bluuebunny/crossref_metadata_2025 huggingface dataset:
Strigolactone Acts Downstream of Auxin to Regulate Bud Outgrowth in Pea and Arabidopsis
Authors: Brewer Philip B. , Dun Elizabeth A. , Ferguson Brett J. , Rameau Catherine , Beveridge Christine A.
Published: March 2009

During the last century, two key hypotheses have been proposed to explain apical dominance in plants: auxin promotes the production of a second messenger that moves up into buds to repress their outgrowth, and auxin saturation in the stem inhibits auxin transport from buds, thereby inhibiting bud outgrowth. The recent discovery of strigolactone as the novel shoot-branching inhibitor allowed us to test its mode of action in relation to these hypotheses. We found that exogenously applied strigolactone inhibited bud outgrowth in pea (Pisum sativum) even when auxin was depleted after decapitation. We also found that strigolactone application reduced branching in Arabidopsis (Arabidopsis thaliana) auxin response mutants, suggesting that auxin may act through strigolactones to facilitate apical dominance. Moreover, strigolactone application to tiny buds of mutant or decapitated pea plants rapidly stopped outgrowth, in contrast to applying N-1-naphthylphthalamic acid (NPA), an auxin transport inhibitor, which significantly slowed growth only after several days. Whereas strigolactone or NPA applied to growing buds reduced bud length, only NPA blocked auxin transport in the bud. Wild-type and strigolactone biosynthesis mutant pea and Arabidopsis shoots were capable of instantly transporting additional amounts of auxin in excess of endogenous levels, contrary to predictions of auxin transport models. These data suggest that strigolactone does not act primarily by affecting auxin transport from buds. Rather, the primary repressor of bud outgrowth appears to be the auxin-dependent production of strigolactones.
Studies ofaberrant phyllotaxy1Mutants of Maize Indicate Complex Interactions between Auxin and Cytokinin Signaling in the Shoot Apical Meristem
Authors: Lee Byeong-ha , Johnston Robyn , Yang Yan , Gallavotti Andrea , Kojima Mikiko , Travençolo Bruno A.N. , Costa Luciano da F. , Sakakibara Hitoshi , Jackson David
Published: March 2009

One of the most fascinating aspects of plant morphology is the regular geometric arrangement of leaves and flowers, called phyllotaxy. The shoot apical meristem (SAM) determines these patterns, which vary depending on species and developmental stage. Auxin acts as an instructive signal in leaf initiation, and its transport has been implicated in phyllotaxy regulation in Arabidopsis (Arabidopsis thaliana). Altered phyllotactic patterns are observed in a maize (Zea mays) mutant, aberrant phyllotaxy1 (abph1, also known as abphyl1), and ABPH1 encodes a cytokinin-inducible type A response regulator, suggesting that cytokinin signals are also involved in the mechanism by which phyllotactic patterns are established. Therefore, we investigated the interaction between auxin and cytokinin signaling in phyllotaxy. Treatment of maize shoots with a polar auxin transport inhibitor, 1-naphthylphthalamic acid, strongly reduced ABPH1 expression, suggesting that auxin or its polar transport is required for ABPH1 expression. Immunolocalization of the PINFORMED1 (PIN1) polar auxin transporter revealed that PIN1 expression marks leaf primordia in maize, similarly to Arabidopsis. Interestingly, maize PIN1 expression at the incipient leaf primordium was greatly reduced in abph1 mutants. Consistently, auxin levels were reduced in abph1, and the maize PIN1 homolog was induced not only by auxin but also by cytokinin treatments. Our results indicate distinct roles for ABPH1 as a negative regulator of SAM size and a positive regulator of PIN1 expression. These studies highlight a complex interaction between auxin and cytokinin signaling in the specification of phyllotactic patterns and suggest an alternative model for the generation of altered phyllotactic patterns in abph1 mutants. We propose that reduced auxin levels and PIN1 expression in abph1 mutant SAMs delay leaf initiation, contributing to the enlarged SAM and altered phyllotaxy of these mutants.
A Signaling Pathway Linking Nitric Oxide Production to Heterotrimeric G Protein and Hydrogen Peroxide Regulates Extracellular Calmodulin Induction of Stomatal Closure in Arabidopsis
Authors: Li Jian-Hua , Liu Yin-Qian , Lü Pin , Lin Hai-Fei , Bai Yang , Wang Xue-Chen , Chen Yu-Ling
Published: March 2009

