bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic Analysis of Daily Hemofiltration
Authors: Yamashita A.C. , Kawanishi H.
Published: December 2004

Daily hemofiltration (D‐HF) is a new treatment modality that shows unique solute removal characteristics and possibly provides high quality of life for patients with end‐stage renal disease.

Objective:  To evaluate solute‐removal characteristics of D‐HF by kinetic modeling analysis.

Methods:  Five HD patients with normal 4 h × 3 times/week were switched to D‐HF (2 h × 6 times/week). Ultrafiltration rates (QF) or small solute clearances were approximately 100 mL/min. All the necessary kinetic parameters were determined from patients' physical data and HD portion of the clinical measurements. The two‐compartment kinetic model predicted the concentration changes after switching from normal HD to D‐HF.

Results:  Concentrations of small solutes such as urea–nitrogen (UN) increased, whereas that of β2‐microglobulin (β2‐MG) decreased after switching from normal HD to D‐HF (Figure 1). Predicted solute concentrations for UN as well as β2‐MG correlated well with the clinical results. The model predicted that QF = 140 mL/min may be required for time‐averaged concentration (TAC) of UN to be unchanged. The model also predicted that the 7‐times/week D‐HF may not increase the TAC of UN very much even after switching from normal HD to D‐HF.

Conclusion:  D‐HF is suitable for removing larger solutes but may not be good enough for removing small solutes. A 7‐day treatment (7 times/week) may greatly improve the solute removal capacity of the so‐called daily treatment (6 times/week) not only for larger solutes but also for small solutes.
SARS
Authors: Ignacio C. , Jayoma M.
Published: December 2004

In March 2003, a series of cases of sudden respiratory disease syndrome (SARS) has been reported to be spreading in Toronto. With limited knowledge of the causative agent, an immediate strategy that would help contain and prevent the dissemination of the disease especially among our immunosuppressed hemodialysis patients was required.

Objective:  To share the precautionary measures implemented in our unit in containing or preventing the spread of the virus among our hemodialysis patients.

Methods:  Retrospective analysis of the impact of the implementation of strict measure of disease control and education of all staff. Other data were gathered through interviews of some Microbiologists in Toronto, St. Michael's Hospital Infection Control Department and Health, Canada.

Result:  The precautionary measure implemented has been successful. None of our dialysis patients or health care workers were affected.

Conclusion:  The measures implemented has not been proven 100% effective in protecting our dialysis patients and our staff, but we hope that the data will help prepare other health care professionals and other dialysis institutions in the event of another outbreak.
Annual Q10 of soil respiration reflects plant phenological patterns as well as temperature sensitivity
Authors: Curiel yuste J. , Janssens I. A. , Carrara A. , Ceulemans R.
Published: December 2004

The temperature sensitivity of soil respiration (SR) is often estimated from the seasonal changes in the flux relative to those in soil temperature, and subsequently used in models to interpolate or predict soil fluxes. However, temperature sensitivities derived from seasonal changes in SR (from here on denoted seasonal Q10) may not solely reflect the temperature sensitivity of SR, because seasonal changes in SR can also be affected by other seasonally fluctuating conditions and processes. In this manuscript, we present a case study of how the seasonal Q10 of SR can be decoupled from the temperature sensitivity of SR. In a mixed temperate forest, we measured SR under vegetations with different leaf strategies: pure evergreen, pure deciduous, and mixed. Seasonal Q10 was much higher under deciduous than under evergreen canopies. However, at a shorter time scale, both vegetation types exhibited very similar Q10 values, indicating that the large differences in seasonal Q10 do not represent differences in the temperature sensitivity of the soil metabolism. The seasonal Q10 depends strongly on the amplitude of the seasonal changes in SR (SRs), which, under the particular climatic and edaphic conditions of our forest study site, were significantly larger in deciduous forest. In turn, SRs was positively correlated with the seasonal changes in leaf area index (LAIs), a measure of the deciduousness of the vegetation. Thus, in this temperate maritime forest, seasonal Q10 of SR was strongly influenced by the deciduousness of the vegetation. We conclude that the large differences in seasonal Q10 were not entirely due to different temperature sensitivities, but also to different seasonal patterns of plant activity in the evergreen and deciduous plants of this site. Some coniferous forests may be more seasonal than the one we studied, and the deciduous–evergreen differences observed here may not be broadly applicable, but this case study demonstrates that variation of plant phenological process can significantly contribute to the seasonality of SR, and, hence, calculated Q10 values. Where this occurs, the seasonal Q10 value for SR does not accurately represent temperature sensitivity. Because the strong seasonal correlation between SR and temperature does not necessarily imply a causal relationship, Q10 values derived form annual patterns of SR should be used with caution when predicting future responses of SR to climatic change.
The potential to mitigate global warming with no‐tillage management is only realized when practised in the long term
Authors: Six Johan , Ogle Stephen M. , Jay breidt F. , Conant Rich T. , Mosier Arvin R. , Paustian Keith
Published: December 2004

