bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells
Authors: Baba Masanori , Okamoto Mika , Hamasaki Takayuki , Horai Sawako , Wang Xin , Ito Yuji , Suda Yasuo , Arima Naomichi
Published: February 2008

Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). In Japan, the number of HTLV-1 carriers is estimated to be 1.2 million and more than 700 cases of ATL have been diagnosed every year. Considering the poor prognosis and lack of curative therapy of ATL, it seems mandatory to establish an effective strategy for the treatment of ATL. In this study, we attempted to identify the cell surface molecules that will become suitable targets of antibodies for anti-ATL therapy. The expression levels of approximately 40,000 host genes of three human T-cell lines carrying HTLV-1 genomes were analyzed by oligonucleotide microarray and compared with the expression levels of the genes in an HTLV-1-negative T-cell line. The HTLV-1-carrying T-cell lines used for experiments had totally different expression patterns of viral genome. Among the genes evaluated, the expression levels of 108 genes were found to be enhanced more than 10-fold in all of the T-cell lines examined and 11 of the 108 genes were considered to generate the proteins expressed on the cell surface. In particular, the CD70 gene was upregulated more than 1,000-fold and the enhanced expression of the CD70 molecule was confirmed by laser flow cytometry for various HTLV-1-carrying T-cell lines and primary CD4+T cells isolated from acute-type ATL patients. Such expression was not observed for primary CD4+T cells isolated from healthy donors. Since CD70 expression is strictly restricted in normal tissues, such as highly activated T and B cells, CD70 appears to be a potential target for effective antibody therapy against ATL.
hAda3 Degradation by Papillomavirus Type 16 E6 Correlates with Abrogation of the p14ARF-p53 Pathway and Efficient Immortalization of Human Mammary Epithelial Cells
Authors: Shamanin Vladimir A. , Sekaric Pedja , Androphy Elliot J.
Published: February 2008

Two activities of human papillomavirus type 16 E6 (HPV16 E6) are proposed to contribute to the efficient immortalization of human epithelial cells: the degradation of p53 protein and the induction of telomerase. However, the requirement for p53 inactivation has been debated. Another E6 target is the hAda3 protein, a p53 coactivator and a component of histone acetyltransferase complexes. We have previously described the role of hAda3 and p53 acetylation in p14ARF-induced human mammary epithelial cell (MEC) senescence (P. Sekaric, V. A. Shamanin, J. Luo, and E. J. Androphy, Oncogene 26:6261-6268, 2007). In this study, we analyzed a set of HPV16 E6 mutants for the ability to induce hAda3 degradation. E6 mutants that degrade hAda3 but not p53 could abrogate p14ARF-induced growth arrest despite the presence of normal levels of p53 and efficiently immortalized MECs. However, two E6 mutants that previously were reported to immortalize MECs with low efficiency were found to be defective for both p53 and hAda3 degradation. We found that these immortal MECs select for reduced p53 protein levels through a proteasome-dependent mechanism. The findings strongly imply that the inactivation of the p14ARF-p53 pathway, either by the E6-mediated degradation of p53 or hAda3 or by cellular adaptation, is required for MEC immortalization.
Role for MyD88 Signaling in Murine Gammaherpesvirus 68 Latency
Authors: Gargano Lisa M. , Moser Janice M. , Speck Samuel H.
Published: February 2008

Toll-like receptors (TLRs) are known predominantly for their role in activating the innate immune response. Recently, TLR signaling via MyD88 has been reported to play an important function in development of a B-cell response. Since B cells are a major latency reservoir for murine gammaherpesvirus 68 (MHV68), we investigated the role of TLR signaling in the establishment and maintenance of MHV68 latency in vivo. Mice deficient in MyD88 (MyD88
−/−
) or TLR3 (TLR3
−/−
) were infected with MHV68. Analysis of splenocytes recovered at day 16 postinfection from MyD88
−/−
mice compared to those from wild-type control mice revealed a lower frequency of (i) activated B cells, (ii) germinal-center B cells, and (iii) class-switched B cells. Accompanying this substantial defect in the B-cell response was an approximately 10-fold decrease in the establishment of splenic latency. In contrast, no defect in viral latency was observed in TLR3
−/−
mice. Analysis of MHV68-specific antibody responses also demonstrated a substantial decrease in the kinetics of the response in MyD88
−/−
mice. Analysis of wild-type × MyD88
−/−
mixed-bone-marrow chimeric mice demonstrated that there is a selective failure of MyD88
−/−
B cells to participate in germinal-center reactions as well as to become activated and undergo class switching. In addition, while MHV68 established latency efficiently in the MyD88-sufficient B cells, there was again a ca. 10-fold reduction in the frequency of MyD88
−/−
B cells harboring latent MHV68. This phenotype indicates that MyD88 is important for the establishment of MHV68 latency and is directly related to the role of MyD88 in the generation of a B-cell response. Furthermore, the generation of a B-cell response to MHV68 was intrinsic to B cells and was independent of the interleukin-1 receptor, a cytokine receptor that also signals through MyD88. These data provide evidence for a unique role for MyD88 in the establishment of MHV68 latency.
Human CAR Gene Expression in Nonpermissive Hamster Cells Boosts Entry of Type 12 Adenovirions and Nuclear Import of Viral DNA
Authors: Hochstein Norbert , Webb Dennis , Hösel Marianna , Seidel Werner , Auerochs Sabrina , Doerfler Walter
Published: February 2008