Extracellular calmodulin (ExtCaM) regulates stomatal movement by eliciting a cascade of intracellular signaling events including heterotrimeric G protein, hydrogen peroxide (H2O2), and Ca2+. However, the ExtCaM-mediated guard cell signaling pathway remains poorly understood. In this report, we show that Arabidopsis (Arabidopsis thaliana) NITRIC OXIDE ASSOCIATED1 (AtNOA1)-dependent nitric oxide (NO) accumulation plays a crucial role in ExtCaM-induced stomatal closure. ExtCaM triggered a significant increase in NO levels associated with stomatal closure in the wild type, but both effects were abolished in the Atnoa1 mutant. Furthermore, we found that ExtCaM-mediated NO generation is regulated by GPA1, the Gα-subunit of heterotrimeric G protein. The ExtCaM-dependent NO accumulation was nullified in gpa1 knockout mutants but enhanced by overexpression of a constitutively active form of GPA1 (cGα). In addition, cGα  Atnoa1 and gpa1-2 Atnoa1 double mutants exhibited a similar response as did Atnoa1. The defect in gpa1 was rescued by overexpression of AtNOA1. Finally, we demonstrated that G protein activation of NO production depends on H2O2. Reduced H2O2 levels in guard cells blocked the stomatal response of cGα lines, whereas exogenously applied H2O2 rescued the defect in ExtCaM-mediated stomatal closure in gpa1 mutants. Moreover, the atrbohD/F mutant, which lacks the NADPH oxidase activity in guard cells, had impaired NO generation in response to ExtCaM, and H2O2-induced stomatal closure and NO accumulation were greatly impaired in Atnoa1. These findings have established a signaling pathway leading to ExtCaM-induced stomatal closure, which involves GPA1-dependent activation of H2O2 production and subsequent AtNOA1-dependent NO accumulation.
Disruption of Glycosylphosphatidylinositol-Anchored Lipid Transfer Protein Gene Altered Cuticular Lipid Composition, Increased Plastoglobules, and Enhanced Susceptibility to Infection by the Fungal Pathogen Alternaria brassicicola
Authors: Lee Saet Buyl , Go Young Sam , Bae Hyun-Jong , Park Jong Ho , Cho Sung Ho , Cho Hong Joo , Lee Dong Sook , Park Ohkmae K. , Hwang Inhwan , Suh Mi Chung
Published: March 2009

All aerial parts of vascular plants are covered with cuticular waxes, which are synthesized by extensive export of intracellular lipids from epidermal cells to the surface. Although it has been suggested that plant lipid transfer proteins (LTPs) are involved in cuticular lipid transport, the in planta evidence is still not clear. In this study, a glycosylphosphatidylinositol-anchored LTP (LTPG1) showing higher expression in epidermal peels of stems than in stems was identified from an Arabidopsis (Arabidopsis thaliana) genome-wide microarray analysis. The expression of LTPG1 was observed in various tissues, including the epidermis, stem cortex, vascular bundles, mesophyll cells, root tips, pollen, and early-developing seeds. LTPG1 was found to be localized in the plasma membrane. Disruption of the LTPG1 gene caused alterations of cuticular lipid composition, but no significant changes on total wax and cutin monomer loads were seen. The largest reduction (10 mass %) in the ltpg1 mutant was observed in the C29 alkane, which is the major component of cuticular waxes in the stems and siliques. The reduced content was overcome by increases of the C29 secondary alcohols and C29 ketone wax loads. The ultrastructure analysis of ltpg1 showed a more diffuse cuticular layer structure, protrusions of the cytoplasm into the vacuole in the epidermis, and an increase of plastoglobules in the stem cortex and leaf mesophyll cells. Furthermore, the ltpg1 mutant was more susceptible to infection by the fungus Alternaria brassicicola than the wild type. Taken together, these results indicated that LTPG1 contributed either directly or indirectly to cuticular lipid accumulation.
High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers
Authors: Shimada Mai , Kitagawa Kyoko , Dobashi Yoh , Isobe Tomoyasu , Hattori Takayuki , Uchida Chiharu , Abe Kenji , Kotake Yojiro , Oda Toshiaki , Suzuki Hiroyuki , Hashimoto Kenji , Kitagawa Masatoshi
Published: March 2009

Downregulation of the cyclin‐dependent kinase inhibitory protein p27 is frequently observed in various cancers due to enhancement of its degradation. We recently reported that p53‐inducible protein with RING‐H2 domain (Pirh2) is a novel ubiquitin ligase for p27, required for the ubiquitylation and consequent degradation of p27 protein. However, there is no reports about the involvement of Pirh2 in both p27 downregulation and pathogenesis in human cancers. In the present study, we investigated them using cultured cell lines and surgical specimens derived from human head and neck squamous cell carcinoma (HNSCC). Depletion of Pirh2 by short interfering RNA induced accumulation of p27 and inhibited the growth of cultured HNSCC cells. By immunohistochemical analysis in 57 cases of HNSCC specimens, higher levels of Pirh2 expression (labeling index ≥ 60%) were found in 61.4% of HNSCC in comparison with 0% of normal mucosa. In addition, 83.3% of HNSCC with lower p27 expression (labeling index < 20%) displayed high Pirh2 levels. Therefore, Pirh2 expression was inversely correlated with p27 expression. Finally, Pirh2 expression was well correlated with poor prognosis. These findings suggest that Pirh2 overexpression may have an important role in the development and maintenance of HNSCC at least partially through p27 degradation, and that Pirh2 may be a potential molecular target for human HNSCC. (Cancer Sci 2009; 100: 866–872)
T‐lymphocyte maturation‐associated protein gene as a candidate metastasis suppressor for head and neck squamous cell carcinomas
Authors: Beder Levent Bekir , Gunduz Mehmet , Hotomi Muneki , Fujihara Keiji , Shimada Jun , Tamura Shinji , Gunduz Esra , Fukushima Kunihiro , Yaykasli Kursat , Grenman Reidar , Shimizu Kenji , Yamanaka Noboru
Published: March 2009