No‐tillage (NT) management has been promoted as a practice capable of offsetting greenhouse gas (GHG) emissions because of its ability to sequester carbon in soils. However, true mitigation is only possible if the overall impact of NT adoption reduces the net global warming potential (GWP) determined by fluxes of the three major biogenic GHGs (i.e. CO2, N2O, and CH4). We compiled all available data of soil‐derived GHG emission comparisons between conventional tilled (CT) and NT systems for humid and dry temperate climates. Newly converted NT systems increase GWP relative to CT practices, in both humid and dry climate regimes, and longer‐term adoption (>10 years) only significantly reduces GWP in humid climates. Mean cumulative GWP over a 20‐year period is also reduced under continuous NT in dry areas, but with a high degree of uncertainty. Emissions of N2O drive much of the trend in net GWP, suggesting improved nitrogen management is essential to realize the full benefit from carbon storage in the soil for purposes of global warming mitigation. Our results indicate a strong time dependency in the GHG mitigation potential of NT agriculture, demonstrating that GHG mitigation by adoption of NT is much more variable and complex than previously considered, and policy plans to reduce global warming through this land management practice need further scrutiny to ensure success.
An increase in the abundance of anchovies and sardines in the north‐western North Sea since 1995
Authors: Beare Doug , Burns Finlay , Jones Emma , Peach Kevin , Portilla Enrique , Greig Tony , McKenzie Eddie , Reid Dave
Published: December 2004

Trawl data from Scottish research vessels dating from January 1925 show that catches of the warm water pelagic species, anchovy (Engraulis encrasicholus) and sardine (Sardina pilchardus), increased suddenly after 1995. Most were observed in the first quarter of each year, with 1998 and 2003 having the largest numbers, although few data are available for the last quarter. The authors believe that these long‐term changes are related to rising sea temperatures although the exact causal mechanism is not clear.
Does nitrogen deposition affect soil microfungal diversity and soil N and P dynamics in a high Arctic ecosystem?
Authors: Robinson Clare H. , Saunders Philip W. , Madan Nanette J. , Janie Pryce‐Miller E. , Pentecost Allan
Published: December 2004

In a high Arctic polar semidesert ecosystem (ambient N deposition c. 0.1 g N m−2 a−1), the effects of N enrichment on the diversity of soil microfungi and on N content and availability in organic and mineral soils were determined. Three N (total: 0, 0.5, 5 g N m−2 a−1) and two P (total 0, 1 g m−2 a−1) treatments were applied, since P may limit response to N in this ecosystem. Organic and mineral soils were sampled in June and August in the second year of treatment for microfungi, pH, moisture content, and total N and P. In the third year, soils were resampled for extractable and total N and P. The fungi isolated were typical of high pH soils in the High Arctic and Antarctic. The species richness and diversity of soil microfungi were very low, with ranges as follows: Shannon diversity, 0.56–1.5; richness, 2–6; evenness, 0.79–0.9. There was no significant effect of treatment on the frequency of occurrence of different taxa of soil microfungi. Time of sampling also had no significant impact on fungal assemblages, although different, more diverse communities were isolated from organic, rather than mineral, soils. Nitrate‐N in organic soil decreased significantly when P was added alone, but not when P and N were added together. Addition of 0.5 g N m−2 a−1, a rate deposition already occurring in Greenland and Iceland, appeared to exceed N demand even when P limitation was relieved. There was no apparent soil acidification as a result of the N treatments.
Carbon balance of different aged Scots pine forests in Southern Finland
Authors: Kolari Pasi , Pumpanen Jukka , Rannik Üllar , Ilvesniemi Hannu , Hari Pertti , Berninger Frank
Published: December 2004

We estimated annual net ecosystem exchange (NEE) of a chronosequence of four Scots pine stands in southern Finland during years 2000–2002 using eddy covariance (EC). Net ecosystem productivity (NEP) was estimated using growth measurements and modelled mass losses of woody debris. The stands were 4, 12, 40 and 75 years old. The 4‐year‐old clearcut was a source of carbon throughout the year combining a low gross primary productivity (GPP) with a total ecosystem respiration (TER) similar to the forest stands. The annual NEE of the clearcut, measured by EC, was 386 g C m−2. Tree growth was negligible and the estimated NEP was −262 g C m−2 a−1. The annual GPPs at the other sites were close to each other (928−1072 g C m−2 a−1), but TER differed markedly, being greatest at the 12‐year‐old site (905 g C m−2 a−1) and smallest in the 75‐year‐old stand (616 g C m−2 a−1). Measurements of soil CO2 efflux showed that different rates of soil respiration largely explained the differences in TER. The NEE and NEP of the 12‐year‐old stand were close to zero. The forested stands were sinks of carbon. They had similar annual patterns of carbon exchange and half‐hourly eddy fluxes were highly correlated, indicating similar responses to the environment. The NEE in the 40‐year‐old stand varied between −179 and –192 g C m−2 a−1, while NEP was between 214 and 242 g C m−2 a−1. The annual NEE of the 75‐year‐old stand was 323 g C m−2 and NEP was 252 g C m−2. This indicates that there was no reduction in carbon sink strength with stand age.
Laughing Matters: A Case Study of Humor in Multicultural Business Negotiations
Authors: Vuorela Taina
Published: December 2004

