bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematic analysis of the Pakuashan fault tip fold, west central Taiwan: Shortening rate and age of folding inception
Authors: Simoes Martine , Avouac Jean Philippe , Chen Yue‐Gau , Singhvi Ashok K. , Wang Chien‐Ying , Jaiswal Manoj , Chan Yu‐Chang , Bernard Sylvain
Published: February 2007

The Pakuashan anticline is an active fault tip fold that constitutes the frontal most zone of deformation along the western piedmont of the Taiwan Range. Assessing seismic hazards associated with this fold and its contribution to crustal shortening across central Taiwan requires some understanding of the fold structure and growth rate. To address this, we surveyed the geometry of several deformed strata and geomorphic surfaces, which recorded different cumulative amounts of shortening. These units were dated to ages ranging from ∼19 ka to ∼340 ka using optically stimulated luminescence (OSL). We collected shallow seismic profiles and used previously published seismic profiles to constrain the deep structure of the fold. These data show that the anticline has formed as a result of pure shear with subsequent limb rotation. The cumulative shortening along the direction of tectonic transport is estimated to be 1010 ± 160 m. An analytical fold model derived from a sandbox experiment is used to model growth strata. This yields a shortening rate of 16.3 ± 4.1 mm/yr and constrains the time of initiation of deformation to 62.2 ± 9.6 ka. In addition, the kinematic model of Pakuashan is used to assess how uplift, sedimentation, and erosion have sculpted the present‐day fold topography and morphology. The fold model, applied here for the first time on a natural example, appears promising in determining the kinematics of fault tip folds in similar contexts and therefore in assessing seismic hazards associated with blind thrust faults.
Tropical cirrus clouds near cold point tropopause under ice supersaturated conditions observed by lidar and balloon‐borne cryogenic frost point hygrometer
Authors: Shibata Takashi , Vömel Holger , Hamdi Saipul , Kaloka Sri , Hasebe Fumio , Fujiwara Masatomo , Shiotani Masato
Published: February 2007

Simultaneous vertical profiles of cirrus cloud backscattering and frost point temperature were obtained for the first time in the tropopause region over Bandung, Indonesia, (6.9°S, 107.6°E). These profiles were measured by ground‐based lidar and by balloon‐borne Cryogenic Frost point Hygrometer (CFH) sondes. Supersaturation up to several ten percent was observed by the CFH just below the cold point tropopause at the altitude where a cirrus cloud was observed by lidar. The water vapor mixing ratio decreased slightly at the altitude of the cirrus cloud, suggesting that this decrease was caused by uptake in the cirrus cloud and that the water vapor reduction corresponds to the lower limit of the cloud water content of the observed cirrus cloud. Theoretical calculations of the scattering parameters for the observed cirrus cloud particles and estimations of the time constants for sedimentation and for condensational growth indicate that particles size range is between 4 μm and 30 μm.
Photon recollision probability in heterogeneous forest canopies: Compatibility with a hybrid GO model
Authors: Mõttus Matti , Stenberg Pauline , Rautiainen Miina
Published: February 2007

Photon recollision probability, or the probability by which a photon scattered from a phytoelement in the canopy will interact within the canopy again, has previously been shown to approximate well the fractions of radiation scattered and absorbed by homogeneous plant covers. To test the applicability of the recollision probability theory to more complicated canopy structures, a set of modeled stands was generated using allometric relations for Scots pine trees growing in central Finland. A hybrid geometric‐optical model (FRT, or the Kuusk‐Nilson model) was used to simulate the reflectance and transmittance of the modeled forests consisting of ellipsoidal tree crowns and, on the basis of the simulations, the recollision probability (p) was calculated for the canopies. As the recollision probability theory assumes energy conservation, a method to check and ensure energy conservation in the model was first developed. The method enabled matching the geometric‐optical and two‐stream submodels of the hybrid FRT model, and more importantly, allowed calculation of the recollision probability from model output. Next, to assess the effect of canopy structure on the recollision probability, the obtained p‐values were compared to those calculated for structureless (homogeneous) canopies with similar effective LAI using a simple two‐stream radiation transfer model. Canopy structure was shown to increase the recollision probability, implying that structured canopies absorb more efficiently the radiation interacting with the canopy, and it also changed the escape probabilities for different scattering orders. Most importantly, the study demonstrated that the concept of recollision probability is coherent with physically based canopy reflectance models which use the classical radiative transfer theory. Furthermore, it was shown that as a first approximation, the recollision probability can be considered to be independent of wavelength. Finally, different algorithms for calculation of the recollision probability from measured or modeled radiation fluxes are presented and discussed in the article.
Comparisons between bupropion and dexamphetamine in a range of in vivo tests exploring dopaminergic transmission
Authors: Bredeloux P , Dubuc I , Costentin J
Published: February 2007

Background and purpose:

In the present study we investigated, in a range of in vivo tests whether the antidepressant bupropion, and its metabolites shared the dopamine releasing effect of the chemically related dexamphetamine.

Experimental approach:

We compared bupropion and dexamphetamine in different neurochemical (microdialysis, DOPAC and HVA contents) and behavioural tests, assessing their effects in animals pretreated with a variety of agents (reserpine, sodium hydroxy‐4‐butyrate or haloperidol) known to modify dopaminergic transmission.

