bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular program controlling the recovery of adipose tissue mass: An
in vivo
imaging approach
Authors: Birsoy Kıvanç , Soukas Alexander , Torrens Javier , Ceccarini Giovanni , Montez Jason , Maffei Margherita , Cohen Paul , Fayzikhodjaeva Gulnorakhon , Viale Agnes , Socci Nicholas D. , Friedman Jeffrey M.
Published: August 2008

The cellular program responsible for the restoration of adipose tissue mass after weight loss is largely uncharacterized. Leptin mRNA levels are highly correlated with adipose tissue mass, and leptin expression can thus be used as a surrogate for changes in the amount of adipose tissue. To further study the responses of adipocytes to changes in weight, we created a transgenic mouse expressing the luciferase reporter gene under the control of leptin regulatory sequences, which allows noninvasive imaging of the leptin expression of mice
in vivo
. We used these animals to show that weight loss induced by fasting or leptin treatment results in the retention of lipid-depleted adipocytes in adipose depots. To further study the cellular response to weight regain after leptin treatment, a leptin withdrawal protocol was used to induce a state of acute leptin deficiency in wild type mice. Acute leptin deficiency led to the transient deposition of large amounts of glycogen within pre-existing, lipid-depleted adipocytes. This was followed by rapid reaccumulation of lipid. Transcriptional profiling revealed that this cellular response was associated with induction of mRNAs for the entire pathway of enzymes necessary to convert glucose into acetyl-CoA and glycerol, key substrates for the synthesis of triglycerides.
Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor
Authors: Zhang Da-Wei , Garuti Rita , Tang Wan-Jin , Cohen Jonathan C. , Hobbs Helen H.
Published: August 2008

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that controls plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor (LDLR). Previously, we showed that PCSK9 binds specifically to an EGF-like repeat (EGF-A) in LDLR and reroutes the receptor from endosomes to lysosomes rather than to the cell surface. Here, we defined the regions in LDLR and PCSK9 that are required for receptor degradation and examined the relationship between PCSK9 binding and LDLR conformation. Addition of PCSK9 to cultured hepatocytes promoted degradation of WT LDLR and of receptors lacking up to four ligand binding domains, EGF-B or the clustered O-linked sugar region. In contrast, LDLRs lacking the entire ligand binding domain or the β-propeller domain failed to be degraded, although they bound and internalized PCSK9. Using gel filtration chromatography, we assessed the effects of PCSK9 binding on an acid-dependent conformational change that happens in the extracellular domain of the LDLR. Although PCSK9 prevented the reduction in hydrodynamic radius of the receptor that occurs at a reduced pH, the effect was not sufficient for LDLR degradation. A truncated version of PCSK9 containing the prodomain and the catalytic domain, but not the C-terminal domain, bound the receptor but did not stimulate LDLR degradation. Thus, domains in both the LDLR and PCSK9 that are not required for binding (or internalization) are essential for PCSK9-mediated degradation of the LDLR.
Case-Control Study of Clinical Features of Influenza in Hospitalized Patients
Authors: Babcock Hilary M. , Merz Liana R. , Dubberke Erik R. , Fraser Victoria J.
Published: August 2008

Background.

The symptoms of influenza infection in outpatients are well described. The Centers for Disease Control and Prevention (CDC) definition of an influenza-like illness (ILI) includes fever and cough or sore throat. Few data exist on the clinical presentation of influenza in hospitalized patients, which may be distinct from the clinical presentation of influenza in ambulatory patients because of underlying medical conditions and medications.

Design.

Retrospective case-control study.

Setting.

A 1,250-bed urban teaching hospital.

Patients.

A total of 369 patients were admitted to the general medicine wards during 3 consecutive influenza seasons (2001-2004): 123 case patients with laboratory-confirmed influenza that was diagnosed during routine medical care and 246 control patients with active surveillance culture results negative for influenza.

Methods.

Data on demographic characteristics, comorbidities, and signs and symptoms were obtained from a review of the medical records of the case and control patients. Analysis included stratified analysis and logistic regression.

Results.

Cough, coryza, sore throat, and fever were more common in patients with influenza infection. The CDC's definition of an ILI had a sensitivity of 43% and specificity of 86% in the study population, with a crude odds ratio (OR) of 4.7 (95% confidence interval [CI], 2.8-7.8). The sensitivity of the CDC's definition of an ILI decreased to 21% among asthmatic patients, who had similar rates of fever and/or ILI with or without influenza. By logistic regression, ILI was strongly associated with influenza infection in patients without asthma (adjusted OR, 7.5 [95% CI, 4.1-13.7]) but not in patients with asthma (adjusted OR, 1.1 [95% CI, 0.13-10]). The positive predictive value of an ILI in asthmatic patients was 50%.

Conclusions.

