affected haplotypes for Asian and Western breeds were found, each containing different single-base changes in the upstream sequence (pZRS) of the ZRS. Unlike the previously characterized cases of PPD identified in the mouse and human ZRS regions, the canine mutations in pZRS lacked the ectopic expression of sonic hedgehog in the anterior limb bud, distinguishing its role in limb development from that of the ZRS.
Developmental and Environmental Signals Induce Distinct Histone Acetylation Profiles on Distal and Proximal Promoter Elements of theC4-PepcGene in Maize
Authors: Offermann Sascha , Dreesen Björn , Horst Ina , Danker Tanja , Jaskiewicz Michal , Peterhansel Christoph 
Published: August 2008

AbstractThe maize C4-Pepc gene is expressed in an organ- and cell-type-specific manner, inducible by light and modulated by nutrient availability and the metabolic state of the cell. We studied the contribution of histone acetylation at five lysine residues to the integration of these signals into a graduated promoter response. In roots and coleoptiles, where the gene is constitutively inactive, three of the five lysines were acetylated and the modifications showed unique patterns with respect to their distribution on the gene. A similar pattern was observed in etiolated leaves, where the gene is poised for activation by light. Here, illumination selectively induced the acetylation of histone H4 lysine 5 and histone H3 lysine 9 in both the promoter and the transcribed region, again with unique distribution patterns. Induction was independent of transcription and fully reversible in the dark. Nitrate and hexose availability modulated acetylation of all five lysines restricted to a distal promoter region, whereas proximal promoter acetylation was highly resistant to these stimuli. Our data suggest that light induction of acetylation is controlled by regulating HDAC activity, whereas metabolic signals regulate HAT activity. Acetylation turnover rates were high in the distal promoter and the transcribed regions, but low on the proximal promoter. On the basis of these results, we propose a model with three levels of stimulus-induced histone modifications that collectively adjust promoter activity. The results support a charge neutralization model for the distal promoter and a stimulus-mediated, but transcription-independent, histone acetylation pattern on the core promoter, which might be part of a more complex histone code.
Genomewide Screen for Negative Regulators of Sirtuin Activity inSaccharomyces cerevisiaeReveals 40 Loci and Links to Metabolism
Authors: Raisner Ryan M , Madhani Hiten D 
Published: August 2008

AbstractSirtuins are conserved proteins implicated in myriad key processes including gene control, aging, cell survival, metabolism, and DNA repair. In Saccharomyces cerevisiae, the sirtuin Silent information regulator 2 (Sir2) promotes silent chromatin formation, suppresses recombination between repeats, and inhibits senescence. We performed a genomewide screen for factors that negatively regulate Sir activity at a reporter gene placed immediately outside a silenced region. After linkage analysis, assessment of Sir dependency, and knockout tag verification, 40 loci were identified, including 20 that have not been previously described to regulate Sir. In addition to chromatin-associated factors known to prevent ectopic silencing (Bdf1, SAS-I complex, Rpd3L complex, Ku), we identified the Rtt109 DNA repair-associated histone H3 lysine 56 acetyltransferase as an anti-silencing factor. Our findings indicate that Rtt109 functions independently of its proposed effectors, the Rtt101 cullin, Mms1, and Mms22, and demonstrate unexpected interplay between H3K56 and H4K16 acetylation. The screen also identified subunits of mediator (Soh1, Srb2, and Srb5) and mRNA metabolism factors (Kem1, Ssd1), thus raising the possibility that weak silencing affects some aspect of mRNA structure. Finally, several factors connected to metabolism were identified. These include the PAS-domain metabolic sensor kinase Psk2, the mitochondrial homocysteine detoxification enzyme Lap3, and the Fe-S cluster protein maturase Isa2. We speculate that PAS kinase may integrate metabolic signals to control sirtuin activity.
Molecular Cytogenetic Evidence of Rearrangements on the Y Chromosome of the Threespine Stickleback Fish
Authors: Ross Joseph A , Peichel Catherine L 
Published: August 2008