This article reports the results of an ongoing study of multicultural business negotiations. Two meetings were under scrutiny: (1) the internal strategy meeting of a company's sales team (sellers’ internal meeting or SIM); and (2) a negotiation between the same sellers and a potential customer (client negotiation or CN). The analysis revealed that there were interesting differences in the ways humor was used at the two meetings. The meetings lasted equally long, but SIM featured more humor than CN. Based on the analysis of these meetings, humor seems to have strategic potential for negotiations: it can be used to diffuse tension, mitigate a possible offense, introduce a difficult issue, and thus to pursue one's own goals. Among the most common subjects of humor were the national characteristics of the Finns (the parent‐selling company is Finnish), the project itself, and the selling activity. The most common types of joking in the two meetings were ironic exaggerations and jokes expressing an incongruity. Irony, however, was used more cautiously in CN, where outsiders were present, than in SIM. Joking seems related to power, and power is a factor that influences who has the right to begin and end a joke, and also seems to determine whose joke is laughed at. It is also, not surprisingly, in the sellers’ interest to humor the buyers in the competitive stages of the buying process (e.g., supplier search) in order to “stay in the game,” which is reflected in the use of humor during the meeting.
Evaluating the Communication between Groups in Dispute: Equality in Contact Interventions between Jews and Arabs in Israel
Authors: Maoz Ifat
Published: December 2004

This article examines a new approach for evaluating the process of interactive conflict‐resolution interventions by focusing on the quality of communication between the groups in dispute. This approach assesses the extent to which contact interventions, aimed at improving relations between sides in dispute, actually promote among their participants relationships, behaviors, and interactions that fulfill standards of social justice, equality, and fairness. Creating equality in communication models and reinforces values of mutual respect and tolerance. Thus, establishing symmetrical communication can be especially important for many interventions conducted to resolve conflicts marked by unequal distribution of power. One such asymmetrical conflict is the one between the Jewish majority and the Arab minority in Israel. This article describes a study that applies our process‐evaluation approach to assess equality and social justice in planned contact interventions between Israeli Jews and Arabs by measuring the degree to which members of the two groups contributed equally to the communication between them. Finally, the article presents guidelines, derived from this and other similar studies, for establishing communication equality in other planned contact interventions.
Lupus‐like phototriggering in a young woman with benign summer light eruption
Authors: Marguery M.‐C. , Lamant L. , Bayle P. , Journé F. , Bazex J.
Published: December 2004

We report the case of a young woman with a single history of benign summer light eruption (BSLE) who developed delayed onset annular lupus‐like lesions triggered by a polychromatic phototest, 6 weeks after the irradiation. BSLE of French authors is an idiopathic photodermatosis that corresponds to the minor form of polymorphic light eruption (PLE) of Anglo‐Saxon authors. This patient may develop a true lupus erythematosus in the future as indicated by this lupus‐like phototriggering and in view of the high prevalence of PLE in lupus patients.
Analysis of photodermatoses seen in a predominantly Asian population at a photodermatology clinic in Singapore
Authors: Wong S. N. , Khoo L. S. W.
Published: December 2004

Background: The idiopathic photodermatoses have been reported to be rarer in tropical Singapore than in countries of higher latitude, with photoaggravated dermatoses and systemic phototoxicity making up most of the photodermatoses seen here. This study aims to reassess the spectrum of photodermatoses seen at the National Skin Centre, Singapore, compared with almost a decade ago, and analyse the clinical and photobiological characteristics, as compared with other countries.

Materials and methods: We reviewed the clinical data of 141 patients phototested from January 2000 to December 2001, and analysed the epidemiological, clinical and photobiological features.

Results: Photosensitive dermatoses were diagnosed in 88% (124/141) of patients phototested. In those diagnosed with photodermatoses, polymorphic light eruption (PMLE) (28%) was the most common diagnosis, followed by photoaggravated dermatoses (26%), chronic actinic dermatitis (CAD) (15%), systemic phototoxicity (15%), solar urticaria (SU) (7%), actinic prurigo (AP) (5%) and photoallergic contact dermatitis (4%). Ethnic Indians appeared to be more predisposed to PMLE; AP was diagnosed only in ethnic Chinese. The other photodermatoses occurred proportionally in all racial groups. AP differed from that found in Caucasians, being of adult onset and persistent. Abnormal phototest results were obtained in all patients with CAD, SU and AP, but only in 56% and 49% of systemic phototoxicity and PMLE, respectively.

Conclusion: Idiopathic photodermatoses are more commonly diagnosed in Singapore than a decade ago, while the incidence of systemic phototoxicity has remained stable. The spectrumof photodermatoses in our Asian population now approximates that seen in Caucasian cohorts.
Mentoring in Family Firms: A Reflective Analysis of Senior Executives' Perceptions
Authors: Boyd John , Upton Nancy , Wircenski Michelle
Published: December 2004

This paper reflectively analyzes 76 family business senior executives' perceptions of their personal experiences of being mentored. Although mentoring in family firms is a common recommendation, there is little empirical research supporting its use or efficacy. The findings from this research reveal that those who were mentored believe it is a vital tool for success. The data indicate a strong belief that the selection of the mentoring technique—formal or informal, performed by a family or nonfamily member—should depend on the parties involved and the situation. The analysis provides family businesses with a practical tool for the selection of appropriate mentoring methodologies. The paper also presents recommendations for future research.
In the Founder's Shadow: Conflict in the Family Firm
Authors: Davis Peter S. , Harveston Paula D.
Published: December 2004