Previous gene expression profiles revealed the T‐lymphocyte maturation‐associated protein (MAL) gene as being frequently downregulated in head and neck cancer. To define the relationship between the MAL gene and the metastatic process, we evaluated the expression status of the gene in matched primary and metastatic tumors of head and neck cancer by semiquantitative reverse transcription–polymerase chain reaction. Furthermore, we aimed to identify potential genetic and epigenetic mechanisms associated with downregulation of MAL, including loss of heterozygosity (LOH), mutation, and hypermethylation. Thirty‐five cell lines of University of Turko squamous cell carcinoma (UT‐SCC) series derived from head and neck cancer, including nine pairs from matched primary and metastatic tumors, and 30 pairs of matched primary and metastatic tumor samples were analyzed. Twenty out of 35 (57%) cell lines showed downregulation of MAL expression, whereas no expression was found in 10 cell lines (29%). Considering matched primary and metastatic tumor‐derived cell‐line pairs, four pairs showed decreased expression only in metastasis‐derived cells compared with their primary counterparts. Expression analysis of 21 tissue samples demonstrated decreased or no expression of MAL mRNA in 43% of metastatic tumors compared with matched primary tumors. Relating to mechanisms of downregulation, LOH was observed in 30% of primary tumors and 38% of their metastatic counterparts by a MAL‐specific microsatellite marker. Furthermore, we found restoration of MAL mRNA after treatment with demethylating agent (5‐aza‐2′‐deoxycytidine) in 9 (45%) out of 20 cell lines. No mutation was found in UT‐SCC cell lines. In conclusion, our findings indicate selective downregulation of MAL expression in metastatic cells, suggesting the MAL gene as a new metastasis‐suppressor candidate for head and neck cancer. LOH and hypermethylation appeared to be important mechanisms for inactivation of MAL function. (Cancer Sci 2009; 100: 873–880)
Genesis of an over‐thickened shoreface sandstone tongue: The Rannoch and Etive formations of the Middle Jurassic Brent delta, North Sea
Authors: Helle K. , Helland‐Hansen W.
Published: March 2009

Progradational, wave‐dominated shoreface sandstones are typically reported to have thicknesses of less than 30 m. The shoreface sandstones of the Rannoch and Etive formations in the North Sea Brent Group, however, comprise far greater thicknesses (in places exceeding 100 m). The genesis of these successions have not been well understood, and the purpose of this study is to investigate within the framework of facies geometries in both modern and ancient depositional systems how the Rannoch‐Etive sandstones could have been formed, on a local‐regional scale.

The facies analysis concludes that the Brent delta advance represents a single progradational event, not punctuated by transgressions. In such a scenario, the vertical sandstone thickness would be determined by: 1) shoreline trajectory angle, 2) the horizontal (dip‐directed) length of shoreface sand (typically 1–2 km in modern systems), and 3) shoreface sand pinch‐out depth (typically 5–12 m in modern systems). Within a framework of modern facies geometries, a 100 m thick vertical shoreface sandstone succession could result from a regression characterised by a shoreline trajectory of 2.6–5.4° (implying 80–95 m rise in relative sea level per 1–2 km of progradation), a 5–12 m deep shoreface sand pinch‐out depth, and a 1–2 km shoreface sand length.

If, however, one applies such a model for the entire Brent delta progradation in the study area (200 km) this implies a rise in relative sea level of c. 5000 m, which clearly would be associated with large amounts of deposits accumulating behind and in front of the advancing shoreline. Such deposits are not present, which implies that modern facies geometries do not apply and that rising sea level was not of major importance in defining stratigraphic architecture. It is more likely that the regional overthickening of the Rannoch‐Etive sandstones resulted from progradation with a deep shoreface sand pinch‐out depth.
Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials
Authors: Wheatley Keith , Brookes Cassandra L. , Howman Andrew J. , Goldstone Anthony H. , Milligan Donald W. , Prentice Archibald G. , Moorman Anthony V. , Burnett Alan K. ,   on behalf of the United Kingdom National Cancer Research Institute Haematological Oncology Clinical Studies Group and Acute Myeloid Leukaemia Subgroup
Published: March 2009

This analysis, of 2483 patients with acute myeloid leukaemia (AML) aged 60+ years entered into two UK trials, was performed to determine the baseline parameters related to survival and to develop a risk index. The Medical Research Council (MRC) AML11 trial (n = 1071) was used to develop the index; this was validated using data from the Leukaemia Research fund (LRF) AML14 trial on 1137 intensively (AML14I) and 275 non‐intensively (AML14NI) treated patients. In AML11, cytogenetic group, age, white blood count, performance status and type of AML (de novo, secondary) were all highly significantly related to prognosis in multivariate analysis. The regression coefficients were used to define good, standard and poor risk groups, with 1‐year survival of 53%, 43% and 16% respectively (P < 0·0001). The risk index showed very good discrimination in both AML14I and AML14NI (both P < 0·0001), thereby providing validation, although survival in all groups was very poor in AML14NI. The risk factors for survival in older AML patients were similar to those in younger ones and discrimination of patient groups with relatively good to very poor prognosis was possible. These risk groups apply to both intensively and non‐intensively treated patients. Randomized trials of intensive versus non‐intensive therapy are needed to determine which types of patient should be given which type of treatment.
Prior rituximab correlates with less acute graft‐versus‐host disease and better survival in B‐cell lymphoma patients who received allogeneic peripheral blood stem cell transplantation
Authors: Ratanatharathorn Voravit , Logan Brent , Wang Dan , Horowitz Mary , Uberti Joseph P. , Ringden Olle , Gale Robert Peter , Khoury Hanna , Arora Mukta , Spellman Stephen , Cutler Corey , Antin Joseph , Bornhaüser Martin , Hale Gregory , Verdonck Leo , Cairo Mitchell , Gupta Vikas , Pavletic Steven ,   for the Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI, USA
Published: March 2009