Adenovirus type 12 (Ad12) propagation in hamster BHK21 cells is blocked prior to viral DNA replication. The amounts of Ad12 DNA in the nuclei or cytoplasm of hamster cells are about 2 orders of magnitude (2 h postinfection [p.i.]) and 4 to 5 orders of magnitude (48 h p.i.) lower than in permissive human cells. Cell line BHK21-hCAR is transgenic for and expresses the human coxsackie- and adenovirus receptor (hCAR) gene. Nuclear uptake of Ad12 DNA in BHK21-hCAR cells is markedly increased compared to that in naïve BHK21 cells. Ad12 elicits a cytopathic effect in BHK21-hCAR cells but not in BHK21 cells. Quantitative PCR or [
3
H]thymidine labeling followed by zone velocity sedimentation fails to detect Ad12 DNA replication in BHK21 or BHK21-hCAR cells. Newly assembled Ad12 virions cannot be detected. Thus, the block in Ad12 DNA replication in hamster cells is not released by enhanced nuclear import of Ad12 DNA.
Ownership and uses of human tissue: what are the opinions of surgical in-patients?
Authors: Bryant R J , Harrison R F , Start R D , Chetwood A S A , Chesshire A M , Reed M W R , Cross S S
Published: February 2008

Aims:

To investigate whether patient opinion about the uses of tissue removed at therapeutic operations has changed since the adverse publicity surrounding the Alder Hey and Bristol Royal Infirmary Inquiries, and to see whether it aligns with the Human Tissue Act 2004.

Methods:

A questionnaire was given to 220 postoperative patients in a teaching hospital during an 11 week period. Aggregated responses to each question were ranked in frequency order. Unweighted centroid linkage hierarchical clustering analysis was performed with dendrogram display for the main data on tissue usage.

Results:

203 completed questionnaires were collected (compliance rate 92.3%). 96.3% of patients indicated that they would not object to their tissue being used in research, significantly higher than in the 1996 study (89.1%) with no overlap of the 95% CIs. 29.1% of patients believed that the hospital had ownership of tissue once it has been removed during surgery, 23.2% believed they had ownership, 19.7% believed that the pathology laboratory had ownership, and 15.3% believed that nobody had ownership rights in the case of tissue samples.

Conclusions:

This new survey indicates that despite a turbulent decade for those involved in human tissue retention in the UK, public support for a wide range of human tissue based activities, especially biomedical research, has not diminished and that patient opinion aligns well with the Human Tissue Act 2004.
Effects of simulated insect damage on early growth of nursery-grown hybrid poplars in northern Wisconsin
Authors: Bassman John , Myers Wayne , Dickmann Donald , Wilson Louis
Published: February 2008

Insect damage on hybrid poplars grown from rooted tip cuttings was simulated to assess potential growth impact under nursery conditions. Four experiments were conducted at Rhinelander, Wisconsin, from June 1975 through August 1977. Partial defoliations in several patterns were tested both early and late in the growing season. Basal injury was also investigated.Whereas defoliations of 40% caused negligible growth impact, defoliations of 75 to 80% reduced growth by about 20%. The 75% defoliations did not differ significantly according to distribution in the crown. Timing of defoliations was not significant as a main effect. Faster growing clones suffered greater growth reduction in one experiment where cultural regime was not so intensive. Basal injury did not produce significant impacts unless it was severe enough to weaken the stem almost to the point of collapse.Results indicate that young and vigorous rooted tip cuttings have substantial reserve photosynthetic capacity. Even heavy defoliations do not counterbalance gains that can be realized by genetic selection for rapid growth.
Autumnal nutrient transfers by retranslocation, leaching, and litter fall in a chestnut oak forest in southern Illinois
Authors: Ostman Nancy L. , Weaver George T.
Published: February 2008

Retranslocation from leaves was investigated as a means of retaining nutrients in stands of Quercusprinus L. on two sites in southern Illinois, where wind rapidly moves litter downslope. Foliage samples were collected from late summer until leaf fall to describe the trends of leaf dry weight and nutrient concentration (N, K, P, Ca) changes. Free-falling rain and throughfall were collected to estimate foliar leaching. Foliar concentrations of N, K, and P decreased markedly during senescence while Ca concentrations increased. The pattern of concentration change was unique for each element, and the change in N concentration was closely correlated with change in leaf color. For the study sites as a whole, leaf dry weight decreased to 70% of the original value. Of 84.2 kg N/ha in green foliage, only 22.6% was returned to the site as litter. The canopy gained 0.3 kg N/ha (0.4%) from rainfall. The 78.5% N unaccounted for is attributed to retranslocation. Similarly, from 51.4 kg K/ha; 8.2, P; and 47.8, Ca in green foliage, 9.8, 1.3, and 3.3%, respectively, were removed by leaching; 27.4, 43.7, and 85.1% were returned to the site in litter. The remaining 63.0% K, 55.0% P, and 11.5% Ca unaccounted for is attributed to retranslocation. Retranslocation and leaching of nutrients was greater on the site of higher quality. But on both sites it appears that retranslocation is an important means of retaining and conserving N, K, and P countering the effect of annual litter removal.
Flowering response of western hemlock seedlings to gibberellin and water-stress treatments
Authors: Brix H. , Portlock F. T.
Published: February 2008