The CDC's definition of an ILI lacks sensitivity among hospitalized patients, and the presence of an ILI is not associated with influenza infection in asthmatic patients.
BAH1/NLA, a RING-Type Ubiquitin E3 Ligase, Regulates the Accumulation of Salicylic Acid and Immune Responses toPseudomonas syringaeDC3000
Authors: Yaeno Takashi , Iba Koh
Published: August 2008

Salicylic acid (SA) is a primary factor responsible for exerting diverse immune responses in plants and is synthesized in response to attack by a wide range of pathogens. The Arabidopsis (Arabidopsis thaliana) sid2 mutant is defective in a SA biosynthetic pathway involving ISOCHORISMATE SYNTHASE1 (ICS1) and consequently contains reduced levels of SA. However, the sid2 mutant as well as ICS-suppressed tobacco (Nicotiana benthamiana) still accumulate a small but significant level of SA. These observations along with previous studies suggest that SA might also be synthesized by another pathway involving benzoic acid (BA). Here we isolated a benzoic acid hypersensitive1-Dominant (bah1-D) mutant that excessively accumulated SA after application of BA from activation-tagged lines. This mutant also accumulated higher levels of SA after inoculation with Pseudomonas syringae pv tomato DC3000. Analysis of the bah1-D sid2 double mutant suggested that the bah1-D mutation caused both ICS1-dependent and -independent accumulation. In addition, the bah1-D mutant showed SA-dependent localized cell death in response to P. syringae pv tomato DC3000. The T-DNA insertional mutation that caused the bah1-D phenotypes resulted in the suppression of expression of the NLA gene, which encodes a RING-type ubiquitin E3 ligase. These results suggest that BAH1/NLA plays crucial roles in the ubiquitination-mediated regulation of immune responses, including BA- and pathogen-induced SA accumulation, and control of cell death.
Dynamic Proteomic Analysis Reveals a Switch between Central Carbon Metabolism and Alcoholic Fermentation in Rice Filling Grains
Authors: Xu Sheng Bao , Li Tang , Deng Zhu Yun , Chong Kang , Xue Yongbiao , Wang Tai
Published: August 2008

Accumulation of reserve materials in filling grains involves the coordination of different metabolic and cellular processes, and understanding the molecular mechanisms underlying the interconnections remains a major challenge for proteomics. Rice (Oryza sativa) is an excellent model for studying grain filling because of its importance as a staple food and the available genome sequence database. Our observations showed that embryo differentiation and endosperm cellularization in developing rice seeds were completed approximately 6 d after flowering (DAF); thereafter, the immature seeds mainly underwent cell enlargement and reached the size of mature seeds at 12 DAF. Grain filling began at 6 DAF and lasted until 20 DAF. Dynamic proteomic analyses revealed 396 protein spots differentially expressed throughout eight sequential developmental stages from 6 to 20 DAF and determined 345 identities. These proteins were involved in different cellular and metabolic processes with a prominently functional skew toward metabolism (45%) and protein synthesis/destination (20%). Expression analyses of protein groups associated with different functional categories/subcategories showed that substantially up-regulated proteins were involved in starch synthesis and alcoholic fermentation, whereas the down-regulated proteins in the process were involved in central carbon metabolism and most of the other functional categories/subcategories such as cell growth/division, protein synthesis, proteolysis, and signal transduction. The coordinated changes were consistent with the transition from cell growth and differentiation to starch synthesis and clearly indicated that a switch from central carbon metabolism to alcoholic fermentation may be important for starch synthesis and accumulation in the developmental process.
Genetic Variation for Lettuce Seed Thermoinhibition Is Associated with Temperature-Sensitive Expression of Abscisic Acid, Gibberellin, and Ethylene Biosynthesis, Metabolism, and Response Genes
Authors: Argyris Jason , Dahal Peetambar , Hayashi Eiji , Still David W. , Bradford Kent J.
Published: August 2008

Lettuce (Lactuca sativa ‘Salinas’) seeds fail to germinate when imbibed at temperatures above 25°C to 30°C (termed thermoinhibition). However, seeds of an accession of Lactuca serriola (UC96US23) do not exhibit thermoinhibition up to 37°C in the light. Comparative genetics, physiology, and gene expression were analyzed in these genotypes to determine the mechanisms governing the regulation of seed germination by temperature. Germination of the two genotypes was differentially sensitive to abscisic acid (ABA) and gibberellin (GA) at elevated temperatures. Quantitative trait loci associated with these phenotypes colocated with a major quantitative trait locus (Htg6.1) from UC96US23 conferring germination thermotolerance. ABA contents were elevated in Salinas seeds that exhibited thermoinhibition, consistent with the ability of fluridone (an ABA biosynthesis inhibitor) to improve germination at high temperatures. Expression of many genes involved in ABA, GA, and ethylene biosynthesis, metabolism, and response was differentially affected by high temperature and light in the two genotypes. In general, ABA-related genes were more highly expressed when germination was inhibited, and GA- and ethylene-related genes were more highly expressed when germination was permitted. In particular, LsNCED4, a gene encoding an enzyme in the ABA biosynthetic pathway, was up-regulated by high temperature only in Salinas seeds and also colocated with Htg6.1. The temperature sensitivity of expression of LsNCED4 may determine the upper temperature limit for lettuce seed germination and may indirectly influence other regulatory pathways via interconnected effects of increased ABA biosynthesis.
OPINIONS OF RESEARCHERS BASED IN THE UK ON RECRUITING SUBJECTS FROM DEVELOPING COUNTRIES INTO RANDOMIZED CONTROLLED TRIALS
Authors: NEWTON SAM K. , APPIAH‐POKU JOHN
Published: August 2008

Background:  Explaining technical terms in consent forms prior to seeking informed consent to recruit into trials can be challenging in developing countries, and more so when the studies are randomized controlled trials. This study was carried out to examine the opinions of researchers on ways of dealing with these challenges in developing countries.

Methods:  Recorded in‐depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees.

Results:  Researchers were divided on the feasibility of explaining technical trials in illiterate populations; the majority of them held the view that local analogies could be used to explain these technical terms. Others were of the opinion that this could not be done since it was too difficult to explain technical trials, such as randomized controlled trials, even to people in developed countries.