Key results:

In mice, dexamphetamine, like bupropion, increased at low doses and reduced at high doses, locomotor activity. Dexamphetamine restored the locomotor activity in mice made akinetic by either sodium hydroxy‐4‐butyrate or reserpine, whereas bupropion did not. Moreover, bupropion prevented the dexamphetamine‐induced reversal of akinetic effects of reserpine. Haloperidol abolished the locomotor‐stimulant effects of dexamphetamine but did not suppress stimulation by bupropion. In microdialysis experiments, in chloral hydrate anesthetized rats, low doses of dexamphetamine (1 mg kg−1) markedly increased the extracellular dopamine concentration in striatum (340%), while bupropion (100 mg kg−1) produced only a moderate increase (150%). Finally, in rat striatum, as well as in the nucleus accumbens, bupropion increased the effect of haloperidol on DOPAC and HVA concentrations, whereas dexamphetamine reduced these haloperidol effects.

Conclusions and implications:

Considering only dopaminergic transmission, our results demonstrated that bupropion and metabolites displayed in vivo, as did bupropion in vitro, an inhibition of dopamine uptake and, contrast to dexamphetamine, were devoid of dopamine releasing effects.

British Journal of Pharmacology (2007) 150, 711–719. doi:10.1038/sj.bjp.0707151
iNOS-Derived NO and Nox2-Derived Superoxide Confer Tolerance to Excitotoxic Brain Injury through Peroxynitrite
Authors: Kawano Takayuki , Kunz Alexander , Abe Takato , Girouard Hélène , Anrather Josef , Zhou Ping , Iadecola Costantino
Published: February 2007

Sublethal injurious stimuli induce tolerance to subsequent lethal insults, a phenomenon termed preconditioning. Inducible nitric oxide synthase (iNOS) is essential for the preconditioning induced by transient bilateral common carotid artery occlusion (BCCAO) or by systemic administration of the endotoxin lipopolysaccharide (LPS). We used a model of brain injury produced by neocortical injection of N-methyl-d-aspartate (NMDA) to investigate the mechanisms by which iNOS-derived nitric oxide (NO) contributes to tolerance induced by LPS or BCCAO. We found that the tolerance is blocked by the iNOS inhibitor aminoguanidine, is not observed in iNOS-null mice, and is rescued by the NO donor DTPA NONOate. Lipopolysaccharide failed to induce preconditioning in mice lacking the nox2 subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, suggesting that superoxide derived from NADPH oxidase is needed for the induction of the tolerance. Because superoxide reacts with NO to form peroxynitrite, we investigated the role of peroxynitrite. We found that LPS induces the peroxynitrite marker 3-nitrotyrosine in cortical neurons and that the peroxynitrite decomposition catalyst FeTPPS abolishes LPS-induced preconditioning. These results suggest that the protective effect of iNOS-derived NO is mediated by peroxynitrite formed by the reaction of NO with NADPH oxidase-derived superoxide. Thus, peroxynitrite, in addition to its well-established deleterious role in ischemic brain injury and neurodegeneration, can also be beneficial by inducing tolerance to excitotoxicity.
Deletion of Aldose Reductase Leads to Protection against Cerebral Ischemic Injury
Authors: Lo Amy CY , Cheung Alvin KH , Hung Victor KL , Yeung Chung-Man , He Qing-Yu , Chiu Jen-Fu , Chung Stephen SM , Chung Sookja K
Published: February 2007

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR−/− brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR−/− brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.
Understanding Your Inhibitions: Modulation of Brain Cortical Metabolism by GABABReceptors
Authors: Nasrallah Fatima A , Griffin Julian L , Balcar Vladimir J , Rae Caroline
Published: February 2007

Although the impact of neuronal excitation on the functional activity of brain is well understood, the nature of functional responses to inhibitory modulation is far from clear. In this work, we investigated the effects of modulation of the metabotropic GABABreceptor on brain metabolism using a targeted neuropharmacological,1H/13C nuclear magnetic resonance spectroscopy, and metabolomic approach. While agonists at GABABreceptors (Baclofen and SKF 97541) generally decreased metabolic activity, mild agonist action could also stimulate metabolism. Less potent antagonists (CGP 35348, Phaclofen) significantly decreased metabolic activity, while more potent antagonists (CGP 52432 and SCH 50911) had opposite, stimulatory, effects. Examination of the data by principal components analysis showed clear divisions of the effects into excitatory and inhibitory components. GABAergic modulation can, therefore, have stimulatory, inhibitory, or even neutral net effects on metabolic activity in brain tissue. This is consistent with GABAergic activity being context dependent, and this conclusion should be taken into account when evaluating functional imaging data involving modulation of neuronal inhibition.
Effect of Sustained-Mild and Transient-Severe Hyperglycemia on Ischemia-Induced Blood–Brain Barrier Opening
Authors: Ennis Steven R , Keep Richard F
Published: February 2007