This paper examines the extent to which conflict across generations of family firms is due to the effects of two independent variables—generation and generational shadow. The presence of a generational shadow was indicated by whether either or both of the parents continued to influence the company once the next generation assumed control. Hypotheses predicted nonlinear trends in conflict and interactions between generation and generational shadow. Using data from a national telephone survey of over 1,000 family business owners, the results of an ANOVA test confirmed that the presence of generational shadow, in particular, that of the founder, increases organizational conflict.
Candidate interneurones mediating group I disynaptic EPSPs in extensor motoneurones during fictive locomotion in the cat
Authors: Angel M. J. , Jankowska E. , McCrea D. A.
Published: December 2004

In the present study we sought to find interneurones responsible for the group I‐evoked disynaptic excitation of hindlimb extensor motoneurones that occurs during fictive locomotion. Locomotion was produced by stimulation of the mesencephalic locomotor region (MLR) in decerebrate paralysed cats in which activation of ankle extensor group I afferents evoked a disynaptic excitation of motoneurones during the extension phase of fictive locomotion. Extracellular recordings were used to locate interneurones fulfilling all, or five of the six following criteria: (i) weak or no response to stimulation of extensor group I afferents in the absence of locomotion; (ii) strong group I activation during locomotion; (iii) group I activation at monosynaptic latencies; (iv) strong group I activation during only the extensor phase of locomotion; and (v) antidromic activation from the extensor motor nuclei; but (vi) no antidromic activation from rostral spinal segments. Candidate excitatory interneurones were located in mid to caudal parts of the L7 segments in areas where monosynaptic field potentials were evoked by group I afferents, within 2 mm of the stimulation site in the ventral horn from which they were antidromically activated. All were activated during extension by stimulation of group I afferents in extensor nerves. In the absence of peripheral nerve stimulation, six of the seven candidate excitatory interneurones were rhythmically active with maximal activation during the extension phase of fictive locomotion. Rhythmic activity during extension was also seen in five additional interneurones located near candidate interneurones but not activated by group I strength stimulation of the tested nerves. We suggest that the lumbosacral interneurones located in the intermediate laminae that can be activated by extensor group I afferents during the extension phase are a previously unknown population of interneurones, and may mediate group I‐evoked disynaptic excitation of extensor motoneurones. Their rhythmic activity suggests that they also provide central excitatory drive to extensor motoneurones during locomotion.
THIS ARTICLE HAS BEEN RETRACTED Exercise induces interleukin‐8 expression in human skeletal muscle
Authors: Akerstrom Thorbjorn , Steensberg Adam , Keller Pernille , Keller Charlotte , Penkowa Milena , Pedersen Bente Klarlund
Published: December 2004

Skeletal muscle has been recognized as an endocrine organ, and muscle cell cultures express several cytokines with potential hormonal effects. Interleukin‐8 (IL‐8), a chemokine, which induces angiogenesis, is expressed in working muscles; however, the cell source of origin has not been identified. We aimed to elucidate if IL‐8 protein is: (1) expressed in contracting muscle fibres and (2) whether there is a release of IL‐8 from exercising muscle. Seventeen healthy male volunteers were included in two independent protocols: 3 h of ergometer bicycle exercise at 60% of (n= 6) or rest (n= 5), and 3 h of two‐legged knee‐extensor exercise at 60% of maximal workload (n= 6). Repetitive muscle biopsy samples were obtained from the vastus lateralis in all experiments. A marked increase in IL‐8 mRNA was found in muscle biopsy samples obtained after exercise. A marked IL‐8 protein expression was demonstrated within the cytoplasm of muscle fibres in biopsy samples obtained in the recovery phase following 3 h of bicycle exercise, and the peak occurred 3–6 h postexercise. A small transient net release of IL‐8 from working muscle was found at 1.5 h of knee‐extensor exercise. However, the small release of IL‐8 from muscle did not result in an increase in the systemic plasma concentration of IL‐8, suggesting that muscle‐derived IL‐8 may play a local role, e.g. in angiogenesis.
Two Kir2.1 channel populations with different sensitivities to Mg2+ and polyamine block: a model for the cardiac strong inward rectifier K+ channel
Authors: Yan Ding‐Hong , Ishihara* Keiko
Published: December 2004

The strong inward rectification of the whole cell Kir2.1 current, which is very similar to the cardiac inward rectifier K+ current (IK1), is caused by voltage‐dependent blockade of outward currents by the intracellular polyamines spermine and spermidine. We recently showed that macroscopic Kir2.1 currents obtained from inside‐out patches in the presence of various concentrations of cytoplasmic polyamines are well explained by the sum of the currents through two populations of channels that show differing susceptibilities to polyamine blockade. The outward currents obtained with 5–10 μm cytoplasmic spermine showed current–voltage relationships similar to those of IK1 and were considered to flow mostly through a small population of channels exhibiting lower spermine sensitivity. Here we used inside‐out patches to examine the blockade of macroscopic Kir2.1 currents by cytoplasmic Mg2+ in the absence and presence of cytoplasmic spermine. Outward currents were blocked by 0.6 and 1.1 mm Mg2+ in a concentration‐dependent manner, but a small fraction (∼0.1) of the macroscopic conductance was resistant to Mg2+ at those concentrations, suggesting there are two populations of Kir2.1 channels with different sensitivities to Mg2+. Furthermore, at those concentrations, Mg2+ blocked inward currents by inducing a shallow blocked state that differed from the deeper state causing the inward rectification. In the presence of 1.1 mm Mg2++ 5 μm spermine, Mg2+ blocked a substantial current component during depolarizing pulses and generated transient outward components, which is consistent with findings from earlier whole‐cell experiments. In the steady state, Mg2+ blocked the currents at voltages around and negative to the reversal potential and induced sustained outward components. The steady‐state and time‐dependent current amplitudes and the fractional blockades caused by spermine and Mg2+ could be quantitatively explained by a model in which Mg2+ competes with spermine to block the high‐affinity channel and induces three conductance states. The present results suggest that the outward IK1 flows through two populations of channels with different sensitivities to cytoplasmic blockers.
Otolith and canal reflexes in human standing
Authors: Cathers Ian , Day Brian L. , Fitzpatrick Richard C.
Published: December 2004