Conclusion:  Researchers acknowledged the difficulty in explaining randomized controlled trials but it was also their perception that this was an important part of the ethics of the work of scientific research involving human subjects. These difficulties notwithstanding, efforts should be made to ensure that subjects have sufficient understanding to consent, taking into account the fact that peculiar situations in developing countries might compound this difficulty.
Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma
Authors: Morris T. C. M. , Kettle P. J. , Drake M. , Jones F. C. G. , Hull D. R. , Boyd K. , Morrison A. , Clarke P. , O’Reilly P. , Quinn J.
Published: August 2008

A combination of clarithromycin, low dose of thalidomide and low dose dexamethasone was used in a phase II study to treat patients with relapsed and refractory myeloma. Thirty patients received clarithromycin 250 mg twice daily and thalidomide 50 mg at night on an ongoing basis with 4‐d pulses of 10 mg dexamethasone given monthly. Eight patients had permitted escalation of thalidomide dosage up to 200 mg daily. The combination was well tolerated and could be given to elderly, infirm and severely cytopenic patients. Response rates were high, with 89% achieving at least 50% reduction in paraprotein and a 96% overall response rate. Although clarithromycin has only minimal anti‐myeloma properties when used as a single agent, its combination with thalidomide and dexamethasone appears very effective, allowing these to be used in lower and more tolerable doses with good clinical effects.
Introns 1 and 22 inversions and factor VIII inhibitors in patients with severe haemophilia A in southern Brazil
Authors: LEIRIA L. B. , ROISENBERG I. , SALZANO F. M. , BANDINELLI E.
Published: August 2008

Summary.  A total of 107 unrelated severe haemophilia A patients living in the southern Brazilian state of Rio Grande do Sul were studied in relation to the prevalence of inversions present in introns 22 and 1 and a subsample of them (95) tested for the presence of Factor VIII inhibitors. These data were then incorporated with those from 15 other countries and 3871 patients. The frequencies of these two inversions show a remarkable homogeneity in series collected in different continents, from people with diverse ethnic extraction. The prevalence of inhibitors among patients with inversion 22, on the other hand, varies widely (5–51%; seven countries, 1482 patients), the value observed by us being the highest. The importance of obtaining data from patients throughout the world to clarify the aetiology of this important complicating factor in the therapeutics of the disease is emphasized.
Effect of polyphenol and pH on cocoa Maillard‐related flavour precursors in a lipidic model system
Authors: Noor‐Soffalina S. S. , Jinap S. , Nazamid S. , Nazimah S. A. H.
Published: August 2008

Polyphenol and pH influence the flavour quality of cocoa beans during roasting. Amino acids and reducing sugars are flavour precursors in cocoa beans, which develop into cocoa‐specific aroma through Maillard reactions during roasting. A central composite design was applied to determine the combined effect of polyphenol and pH on the flavour precursors during cocoa roasting at 120 °C for 45 min using a lipidic model system. Polyphenol was added at 40, 80 and 120 g kg−1and pH was adjusted to 4.5, 6 and 7.5. The response surface methodology revealed that a lower concentration of amino acids and reducing sugars was obtained at higher polyphenol concentration (120 g kg−1) and lower pH value (4.5). Based on the constraints set, the best polyphenol concentration of 43–58 g kg−1and pH of 7.0–7.5 was found to be optimum for the formation of flavour precursors in this lipidic model study.
Reliability and validity of the revised Triple C: Checklist of Communicative Competencies for adults with severe and multiple disabilities
Authors: Iacono T. , West D. , Bloomberg K. , Johnson H.
Published: August 2008

Aims  Few tools are available to assess the communication skills of adults with severe and multiple disabilities functioning at unintentional to early symbolic levels. An exception is the Triple C: Checklist of Communicative Competencies. In this study, aspects of support worker and clinician agreement, internal consistency and construct validity of a revised version of the Triple C were explored.

Method  Triple C checklists were completed for 72 adults with severe intellectual disabilities (ID) by 118 support workers and stages were assigned by the researchers. Two support workers completed checklists for each of 68 adults with ID. Three researchers also conducted direct observations of 20 adults with ID.

Results  The average support worker agreement for items across the five stages of the Triple C ranged from 81% to 87%; agreement for stage assignment based on first and second support worker checklists was moderate to high (k = 0.63). Internal consistency was high (KR20 = 0.97); the stages were found to tap one factor (accounting for ∼74% of variance), interpreted to be unintentional to early symbolic communication. Agreements between stages based on researcher observations and support worker‐completed checklists were 35% and 71% across first and second support workers.

Conclusion  The revised Triple C provides a reliable means of gathering data on which to determine the communication skills of adults with severe and multiple disabilities. The results support a collaborative use of the Triple C, such that a speech‐language pathologist or other communication specialist works with a support worker to ensure understanding of the skills observed and development of appropriate intervention strategies.
Imaging amoeboid cancer cell motility in vivo
Authors: PINNER S. , SAHAI E.
Published: August 2008

The availability of multi‐photon intravital microscopy has recently allowed researchers to start to visualise the dynamic behaviour of cancer cells in vivo. This imaging has revealed that many cancer cells ranging from carcinoma to melanoma move in an amoeboid manner in order to invade surrounding tissue and escape from the primary tumour. This mode on cell motility is extremely rapid and does not require the activity of proteases to degrade the extra‐cellular matrix (ECM). This review details the techniques that are available to study cell motility in vivo and discusses the current knowledge about the mechanisms of amoeboid cell motility.
Mechanisms of actin stress fibre assembly
Authors: NAUMANEN P. , LAPPALAINEN P. , HOTULAINEN P.
Published: August 2008