The purpose of this study was to examine what levels of hyperglycemia cause blood–brain barrier (BBB) disruption during permanent and transient middle cerebral artery occlusion in the rat and when the adverse effects of hyperglycemia occur. Cerebrovascular function was assessed by measuring the influx rate constant ( Ki) for 3H-inulin and by measuring cerebral plasma (14C-inulin) and 51Cr-labeled red blood cell (RBC) volume. Different glucose protocols were used to produce mild sustained hyperglycemia (blood glucose ∼150mg/dL) or transient-severe hyperglycemia (with a spike in blood glucose of ∼ 400 mg/dL). As expected, transient-severe hyperglycemia at the time of occlusion induced marked BBB disruption in animals undergoing 2 h of ischemia with 2 h of reperfusion (25-fold increase in permeability compared with the contralateral core). However, the mild hyperglycemia model induced similar disruption. Similarly, after permanent occlusion, both hyperglycemia models enhanced disruption and they both produced marked (∼ 50%) reductions in cerebral plasma volume. Apparent cerebral RBC volume also decreased when measured during the final 5 mins of 2 h of ischemia with transient-severe hyperglycemia. However, there was no decrease if the 51Cr-labeled RBCs were circulated for the whole 2 h, indicating RBC trapping. The spike in blood glucose in the severe hyperglycemia model was used to examine when hyperglycemia induced BBB disruption. Hyperglycemia shortly after occlusion caused severe disruption. In contrast, hyperglycemia after 90 mins of occlusion caused little disruption. These results suggest that mild hyperglycemia has a profound effect on BBB function and that very early correction of hyperglycemia is necessary to prevent adverse effects.
Abdominal pregnancy in a baboon: a first case report
Authors: Schlabritz‐Loutsevitch N.E. , Hubbard G.B. , Frost P.A. , Cummins L.B. , Dick E.J. , Nathanielsz P.W. , McDonald T.J.
Published: February 2007

Abstract:  The abdominal pregnancy is a rare, but life threatening complication of ectopic embryo implantation. Only three cases of abdominal pregnancy have been previously described in primates: in a squirrel monkey, owl monkey and in a rhesus macaque. A 14‐year‐old wild‐caught olive baboon (Papio cynocephalus anubis) was diagnosed at the ultrasound examination with advanced gestational age extrauterine pregnancy. At the initial laparotomy and necropsy the diagnosis of abdominal pregnancy was made on Studdiford's criteria. This case indicates the possibility of developing a model for further study of different types of ectopic pregnancy and indicates a cesarean section as a risk factor for abdominal pregnancy.
EMS in the pastoral industries of western Queensland: from customisation to implementation
Authors: Sallur N. M. , Weier L. Z. , Pahl L. I. , Holmes S. B. , Yeoman C. S.
Published: February 2007

This paper outlines the customisation of Environmental Management Systems (EMS) for the pastoral industry of western Queensland, the recruitment and training of pastoral producers, and their development and implementation of EMS. EMS was simplified to a 7-step process and producers were recruited to trial this customised EMS. Producers from 40 properties received EMS training, either as groups or individually. Of these, 37 commenced Pastoral EMS development through a facilitated approach that allowed them to learn about EMS while developing an EMS for their property. EMS implementation has been more effective with producers who were trained in groups. At this stage, however, most producers do not see value in EMS as there are currently no strong drivers to warrant continued development and implementation. Key findings resulting from this work were that personal contact and assistance is vital to encourage producers to trial EMS, and that a staged approach to EMS implementation, commencing with a self-assessment, is recommended. EMS training is most successful in a group situation; however, an alternative method of delivery should be provided for those producers who, either by choice or isolation, have to work alone. A support network is also necessary to encourage and maintain progress with EMS development and implementation, particularly where no strong drivers exist.
Benefits, threats and getting started with Environmental Management Systems: views of primary producers and catchment managers in Victoria, Australia
Authors: Seymour E. J.
Published: February 2007

In Victoria, as in many parts of Australia, there is a mixed understanding of what comprises an Environmental Management System (EMS), particularly among professionals in government and industry and landholders. To help overcome this issue, the Victorian government (then Natural Resources and Environment) and the Victorian Farmers Federation formed a partnership in 2003 to promote EMS adoption and coordinate EMS activity on a statewide basis. The Natural Resources and Environment and Victorian Farmers Federation partnership held a series of 11 workshops for catchment management authority regions across Victoria. The purpose was to seek advice from primary producers and catchment managers about how EMS might realistically be implemented and promoted. This paper explores the issues raised at these workshops and the implications they have for EMS adoption and promotion in Victoria, with regard to: (i) potential benefits of implementing EMS on farms; (ii) potential threats to the implementation of EMS on farms; and (iii) how to get started with EMS. A total of 213 people participated in the workshops including 144 landholders. There were some important regional differences in the response data. Improved community perception was seen as a major benefit of EMS (13% of all responses), as were possible market benefits (12%). The major threats to implementation included perceived ‘regulatory creep’ and suspicion of government (14% of responses) and that EMS was a political instrument (13%). Primary producers and catchment managers thought that building on existing schemes and groups was an ideal way to get started with EMS. These results provide a useful basis for how EMS is promoted in Victoria. Ensuring that EMS is driven by industry without being government-heavy is perceived as very important. Better coordination between stakeholders, the provision of practical EMS products and the use of existing groups is a sensible way forward, but in practice this will be difficult to achieve.
Voluntary adoption of Environmental Management Systems in the Australian wine and grape industry depends on understanding stakeholder objectives and drivers
Authors: Tee E. , Boland A.-M. , Medhurst A.
Published: February 2007