We used galvanic vestibular stimulation (GVS) to identify human balance reflexes of the semicircular canals and otolith organs. The experiment used a model of vestibular signals arising from GVS modulation of the net signal from vestibular afferents. With the head upright, the model predicts that the GVS‐evoked canal signal indicates lateral head rotation while the otolith signal indicates lateral tilt or acceleration. Both signify body sway transverse to the head. With the head bent forward, the model predicts that the canal signal indicates body spin about a vertical axis but the otolith signal still signifies lateral body motion. Thus, we compared electromyograms (EMG) in the leg muscles and body sway evoked by GVS when subjects stood with the head upright or bent forward. With the head upright, GVS evoked a large sway in the direction of the anodal electrode. This response was abolished with the head bent forward leaving only small, oppositely directed, transient responses at the start and end of the stimulus. With the head upright, GVS evoked short‐latency (60–70 ms), followed by medium‐latency (120 ms) EMG responses, of opposite polarity. Bending the head forward abolished the medium‐latency but preserved the short‐latency response. This is compatible with GVS evoking separate otolithic and canal reflexes, indicating that balance is controlled by independent canal and otolith reflexes, probably through different pathways. We propose that the short‐latency reflex and small transient sway are driven by the otolith organs and the medium‐latency response and the large sway are driven by the semicircular canals.
Off With Your (Fork)Head
Authors: Leslie Mitch
Published: December 2004

To win a crucial game, a coach might decide to keep some good players on the bench. Similarly, cells sideline a key protective pathway to take on DNA-breaking stress, according to new research. The finding could help illuminate how cells decide when they can recover from damage and when their prospects are hopeless.
Genes, Longevity, and Technology: Meeting Report from the 2nd Conference on Functional Genomics of Aging in Crete
Authors: Baumeister Ralf , Hertweck Maren
Published: December 2004

Whole-genome sequences are now available, and methods have evolved for targeting, in parallel, each gene in a genome, offering for the first time the opportunity to study the entire dynamic network of genes involved in aging. At a recent conference in Hersonissos, Crete, around 200 internationally renowned experts gathered to discuss techniques and emerging results as the science of aging undergoes a shift toward systems biology.
Sticky Situation
Authors: Beckman Mary
Published: December 2004

To turn on a lamp at midnight, an insomniac must locate the switch. Researchers trying to illuminate longevity pathways have now found potentially crucial gene switches in DNA. The results should help scientists identify life-span-governing genes.
Gone to Waste
Authors: Leslie Mitch
Published: December 2004

Like a strait-laced businessman cutting loose in Las Vegas, an inflammation-controlling molecule behaves uncharacteristically in a certain milieu. New work suggests that the protein spurs muscle weakness not by prodding inflammation but by directing cells to destroy their own proteins. The work might shed light on how aging undermines strength and could lead to treatments for some types of muscle degradation that are common in the elderly.
Aging-Related Research in the "-omics" Age
Authors: Kaeberlein Matt
Published: December 2004

The application of high-throughput technologies to aging-related research has the potential to dramatically enhance our understanding of how longevity is determined at a molecular level. Genome-scale studies are being carried out in every major model system used for aging-related research, and new technologies are being developed to rapidly identify mutations or small-molecules that increase life span. A meta-analysis of data derived from genome-wide studies of aging in simple eukaryotes will allow the identification of conserved determinants of longevity that can be tested in mammals.
Relay Man
Authors: Davenport R. John
Published: December 2004

In many companies, the CEO snags the press, but it's the mailroom employee who keeps things running smoothly. New research reveals how an unsung cellular hero similarly helps estrogen accomplish its famous bone-saving achievements. The result reveals a crucial step in the bone-preserving chain of command and might point researchers toward new ways of bolstering bone in older women.
Out of Whack, Out of Mind
Authors: Leslie Mitch
Published: December 2004

Your kindergarten teacher was right--neatness counts, even in the brain. Cells that slip out of alignment with age might undermine memory, according to a new study of monkeys. The work might explain the nagging question of why recall falters as we grow older even though we don't normally lose brain cells.
Proteomics in Aging-Related Research
Authors: Gafni Ari
Published: December 2004

Aging is characterized by changes in a variety of cellular phenotypes, which in turn are caused by alterations in the concentrations, compositions, and interactions of cellular proteins. The characterization of these age-associated protein alterations and of their effect on the ability of the organism to maintain homeostasis is thus of critical importance. Proteomics is an emerging scientific discipline that focuses on the determination and analysis of the entire protein complement of a cell (termed the proteome) and of its distribution within the cell. Proteomic analysis provides information about the levels of protein expression under a variety of conditions and about the nature of posttranscriptional modifications, and reveals specific protein complexes. By comparing the proteomes of young and old cells under a variety of conditions, detailed information on the molecular basis of their different phenotypes can be obtained. Although still under development, this scientific discipline holds great promise for aging-related research.
F344BNF1 and BNF344F1 Hybrid Rats
Authors: Holmes Donna J.
Published: December 2004