Prior therapy with rituximab might attenuate disparate histocompatibility antigen presentation by B cells, thus decreased the risk of acute graft‐versus‐host disease (GVHD) and improved survival. We tested this hypothesis by comparing the outcomes of 435 B‐cell lymphoma patients who received allogeneic transplantation from 1999 to 2004 in the Center for International Blood and Marrow Transplant Research database: 179 subjects who received rituximab within 6 months prior to transplantation (RTX cohort) and 256 subjects who did not receive RTX within 6 months prior to transplantation (No‐RTX cohort). The RTX cohort had a significantly lower incidence of treatment‐related mortality (TRM) [relative risk (RR) = 0·68; 95% confidence interval (CI), 0·47–1·0; P = 0·05], lower acute grade II–IV (RR = 0·72; 95% CI, 0·53–0·97; P = 0·03) and III–IV GVHD (RR = 0·55; 95% CI, 0·34–0·91; P = 0·02). There was no difference in the risk of chronic GVHD, disease progression or relapse. Progression‐free survival (PFS) (RR = 0·68; 95% CI 0·50–0·92; P = 0·01) and overall survival (OS) (RR = 0·63; 95% CI, 0·46–0·86; P = 0·004) were significantly better in the RTX cohort. Prior RTX therapy correlated with less acute GVHD, similar chronic GVHD, less TRM, better PFS and OS.
Climate change and cyclic predator–prey population dynamics in the high Arctic
Authors: GILG OLIVIER , SITTLER BENOÎT , HANSKI ILKKA
Published: March 2009

The high Arctic has the world's simplest terrestrial vertebrate predator–prey community, with the collared lemming being the single main prey of four predators, the snowy owl, the Arctic fox, the long‐tailed skua, and the stoat. Using a 20‐year‐long time series of population densities for the five species and a dynamic model that has been previously parameterized for northeast Greenland, we analyzed the population and community level consequences of the ongoing and predicted climate change. Species' responses to climate change are complex, because in addition to the direct effects of climate change, which vary depending on species' life histories, species are also affected indirectly due to, e.g., predator–prey interactions. The lemming–predator community exemplifies these complications, yet a robust conclusion emerges from our modeling: in practically all likely scenarios of how climate change may influence the demography of the species, climate change increases the length of the lemming population cycle and decreases the maximum population densities. The latter change in particular is detrimental to the populations of the predators, which are adapted to make use of the years of the greatest prey abundance. Therefore, climate change will indirectly reduce the predators' reproductive success and population densities, and may ultimately lead to local extinction of some of the predator species. Based on these results, we conclude that the recent anomalous observations about lack of cyclic lemming dynamics in eastern Greenland may well be the first signs of a severe impact of climate change on the lemming–predator communities in Greenland and elsewhere in the high Arctic.
Response of carbon fluxes to drought in a coastal plain loblolly pine forest
Authors: NOORMETS ASKO , GAVAZZI MICHAEL J. , MCNULTY STEVE G. , DOMEC JEAN‐CHRISTOPHE , SUN GE , KING JOHN S. , CHEN JIQUAN
Published: March 2009

Full accounting of ecosystem carbon (C) pools and fluxes in coastal plain ecosystems remains less studied compared with upland systems, even though the C stocks in these systems may be up to an order of magnitude higher, making them a potentially important component in regional C cycle. Here, we report C pools and CO2 exchange rates during three hydrologically contrasting years (i.e. 2005–2007) in a coastal plain loblolly pine plantation in North Carolina, USA. The daily temperatures were similar among the study years and to the long‐term (1971–2000) average, whereas the amount and timing of precipitation differed significantly. Precipitation was the largest in 2005 (147 mm above normal), intermediate in 2006 (48 mm below) and lowest in 2007 (486 mm below normal). The forest was a strong C sink during all years, sequestering 361 ± 67 (2005), 835 ± 55 (2006) and 724 ± 55 (2007) g C m−2 yr−1 according to eddy covariance measurements of net ecosystem CO2 exchange (NEE). The interannual differences in NEE were traced to drought‐induced declines in canopy and whole tree hydraulic conductances, which declined with growing precipitation deficit and decreasing soil volumetric water content (VWC). In contrast, the interannual differences were small in gross ecosystem productivity (GEP) and ecosystem respiration (ER), both seemingly insensitive to drought. However, the drought sensitivity of GEP was masked by higher leaf area index and higher photosynthetically active radiation during the dry year. Normalizing GEP by these factors enhanced interannual differences, but there were no signs of suppressed GEP at low VWC during any given year. Although ER was very consistent across the 3 years, and not suppressed by low VWC, the total respiratory cost as a fraction of net primary production increased with annual precipitation and the contribution of heterotrophic respiration (Rh) was significantly higher during the wettest year, exceeding new litter inputs by 58%. Although the difference was smaller during the other 2 years (Rh : litterfall ratio was 1.05 in 2006 and 1.10 in 2007), the soils lost about 109 g C m−2 yr−1, outlining their potential vulnerability to decomposition, and pointing to potential management considerations to protect existing soil C stocks.
Quantifying the metabolic cost to an Antarctic liverwort of responding to an abrupt increase in UVB radiation exposure
Authors: SNELL K. R. S. , KOKUBUN T. , GRIFFITHS H. , CONVEY P. , HODGSON D. A. , NEWSHAM K. K.
Published: March 2009