Western hemlock (Tsugaheterophylla (Raf.) Sarg.) seedlings, 1–5 years old, were treated with various numbers and durations of soil-drying cycles alone or in combination with a weekly foliar spray of 200 mg/L of a gibberellin A4/7 mixture. Control plants did not flower and water stress alone did not promote flowering. Only sparse flowering was produced with GA4/7 alone but when this was applied with two soil-drying cycles during the 7-week treatment period from mid-June through July an average of seven strobili per plant were induced on one-half of the 1-year-old seedlings (during their second growing season). Two drying cycles were more effective than one, though similar maximum plant water stress at predawn, −25 bars (1 bar = 100 kPa), was attained in both treatments. For the 4-year-old seedlings, 60% flowered, with an average of 64 strobili per plant. As many male as female strobili were produced on the average for all seedling groups. An operational application of these treatments to substantially shorten the natural breeding cycle in tree improvement programs is feasible.
Genetic instability of multiple buds of Pinuscoulteri regenerated from tissue culture
Authors: Patel Kamlesh R. , Berlyn Graeme P.
Published: February 2008

Embryo expiants ofPinuscoulteri D. Don. were cultured on agar media (modified from Campbell and Durzan 1975) only supplemented with 2.25 mg•L−1 of benzyl amino purine (BAP). Nuclear DNA contents were measured in cells of the embryo explants, callus, and buds regenerated from these explants, and sand-germinated seedlings. Measurements were made at weekly intervals during 6 weeks of culture. Absolute amounts of cellular DNA were determined with a microspectrophotometer using chicken erythrocytes as an internal standard. Initially, the nuclei had a DNA level between 2C and 4C with a mean of 3C. The sand-grown seedlings remained within this range, with an increased frequency of 4C nuclei in the 6-week seedlings. However, cells from callus and regenerated buds showed a progressive increase in DNA level over time. After 42 days in culture, the buds contained large populations of cells at the 8C level and a considerable number of cells with DNA levels above 8C. In addition, the nuclei showed a considerable increase in chromosomal aberrations including bridges, micronuclei, lagging chromosomes, and fragmentation. Nuclear volume also increased over time in the regenerated buds. It is therefore concluded that culture conditions, perhaps cytokinin content, increased the levels of nuclear DNA. These increased levels could be the result of polyploidy, polyteny, hyperaneuploidy, or a combination of these types of nuclear organization.
Essai d'une préparation ultra-concentrée de Bacillusthuringiensis contre la tordeuse des bourgeons de l'épinette
Authors: Smirnoff W. A. , Juneau A. , Valéro J. R.
Published: February 2008

Previous studies led to the development of Bacillusthuringiensis formulations providing dispersion of the required 20 × 109 international units (IU) of B. thuringiensis in a final volume of 4.7 L/ha against spruce budworm. Although the use of these formulations was successful, it seemed essential to reduce their cost particularly by developing more concentrated formulations. Thus, a formulation (futura) providing dispersion of the same 20 × 109 IU in a final volume of 2.5 L/ha was developed. In 1979, the physical properties of this formulation were tested for dispersion and, in 1980, it was dispersed over five40-ha forest blocks infested with spruce budworm. The futura formulation showed the same possibilities as the preceding ones in terms of quality of dispersion, larval mortality, and foliage protection.
Quantitative genetics of yield breeding for Populus short rotation culture. I. Dynamics of genetic control and selection model of yield traits
Authors: Wu Rong-Ling , Wang Ming-Xiu , Huang Min-Ren
Published: February 2008

Variation patterns and selection efficiencies for the three growth traits height, diameter, and volume were studied in two selected interspecific hybrid populations of eastern cottonwood (Populusdeltoides Bartr.): P. deltoides × Populussimonii Carr. and P. deltoides × Populusnigra L. Growth variables differed quite significantly (P < 0.01) among clones in each of the two hybrid populations, and they were more dominantly controlled by genetic factors than by environmental regimes. There were higher broad-sense heritablity levels for growth traits in this study than in other related studies. Genetic variances and broad-sense heritabilities for all traits markedly increased with stand development in the two hybrid populations; but the increasing rates with age of these two genetic parameters for diameter and volume were more rapid for P. deltoides × P. simonii hybridization than for P. deltoides × P. nigra hybridization. Selection of the best 5% of the clones from P. deltoides × P. simonii and the best 10% from P. deltoides × P. nigra produced mean 6th-year volume growth increases of 51 and 37%, respectively. Relative to P. deltoides, their high parent, the ratio of clonal heterosis of these selected hybrid clones was 5–23% for 6th-year volume. With different selection intensities, early selection of juvenile growth traits for the two populations, P. deltoides × P. simonii and P. deltoides × P. nigra, can also produce substantial indirect genetic gains for short rotation harvest traits. Further studies of Populus yield breeding and selection models were suggested.
Condition of the fine roots of sugar maple in different stages of decline
Authors: Bauce Eric , Allen Douglas C.
Published: February 2008