Abstract
To identify the processes shaping vertebrate sex chromosomes during the early stages of their evolution, it is necessary to study systems in which genetic sex determination was recently acquired. Previous cytogenetic studies suggested that threespine stickleback fish (Gasterosteus aculeatus) do not have a heteromorphic sex chromosome pair, although recent genetic studies found evidence of an XY genetic sex-determination system. Using fluorescence in situ hybridization (FISH), we report that the threespine stickleback Y chromosome is heteromorphic and has suffered both inversions and deletion. Using the FISH data, we reconstruct the rearrangements that have led to the current physical state of the threespine stickleback Y chromosome. These data demonstrate that the threespine Y is more degenerate than previously thought, suggesting that the process of sex chromosome evolution can occur rapidly following acquisition of a sex-determining region.
The Arp2/3 Activators WAVE and WASP Have Distinct Genetic Interactions With Rac GTPases inCaenorhabditis elegansAxon Guidance
Authors: Shakir M Afaq , Jiang Ke , Struckhoff Eric C , Demarco Rafael S , Patel Falshruti B , Soto Martha C , Lundquist Erik A 
Published: August 2008

AbstractIn the developing nervous system, axons are guided to their targets by the growth cone. Lamellipodial and filopodial protrusions from the growth cone underlie motility and guidance. Many molecules that control lamellipodia and filopodia formation, actin organization, and axon guidance have been identified, but it remains unclear how these molecules act together to control these events. Experiments are described here that indicate that, in Caenorhabditis elegans, two WH2-domain-containing activators of the Arp2/3 complex, WVE-1/WAVE and WSP-1/WASP, act redundantly in axon guidance and that GEX-2/Sra-1 and GEX-3/Kette, molecules that control WAVE activity, might act in both pathways. WAVE activity is controlled by Rac GTPases, and data are presented here that suggest WVE-1/WAVE and CED-10/Rac act in parallel to a pathway containing WSP-1/WASP and MIG-2/RhoG. Furthermore, results here show that the CED-10/WVE-1 and MIG-2/WSP-1 pathways act in parallel to two other molecules known to control lamellipodia and filopodia and actin organization, UNC-115/abLIM and UNC-34/Enabled. These results indicate that at least three actin-modulating pathways act in parallel to control actin dynamics and lamellipodia and filopodia formation during axon guidance (WASP–WAVE, UNC-115/abLIM, and UNC-34/Enabled).
Loss of Least-Loaded Class in Asexual Populations Due to Drift and Epistasis
Authors: Jain Kavita 
Published: August 2008

Abstract
We consider the dynamics of a nonrecombining haploid population of finite size that accumulates deleterious mutations irreversibly. This ratchet-like process occurs at a finite speed in the absence of epistasis, but it has been suggested that synergistic epistasis can halt the ratchet. Using a diffusion theory, we find explicit analytical expressions for the typical time between successive clicks of the ratchet for both nonepistatic and epistatic fitness functions. Our calculations show that the interclick time is of a scaling form that in the absence of epistasis gives a speed that is determined by size of the least-loaded class and the selection coefficient. With synergistic interactions, the ratchet speed is found to approach zero rapidly for arbitrary epistasis. Our analytical results are in good agreement with the numerical simulations.
Regulation of Apical Dominance inAspergillus nidulansHyphae by Reactive Oxygen Species
Authors: Semighini Camile P , Harris Steven D 
Published: August 2008

AbstractIn fungal hyphae, apical dominance refers to the suppression of secondary polarity axes in the general vicinity of a growing hyphal tip. The mechanisms underlying apical dominance remain largely undefined, although calcium signaling may play a role. Here, we describe the localized accumulation of reactive oxygen species (ROS) in the apical region of Aspergillus nidulans hyphae. Our analysis of atmA (ATM) and prpA (PARP) mutants reveals a correlation between localized production of ROS and enforcement of apical dominance. We also provide evidence that NADPH oxidase (Nox) or related flavoproteins are responsible for the generation of ROS at hyphal tips and characterize the roles of the potential Nox regulators NoxR, Rac1, and Cdc42 in this process. Notably, our genetic analyses suggest that Rac1 activates Nox, whereas NoxR and Cdc42 may function together in a parallel pathway that regulates Nox localization. Moreover, the latter pathway may also include Bem1, which we propose represents a p40phox analog in fungi. Collectively, our results support a model whereby localized Nox activity generates a pool of ROS that defines a dominant polarity axis at hyphal tips.
Drosophila LIM-Only Is a Positive Regulator of Transcription During Thoracic Bristle Development
Authors: Zenvirt Shamir , Nevo-Caspi Yael , Rencus-Lazar Sigal , Segal Daniel 
Published: August 2008