We quantified the metabolic cost to the Antarctic leafy liverwort Cephaloziella varians of responding to an abrupt increase in ultraviolet B (UVB) radiation exposure in the natural environment at Rothera Point on the western Antarctic Peninsula (67 °34′S, 68 °07′W). The liverwort was protected from exposure to UVB radiation for 44 days with screens containing Mylar polyester, after which time its thalli, which are normally black in colour, had become green owing to reduced concentrations of an anthocyanidin, identified here as riccionidin A, in thallus tips. Thalli were then exposed to an abrupt increase in UVB radiation by removing the screens. The thalli became visibly darker within 48 h of the screens being removed, resynthesizing riccionidin A to the same concentration as that present in thalli outside screens during this period. Chlorophyll fluorescence measurements indicated that nonphotochemical quenching was higher in the thalli formerly under the screens than in those not previously covered with screens, but that Fv/Fm and photochemical quenching were the same in the two groups of thalli. We used data from aqueous phase oxygen electrode measurements to calculate an estimate for carbon fixation by C. varians during the 48 h after the screens were removed. Assuming a photosynthetic quotient for Antarctic bryophytes of 1, these analyses indicated that the minimum weight of carbon used to synthesize riccionidin A was equivalent to 1.85% of the carbon fixed by thalli during the 48 h after the abrupt increase in UVB radiation exposure.
Carbon accumulation in agricultural soils after afforestation: a meta‐analysis
Authors: LAGANIÈRE JÉRÔME , ANGERS DENIS A. , PARÉ DAVID
Published: March 2009

Deforestation usually results in significant losses of soil organic carbon (SOC). The rate and factors determining the recovery of this C pool with afforestation are still poorly understood. This paper provides a review of the influence of afforestation on SOC stocks based on a meta‐analysis of 33 recent publications (totaling 120 sites and 189 observations), with the aim of determining the factors responsible for the restoration of SOC following afforestation. Based on a mixed linear model, the meta‐analysis indicates that the main factors that contribute to restoring SOC stocks after afforestation are: previous land use, tree species planted, soil clay content, preplanting disturbance and, to a lesser extent, climatic zone. Specifically, this meta‐analysis (1) indicates that the positive impact of afforestation on SOC stocks is more pronounced in cropland soils than in pastures or natural grasslands; (2) suggests that broadleaf tree species have a greater capacity to accumulate SOC than coniferous species; (3) underscores that afforestation using pine species does not result in a net loss of the whole soil‐profile carbon stocks compared with initial values (agricultural soil) when the surface organic layer is included in the accounting; (4) demonstrates that clay‐rich soils (> 33%) have a greater capacity to accumulate SOC than soils with a lower clay content (< 33%); (5) indicates that minimizing preplanting disturbances may increase the rate at which SOC stocks are replenished; and (6) suggests that afforestation carried out in the boreal climate zone results in small SOC losses compared with other climate zones, probably because trees grow more slowly under these conditions, although this does not rule out gains over time after the conversion. This study also highlights the importance of the methodological approach used when developing the sampling design, especially the inclusion of the organic layer in the accounting.
Peripheral blood T4 cell surface CCR5 density as a marker of activity in rheumatoid arthritis treated with anti‐CD20 monoclonal antibody
Authors: Portalès Pierre , Fabre Sylvie , Vincent Thierry , Desmetz Caroline , Réant Brigitte , Noël Danièle , Clot Jacques , Jorgensen Christian , Corbeau Pierre
Published: March 2009

The chemokine (C‐C motif) receptor CCR5 and its ligand CCL5 play key roles in the intra‐articular recruitment of peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Therefore, using quantitative cytofluorometry, we followed T4 cell surface CCR5 density in 27 subjects with RA before and after treatment with the anti‐CD20 monoclonal antibody rituximab. We observed low T4 cell surface CCR5 densities before treatment, which correlated positively with disease activity, as determined using a disease activity score evaluated on 28 joints (DAS 28), and negatively with CCL5 mRNA concentrations in PBMC, contrasting with a high proportion of intracellular CCR5 molecules, a pattern compatible with ligand‐induced CCR5 internalization. At 3 months post‐treatment, CCL5 mRNA expression in PBMC declined, whereas T4 cell surface CCR5 densities increased proportionally to the decrease in DAS 28. Thus, peripheral blood T4 cell surface CCR5 density is a good surrogate marker of RA activity and of the efficiency of anti‐CD20 therapy.
Identification and characterization of the interferon‐β‐mediated p53 signal pathway in human peripheral blood mononuclear cells
Authors: Zhang Fanglin , Sriram Subramaniam
Published: March 2009

The relationship between the p53 signal pathway and the response of human peripheral blood mononuclear cells (PBMC) to interferon (IFN)‐β has hitherto not been examined. Using an oligonucleotide microarray, we found differential expression of at least 70 genes involved in the p53 signal pathway, including p53, which regulate cell proliferation and cell death following stimulation with IFN‐β. We verified our observations on a limited set of p53‐regulated genes at the transcriptional and translational levels. We also examined the consequences of the activation of the p53 signal pathway by IFN‐β in PBMC. When cultured in the presence of T‐cell mitogens, IFN‐β restricted the entry of lymphocytes from the G0/G1 phase to the S phase and reduced the number of cells in the G2 phase. The addition of IFN‐β alone did not increase apoptosis. However, in the presence of actinomycin D, a DNA‐damaging agent, addition of IFN‐β enhanced the susceptibility of PBMC to apoptosis. These observations suggest that, in spite of the activation of a number of mutually overlapping pathways mediating cell death, cell cycle arrest was the most evident consequence of IFN‐β signalling in PBMC.
Adaptation of Feeding and Counter‐Regulatory Hormone Responses to Intermediate Insulin‐Induced Hypoglycaemia in the Ovariectomised Female Rat: Effects of Oestradiol
Authors: Briski K. P. , Nedungadi T. P.
Published: March 2009