Stress fibres are contractile acto‐myosin structures found from many types of non‐muscle cells, where they are involved in adhesion, motility and morphogenesis. Stress fibres typically display a periodic α‐actinin–myosin II pattern and are thus suggested to resemble the sarcomeric actin filament structures of muscle cells. Mammalian cells contain three categories of stress fibres: ventral stress fibres that are attached to focal adhesions at both ends, dorsal stress fibres that are attached to focal adhesions typically at one end and transverse arcs that are curved acto‐myosin bundles, which do not directly attach to focal adhesions. In this review, we discuss the definition of stress fibres, organization of actin filaments and other components within these contractile structures, and the mechanisms of stress fibre assembly.
Roles of cell adhesion molecules nectin and nectin‐like molecule‐5 in the regulation of cell movement and proliferation
Authors: OGITA H. , IKEDA W. , TAKAI Y.
Published: August 2008

In response to chemoattractants, migrating cells form protrusions, such as lamellipodia and filopodia, and structures, such as ruffles over lamellipodia, focal complexes and focal adhesions at leading edges. The formation of these leading edge structures is essential for directional cell movement. Nectin‐like molecule‐5 (Necl‐5) interacts in cis with PDGF receptor and integrin αvβ3, and enhances the activation of signalling molecules associated with these transmembrane proteins, which results in the formation of leading edge structures and enhancement of directional cell movement. When migrating cells come into contact with each other, cell–cell adhesion is initiated, resulting in reduced cell velocity. Necl‐5 first interacts in trans with nectin‐3. This interaction is transient and induces down‐regulation of Necl‐5 expression at the cell surface, resulting in reduced cell movement. Cell proliferation is also suppressed by the down‐regulation of Necl‐5, because the inhibitory effect of Necl‐5 on Sprouty2, a negative regulator of the Ras signalling, is diminished. PDGF receptor and integrin αvβ3, which have interacted with Necl‐5, then form a complex with nectin, which initiates cell–cell adhesion and recruits cadherin to the nectin‐based cell–cell adhesion sites to form stable adherens junctions. The formation of adherens junctions stops cell movement, in part through inactivation of integrin αvβ3 caused by the trans‐interaction of nectin. Thus, nectin and Necl‐5 play key roles in the regulation of cell movement and proliferation.
WASP and WIP regulate podosomes in migrating leukocytes
Authors: CALLE Y. , ANTÓN I.M. , THRASHER A.J. , JONES G.E.
Published: August 2008

Podosomes are specialized adhesion sites found in rapidly migrating and invasive cells, most notably in cells from the myeloid lineage that participate in immune surveillance and phagocyte defence mechanisms. In this review, we describe the nature of leukocyte podosomes and the regulation of their turnover during migration by the key regulatory molecules Wiskott–Aldrich syndrome protein and WASP‐interacting protein.
Regulation of macrophage adhesion and migration by Rho GTP‐binding proteins
Authors: RIDLEY A.J.
Published: August 2008

The Rho family proteins Rac and Rho are believed to be key regulators of cell migration through their effects on the cytoskeleton and cell adhesion. However, recent studies in macrophages indicate that they are not always essential for migration, although they do affect cell shape and adhesion.
Bovine Anterior Pituitary Progenitor Cell Line Expresses Interleukin (IL)‐18 and IL‐18 Receptor
Authors: Nagai Y. , Ogasawara H. , Taketa Y. , Aso H. , Tanaka S. , Kanaya T. , Watanabe K. , Ohwada S. , Muneta Y. , Yamaguchi T.
Published: August 2008

In the anterior pituitary gland, inflammatory mediators regulate cell function through an immuno‐endocrine pathway. Recent studies have shown that undifferentiated stem cells act as immunomodulators. These studies prompted us to establish a progenitor cell line from the bovine anterior pituitary gland and to detail its function. First, we localised interleukin (IL)‐18 by immunohistochemistry to the marginal cell layer of Rathke’s pouch that is assumed to embody a stem/progenitor cell compartment of the postnatal pituitary gland. A cloned anterior pituitary‐derived cell line from the bovine anterior pituitary gland was established from single cell clone by the limiting dilution method and was designated as bovine anterior pituitary‐derived cell line (BAPC)‐1. BAPC‐1 cells constantly expressed mRNAs for IL‐18 and IL‐18 receptor, and grew steadily and rapidly in the medium containing epidermal growth factor and basic fibroblast growth factor. The cell line also expressed the mRNAs for the stem/progenitor cell‐ related factors such as Nanog, Oct‐4, Ptch1, Nestin, Notch1, Hes1, Lrp and Fzd4, and the mRNAs for embryonic pituitary‐related factors, such as Lhx3, PitX1 and Pit‐1. The nuclei of BAPC‐1 were immunostained positively for Pit‐1, Hes1 and β‐catenin antibodies. Furthermore, BAPC‐1 cells expressed mRNAs for cytokine such as IL‐1α, IL‐6, IL‐7, IL‐12 and IL‐15. Stimulation of BAPC‐1 cells with IL‐18 increased expression of mRNAs for IL‐1α, IL‐6, IL‐1β and IL‐8. At day 6 in culture, BAPC‐1 cells also express growth hormone mRNA. These results strongly suggest that BAPC‐1 is a stem/progenitor cell line and modulates the immuno‐endocrine function of the anterior pituitary cells through its cytokine production.
Apoptotic pulsed dendritic cells induce a protective immune response against Toxoplasma gondii
Authors: BERTAUX L. , MEVELEC M.‐N. , DION S. , SURAUD V. , GREGOIRE M. , BERTHON P. , DIMIER‐POISSON I.
Published: August 2008