In recent years, members of the Australian wine and grape industry have been encouraged to participate in a range of Environmental Management System (EMS)-type programs. These have been sponsored by a variety of stakeholders including government organisations, environmental non-government organisations, industry associations and large corporations. Collectively, these stakeholders have a diverse range of objectives they are seeking to address through the adoption of EMS by grape growers. These objectives range from natural resource management outcomes through to maintenance of market access and meeting investor expectations. However, these stakeholder objectives may not align to the individual needs of grape growers, nor to the drivers that may influence the adoption of an EMS by such individuals. To date, there has been variable success with voluntary adoption of EMS (or similar concepts) across viticulture regions throughout Australia. This paper seeks to clarify this variability based on an assessment of the needs and circumstances of various industry groups associated with EMS initiatives. A conceptual framework is proposed which categorises these particular needs according to different scales of influence (e.g. industry, region, business and individual). In addition, the drivers that operate at the individual grower level are further explored through a qualitative field study. This study has implications for the design and promotion of EMS programs for the wine and grape and other agricultural industries. It is clear that a ‘one size fits all’ approach will not meet the varying needs and objectives of all industry participants. Furthermore, grape growers may not perceive a need to change and, therefore, are yet to identify any benefits from voluntary adoption of an EMS. Alternative mechanisms such as market-based or regulatory instruments may need to be considered, dependent on the objectives that are sought.
The Environmental Stewardship System (ESS): a generic system for assuring rural environmental performance
Authors: Andrew M. , Jarvis T. , Howard B. , McLeod G. , Robinson S. , Standen R. , Toohey D. , Williams A.
Published: February 2007

The Environmental Stewardship System (ESS) is proposed as a generic assurance system for demonstrating environmental performance. It incorporates Environmental Management Systems (EMS) and is matched to natural resources management (NRM) and catchment targets. ESS is a framework for aligning and clarifying environmental objectives and targets across scales. It operates at the catchment and farm levels, interdependently, focusing on the main industries, mainstream farming methods and whole-farm business management. For farmers, it provides a staged pathway of increasing levels of performance and audit process that they can progress along, up to full ISO 14001. It is a modular system that is expandable to suit the particular operational needs of land managers, industries and catchment agencies. ESS is an inclusive framework for integrating various industry farm management improvement schemes and other management requirements. It is an auditable system to provide recognition to land managers who deliver environmental stewardship. The ESS was developed from the findings of the Murray–Darling Basin Commission’s Watermark Environmental Stewardship Project. By addressing the four major deficiencies in current arrangements for NRM delivery (the Stewardship Standard is poorly defined at the Murray–Darling Basin and at the local scales; reporting of outcomes is poorly aligned across scales; and auditing arrangements are not integrated) ESS has the potential to significantly improve the delivery of NRM within Australia, when the drivers for uptake are strong enough. In particular, it would reinforce and elaborate the Australian regional NRM delivery model at the subregional scale. The ESS provides a national framework for assured agricultural production and rural land management. It is in the public domain for others to draw from or adopt.
ASP53, a thermostable protein from Acacia erioloba seeds that protects target proteins against thermal denaturation
Authors: Mtwisha Linda , Farrant Jill M. , Brandt Wolf , Hlongwane Caswell , Lindsey George G.
Published: February 2007

ASP53, a 53 kDa heat soluble protein, was identified as the most abundant protein in the mature seeds of Acacia erioloba E.Mey. Immunocytochemistry showed that ASP53 was present in the vacuoles and cell walls of the axes and cotyledons of mature seeds and disappeared coincident with loss of desiccation tolerance. The sequence of the ASP53 transcript was determined and found to be homologous to the double cupin domain-containing vicilin class of seed storage proteins. Mature seeds survived heating to 60°C and this may be facilitated by the presence of ASP53. Circular dichroism spectroscopy demonstrated that the protein displayed defined secondary structure, which was maintained even at high temperature. ASP53 was found to inhibit all three stages of protein thermal denaturation. ASP53 decreased the rate of loss of alcohol dehydrogenase activity at 55°C, decreased the rate of temperature-dependent loss of secondary structure of haemoglobin and completely inhibited the temperature-dependent aggregation of egg white protein.
Contrasting responses by respiration to elevated CO2 in intact tissue and isolated mitochondria
Authors: Bruhn Dan , Wiskich Joseph T. , Atkin Owen K.
Published: February 2007