An 85-year-old even-aged northern hardwood stand was studied to elucidate relations between the crown condition of declining sugar maples, Acersaccharum Marsh., and the condition of maple fine roots. Declining sugar maples had lower fine-root biomass and fewer rootlet tips than apparently healthy trees. However, rootlet mortality did not differ significantly between crown dieback classes. Damage to fine roots caused by Ctenophora sp. was significantly greater on trees in advanced stages of decline.
Metabolic Flux Analysis in Plants: From Intelligent Design to Rational Engineering
Authors: Libourel Igor G.L. , Shachar-Hill Yair
Published: February 2008

Metabolic flux analysis (MFA) is a rapidly developing field concerned with the quantification and understanding of metabolism at the systems level. The application of MFA has produced detailed maps of flow through metabolic networks of a range of plant systems. These maps represent detailed metabolic phenotypes, contribute significantly to our understanding of metabolism in plants, and have led to the discovery of new metabolic routes. The presentation of thorough statistical evaluation with current flux maps has set a new standard for the quality of quantitative flux studies. In microbial systems, powerful methods have been developed for the reconstruction of metabolic networks from genomic and transcriptomic data, pathway analysis, and predictive modeling. This review brings together the recent developments in quantitative MFA and predictive modeling. The application of predictive tools to high quality flux maps in particular promises to be important in the rational metabolic engineering of plants.
Molecular Aspects of Seed Dormancy
Authors: Finkelstein Ruth , Reeves Wendy , Ariizumi Tohru , Steber Camille
Published: February 2008

Seed dormancy provides a mechanism for plants to delay germination until conditions are optimal for survival of the next generation. Dormancy release is regulated by a combination of environmental and endogenous signals with both synergistic and competing effects. Molecular studies of dormancy have correlated changes in transcriptomes, proteomes, and hormone levels with dormancy states ranging from deep primary or secondary dormancy to varying degrees of release. The balance of abscisic acid (ABA):gibberellin (GA) levels and sensitivity is a major, but not the sole, regulator of dormancy status. ABA promotes dormancy induction and maintenance, whereas GA promotes progression from release through germination; environmental signals regulate this balance by modifying the expression of biosynthetic and catabolic enzymes. Mediators of environmental and hormonal response include both positive and negative regulators, many of which are feedback-regulated to enhance or attenuate the response. The net result is a slightly heterogeneous response, thereby providing more temporal options for successful germination.
Coordinating Nodule Morphogenesis with Rhizobial Infection in Legumes
Authors: Oldroyd Giles E.D. , Downie J. Allan
Published: February 2008

The formation of nitrogen-fixing nodules on legumes requires an integration of infection by rhizobia at the root epidermis and the initiation of cell division in the cortex, several cell layers away from the sites of infection. Several recent developments have added to our understanding of the signaling events in the epidermis associated with the perception of rhizobial nodulation factors and the role of plant hormones in the activation of cell division leading to nodule morphogenesis. This review focuses on the tissue-specific nature of the developmental processes associated with nodulation and the mechanisms by which these processes are coordinated during the formation of a nodule.
Studies on localization and function of annexin A4a within urinary bladder epithelium using a mouse knockout model
Authors: Hill Warren G. , Meyers Susan , von Bodungen Maximilian , Apodaca Gerard , Dedman John R. , Kaetzel Marcia A. , Zeidel Mark L.
Published: February 2008

Annexin A4 (anxA4) is a member of the Ca2+-dependent membrane-binding family of proteins implicated in the regulation of ion conductances, Ca2+homeostasis, and membrane trafficking. We demonstrate, in mice, that annexins 1–6 are present in whole bladder and exhibit differential expression in the urothelium. An anxA4a-knockout (anxA4a−/−) mouse model shows no protein in the urothelium by immunofluorescence and immunoblotting. In wild-type bladders, anxA4a in umbrella cells showed uniform cytoplasmic staining and some association with the nuclear membrane. Application of a hydrostatic pressure to bladders mounted in Ussing chambers resulted in redistribution of anxA4a from cytoplasm to cellular boundaries in the basal and intermediate cells but not in superficial umbrella cells. We hypothesized that anxA4a might be important for barrier function or for stretch-activated membrane trafficking. To test these hypotheses, we conducted a series of functional and morphological analyses on bladders from control and anxA4a−/−animals. The transepithelial resistances, water permeabilities, and urea permeabilities of anxA4a−/−bladders were not different from controls, indicating that barrier function was intact. Membrane trafficking in response to hydrostatic pressure as measured by capacitance increases was also normal for anxA4a−/−bladders. Cystometrograms performed on live animals showed that voiding frequency and intrabladder pressures were also not different. There were no differences in bladder surface morphology or cellular architecture examined by scanning and transmission electron microscopy, respectively. We conclude that loss of anxA4 from the urothelium does not affect barrier function, membrane trafficking, or normal bladder-voiding behavior.
Effects of acid aspiration-induced acute lung injury on kidney function
Authors: Hoag Jeffrey B. , Liu Manchang , Easley R. Blaine , Britos-Bray Martin F. , Kesari Priya , Hassoun Heitham , Haas Mark , Tuder Rubin M. , Rabb Hamid , Simon Brett A.
Published: February 2008