Infection with the intracellular protozoan parasite Toxoplasma gondii may cause severe sequelae in foetuses and life‐threatening neuropathy in immunocompromised patients. We recently reported that vaccination with T. gondii‐pulsed dendritic cells induces protective humoral and cellular immune responses against this intracellular pathogen in CBA/J mice. We assessed the feasibility of using a nonlive vaccine, by inducing the apoptosis of T. gondii‐pulsed dendritic cells before injecting them into mice. Apoptosis was induced by culturing cells to confluence. We investigated whether these apoptotic T. gondii‐pulsed dendritic cells elicited an immune response in vivo. Some studies have shown that immunization with apoptotic cells leads to the activation of innate and adaptive immune mechanisms. Our results are consistent with apoptotic cells having immunomodulatory properties in a model of parasite infection. We showed that the adoptive transfer of T. gondii‐pulsed apoptotic dendritic cells elicited humoral and cellular Toxoplasma‐specific immune responses with a Th1/Th2 profile, and conferred specific protection. The protective immune response induced was independent of inducible HSP70 production by apoptotic dendritic cells.
Germinal centre and marginal zone B cells expand quickly in a second Plasmodium chabaudi malaria infection producing mature plasma cells
Authors: STEPHENS R. , NDUNGU F. M , LANGHORNE J.
Published: August 2008

Antibodies and B cells are critical in the protective immune response to the blood stage of the malaria parasite, Plasmodium chabaudi. However, little is known about the development of memory B cells and their differentiation into plasma cells during infection or after re‐infection. Here we have shown that B cells with phenotypic characteristics of memory cells (CD19+IgD− CD38+, IgG1+) are generated in a primary Plasmodium chabaudi chabaudi infection of mice. In addition, we observed that germinal centre cells (CD19+, GL7+, MHCIIhi) and Marginal Zone B cells (CD19+CD23−IgD−) show faster expansion on re‐infection than in the primary, though other subsets do not. Interestingly, though both IgM− and IgM+ memory cells are produced, IgM+ memory cells do not expand on second infection. The second infection quickly produced mature bone marrow plasma cells (intracellular Ighi, CD138hi, CD9+, B220−), compared to primary infection; which generates a very large population of immature splenic plasma cells (B220+). This analysis suggests that a memory B cell population is generated after a single infection of malaria, which on re‐infection responds quickly producing germinal centres and generating long‐lived plasma cells making the second encounter with parasite more efficient.
Leaf water relations during summer water deficit: differential responses in turgor maintenance and variation in leaf structure among different plant communities in south‐western Australia
Authors: MITCHELL PATRICK J. , VENEKLAAS ERIK J. , LAMBERS HANS , BURGESS STEPHEN S. O.
Published: August 2008

We measured leaf water relations and leaf structural traits of 20 species from three communities growing along a topographical gradient. Our aim was to assess variation in seasonal responses in leaf water status and leaf tissue physiology between sites and among species in response to summer water deficit. Species from a ridge‐top heath community showed the greatest reductions in pre‐dawn leaf water potentials (Ψleaf) and stomatal conductance during summer; species from a valley‐floor woodland and a midslope mallee community showed less reductions in these parameters. Heath species also displayed greater seasonal reduction in turgor‐loss point (ΨTLP) than species from woodland or mallee communities. In general, species that had larger reductions in Ψleaf during summer showed significant shifts in either their osmotic potential at full turgor (Ψπ 100; osmotic adjustment) or in tissue elasticity (εmax). Ψπ 100 and εmax were negatively correlated, during both spring and summer, suggesting a trade‐off between these different mechanisms to cope with water stress. Specific leaf area varied greatly among species, and was significantly correlated with seasonal changes in ΨTLP and pre‐dawn Ψleaf. These correlations suggest that leaf structure is a prerequisite for cellular mechanisms to be effective in adjusting to water deficit.
Stratigraphic evolution of an outcropping continental slope system, Tres Pasos Formation at Cerro Divisadero, Chile
Authors: ROMANS BRIAN W. , HUBBARD STEPHEN M. , GRAHAM STEPHAN A.
Published: August 2008