The question of whether elevated concentrations of CO2 directly inhibit mitochondrial respiration in plants has received considerable attention. Although there is a growing consensus that elevated [CO2] rarely inhibits respiration of intact tissues, past studies have reported that elevated [CO2] does impact on O2 uptake in isolated mitochondria; what remains unclear, however, is the site(s) where elevated [CO2] impacts on mitochondrial electron transport (ETC). Here we investigated direct effects of [CO2] on respiratory activity of ETC enzymes, intact mitochondria and whole tissues using potato tubers (Solanum tuberosum L. cv. Desiree). Plots of O2 uptake against the redox poise of the ubiquinone (UQ) pool in isolated mitochondria were used to determine whether elevated [CO2] inhibits UQ-reducing and UQ-oxidising pathways differentially. Our results show that mitochondrial respiration was more inhibited via [CO2]/[HCO3–] effects on cytochrome c oxidase (COX) than on succinate dehydrogenase, with [HCO3–] rather than [CO2] inhibiting COX. However, the inhibitory effects at the mitochondrial level did not translate into inhibitory effects at the tissue level. Alternative oxidase (AOX) activity is normally absent in young potato tubers, as was the case in the present study. Thus, the lack of CO2-mediated inhibition at the tissue level was not the result of increases in AOX activity masking the effects of CO2 elsewhere in the respiratory system. We discuss whether the direct impact of elevated [CO2] on respiration is dependent on the rate of metabolic activity and flux control coefficients in individual tissues.
Molecular analysis of human forearm superficial skin bacterial biota
Authors: Gao Zhan , Tseng Chi-hong , Pei Zhiheng , Blaser Martin J.
Published: February 2007

The microbial ecology of human skin is complex, but little is known about its species composition. We examined the diversity of the skin biota from the superficial volar left and right forearms in six healthy subjects using broad-range small subunit rRNA genes (16S rDNA) PCR-based sequencing of randomly selected clones. For the initial 1,221 clones analyzed, 182 species-level operational taxonomic units (SLOTUs) belonging to eight phyla were identified, estimated as 74.0% [95% confidence interval (C.I.), ≈64.8–77.9%] of the SLOTUs in this ecosystem; 48.0 ± 12.2 SLOTUs were found in each subject. Three phyla (
Actinobacteria
,
Firmicutes
, and
Proteobacteria
) accounted for 94.6% of the clones. Most (85.3%) of the bacterial sequences corresponded to known and cultivated species, but 98 (8.0%) clones, comprising 30 phylotypes, had <97% similarity to prior database sequences. Only 6 (6.6%) of the 91 genera and 4 (2.2%) of the 182 SLOTUs, respectively, were found in all six subjects. Analysis of 817 clones obtained 8–10 months later from four subjects showed additional phyla (numbering 2), genera (numbering 28), and SLOTUs (numbering 65). Only four (3.4%) of the 119 genera (
Propionibacteria
,
Corynebacteria
,
Staphylococcus
, and
Streptococcus
) were observed in each subject tested twice, but these genera represented 54.4% of all clones. These results show that the bacterial biota in normal superficial skin is highly diverse, with few well conserved and well represented genera, but otherwise low-level interpersonal consensus.
Exploring the proton pump mechanism of cytochrome
c
oxidase in real time
Authors: Belevich Ilya , Bloch Dmitry A. , Belevich Nikolai , Wikström Mårten , Verkhovsky Michael I.
Published: February 2007

Cytochrome
c
oxidase catalyzes most of the biological oxygen consumption on Earth, a process responsible for energy supply in aerobic organisms. This remarkable membrane-bound enzyme also converts free energy from O
2
reduction to an electrochemical proton gradient by functioning as a redox-linked proton pump. Although the structures of several oxidases are known, the molecular mechanism of redox-linked proton translocation has remained elusive. Here, correlated internal electron and proton transfer reactions were tracked in real time by spectroscopic and electrometric techniques after laser-activated electron injection into the oxidized enzyme. The observed kinetics establish the long-sought reaction sequence of the proton pump mechanism and describe some of its thermodynamic properties. The 10-μs electron transfer to heme
a
raises the pK
a
of a “pump site,” which is loaded by a proton from the inside of the membrane in 150 μs. This loading increases the redox potentials of both hemes
a
and
a
3
, which allows electron equilibration between them at the same rate. Then, in 0.8 ms, another proton is transferred from the inside to the heme
a
3
/Cu
B
center, and the electron is transferred to Cu
B
. Finally, in 2.6 ms, the preloaded proton is released from the pump site to the opposite side of the membrane.
Differentiation of ES cells into cerebellar neurons
Authors: Salero Enrique , Hatten Mary E.
Published: February 2007

The neuronal circuits of the cerebellar cortex are essential for motor and sensory learning, associative memory formation, and the vestibular ocular reflex. In children and young adults, tumors of the granule cell, the medulloblastomas, represent 40% of brain tumors. We report the differentiation of E14 ES cells into mature granule neurons by sequential treatment with secreted factors (WNT1, FGF8, and RA) that initiate patterning in the cerebellar region of the neural tube, bone morphogenic proteins (BMP6/7 and GDF7) that induce early granule cell progenitor markers (MATH1, MEIS1, ZIC1), mitogens (SHH, JAG1) that control proliferation and induce additional granule cell markers (Cyclin D2, PAX2/6), and culture in glial-conditioned medium to induce markers of mature granule neurons (GABAα
6
r), including ZIC2, a unique marker for granule neurons. Differentiated ES cells formed classic “T-shaped” granule cell axons
in vitro
, and implantation of differentiated
Pde1c-Egfp-
BAC transgenic ES cells into the external granule cell layer of neonatal mice resulted in the extension of parallel fibers, migration across the molecular layer, incorporation into the internal granule cell layer, and extension of short dendrites, typical of young granule cells forming synaptic connections with afferent mossy fibers. These results underscore the utility of treating ES cells with local, inductive signals that regulate CNS neuronal development
in vivo
as a strategy for cell replacement therapy of defined neuronal populations.
Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-γ-induciblegbp2gene
Authors: Ramsauer Katrin , Farlik Matthias , Zupkovitz Gordin , Seiser Christian , Kröger Andrea , Hauser Hansjörg , Decker Thomas
Published: February 2007