Acute lung injury (ALI) in combination with acute kidney injury carries a mortality approaching 80% in the intensive care unit. Recently, attention has focused on the interaction of the lung and kidney in the setting of ALI and mechanical ventilation (MV). Small animal models of ALI and MV have demonstrated changes in inflammatory mediators, water channels, apoptosis, and function in the kidney early in the course of injury. The purpose of this investigation was to test the hypothesis that ALI and injurious MV cause early, measurable changes in kidney structure and function in a canine HCl aspiration model of ALI when hemodynamics and arterial blood gas tensions are carefully controlled. Intratracheal HCl induced profound ALI as demonstrated by increased shunt fraction and airway pressures compared with sham injury. Sham-injured animals had similar mean arterial pressure and arterial Pco2 and HCO3 levels compared with injured animals. Measurements of renal function including renal blood flow, urine flow, serum creatinine, glomerular filtration rate, urine albumin-to-creatinine ratio, and kidney histology scores were not different between groups. With maintenance of hemodynamic parameters and alveolar ventilation, ALI and injurious MV do not alter kidney structure and function early in the course of injury in this acid aspiration canine model. Kidney injury in large animal models may be more similar to humans and may differ from results seen in small animal models.
Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice
Authors: Cunningham Rochelle , Esmaili Ali , Brown Eric , Biswas Rajat S. , Murtazina Rakhilya , Donowitz Mark , Dijkman Henry B. , van der Vlag Johan , Hogema Boris M. , De Jonge Hugo R. , Shenolikar Shirish , Wade James B. , Weinman Edward J.
Published: February 2008

The adaptor proteins sodium/hydrogen exchanger regulatory factor (NHERF)-1 and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. To compare the kidney-specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared with wild-type control mice. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-type animals. The glomerular expression of podocalyxin and ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-type control and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxin in glomeruli and ClC-5 in the renal proximal tubule, the urinary excretion of protein was determined. There were no differences in the urinary excretion of protein or low-molecular-weight proteins between wild-type control, NHERF-1−/−, and NHERF-2−/−mice. These studies indicate that the increased urinary excretion of phosphate and uric acid are specific to NHERF-1 null mice and highlight the fact that predictions about the role of adaptor proteins such as the NHERF proteins obtained from studies of model cell systems must be confirmed in whole animals.
Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETAand ETBreceptors
Authors: Just Armin , Whitten Christina L. , Arendshorst William J.
Published: February 2008

Reactive oxygen species (ROS) play important roles in renal vasoconstrictor responses to acute and chronic stimulation by angiotensin II and norepinephrine, as well as in long-term effects of endothelin-1 (ET-1). Little is known about participation of ROS in acute vasoconstriction produced by ET-1. We tested the influence of NAD(P)H oxidase inhibition by apocynin [4 mg·kg−1·min−1, infused into the renal artery (ira)] on ETAand ETBreceptor signaling in the renal microcirculation. Both receptors were stimulated by ET-1, ETAreceptors by ET-1 during ETBantagonist BQ-788, and ETBby ETBagonist sarafotoxin 6C. ET-1 (1.5 pmol injected ira) reduced renal blood flow (RBF) 17 ± 4%. Apocynin raised baseline RBF (+10 ± 1%, P < 0.001) and attenuated the ET-1 response to 10 ± 2%, i.e., 35 ± 9% inhibition ( P < 0.05). Apocynin reduced ETA-induced vasoconstriction by 42 ± 12% ( P < 0.05) and that of ETBstimulation by 50 ± 8% ( P < 0.001). During nitric oxide (NO) synthase inhibition ( Nω-nitro-l-arginine methyl ester), apocynin blunted ETA-mediated vasoconstriction by 60 ± 8% ( P < 0.01), whereas its effect on the ETBresponse (by 87 ± 8%, P < 0.001) was even larger without than with NO present ( P < 0.05). The cell-permeable superoxide dismutase mimetic tempol (5 mg·kg−1·min−1ira), which reduces O2−and may elevate H2O2, attenuated ET-1 responses similar to apocynin (by 38 ± 6%, P < 0.01). We conclude that ROS, O2−rather than H2O2, contribute substantially to acute renal vasoconstriction elicited by both ETAand ETBreceptors and to basal renal vasomotor tone in vivo. This physiological constrictor action of ROS does not depend on scavenging of NO. In contrast, scavenging of O2−by NO seems to be more important during ETBstimulation.
Prevalence of Increased Albumin Excretion Rate in Young Saudi Adults
Authors: Abo-Zenah H. , El-Benayan A. , El Nahas A.M.
Published: February 2008