Oestradiol regulates basal food intake and glucagon and corticosterone secretion, but its influence on these responses to acute and recurring hypoglycaemia remains unclear. The present study utilised an experimental model for repeated intermediate‐acting insulin‐induced hypoglycaemia that replicates the route of delivery, frequency of administration, and duration of insulin action in the clinical setting. Groups of ovariectomised (OVX) rats were implanted with s.c. capsules containing oestradiol benzoate (EB) or oil, and injected with one or four doses of Humulin neutral protamine Hagedorn (HN), on as many days, or diluent alone. Baseline feeding followed divergent trends in EB‐ versus oil‐implanted animals over a 9‐h period after final injections. Recurring HN‐induced hypoglycaemia resulted in significantly greater baseline‐corrected food intake in OVX + EB and OVX + oil groups, relative to acute hypoglycaemic hyperphagia. Although oestradiol did not modify net food consumption after single or serial HN doses, EB replacement maintained uniform feeding over time in each treatment paradigm. Baseline glucagon and corticosterone secretion was higher in EB‐ versus oil‐treated OVX rats. Oestradiol prolonged acute hypoglycaemic glucagonemia, and increased the magnitude, but shortened the duration, of glucagon secretion during recurring hypoglycaemia. OVX + oil rats responded to both acute and recurring hypoglycaemia with elevated corticosterone secretion at a single time point, which was advanced from +6 to +4 h during recurrent insulin‐induced hypoglycemia, whereas OVX + EB animals exhibited increased plasma hormone levels at both +4 and +6 h in response to each paradigm. Area‐under‐the curve analyses showed that total glucagon and corticosterone release was greater in EB‐ versus oil‐implanted rats after both single and serial dosing with HN. These results demonstrate that repeated HN administration increases food intake in female rats via oestrogen‐independent mechanisms, but that oestradiol preserves temporal patterns of hypoglycaemic hyperphagia. The data also reveal that normo‐ and hypoglyacemic glucagon and corticosterone secretion are enhanced in the presence of oestrogen. Further studies are necessary to identify the sites and cellular substrates that are responsible for this hormonal regulation of behavioural and endocrine responses to prolonged hypoglycaemia.
Female executives are particularly prone to the sleep‐disturbing effect of isolated high‐strain jobs: a cross‐sectional study in German‐speaking executives
Authors: GADINGER MICHAEL C. , FISCHER JOACHIM E. , SCHNEIDER SVEN , FISCHER GISELA C. , FRANK GUNTER , KROMM WALTER
Published: March 2009

This study assessed the main, curvilinear, interactive and gender‐dependent effects of job demands, job control and social support in the prediction of sleep quality. Participants were 348 male and 76 female executives and managers from Germany, Austria and Switzerland. A multiple regression controlling for age, occupational hierarchy and various health behaviors was computed. On the level of the main effects of the Job–Demand–Control–Support (JDCS) model, the results indicate a sleep‐promoting effect of social support. A significant three‐way interaction of job demands, job control and social support was observed. This interaction confirms the buffering effect of high job control and high social support on high job demands. Further, this three‐way interaction of the JDCS dimensions is moderated by gender as indicated by a significant four‐way interaction. The directions of the significant interactions suggest that female executives are especially prone to react with impaired sleep quality when exposed to isolated high‐strain jobs. The study seems to imply that the JDCS model is a suitable framework for the prediction of sleep quality among executives and managers. The results suggest that the JDCS model might contribute to a better understanding of the higher prevalence of poor sleep amongst female executives. Further, the results imply that high job control and high social support might help executives to maintain good sleep quality despite experiencing high job demands.
Peginterferon alfa‐2a (40kDa) and ribavirin: comparable rates of sustained virological response in sub‐sets of older and younger HCV genotype 1 patients
Authors: Reddy K. R. , Messinger D. , Popescu M. , Hadziyannis S. J.
Published: March 2009

Summary.  The average age of patients initiating therapy for HCV is increasing, with older patients exhibiting lower responses to therapy than younger patients. Identification of those older patients likely to respond needs to be addressed. Using data from 569 genotype‐1 patients enrolled in two phase III studies (NV15801/NV15942) randomized to peginterferon alfa‐2a (40KDa) 180 μg/week plus ribavirin 1000/1200 mg/day for 48‐weeks, we investigated factors associated with sustained virological response (SVR; undetectable HCV‐RNA 24‐weeks post‐treatment) in patients >50 years. SVR rates among patients ≤50 was greater than those >50 years (52%vs 39%; P = 0.0073). Older patients with a rapid virological response (RVR; undetectable HCV‐RNA at treatment week 4) or complete early virological response (cEVR; detectable HCV‐RNA at week 4 but HCV‐RNA <50 IU/mL at week‐12) demonstrated high SVR rates (83% and 61% respectively). Older patients had lower cumulative peginterferon alfa‐2a exposure and significantly lower cumulative ribavirin exposure (252 g vs 304 g in younger patients; P < 0.0001). Higher relapse rates were observed in older patients (41%vs 25%; P = 0.0042). Cumulative drug exposure and achievement of RVR or cEVR were significantly predictive of SVR by multiple logistic regression analysis in patients >50 years. Other baseline characteristics predictive of SVR in those >50 years of age were lower baseline HCV‐RNA level (P = 0.0067), higher ALT‐ratio (P = 0.0113) and absence of cirrhosis (P = 0.0482). Response rates were high among patients >50 years without cirrhosis who maintained adequate drug exposure and those achieving an RVR or cEVR. More frequent dose modifications of ribavirin in those >50 years likely contributed to the observed higher relapse rates.
Antiviral resistance and specifically targeted therapy for HCV (STAT‐C)
Authors: Thompson A. J. V. , McHutchison J. G.
Published: March 2009