A subgroup of genes induced by IFN-γ requires both STAT1 and IRF1 for transcriptional activation. Using WT,stat1−/−, orirf1−/−cells, we analyzed the changes induced by IFN-γ ingbp2promoter chromatin. STAT1 associated with the promoter independently of IRF1 and played an essential role in the ordered recruitment of the coactivator/histone acetyl transferase CREB-binding protein (CBP) and the histone deacetylase HDAC1. Hyperacetylation of histone 4 also required STAT1. Phosphorylation at S727 in the transactivating domain increased transcriptional activity of STAT1. In cells expressing a STAT1S727A-mutant CBP recruitment, histone 4 hyperacetylation and RNA polymerase II association with thegbp2promoter were strongly reduced. IRF1 association with thegbp2promoter followed that of STAT1, but STAT1 association with DNA or histone hyperacetylation were not necessary for IRF1 binding. RNA polymerase II association with thegbp2promoter required both STAT1 and IRF1, suggesting that both proteins mediate essential steps in transcriptional activation. IRF1, but not STAT1, was found to coimmunoprecipitate with RNA polymerase II. Together, the data support the assumption that the main role of STAT1 in activatinggbp2transcription is to provide transcriptionally competent chromatin, whereas the function of IRF1 may lie in directly contacting RNA polymerase II-containing transcriptional complexes.
CD34+ hematopoietic stem-progenitor cell microRNA expression and function: A circuit diagram of differentiation control
Authors: Georgantas Robert W. , Hildreth Richard , Morisot Sebastien , Alder Jonathan , Liu Chang-gong , Heimfeld Shelly , Calin George A. , Croce Carlo M. , Civin Curt I.
Published: February 2007

MicroRNAs (miRNAs) are a recently identified class of epigenetic elements consisting of small noncoding RNAs that bind to the 3′ untranslated region of mRNAs and down-regulate their translation to protein. miRNAs play critical roles in many different cellular processes including metabolism, apoptosis, differentiation, and development. We found 33 miRNAs expressed in CD34+ hematopoietic stem-progenitor cells (HSPCs) from normal human bone marrow and mobilized human peripheral blood stem cell harvests. We then combined these data with human HSPC mRNA expression data and with miRNA-mRNA target predictions, into a previously undescribed miRNA:mRNA interaction database called the Transcriptome Interaction Database. The
in silico
predictions from the Transcriptome Interaction Database pointed to miRNA control of hematopoietic differentiation through translational control of mRNAs critical to hematopoiesis. From these predictions, we formulated a model for miRNA control of stages of hematopoiesis in which many of the genes specifying hematopoietic differentiation are expressed by HSPCs, but are held in check by miRNAs until differentiation occurs. We validated miRNA control of several of these target mRNAs by demonstrating that their translation in fact is decreased by miRNAs. Finally, we chose
miRNA-155
for functional characterization in hematopoiesis, because we predicted that it would control both myelopoiesis and erythropoiesis. As predicted,
miRNA-155
transduction greatly reduced both myeloid and erythroid colony formation of normal human HSPCs.
An
in vitro
and
in vivo
disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists
Authors: Eubanks Lisa M. , Hixon Mark S. , Jin Wei , Hong Sukwon , Clancy Colin M. , Tepp William H. , Baldwin Michael R. , Malizio Carl J. , Goodnough Michael C. , Barbieri Joseph T. , Johnson Eric A. , Boger Dale L. , Dickerson Tobin J. , Janda Kim D.
Published: February 2007

Among the agents classified as “Category A” by the U.S. Centers for Disease Control and Prevention, botulinum neurotoxin (BoNT) is the most toxic protein known, with microgram quantities of the protein causing severe morbidity and mortality by oral or i.v. routes. Given that this toxin easily could be used in a potential bioterrorist attack, countermeasures urgently are needed to counteract the pathophysiology of BoNT. At a molecular level, BoNT exerts its paralytic effects through intracellular cleavage of vesicle docking proteins and subsequent organism-wide autonomic dysfunction. In an effort to identify small molecules that would disrupt the interaction between the light-chain metalloprotease of BoNT serotype A and its cognate substrate, a multifaceted screening effort was undertaken. Through the combination of
in vitro
screening against an optimized variant of the light chain involving kinetic analysis, cellular protection assays, and
in vivo
mouse toxicity assays, molecules that prevent BoNT/A-induced intracellular substrate cleavage and extend the time to death of animals challenged with lethal toxin doses were identified. Significantly, the two most efficacious compounds
in vivo
showed less effective activity in cellular assays intended to mimic BoNT exposure; indeed, one of these compounds was cytotoxic at concentrations three orders of magnitude below its effective dose in animals. These two lead compounds have surprisingly simple molecular structures and are readily amenable to optimization efforts for improvements in their biological activity. The findings validate the use of high-throughput screening protocols to define previously unrecognized chemical scaffolds for the development of therapeutic agents to treat BoNT exposure.
Tissue-specific activity of the blind mole rat and the two nucleotide-mutated mouse αB-crystallin promoter in transgenic mice
Authors: Li Yan , Hough R. Barry , Piatigorsky Joram
Published: February 2007