Introduction: Albuminuria is an important risk predictor of chronic kidney disease and cardiovascular disease. In this study, we aim to evaluate the prevalence of increased urinary albumin excretion (UAE) rate amongst a subgroup of young Saudi army/navy recruits. Methods: 2,000 Saudi military recruits were tested for microalbuminuria by dipstick and 24-hour urine collection for quantitative evaluation. Results: In the whole group studied, the rate of microalbuminuria-positive dipstick testing was 10.3% (n = 206), but decreased on quantitative evaluation of 24-hour urine collection to 6.2% (n = 124). Increased UAE was independently associated with diabetes mellitus (DM), hypertension (HT), obesity, male gender and hypercholesterolemia. 55 of the 124 (44.4%) were diabetics while 14 (11.3%) were hypertensives. Around 21% of individuals with albuminuria were obese; body mass index for the whole group with albuminuria = 31.15 ± 5.8 kg/m2 and showed no gender difference. Increased risk of albuminuria was noted with DM (OR = 5.07 [3.5–7.4], p < 0.0001), obesity (OR = 1.59 [1.0–2.5], p = 0.042) and HT (OR = 1.8 [1.0–3.2], p = 0.046). An estimated glomerular filtration rate of ∼77 ml/min/1.73 m2 was present in the whole group with a significantly lower level in macroalbuminuric subjects compared to those with microalbuminuria (p = 0.03). Also, age was higher in the macroalbuminuric group (p = 0.004) with comparable prevalence of DM (47.4 vs. 45.2%, p = NS). Conclusions: This is the first description of increased UAE in a small percentage of young adult Arab subjects from Saudi Arabia detected through a selective screening process carried out on potential army recruits. It highlights the association of albuminuria in the general population with predisposing conditions such as DM, HT and obesity.
Salicylic Acid Injection before Noise Exposure Reduces Permanent Threshold Shift
Authors: Adelman Cahtia , Freeman Sharon , Paz Ziv , Sohmer Haim
Published: February 2008

The permanent threshold shift (PTS) following exposure to intense noise may be due to the noise-induced excessive vibrations in the cochlea or to the generation of elevated levels of reactive oxygen species. Thus, it is possible that the resulting PTS may be reduced if the cochlear amplifier could be temporarily depressed beginningjust before the onset of the noise and continuing during the noise exposure or if antioxidant drugs were administered. These possibilities were assessed in mice by administering a single injection of salicylic acid (an antioxidant drug which also reversibly depresses the motor protein prestin of the cochlear amplifier) just before, and in other mice, just after, 3.5 h of 113-dB SPL broadband noise exposure. The PTS in the mice injected with salicylic acid just before the noise exposure was significantly smaller than that in mice exposed to the same noise without salicylic acid. The PTS in the latter was not significantly different from that in mice who received the drug just after the noise. Thus a single injection of salicylic acid, just before a noise exposure, can protect the ear from a noise-induced hearing loss.
Prevalence and Pattern of Cognitive Impairment in a Community Cohort of Men in South Wales: Methodology and Findings from the Caerphilly Prospective Study
Authors: Fish M. , Bayer A.J. , Gallacher J.E.J. , Bell T. , Pickering J. , Pedro S. , Dunstan F.D. , Ben-Shlomo Y. , Ebrahim S.
Published: February 2008

Background/Aims: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65–84 years). Methods: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG <83 or decline in CAMCOG >9) being neurologically examined. Results: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. Conclusion: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority.
Subseasonal Variability Associated with Asian Summer Monsoon Simulated by 14 IPCC AR4 Coupled GCMs
Authors: Lin Jia-Lin , Weickman Klaus M. , Kiladis George N. , Mapes Brian E. , Schubert Siegfried D. , Suarez Max J. , Bacmeister Julio T. , Lee Myong-In
Published: February 2008

This study evaluates the subseasonal variability associated with the Asian summer monsoon in 14 coupled general circulation models (GCMs) participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). Eight years of each model’s twentieth-century climate simulation are analyzed. The authors focus on the three major components of Asian summer monsoon: the Indian summer monsoon (ISM), the western North Pacific summer monsoon (WNPSM), and the East Asian summer monsoon (EASM), together with the two dominant subseasonal modes: the eastward- and northward-propagating boreal summer intraseasonal oscillation (BSIO) and the westward-propagating 12–24-day mode.

The results show that current state-of-the-art GCMs still have difficulties and display a wide range of skill in simulating the subseasonal variability associated with Asian summer monsoon. During boreal summer (May–October), most of the models produce reasonable seasonal-mean precipitation over the ISM region, but excessive precipitation over the WNPSM region and insufficient precipitation over the EASM region. In other words, models concentrate their rain too close to the equator in the western Pacific. Most of the models simulate overly weak total subseasonal (2–128 day) variance, as well as too little variance for BSIO and the 12–24-day mode. Only 4–5 models produce spectral peaks in the BSIO and 12–24-day frequency bands; instead, most of the models display too red a spectrum, that is, an overly strong persistence of precipitation. For the seven models with three-dimensional data available, five reproduce the preconditioning of moisture in BSIO but often with a too late starting time, and only three simulate the phase lead of low-level convergence. Interestingly, although models often have difficulty in simulating the eastward propagation of BSIO, they tend to simulate well the northward propagation of BSIO, together with the westward propagation of the 12–24-day mode. The northward propagation in these models is thus not simply a NW–SE-tilted tail protruding off of an eastward-moving deep-tropical intraseasonal oscillation.
Itch−/−αβ and γδ T cells independently contribute to autoimmunity in Itchy mice
Authors: Parravicini Valentino , Field Anne-Christine , Tomlinson Peter D. , Albert Basson M. , Zamoyska Rose
Published: February 2008