Abstract
The Drosophila LIM-only (LMO) protein DLMO functions as a negative regulator of transcription during development of the fly wing. Here we report a novel role of DLMO as a positive regulator of transcription during the development of thoracic sensory bristles. We isolated new dlmo mutants, which lack some thoracic dorsocentral (DC) bristles. This phenotype is typical of malfunction of a thoracic multiprotein transcription complex, composed of CHIP, PANNIER (PNR), ACHAETE (AC), and DAUGHTERLESS (DA). Genetic interactions reveal that dlmo synergizes with pnr and ac to promote the development of thoracic DC bristles. Moreover, loss-of-function of dlmo reduces the expression of a reporter target gene of this complex in vivo. Using the GAL4-UAS system we also show that dlmo is spatially expressed where this complex is known to be active. Glutathione-S-transferase (GST)-pulldown assays showed that DLMO can physically bind CHIP and PNR through either of the two LIM domains of DLMO, suggesting that DLMO might function as part of this transcription complex in vivo. We propose that DLMO exerts its positive effect on DC bristle development by serving as a bridging molecule between components of the thoracic transcription complex.
The Y Chromosome That Lost the Male-Determining Function Behaves as an X Chromosome in the Medaka Fish,Oryzias latipes
Authors: Otake Hiroyuki , Hayashi Yusuke , Hamaguchi Satoshi , Sakaizumi Mitsuru 
Published: August 2008

AbstractThe medaka, Oryzias latipes, has an XX/XY sex-determination system, and a Y-linked DM-domain gene, DMY, is the sex-determining gene in this species. Since DMY appears to have arisen from a duplicated copy of the autosomal DMRT1 gene ∼10 million years ago, the medaka Y chromosome is considered to be one of the youngest male-determining chromosomes in vertebrates. In the screening process of sex-reversal mutants from wild populations, we found a population that contained a number of XY females. PCR, direct sequencing, and RT–PCR analyses revealed two different null DMY mutations in this population. One mutation caused loss of expression during the sex-determining period, while the other comprised a large deletion in putative functional domains. YY females with the mutant-type DMY genes on their Y chromosomes were fully fertile, indicating that the X and Y chromosomes were functionally the same except for the male-determining function. In addition, we investigated the frequencies of the sex chromosome types in this population over four successive generations. The Y chromosomes bearing the mutant-type DMY genes were detected every year with no significant differences in their frequencies. These results demonstrate that aberrant Y chromosomes behaving as X chromosomes have been maintained in this population.
Gene Dosage and Gene Duplicability
Authors: Qian Wenfeng , Zhang Jianzhi 
Published: August 2008

Abstract
The evolutionary process leading to the fixation of newly duplicated genes is not well understood. It was recently proposed that the fixation of duplicate genes is frequently driven by positive selection for increased gene dosage (i.e., the gene dosage hypothesis), because haploinsufficient genes were reported to have more paralogs than haplosufficient genes in the human genome. However, the previous analysis incorrectly assumed that the presence of dominant abnormal alleles of a human gene means that the gene is haploinsufficient, ignoring the fact that many dominant abnormal alleles arise from gain-of-function mutations. Here we show in both humans and yeast that haploinsufficient genes generally do not duplicate more frequently than haplosufficient genes. Yeast haploinsufficient genes do exhibit enhanced retention after whole-genome duplication compared to haplosufficient genes if they encode members of stable protein complexes, but the same phenomenon is absent if the genes do not encode protein complex members, suggesting that the dosage balance effect rather than the dosage effect is the underlying cause of the phenomenon. On the basis of these and other results, we conclude that selection for higher gene dosage does not play a major role in driving the fixation of duplication genes.