The α
B-crystallin
and
HspB2
genes are located ≈0.9 kb apart in a head-to-head arrangement in mammals. Previous experiments have shown that a truncated −668/+45 αB-crystallin enhancer/promoter fragment from blind mole rats (
Spalax ehrenbergi
), which have nonfunctional lenses, lacks lens activity and has enhanced muscle activity in transgenic mice. Here we show that the full-length mole rat αB-crystallin intergenic region behaves similarly in transgenic mice. A two-nucleotide mutation (
−273
CA→G) in the mouse αB-crystallin enhancer/promoter fragment mimicking the wild-type mole rat sequence functionally converted the mouse promoter fragment to that of the wild-type mole rat promoter when tested in transgenic mice. The reciprocal mutation in the mole rat promoter fragment (
−272
G→CA) did not affect its activity. Oligonucleotides from the wild-type mouse and mole rat αB-crystallin promoter region under study formed distinct complexes with nuclear proteins from cultured cells. The mouse mutant sequence lost binding ability, whereas the mutated mole rat sequence gained the ability to form a complex similar in size to that of the wild-type mouse oligonucleotide. Our data support the idea that blind mole rats' αB-crystallin promoter activity was modified during the evolution of subterranean life and shows that tissue-specific promoter activity can be modulated by changing as few as two apparently neutral nucleotides in the mouse αB-crystallin enhancer region, implying the importance of the context of regulatory sequences for promoter activity.
Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells
Authors: Kothapalli Devashish , Zhao Liang , Hawthorne Elizabeth A. , Cheng Yan , Lee Eric , Puré Ellen , Assoian Richard K.
Published: February 2007

High molecular weight (HMW) hyaluronan (HA) is widely distributed in the extracellular matrix, but its biological activities remain incompletely understood. We previously reported that HMW-HA binding to CD44 antagonizes mitogen-induced S-phase entry in vascular smooth muscle cells (SMCs; Cuff, C.A., D. Kothapalli, I. Azonobi, S. Chun, Y. Zhang, R. Belkin, C. Yeh, A. Secreto, R.K. Assoian, D.J. Rader, and E. Puré. 2001. J. Clin. Invest. 108:1031–1040); we now characterize the underlying molecular mechanism and document its relevance in vivo. HMW-HA inhibits the mitogen-dependent induction of cyclin D1 and down-regulation of p27kip1 in vascular SMCs. p27kip1 messenger RNA levels were unaffected by HMW-HA, but the expression of Skp2, the rate-limiting component of the SCF complex that degrades p27kip1, was reduced. Rescue experiments identified cyclin D1 as the primary target of HMW-HA. Similar results were observed in fibroblasts, and these antimitogenic effects were not detected in CD44-null cells. Analysis of arteries from wild-type and CD44-null mice showed that the effects of HMW-HA/CD44 on cyclin D1 and Skp2 gene expression are detected in vivo and are associated with altered SMC proliferation after vascular injury.
Cultural Differences in Brand Extension Evaluation: The Influence of Analytic versus Holistic Thinking
Authors: Monga Alokparna Basu , John Deborah Roedder
Published: February 2007

Consumers evaluate brand extensions by judging how well they fit with the parent brand. We examine this process across cultures. We predict that consumers from Eastern cultures, characterized by holistic thinking, perceive higher brand extension fit and evaluate brand extensions more favorably than do Western consumers, characterized by analytic thinking. Study 1 supports the existence of these cultural differences, with study 2 providing support for styles of thinking (analytic vs. holistic) as the drivers of cultural differences in brand extension evaluations.
Perillyl Alcohol Protects against Fe‐NTA‐Induced Nephrotoxicity and Early Tumor Promotional Events in Rat Experimental Model
Authors: Jahangir Tamanna , Sultana Sarwat
Published: February 2007

Plants have been widely used as protective agents against a wide variety of processes and compounds that damage tissues via free radical mechanisms. Perillyl alcohol (PA) is a naturally occurring monoterpene found in the essential oils of numerous species of plants including mints, cherries and celery seeds. This monocyclic monoterpene has shown antioxidant and therapeutic activity in various studies against various xenobiotics. In this study, we have analyzed the effects of PA against single intraperitoneal dose of ferric nitrilotriacetate (Fe‐NTA) (9 mg iron per kg body weight)‐induced nephrotoxicity and early tumor promotional events. The pretreatment of Fe‐NTA‐treated rats with 0.5% per kg body weight dose and 1% per kg body weight dose of PA for seven consecutive days significantly reversed the Fe‐NTA‐induced malondialdehyde formation, xanthine oxidase activity (P < 0.001), ornithine decarboxylase activity (P < 0.001) and 3[H]thymidine incorporation in renal DNA (P < 0.001) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen and creatinine (P < 0.001). Significant restoration at both the doses was recorded in depleted renal glutathione content, and its dependent enzymes with prophylactic treatment of PA. Present results suggest that PA potentially attenuates against Fe‐NTA‐induced oxidative damage and tumor promotional events that preclude its development as a future drug to avert the free radical‐induced toxicity.
Two Kampo Medicines, Jidabokuippo and Hachimijiogan Alleviate Sprains, Bruises and Arthritis
Authors: Hijikata Yasuyo , Miyamae Yuko , Takatsu Hisako , Sentoh Seishiro
Published: February 2007