E3 ubiquitin ligases determine which intracellular proteins are targets of the ubiquitin conjugation pathway and thus play a key role in determining the half-life, subcellular localization and/or activation status of their target proteins. Itchy mice lack the E3 ligase, Itch, and show dysregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition. Itch is widely expressed in hematopoietic and nonhematopoietic cells, and we demonstrate that disease is transferred exclusively by hematopoietic cells. Moreover, distinct manifestations of the autoimmune inflammatory phenotype are contributed by discrete populations of lymphocytes. The presence of Itch-deficient αβ T cells drives expansion of peritoneal B1b cells and elevated IgM levels, which correlate with itching and pathology. In contrast, Itch−/− interleukin-4–producing γδ T cells, even in the absence of αβ T cells, are associated with elevated levels of IgE and an inflammatory condition. These data indicate that disruption of an E3 ubiquitin ligase in αβ T cells can subvert a B-cell subpopulation, which normally functions to control particular microbial pathogens in a T-independent manner, to contribute to autoimmunity. In addition, disruption of Itch in innate γδ T cells can influence autoimmune pathology and might therefore require distinct therapeutic intervention.
Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study
Authors: Larson Richard A. , Druker Brian J. , Guilhot Francois , O'Brien Stephen G. , Riviere Gilles J. , Krahnke Tillmann , Gathmann Insa , Wang Yanfeng
Published: February 2008

Imatinib at 400 mg daily is standard treatment for chronic myeloid leukemia in chronic phase. We here describe the correlation of imatinib trough plasma concentrations (Cmins) with clinical responses, event-free survival (EFS), and adverse events (AEs). Trough level plasma samples were obtained on day 29 (steady state, n = 351). Plasma concentrations of imatinib and its metabolite CGP74588 were determined by liquid chromatography/mass spectrometry. The overall mean (± SD, CV%) steady-state Cmin for imatinib and CGP74588 were 979 ng/mL (± 530 ng/mL, 54.1%) and 242 ng/mL (± 106 ng/mL, 43.6%), respectively. Cumulative estimated complete cytogenetic response (CCyR) and major molecular response (MMR) rates differed among the quartiles of imatinib trough levels (P = .01 for CCyR, P = .02 for MMR). Cmin of imatinib was significantly higher in patients who achieved CCyR (1009 ± 544 ng/mL vs 812 ± 409 ng/mL, P = .01). Patients with high imatinib exposure had better rates of CCyR and MMR and EFS. An exploratory analysis demonstrated that imatinib trough levels were predictive of higher CCyR independently of Sokal risk group. AE rates were similar among the imatinib quartile categories except fluid retention, rash, myalgia, and anemia, which were more common at higher imatinib concentrations. These results suggest that an adequate plasma concentration of imatinib is important for a good clinical response. This study is registered at http://clinicaltrials.gov as NCT00333840.
Impact of light on Hypocrea jecorina and the multiple cellular roles of ENVOY in this process
Authors: Schuster Andrè , Kubicek Christian P , Friedl Martina A , Druzhinina Irina S , Schmoll Monika
Published: February 2008

Background

In fungi, light is primarily known to influence general morphogenesis and both sexual and asexual sporulation. In order to expand the knowledge on the effect of light in fungi and to determine the role of the light regulatory protein ENVOY in the implementation of this effect, we performed a global screen for genes, which are specifically effected by light in the fungus Hypocrea jecorina (anamorph Trichoderma reesei) using Rapid Subtraction Hybridization (RaSH). Based on these data, we analyzed whether these genes are influenced by ENVOY and if overexpression of ENVOY in darkness would be sufficient to execute its function.

Results

The cellular functions of the detected light responsive genes comprised a variety of roles in transcription, translation, signal transduction, metabolism, and transport. Their response to light with respect to the involvement of ENVOY could be classified as follows: (i) ENVOY-mediated upregulation by light; (ii) ENVOY-independent upregulation by light; (iii) ENVOY-antagonized upregulation by light; ENVOY-dependent repression by light; (iv) ENVOY-independent repression by light; and (v) both positive and negative regulation by ENVOY of genes not responsive to light in the wild-type. ENVOY was found to be crucial for normal growth in light on various carbon sources and is not able to execute its regulatory function if overexpressed in the darkness.

Conclusion

The different responses indicate that light impacts fungi like H. jecorina at several cellular processes, and that it has both positive and negative effects. The data also emphasize that ENVOY has an apparently more widespread cellular role in this process than only in modulating the response to light.
CT scanning for diagnosing blunt ureteral and ureteropelvic junction injuries
Authors: Ortega Sarah J , Netto Fernado S , Hamilton Paul , Chu Peter , Tien Homer C
Published: February 2008

Background

Blunt ureteral and ureteropelvic (UPJ) injuries are extremely rare and very difficult to diagnose. Many of these injuries are missed by the initial trauma evaluation.

Methods

Trauma registry data was used to identify all blunt trauma patients with ureteral or UPJ injuries, from 1 April 2001 to 30 November 2006. Demographics, injury information and outcomes were determined. Chart review was then performed to record initial clinical and all CT findings.

Results

Eight patients had ureteral or UPJ injuries. Subtle findings such as perinephric stranding and hematomas, and low density retroperitoneal fluid were evident on all initial scans, and prompted delayed excretory scans in 7/8 cases. As a result, ureteral and UPJ injuries were diagnosed immediately for these seven patients. These findings were initially missed in the eighth patient because significant associated visceral findings mandated emergency laparotomy. All ureteral and UPJ injuries have completely healed except for the case with the delay in diagnosis.