Depositional slope systems along continental margins contain a record of sediment transfer from shallow‐water to deep‐water environments and represent an important area for natural resource exploration. However, well‐preserved outcrops of large‐scale depositional slopes with seismic‐scale exposures and tectonically intact stratigraphy are uncommon. Outcrop characterization of smaller‐scale depositional slope systems (i.e. < 700 m of undecompacted shelf‐to‐basin relief) has led to increased understanding of stratigraphic packaging of prograding slopes. Detailed stacking patterns of facies and sedimentary body architecture for larger‐scale slope systems, however, remain understudied. The Cretaceous Tres Pasos Formation of the Magallanes Basin, southern Chile, presents a unique opportunity to evaluate the stratigraphic evolution of such a slope system from an outcrop perspective. Inherited tectonic relief from a precursor oceanic basin phase created shelf‐to‐basin bathymetry comparable with continental margin systems (∼1000 m). Sedimentological and architectural data from the Tres Pasos Formation at Cerro Divisadero reveal a record of continental margin‐scale depositional slope progradation and aggradation. Slope progradation is manifested as a vertical pattern exhibiting increasing amounts of sediment bypass upwards, which is interpreted as reflecting increasing gradient conditions. The well‐exposed, seismic‐scale outcrop is characterized by four 20 to 70 m thick sandstone‐rich successions, separated by mudstone‐rich intervals of comparable thickness (40 to 90 m). Sedimentary body geometry, facies distribution, internal bedding architecture, sandstone richness and degree of amalgamation were analysed in detail across a continuous 2·5 km long transect parallel to depositional dip. Deposition in the lower section (Units 1 and 2) was dominated by poorly channellized to unconfined sand‐laden flows and accumulation of mud‐rich mass transport deposits, which is interpreted as representing a base of slope to lower slope setting. Evidence for channellization and indicators of bypass of coarse‐grained turbidity currents are more common in the upper part of the > 600 m thick succession (Units 3 and 4), which is interpreted as reflecting increased gradient conditions as the system accreted basinward.
RcDhn5, a cold acclimation‐responsive dehydrin from Rhododendron catawbiense rescues enzyme activity from dehydration effects in vitro and enhances freezing tolerance in RcDhn5‐overexpressing Arabidopsis plants
Authors: Peng Yanhui , Reyes Jose L. , Wei Hui , Yang Yongil , Karlson Dale , Covarrubias Alejandra A. , Krebs Stephen L. , Fessehaie Anania , Arora Rajeev
Published: August 2008

Dehydrins (DHNs) are typically induced in response to abiotic stresses that impose cellular dehydration. As extracellular freezing results in cellular dehydration, accumulation of DHNs and development of desiccation tolerance are believed to be key components of the cold acclimation (CA) process. The present study shows that RcDhn5, one of the DHNs from Rhododendron catawbiense leaf tissues, encodes an acidic, SK2 type DHN and is upregulated during seasonal CA and downregulated during spring deacclimation (DA). Data from in vitro partial water loss assays indicate that purified RcDhn5 protects enzyme activity against a dehydration treatment and that this protection is comparable with acidic SKn DHNs from other species. To investigate the contribution of RcDhn5 to freezing tolerance (FT), Arabidopsis plants overexpressing RcDhn5 under the control of 35S promoter were generated. Transgenic plants exhibited improved ‘constitutive’ FT compared with the control plants. Furthermore, a small but significant improvement in FT of RcDhn5‐overexpressing plants was observed after 12 h of CA; however, this gained acclimation capacity was not sustained after a 6‐day CA. Transcript profiles of cold‐regulated native Arabidopsis DHNs (COR47, ERD10 and ERD14) during a CA time–course suggests that the apparent lack of improvement in cold‐acclimated FT of RcDhn5‐overexpressing plants over that of wild‐type controls after a 6‐day CA might have been because of the dilution of the effect of RcDhn5 overproduction by a strong CA‐induced expression of native Arabidopsis DHNs. This study provides evidence that RcDhn5 contributes to freezing stress tolerance and that this could be, in part, because of its dehydration stress‐protective ability.
PIOGLITAZONE INHIBITS HOMOCYSTEINE‐INDUCED MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS THROUGH A PEROXISOME PROLIFERATOR‐ACTIVATED RECEPTOR γ‐INDEPENDENT MECHANISM
Authors: Li Li , Gao Ping‐Jin , Xi Rui , Wu Chun‐Fang , Zhu Ding‐Liang , Yan Jing , Lu Guo‐Ping
Published: August 2008

Peroxisome proliferator‐activated receptor (PPAR)‐γ agonists have been demonstrated to exert protective effects against homocysteine (Hcy)‐induced pathogenesis. However, the effects of PPAR‐γ agonists on Hcy‐induced migration are unknown. In the present study, we examined the effect of pioglitazone on the migration of vascular smooth muscle cells (VSMC) induced by Hcy and the possible mechanism involved.

Vascular smooth muscle cells were isolated from the thoracic aortas of male Sprague‐Dawley rats. The migration of VSMC was examined using a transwell technique. The generation of intracellular reactive oxygen species (ROS) was measured using the ROS‐sensitive fluoroprobe 2′,7′‐dichlorodihydrofluorescein diacetate. The activity of NAD(P)H oxidase was assessed by lucigenin enhanced chemiluminescence. Activation of p38 mitogen‐activated protein kinase (MAPK) was determined by western blotting.

The results showed that pioglitazone dose‐dependently inhibited the migration of VSMC induced by Hcy. This was not reversed by the PPAR‐γ antagonist GW9662. In addition, pretreatment with the NAD(P)H oxidase inhibitor diphenylene iodonium (DPI), the free radical scavenger N‐acetylcysteine and the p38 MAPK inhibitor SB202190 blocked Hcy‐induced VSMC migration. Furthermore, we observed that pioglitazone suppressed Hcy‐induced intracellular ROS production; similar effects were observed with DPI and NAC. Pioglitazone attenuated Hcy‐induced activation of NAD(P)H oxidase. Moreover, pioglitazone blocked Hcy‐induced p38 MAPK phosphorylation; similar effects were observed for DPI, NAC and SB202190.

The data demonstrate that pioglitazone inhibits Hcy‐induced VSMC migration that is independent of PPAR‐γ. Furthermore, part of the biological effect of pioglitazone involves a decrease in the levels of NAD(P)H oxidase derived‐ROS and p38 MAPK activation.
MITOCHONDRIAL DNA HAPLOGROUPS IN A CHINESE UYGUR POPULATION AND THEIR POTENTIAL ASSOCIATION WITH LONGEVITY
Authors: Ren Wei‐Hong , Li Xiao‐Hui , Zhang Hai‐Gang , Deng Feng‐Mei , Liao Wen‐Qiang , Pang Yan , Liu Yan‐Hua , Qiu Meng‐Jie , Zhang Guo‐Yuan , Zhang Yi‐Guan
Published: August 2008

The haplogroups and polymorphisms of mitochondrial (mt) DNA are associated with longevity. This association is highly geographically dependent. The aim of the present study was to determine the relationship between mtDNA haplogroups, single nucleotide polymorphisms (SNPs) and longevity in the Chinese Uygur population.