In traditional Chinese medicine theory (TCM), the affected parts of sprains, bruises and arthritis are considered to be under certain conditions of TCM concept. We administered two Kampo medicines with synergistic effects to promote quick recovery from these conditions. Jidabokuippo (Zhidapuyifang in Chinese), which means ‘decoction for contusions’ is expected to remove these conditions. Hachimijiogan (Baweidihuangwan in Chinese), which translates as ‘eight‐ingredient pill with Rehmannia’ is expected to restore presumed minute bone injury and regulates bone metabolism by changing such conditions based on TCM theory. We administered the two prescriptions to 10 patients (age range: 40–85 years; 1 male, 9 females) suffering from bruises, sprains, arthritis and spinal compression fracture without changing their routine intake of other drugs. Patients reported on changes in the pain of affected body parts by using the visual analog scale (VAS) before and after administration of Kampo medicine. In almost all cases, recovery began promptly after administration and the pain disappeared within ~2 weeks. Large doses for a short time brought about much quicker recovery than small doses. Administration of a combination of two Kampo medicines, Jidabokuippo and Hachimijiogan, quickly resolved the pain of bruises, sprains, arthritis and one spinal compression fracture.
Amelioration of Heat Stress Induced Disturbances of Antioxidant Defense System in Chicken by Brahma Rasayana
Authors: Ramnath V. , Rekha P. S. , Sujatha K. S.
Published: February 2007

Since the range of comfort zone or thermo neutral zone of domestic chickens is narrow, they become easily susceptible to heat and cold environmental stress. We evaluated Brahma Rasayana (BR) supplementation on concentrations of certain oxidative stress markers associated with heat stress. A total of 48 egg type male chickens of local strain were divided into six groups (n = 8) for the study. Three groups were fed with BR orally at the rate of 2 g/kg bw daily for 10 days prior to and during the period of experiment. Two of the four groups that were exposed to heat stress (HST i.e. to a temperature of 40 ± 1°C and relative humidity of 80 ± 5% in an environmental chamber) for 4 h daily for 5 or 10 days, received BR orally. The other two groups remained as BR treated and untreated non‐heat stressed (NHST) controls. There was a significant (P < 0.05) increase in the activities of antioxidant enzymes in blood such as catalase (CAT) and superoxide dismutase (SOD), as well as liver CAT, glutathione peroxidase (GPX) and glutathione reductase (GR) in NHST‐BR treated and HST‐BR treated (both 5 and 10 days) chickens when compared with untreated controls. A great deal of significant (P < 0.05) variations were seen in serum and liver reduced glutathione (GSH) concentration in NHST‐BR treated and HST‐BR treated (both 5 and 10 days) chickens. Serum and liver lipid peroxidation levels were found to be significantly (P < 0.05) higher in HST‐untreated (both 5 and 10 days) chickens when compared with other groups. Thus BR supplementation during HST brings about enhanced action of enzymatic and non‐enzymatic antioxidants, which nullified the undesired side effects of free radicals that are generated during HST.
F-Box Proteins in Rice. Genome-Wide Analysis, Classification, Temporal and Spatial Gene Expression during Panicle and Seed Development, and Regulation by Light and Abiotic Stress
Authors: Jain Mukesh , Nijhawan Aashima , Arora Rita , Agarwal Pinky , Ray Swatismita , Sharma Pooja , Kapoor Sanjay , Tyagi Akhilesh K. , Khurana Jitendra P.
Published: February 2007

F-box proteins constitute a large family in eukaryotes and are characterized by a conserved F-box motif (approximately 40 amino acids). As components of the Skp1p-cullin-F-box complex, F-box proteins are critical for the controlled degradation of cellular proteins. We have identified 687 potential F-box proteins in rice (Oryza sativa), the model monocotyledonous plant, by a reiterative database search. Computational analysis revealed the presence of several other functional domains, including leucine-rich repeats, kelch repeats, F-box associated domain, domain of unknown function, and tubby domain in F-box proteins. Based upon their domain composition, they have been classified into 10 subfamilies. Several putative novel conserved motifs have been identified in F-box proteins, which do not contain any other known functional domain. An analysis of a complete set of F-box proteins in rice is presented, including classification, chromosomal location, conserved motifs, and phylogenetic relationship. It appears that the expansion of F-box family in rice, in large part, might have occurred due to localized gene duplications. Furthermore, comprehensive digital expression analysis of F-box protein-encoding genes has been complemented with microarray analysis. The results reveal specific and/or overlapping expression of rice F-box protein-encoding genes during floral transition as well as panicle and seed development. At least 43 F-box protein-encoding genes have been found to be differentially expressed in rice seedlings subjected to different abiotic stress conditions. The expression of several F-box protein-encoding genes is also influenced by light. The structure and function of F-box proteins in plants is discussed in light of these results and the published information. These data will be useful for prioritization of F-box proteins for functional validation in rice.