This document contains a summary of the biological characteristics of the F344BNF1 and BNF344F1 hybrid rats, which are the result of crosses between Brown Norway and Fischer 344 rats. The F344BNF1 hybrid is available from the National Institute of Aging.
Pay by the Pound
Authors: Leslie Mitch
Published: December 2004

Packing extra pounds burdens the heart, forces the kidneys to labor harder, and strains the joints. It might also promote shrinkage of a brain region involved in memory, according to a new study.
Heads and Tails
Authors: Beckman Mary
Published: December 2004

Like a coin, the p53 protein has two sides. It lengthens human life span but more than doubles the likelihood of death by cancer, new research shows. The observation supports the notion that animals give up extra years in order to be free of malignancies.
Paying the Price
Authors: Davenport R. John
Published: December 2004

Like the "gift with purchase" at the makeup counter, long life isn't free. Worms with a life-extending mutation can't hold their own against normal worms, research now reveals. Some previous findings suggested that the animals endured without paying a penalty, but the new work challenges that notion.
Toxic Spill
Authors: Beckman Mary
Published: December 2004

WASHINGTON, D.C.
--Rust can ruin train tracks, causing wrecks that spill toxins. Similarly, a particular insecticide splinters transportation conduits inside motor neurons, derailing containers holding a deadly chemical, according to work presented here 5 December 2004 at the American Society for Cell Biology Annual Meeting. The study also shows that parkin, a protein implicated in Parkinson's disease (PD), helps keep the tracks safe. The results could help researchers understand how PD knocks off only a subset of neurons.
Farming and the Fate of Wild Nature
Authors: Green Rhys E. , Cornell Stephen J. , Scharlemann Jörn P. W. , Balmford Andrew
Published: December 2004

World food demand is expected to more than double by 2050. Decisions about how to meet this challenge will have profound effects on wild species and habitats. We show that farming is already the greatest extinction threat to birds (the best known taxon), and its adverse impacts look set to increase, especially in developing countries. Two competing solutions have been proposed: wildlife-friendly farming (which boosts densities of wild populations on farmland but may decrease agricultural yields) and land sparing (which minimizes demand for farmland by increasing yield). We present a model that identifies how to resolve the trade-off between these approaches. This shows that the best type of farming for species persistence depends on the demand for agricultural products and on how the population densities of different species on farmland change with agricultural yield. Empirical data on such density-yield functions are sparse, but evidence from a range of taxa in developing countries suggests that high-yield farming may allow more species to persist.
Migrate, Differentiate, Proliferate, or Die: Pleiotropic Functions of an Apical "Apoptotic Caspase"
Authors: Kumar Sharad
Published: December 2004

Caspases, the cysteine proteases that cleave their substrates following an aspartate residue, primarily carry out two distinct functions: (i) activation of proinflammatory cytokines and (ii) execution of apoptosis. These two functions are considered to be unique to individual caspases; thus, some caspases act in apoptosis, whereas others have a role in inflammation. However, this dogma is now being challenged as nonapoptotic functions are ascribed to caspases that, until recently, were only known to function in cell death pathways. Recent work suggests that DRONC, the only initiator cell death caspase in
Drosophila
, may play a direct or indirect role in cell migration, sperm differentiation, and cell proliferation in addition to its function in cell death.
Coactivation of D1 and D2 Dopamine Receptors: In Marriage, a Case of His, Hers, and Theirs
Authors: Pollack Alexia
Published: December 2004

D1 and D2 dopamine receptors exert opposing effects on the same signaling pathway mediated by heterotrimeric GTP-binding proteins. D1 receptor activation positively affects adenylyl cyclase, and D2 receptor activation is either uncoupled from adenylyl cyclase or negatively affects it. These data suggest that coactivation of D1 and D2 receptors should produce opposite or competing intracellular signals through activation of separate D1- and D2-mediated signaling pathways. Unexpectedly, recent research suggests that D1 and D2 receptor coactivation in cells that coexpress both receptors leads to the recruitment of a novel signaling pathway, involving phospholipase C (PLC)–mediated calcium mobilization, that is distinct from the intracellular responses observed after stimulation of either dopamine receptor alone. This observation suggests that stimulation of D1 and D2 dopamine receptors has the potential to give rise to different intracellular signals depending on whether D1 or D2 receptors are activated alone or together.
Detecting ATP Release by a Biosensor Method
Authors: Hayashi Seiji , Hazama Akihiro , Dutta Amal K. , Sabirov Ravshan Z. , Okada Yasunobu
Published: December 2004