Ninety‐eight Uygur Chinese subjects aged over 90 years (vitality 90+) and 117 healthy young controls living in the Xinjiang Uygur Autonomous Region of China were chosen for the present study. Frequencies of mtDNA haplogroups and SNPs in the subjects were analysed using polymerase chain reaction. The entire mtDNA genome was sequenced and the mtDNA haplogroups and SNPs were determined.

Nine haplogroups were identified in the Chinese Uygur population and the frequency of haplogroup J was higher in control subjects than in the vitality 90+ group (odds ratio = 0.384; 95% confidence interval = 0.163–0.906; P = 0.025). Interestingly, most of the SNPs were in the D‐loop region, with frequencies higher in the control group than in the vitality 90+ group.

In conclusion, mtDNA haplogroups are potentially associated with longevity in the Uygur Chinese population and the D‐loop region is strongly involved in ageing‐related events.
CYCLO‐OXYGENASE‐1 INHIBITION INCREASES ACID SECRETION BY MODULATING H+,K+‐ATPase EXPRESSION AND ACTIVATION IN RABBIT PARIETAL CELLS
Authors: Nandi Jyotirmoy , Das Pratap K , Zinkievich J Michael , Baltodano Juan D , Levine Robert A
Published: August 2008

In the present study, we evaluated the role of cyclo‐oxygenase (COX)‐1 and COX‐2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [14C]‐aminopyrine uptake, prostaglandin (PG) E2synthesis and COX‐1, COX‐2 and proton pump expression at baseline and after treatment with various concentrations of specific COX‐1 (SC‐560), COX‐2 (5,5‐dimethyl‐3‐(3‐fluorophenyl)‐4‐(4‐methyl‐sulphonyl)phenyl‐2 (5H)‐furanone; DFU) and non‐specific COX (indomethacin) inhibitors.

In parietal cells, SC‐560 and indomethacin, over the concentration range 10−8to 10−4 mol/L, dose‐dependently increased basal and 10−4 mol/L histamine‐stimulated aminopyrine uptake and inhibited PGE2synthesis, whereas DFU (10−8to 10−5 mol/L) had no effect. However, at 10−4 mol/L, DFU augmented histamine‐stimulated aminopyrine uptake by 135% and inhibited PGE2synthesis by 39%, indicating an inhibition of COX‐1 at this higher concentration.

The SC‐560‐, DFU‐ and indomethacin‐induced augmentation of histamine‐stimulated aminopyrine uptake was reduced to basal levels after 10−5 mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10−4 mol/L ranitidine only partially inhibited such augmentation.

Only COX‐1 was detected in parietal cells. However, both COX‐1 and COX‐2 were expressed in gastric glands, with relative protein density of COX‐1 being sixfold higher than that of COX‐2. Protein levels of COX‐1 in parietal cells and those of COX‐1 and COX‐2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine.

Parietal cell proton pump expression was significantly enhanced by 10−5 mol/L SC‐560 and 10−4 mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10−5 mol/L DFU had no effect.

In conclusion, the data indicate that inhibition of COX‐1‐ but not COX‐2‐derived PGE2synthesis is involved in augmentation of non‐steroidal anti‐inflammatory drug‐induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.
EARLY ORIGINS OF CARDIAC HYPERTROPHY: DOES CARDIOMYOCYTE ATTRITION PROGRAMME FOR PATHOLOGICAL ‘CATCH‐UP’ GROWTH OF THE HEART?
Authors: Porrello Enzo R , Widdop Robert E , Delbridge Lea MD
Published: August 2008

Epidemiological and experimental evidence suggests that adult development of cardiovascular disease is influenced by events of prenatal and early postnatal life. Cardiac hypertrophy is recognized as an important predictor of cardiovascular morbidity and mortality, but the developmental origins of this condition are not well understood.

In the heart, a switch from hyperplastic to hypertrophic cellular growth occurs during late prenatal or early postnatal life. Postnatal growth of the heart is almost entirely reliant on hypertrophy of individual cardiomyocytes, and damage to heart muscle in adulthood is typically not reparable by cell replacement. Therefore, a reduced number of cardiomyocytes may render the heart more vulnerable in situations where an increased workload is required.

A number of different animal models have been used to study fetal programming of adult diseases, including nutritional, hypoxic, maternal/neonatal endocrine stress and genetic models. Although studies investigating the cellular basis of myocardial disease in growth‐restricted models are limited, a reduction in cardiomyocyte number through either reduced cellular proliferation or increased apoptosis appears to be a central feature.

The mechanisms responsible for the programming of adult cardiovascular disease are poorly understood. We hypothesize that cardiac hypertrophy can have a developmental origin in excess cardiomyocyte attrition during a critical perinatal growth window. Findings that have directly assessed the impact of fetal growth restriction on the myocardium are considered and cellular and molecular mechanisms involved in the potential pathological ‘catch‐up’ growth of the heart during later maturation are identified.
Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma
Authors: JUNGRAITHMAYR Wolfgang , FRINGS Christina , ZISSEL Gernot , PRASSE Antje , PASSLICK Bernward , STOELBEN Erich
Published: August 2008

Background and objective:  Pulmonary resection may cause inflammatory changes with subsequent injury to the remaining lung and deterioration in respiratory function. This study investigated the pattern of serum inflammatory markers and exhaled breath condensate (EBC) in patients undergoing major lung resection due to bronchial carcinoma compared with minimally invasive thoracic surgery.