Conclusion

Most blunt ureteral and UPJ injuries can be identified if delayed excretory CT scans are performed based on initial CT findings of perinephric stranding and hematomas, or the finding of low density retroperitoneal fluid.
Advances in Adjuvant Endocrine Therapy for Postmenopausal Women
Authors: Lin Nancy U. , Winer Eric P.
Published: February 2008

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.
Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation
Authors: Osorio Karen M. , Lee Song Eun , McDermitt David J. , Waghmare Sanjeev K. , Zhang Ying V. , Woo Hyun Nyun , Tumbar Tudorita
Published: February 2008

Aml1/Runx1 controls developmental aspects of several tissues, is a master regulator of blood stem cells, and plays a role in leukemia. However, it is unclear whether it functions in tissue stem cells other than blood. Here, we have investigated the role of Runx1 in mouse hair follicle stem cells by conditional ablation in epithelial cells. Runx1 disruption affects hair follicle stem cell activation, but not their maintenance, proliferation or differentiation potential. Adult mutant mice exhibit impaired de novo production of hair shafts and all temporary hair cell lineages, owing to a prolonged quiescent phase of the first hair cycle. The lag of stem cell activity is reversed by skin injury. Our work suggests a degree of functional overlap in Runx1 regulation of blood and hair follicle stem cells at an equivalent time point in the development of these two tissues.
Rejecting the United States of the World: The consequences of Woodrow Wilson's new diplomacy on the 1921 Immigration Act
Authors: Allerfeldt Kristofer
Published: February 2008

In January 1919 Woodrow Wilson attended the Paris Peace Conference to thrash out terms for the end of the world's most bloody war to that date. Wilson arrived with a plan for a permanent end to war as a means of settling international disputes. Central to this desire was a belief in
international law, which would be backed by an international police body the League of Nations. During and after the Conference, Wilson's ambitions ran into increasing opposition. When domestic considerations led to the failure of his Treaty plans, the United States entered a period of introspection
and isolation. This study argues that Wilson's actions in Paris and his attempts to sell his plans to America in the following months made the passage of the 1921 Immigration Act, with its quotas on Europeans, inevitable. Where other studies have placed the War itself in the central position
in the change of heart behind the limitation of European immigrants, this study sees the peace as equally important.
Andronikos Komnenos, Prinz Belthandros und der Zyklop. Zwei Glossen zu Niketas Choniates' Хϱονιϰὴ διήγησις
Authors: Gaul Niels
Published: February 2008

Der erste Andronikos erwies sich unter jenen Kaisern, welchen auf dem Thron des byzantinischen Reiches nur eine kurze Zeitspanne beschieden war, als besonderer Liebling der Nymphe Echo. Geboren um 1120, tritt dieser kaiserliche Neffe und Ziehbruder eines Kaisers als eine im wahren Wortsinn changierende Gestalt des 12. Jahrhunderts vor unsere Augen. Zeitlebens war er der vornehmste Opponent seines Vetters, des Kaisers Manuel Komnenos (reg. 1143–1180); er verbrachte neun Jahre im Kerker (1154/55–Herbst 1164) und lebte nach abenteuerlicher Flucht für weitere fünfzehn Jahre in Verbannung (1164/65, 1166–1180). Als er spät im Jahr 1183 schließlich zum Basileus der Rhomäer avancierte, schreckte er vor dem Meuchelmord an seinem Neffen, dem jungen Kaiser Alexios, nicht zurück – um seinerseits kaum zwei Jahre später von Hand des konstantinopolitanischen Pöbels das wohl grausamste Ende zu finden, das jemals einem byzantinischen Autokrator zuteil wurde (September 1185): Das prophezeite AIMA der Komnenoi hatte sich erfüllt. Andronikos' kurze Tyrannis ist eingerahmt von den blutigen Ausschreitungen der Konstantinopolitaner wider die Lateiner (April 1182) und deren Nemesis, der normannischen Eroberung und Plünderung Thessalonikes (August 1185). Einige beherzte Maßnahmen seinerseits, groben Mißständen Abhilfe zu leisten, wurden bereits von den Zeitgenossen mit Lob bedacht. Die folgenden Glossen richten den Fokus allerdings vor allem auf jene Jahre, in denen odysseusgleiche Irrfahrten Andronikos bis hinauf in die Lande der Rus' (1164/65) und schließlich von Jerusalem über Damaskus und Bagdad nach Georgien führten (zwischen 1167 und 1180), ehe er in der Herrschaft der Saltuḳ-oġullari im nordöstlichen Winkel Kleinasiens, bei Koloneia (türk. Şebinkarahisar), Zuflucht fand.
AmI-Based Indoor Emergency Detection and Avoidance (AmI-gestützte Notfallerkennung und -prävention im häuslichen Umfeld)
Authors: Nehmer Jürgen , Rombach Dieter
Published: February 2008

Humans are getting permanently older. Age-related disabilities and diseases increase dramatically with growing age, and often force the respective persons to continue their life in nursing homes. Can ambient-intelligent technology help to extend a self-conducted life of elderly people in their own homes? This article attempts to provide answers to this question. We present the concept of an AmI-based assistance system which detects actual emergencies and tries to avoid their occurrence.