Cells release adenosine 5′-triphosphate (ATP) into the extracellular space in response to various stimuli. This released ATP plays an important physiological role in cell-to-cell signal transduction. The bulk ATP concentration can be detected using a conventional luciferin-luciferase assay. However, the ATP concentration in the vicinity of the cell surface is often different from the bulk concentration because of its rapid degradation by ecto-ATPases and because of delayed diffusion due to unstirred layer effects. Here, we describe a simple biosensor method to measure the local ATP concentration on the cell surface in real time. The method is based on the ATP-dependent opening of ligand-gated cation channels of purinergic P2X receptors expressed in undifferentiated pheochromocytoma (PC12) cells or in human embryonic kidney 293 (HEK293) cells stably transfected with recombinant P2X
2
purinergic receptors. Under the whole-cell configuration of patch-clamp, a sensor PC12 cell or HEK293 is positioned within the proximity of a target cell, and the P2X-mediated currents induced by ATP released from a given site on the target cell surface is measured. The ATP release is quantified by a calibration procedure utilizing local puff applications of ATP at preset concentrations.
Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats
Authors: Yoshiji Hitoshi , Noguchi Ryuichi , Kuriyama Shigeki , Ikenaka Yasuhide , Yoshii Junichi , Yanase Koji , Namisaki Tadashi , Kitade Mitsuteru , Masaki Tsutomu , Fukui Hiroshi
Published: December 2004

It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in development of liver fibrosis. A platelet-derived growth factor (PDGF) is the most potent mitogen for HSC. The aim of this study was to examine the effect of imatinib mesylate (STI-571, Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor, on development of experimental liver fibrosis. The rat model of pig serum-induced hepatic fibrosis was used to assess the effect of daily oral administration of STI-571 on the indexes of fibrosis. STI-571 markedly attenuated development of liver fibrosis and hepatic hydroxyproline and serum fibrosis markers. The number of α-smooth muscle actin-positive cells and mRNA expression of α2-(I)-procollagen, tissue inhibitor of metalloproteinases-1, and transforming growth factor-β were also significantly suppressed by STI-571. Our in vitro study showed that STI-571 markedly attenuated PDGF-BB-induced proliferation and migration and α-SMA and α2-(I)-procollagen mRNA of activated HSC in a dose-dependent manner. STI-571 also significantly attenuated PDGF-BB-induced phosphorylation of PDGFR-β, MEK1/2, and Akt in activated HSC. Because STI-571 is widely used in clinical practice, it may provide an effective new strategy for antifibrosis therapy.
Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum
Authors: Hoque Kazi Mirajul , Rajendran Vazhaikkurichi M. , Binder Henry J.
Published: December 2004

Zn, an essential micronutrient and second most abundant trace element in cell and tissues, reduces stool output when administered to children with acute diarrhea. The mechanism by which Zn improves diarrhea is not known but could result from stimulating Na absorption and/or inhibiting anion secretion. The aim of this study was to investigate the direct effect of Zn on intestinal epithelial ion absorption and secretion. Rat ileum was partially stripped of serosal and muscle layers, and the mucosa was mounted in lucite chambers. Potential difference and short-circuit current were measured by conventional current-voltage clamp method.86Rb efflux and uptake were assessed for serosal K channel and Na-K-2Cl cotransport activity, respectively. Efflux experiments were performed in isolated cells preloaded with86Rb in the presence of ouabain and bumetanide, whereas uptake experiments were performed in low-Cl isotonic buffer containing Ba and ouabain. Neither mucosal nor serosal Zn affected glucose-stimulated Na absorption. In contrast, forskolin-induced Cl secretion was markedly reduced by serosal but not mucosal addition of Zn. Zn also substantially reversed the increase in Cl secretion induced by 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) with half-maximal inhibitory concentration of 0.43 mM. In contrast, serosal Zn did not alter Cl secretion stimulated by carbachol, a Ca-dependent agonist. Zn inhibited 8-BrcAMP-stimulated86Rb efflux but not carbachol-stimulated86Rb efflux. Zn had no effect on bumetanide-sensitive86Rb uptake, Na-K-ATPase, or CFTR. We conclude from these studies that Zn inhibits cAMP-induced Cl secretion by blocking basolateral membrane K channels.
Inhibition of the preoptic area and anterior hypothalamus by tetrodotoxin alters thermoregulatory functions in exercising rats
Authors: Hasegawa Hiroshi , Ishiwata Takayuki , Saito Takehito , Yazawa Toru , Aihara Yasutsugu , Meeusen Romain
Published: December 2004

We have previously demonstrated a functional role of the preoptic area and anterior hypothalamus (PO/AH) in thermoregulation in freely moving rats at various temperature conditions by using microdialysis and biotelemetry methods. In the present study, we perfused tetrodotoxin (TTX) solution into the PO/AH to investigate whether this manipulation can modify thermoregulation in exercising rats. Male Wistar rats were trained for 3 wk by treadmill running. Body core temperature (Tb), heart rate (HR), and tail skin temperature (Ttail) were measured. Rats ran for 120 min at speed of 10 m/min, with TTX (5 μM) perfused into the left PO/AH during the last 60 min of exercise through a microdialysis probe (control, n = 12; TTX, n = 12). Tb, HR, and Ttailincreased during the first 20 min of exercise. Thereafter, Tb, HR, and Ttailwere stable in both groups. Perfusion of TTX into the PO/AH evoked an additional rise in Tb(control: 38.2 ± 0.1°C, TTX: 39.3 ± 0.2°C; P < 0.001) with a significant decrease in Ttail(control: 31.2 ± 0.5°C, TTX: 28.3 ± 0.7°C; P < 0.01) and a significant increase in HR (control: 425.2 ± 12 beats/min, TTX: 502.1 ± 13 beats/min; P < 0.01). These results suggest that the TTX-induced hyperthermia was the result of both an impairment of heat loss and an elevation of heat production during exercise. We therefore propose the PO/AH as an important thermoregulatory site in the brain during exercise.
Molecular Mechanisms Underlying the Proangiogenic Effect of Factor XIII
Authors: Dardik Rima , Loscalzo Joseph , Eskaraev Regina , Inbal Aida
Published: December 2004

Objective—

Coagulation Factor XIII (FXIII) was previously shown by us to induce angiogenesis. The aim of this study was to elucidate the molecular events underlying the proangiogenic effects of activated FXIII (FXIIIa) on human umbilical vein endothelial cells (HUVECs).