Summary.  As health care providers, we find ourselves on the verge of a new era in the treatment of chronic hepatitis C virus (HCV) infection. A number of directly acting antiviral agents are now in the latter stages of clinical development. The more promising candidates include direct inhibitors of the HCV nonstructural 3 protease, as well as both nucleoside and non‐nucleoside inhibitors of the NS5B RNA‐dependent RNA polymerase. Although these agents have demonstrated potent antiviral effect, monotherapy has been complicated by rapid virological breakthrough due to the selection of drug‐resistant mutants. As for HIV and HBV, combination therapy will therefore be necessary. This brief review summarizes the current literature concerning resistance and directly acting antiviral agents, and identifies key challenges facing this emerging field.
Comparative genetic analyses of historical and contemporary collections highlight contrasting demographic histories for the bumble beesBombus pensylvanicusandB.impatiensin Illinois
Authors: LOZIER JEFFREY D. , CAMERON SYDNEY A.
Published: March 2009

Direct comparison of genetic patterns between museum specimens and contemporary collections can be a powerful approach for detecting recent demographic changes. Using microsatellite markers, we examined historical and contemporary genetic variation from an apparently declining bumble bee species,Bombus pensylvanicus, and from a stable species,Bombus impatiens, in central Illinois. For each species, we genotyped specimens from the Illinois Natural History Survey collected from three populations between 1969–1972 and from a resurvey of the same areas conducted in 2008. Population structure inB.pensylvanicusincreased markedly over the last four decades (from θST = 0.001 to 0.027) while no structure was detected inB.impatiensfor either time period (θST = –0.006 to –0.003). Changes in genetic diversity were not significant for either species, although small reductions were observed forB.pensylvanicusin all three populations. Coalescent simulations incorporating both contemporary and historical samples suggest that this small change is not surprising for recent population declines, as large reductions in genetic diversity were only apparent under the most severe bottleneck scenarios. These results demonstrate how comparisons of genetic patterns between temporal periods and species can help elucidate potential threats to population health and suggest several strategies that might be useful in the conservation ofB.pensylvanicusin the Midwestern USA.
Ethnopathology: local knowledge of plant health problems in Bangladesh, Uganda and Bolivia
Authors: Bentley J. W. , Boa E. R. , Kelly P. , Harun‐Ar‐Rashid M. , Rahman A. K. M. , Kabeere F. , Herbas J.
Published: March 2009

All peoples have names for and knowledge of plants, animals and other things in the real world. An ethnopathology (or, more strictly, ‘ethnophytopathology’) – study in Bangladesh, Uganda and Bolivia revealed that smallholder farmers label plant health problems with meaningful names. A local name for a plant health problem typically has two kinds of meaning. The first is a literal translation of the name, often a kind of shorthand description of the symptom. The second and most important kind of meaning is the denotative meaning (the thing in the real world which the name actually refers to). Local words for plant health problems often label the symptom rather than the actual disease. This is logical, since smallholders cannot observe microscopic causal organisms. Local concepts for plant health problems do not necessarily classify the natural world in exactly the same way that scientists do, yet local terms for plant health problems are still meaningful. It is not clear if folk classifications of plant health problems are phylogenetic classifications (e.g. ‘mammals’ vs. ‘fish’) or ecological (e.g. ‘seafood’ vs. ‘meat and poultry’). Cross‐culturally, local knowledge recognizes that plants are alive, and that they may be ill or healthy, perhaps in analogy with human health.
The Arabidopsis ABA‐INSENSITIVE (ABI) 4 factor acts as a central transcription activator of the expression of its own gene, and for the induction of ABI5 and SBE2.2 genes during sugar signaling
Authors: Bossi Flavia , Cordoba Elizabeth , Dupré Patricia , Mendoza Mónica Santos , Román Carolina San , León Patricia
Published: March 2009

The transcription factor ABA INSENSITIVE 4 (ABI4), discovered nearly 10 years ago, plays a central role in a variety of functions in plants, including sugar responses. However, not until very recently has its mechanism of action begun to be elucidated. Modulating gene expression is one of the primary mechanisms of sugar regulation in plants. Nevertheless, the transcription factors involved in regulating sugar responses and their role(s) during the signal transduction cascade remain poorly defined. In this paper we analyzed the participation of ABI4, as it is one of the main transcription factors implicated in glucose signaling during early seedling development. Our studies show that ABI4 is an essential activator of its own expression during development, in ABA signaling and in sugar responses. It is also important for the glucose‐mediated expression of the genes ABI5 and SBE2.2. We demonstrate that ABI4 binds directly to the promoter region of all three genes and activates their expression in vivo through at CE1‐like element. Previous studies found that ABI4 also functions as a transcriptional repressor of sugar‐regulated genes, therefore this transcription factor is a versatile protein with dual functions for modulating gene expression.
Identification of a novel HLA‐DRB1 allele, HLA‐DRB1*1217, in a Korean individual
Authors: Park M. H. , Kim Y. , Lee J. Y.
Published: March 2009

We report a new DRB1 allele, DRB1*1217, identified by direct sequencing of a bacterial artificial chromosome (BAC) clone originated from genomic DNA of a Korean donor. DRB1*1217 differs from previously reported DRB1*120201 by a single nucleotide substitution, which results in an amino acid change at codon 67 [TTC→ATC (F>I)].
Association of the leukocyte immunoglobulin G (Fcγ) receptor IIIa‐158V/F polymorphism with inflammatory myopathies in Dutch patients
Authors: Bronner I. M. , Hoogendijk J. E. , De Visser M. , Van De Vlekkert J. , Badrising U. A. , Wintzen A. R. , Uitdehaag B. M. J. , Blokland‐Fromme M. , Leusen J. H. W. , Van Der Pol W.‐L.
Published: March 2009