Methods:  The pro‐inflammatory markers IL‐1‐β, IL‐6, IL‐8, tumor necrosis factor‐α (TNF‐α) and soluble intercellular adhesion molecule‐1 (sICAM‐1) were measured preoperatively (day −1) and on three postoperative days (day 1, 3, 7) in serum and EBC in patients after lobectomy or pneumonectomy due to bronchial carcinoma (test group) and in patients undergoing thoracoscopy with minimal wedge resection (control group).

Results:  All mediators were detectable in serum and all but IL‐8 were detectable in EBC. No patient suffered postoperative respiratory failure. In the test group, serum IL‐6 was significantly higher postoperatively compared with day −1 (P < 0.001). For EBC (test group), the postoperative values of IL‐1‐β were significantly higher compared with day −1 (P = 0.005). In EBC (test group), day −1 TNF‐α and sICAM‐1 were significantly higher compared with controls (P < 0.029 and P = 0.032, respectively). There was no correlation between the levels of mediators and the extent of resection.

Conclusions:  Pro‐inflammatory markers are detected in EBC following pulmonary surgery. Mediators are detectable in both serum and EBC in patients with bronchial carcinoma undergoing pulmonary resection, but the levels are higher in EBC.
Effect of hydrofluoroalkane–ethanol inhalers on estimated alcohol levels in asthmatic subjects
Authors: BRUCE Colleen , CHAN Hiang Ping , MUELLER Lyndall , THOMAS Paul S. , YATES Deborah H.
Published: August 2008

Background and objective:  Inhaled medication administered via a metered dose inhaler (MDI) is often used to treat asthma. Hydrofluoroalkane (HFA) has replaced chlorofluorocarbons (CFC) as the propellant and these new MDI may contain alcohol. This raises concerns that their use may transiently increase breath ethanol concentration (BEC), thereby interfering with random breath testing. It was hypothesized that HFA–ethanol MDI may contribute to raising BEC above the legal limit.

Methods:  The effect of a HFA–ethanol MDI on BEC was compared with that of CFC and placebo MDI and the effect of ingesting a standard amount of alcohol was also investigated. Asthmatic (n = 16) and normal control subjects (n = 15) were recruited for the double‐blind, placebo‐controlled study. Each subject used the three MDI in random sequence. BEC was measured at baseline and at 2, 5 and 15 min after inhalation of each MDI, using the Lion Alcometer SD‐400TM. Spirometry was performed at baseline and 20 min after the last inhalation. An identical procedure was followed after alcohol consumption.

Results:  Use of the HFA–ethanol MDI resulted in a significant increase in BEC from 0.002 to 0.0138 mg/100 mL (28 mg/100 mL of blood, P = 0.001) in asthmatics, and from 0.001 mg/100 mL to 0.016 mg/100 mL (33 mg/100 mL of blood, P = 0.002) in normal subjects. By 5 min, there were no significant differences in BEC of asthmatics (0.0031 mg/100 mL) and normal subjects (0.003 mg/100 mL), when compared with baseline (P > 0.2).

Conclusions:  BEC are transiently elevated after inhalation of HFA–ethanol MDI; however, by 5 min, BEC had already returned to baseline levels. Thus the effect of HFA–ethanol MDI on BEC is transient and would be negligible after 5 min.
Head Position Preference in the Human Newborn: A New Look
Authors: Rönnqvist Louise , Hopkins Brian
Published: August 2008

Head position preference was studied in 20 awake newborns who differed in terms of delivery and sex. They were placed supine on a custom‐built platform to reduce the effects of gravity and asymmetries in trunk posture and skull shape. A global and a specific scoring method were used, the infants being in State 3 (quiet wakefulness) or 4 (active wakefulness, excluding crying). Delivery and sex did not account for differences in head position. The head turned more often to the right and was maintained longer in this position during State 3, regardless of scoring method. The maintenance of the head in midline was comparable in duration to that reported for infants at 2–3 months when using the global scoring method. This suggests that the neural mechanisms responsible for attaining and maintaining a midline position are present at birth, but are not functionally expressed due to a lack of adequate power in the antigravity muscles of the neck.
Five‐ and Eight‐Month‐Old Infants Recognize Their Faces and Voices as Familiar and Social Stimuli
Authors: Legerstee Maria , Anderson Diane , Schaffer Alliza
Published: August 2008

Five‐ and 8‐month‐old infants were presented with silent moving and static video images of self, peer, and doll and with sounds of self, peer, and nonsocial objects. In the visual conditions, infants at both ages showed a significant looking preference to peer over self when the faces were moving. When the faces were static, older infants showed the same significant discriminations, but the younger infants showed a significant looking preference for their own faces over peer and doll. These data suggest that recognition of one's own image develops through experience with dynamic facial stimulation during the first 8 months of life. In the auditory conditions, infants at both ages showed significant looking preferences for sounds of peer over self or nonsocial objects. In general, infants of both ages smiled and produced more vocalizations to social faces and social sounds than to nonsocial faces and nonsocial sounds. Thus, at 5 months infants treat their faces and voices as familiar and social stimuli. The findings forge important links among studies of self‐perception, self‐recognition, and social knowledge.