Methods and Results—

As shown by coimmunoprecipitation studies, FXIIIa crosslinked α
v
β
3
with vascular endothelial growth factor receptor 2 (VEGFR-2) and enhanced the noncovalent interaction between the 2 receptors. In addition, FXIIIa induced tyrosine phosphorylation of VEGFR-2 in both the crosslinked high-molecular-weight and the noncovalent VEGFR-2/α
v
β
3
complexes. These effects as well as FXIIIa-induced proliferation and migration of HUVECs were abolished by iodoacetamide treatment of FXIIIa (I-FXIII) or by PTKI, an inhibitor of VEGFR-2. FXIIIa induced upregulation of c-Jun and Egr-1 as revealed by quantitative RT-PCR. Electrophoretic mobility-shift assay experiments showed that FXIIIa treatment of HUVECs enhanced binding of Wilm’s tumor-1 (WT-1) but not of early growth response (Egr)-1 to the thrombospondin-1 (TSP-1) promoter sequence, suggesting that WT-1 but not Egr-1 is involved in downregulation of TSP-1 expression.

Conclusions—

The proangiogenic effect of FXIIIa is mediated by (1) enhancement of crosslinked and noncovalent α
v
β
3
/VEGFR-2 complex formation; (2) tyrosine phosphorylation and activation of VEGFR-2; (3) upregulation of c-Jun and Egr-1; and (4) downregulation of TSP-1 induced indirectly by c-Jun through WT-1. These processes may clarify FXIII role in vascular remodeling and tissue repair.
Human Urotensin II Is a Novel Activator of NADPH Oxidase in Human Pulmonary Artery Smooth Muscle Cells
Authors: Djordjevic Talija , BelAiba Rachida S. , Bonello Steve , Pfeilschifter Josef , Hess John , Görlach Agnes
Published: December 2004

Background—

Human urotensin II (hU-II) is a potent vasoactive peptide possibly involved in pulmonary hypertension. Because the signaling mechanisms activated by this peptide in the pulmonary vasculature are largely unknown, we investigated the role of hU-II in the activation of NADPH oxidase and the control of redox-sensitive kinase pathways, expression of plasminogen activator inhibitor-1 (PAI-1), and proliferation in pulmonary artery smooth muscle cells (PASMCs).

Methods and Results—

hU-II upregulated expression of the NADPH oxidase subunits p22phox and NOX4 and increased the levels of reactive oxygen species (ROS), which were abrogated by transfecting p22phox or NOX4 antisense vectors. p22phox and NOX4 also contributed to hU-II–induced activation of extracellular signal–regulated kinase 1/2, p38 mitogen-activated protein kinase, c-Jun
N
-terminal kinase, and protein kinase B (Akt). Furthermore, hU-II increased the expression of PAI-1 and enhanced PASMC proliferation in an NADPH oxidase– and kinase-dependent manner.

Conclusions—

hU-II is a potent activator of ROS generation by NADPH oxidase in PASMCs, leading to redox-sensitive activation of mitogen-activated protein kinases and Akt and subsequently to enhanced PAI-1 expression and increased proliferation. These findings suggest that hU-II may play a novel role in pulmonary hypertension by promoting remodeling processes via activation of NADPH oxidases.
Stable Knock-Down of the Sphingosine 1-Phosphate Receptor S1P
1
Influences Multiple Functions of Human Endothelial Cells
Authors: Krump-Konvalinkova Vera , Yasuda Satoshi , Rubic Tina , Makarova Natalia , Mages Jörg , Erl Wolfgang , Vosseler Claudia , Kirkpatrick C. James , Tigyi Gabor , Siess Wolfgang
Published: December 2004

Objectives—

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid acting both as a ligand for the G protein–coupled receptors S1P
1-5
and as a second messenger. Because S1P
1
knockout is lethal in the transgenic mouse, an alternative approach to study the function of S1P
1
in endothelial cells is needed.

Methods and Results—

All human endothelial cells analyzed expressed abundant S1P
1
transcripts. We permanently silenced (by RNA interference) the expression of S1P
1
in the human endothelial cell lines AS-M.5 and ISO-HAS.1. The S1P
1
knock-down cells manifested a distinct morphology and showed neither actin ruffles in response to S1P nor an angiogenic reaction. In addition, these cells were more sensitive to oxidant stress–mediated injury. New S1P
1
-dependent gene targets were identified in human endothelial cells. S1P
1
silencing decreased the expression of platelet–endothelial cell adhesion molecule-1 and VE-cadherin and abolished the induction of E-selectin after cell stimulation with lipopolysaccharide or tumor necrosis factor-α. Microarray analysis revealed downregulation of further endothelial specific transcripts after S1P
1
silencing.

Conclusions—

Long-term silencing of S1P
1
enabled us for the first time to demonstrate the involvement of S1P
1
in key functions of endothelial cells and to identify new S1P
1
-dependent gene targets.