Leukocytes are involved in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Immunoglobulin G (IgG) receptors (FcγR) link the specificity of IgG to the effector functions of leukocytes. Several FcγR subclasses display functional polymorphisms that determine in part the vigour of the inflammatory response. FcγRIIIa genotypes were differentially distributed among 100 IIM patients compared with 514 healthy controls with a significant increase of the homozygous FcγRIIIa‐V‐158 genotype (3 × 2 contingency table, χ2 = 6.3, P = 0.04). Odds ratios (ORs) increased at the addition of each FcγRIIIa‐V‐158 allele, in particular among patients with non‐specific myositis and dermatomyositis {OR 2.1 [95% confidence interval (CI) 1.1–4.3] and 2.7 (95% CI 1.1–6.4) for FcγRIIIa‐V/F158 and FcγRIIIa‐V/V158 genotypes, respectively, using FcγRIIIa‐F/F158 as a reference group}. These data suggest that the FcγRIIIa‐V‐158 allele may constitute a genetic risk marker for IIM.
Bone microstructures and mode of skeletogenesis in osteoderms of three pareiasaur taxa from the Permian of South Africa
Authors: SCHEYER T. M. , SANDER P. M.
Published: March 2009

The extinct parareptilian clade of pareiasaurs was in the past often presented to constitute a morphocline from larger, less armoured forms to smaller, well armoured forms, indicating that the osteoderm cover became an increasingly prominent aspect in the post‐cranial skeleton of these animals. Here, we describe microanatomical and microstructural aspects of osteoderms of the three pareiasaur taxa Bradysaurus, Pareiasaurus and Anthodon from the Permian of South Africa. A generalized mode of osteoderm formation, consistent with intramembraneous skeletogenesis, is hypothesized to be present in all pareiasaurs. Few characters are shared between pareiasaur dermal armour and turtle shell bones and osteoderms. Otherwise, there is strong evidence from microanatomy and histology (i.e. absence of structures that formed via metaplasia of dermal tissue) that indicates nonhomology between pareiasaur dermal armour and the armour of living eureptiles. Analysis with bone profiler revealed no clear connection between bone compactness and lifestyle in the amniote osteoderm sample.
In vivo confocal microscopy, an inner vision of the cornea – a major review
Authors: Guthoff Rudolf F , Zhivov Andrey , Stachs Oliver
Published: March 2009

Abstract

The demands of modern ophthalmology have evolved from descriptive findings from the slit lamp to in vivo assessment of cellular level changes. Nowadays, the latter can be provided by in vivo confocal microscopy. This article gives an overview of confocal principles using tandem scanning, scanning slit and laser scanning techniques used in ophthalmology. The main part of the paper describes the clinical applications emphasizing the anatomy of the normal and pathological cornea, and illustrates side‐effects of topical medication, contact lens wear, cross‐linking and refractive surgery. Finally, a summary about experimental applications, including animal studies, surface characterization and volume rendering as well as future developments, is given.
Ubiquitin hydrolase (protein gene product 9.5) in the obstructed bladder: evidence for tissue remodelling involving a subset of interstitial cells
Authors: Grol Simone , Essers Paul B.M. , Van Koeveringe Gommert A. , De Vente Jan , Gillespie James I.
Published: March 2009

OBJECTIVE

To examine the expression of ubiquitin hydrolase (UH), an enzyme which is part of the ubiquitin‐proteasome system involved in the regulation of cell growth and differentiation, to gain an insight into the cell types and processes underlying the tissue remodelling that occur after bladder neck damage.

MATERIALS AND METHODS

Three groups of male guinea pigs were used, comprising controls (not operated, four), sham (five) and obstructed (six). The bladder outlet was obstructed by implanting a silver ring around the urethra, which was left in situ for 2–4 weeks. Sham‐operated guinea pigs had the same operative procedure but no ring was implanted. The bladders were removed and incubated in Krebs’ solution at 36 °C, gassed with 95% O2 and 5% CO2, Tissues were then fixed in 4% depolymerized paraformaldehyde and processed for immunohistochemistry. We used antibodies raised against UH, cyclooxygenase type I and vimentin. Specific antibody binding was visualized using the appropriate secondary antibodies.

RESULTS

Staining with an antibody to UH showed the presence of both sensory and motor nerves in control, sham and obstructed bladders. In the control bladders this was the predominant staining pattern. In the sham and obstructed bladders UH staining revealed additional positive cell types; cells associated with the outermost layers of the urothelium (the umbrella cells), in the lamina propria (the lamina propria interstitial cells (lp‐ICs), on the surface of the muscle bundles (surface muscle, sm‐ICs) and on the serosal surface (muscle coat, mc‐ICs). All ICs stained with vimentin. The ICs within the muscle bundles (intramuscular, im‐ICs) did not stain with UH. The number and density of the UH‐positive cells was greater in the obstructed than in the sham bladders, suggesting a change in relation to the severity of damage to the bladder neck.

CONCLUSION

The expression of UH implies the re‐targeting of proteins marked for degradation in the proteasome. Increased expression of UH in the lp‐ICs and sm‐ICs shows that these cells are active in the early and late stages of the tissue remodelling resulting from obstruction. These results show a further subset of ICs that might be involved in the increased deposition of extracellular material and tissue remodelling.