bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of prophylaxis in bleeding disorders
Authors: BERNTORP E. , De MOERLOOSE P. , LJUNG R. C. R.
Published: June 2010

Summary.  The rationale for long‐term prophylaxis in more severe forms of von Willebrand’s disease (VWD) is obvious, as mucosal bleeding and haemophilia‐like joint bleeds resulting in chronic morbidity may occur. However, the experience with prophylactic treatment in this group is scanty. An international VWD Prophylaxis Network (VWD PN) was established in 2006. The VWD PN will investigate prophylaxis with retrospective and prospective studies. Eighteen centres in Europe and North America are recruiting patients and an additional 40 centres are preparing for or evaluating participation. In the absence of randomized prospective studies for most rare bleeding disorders, guidelines for prophylaxis are a subject of controversy. In situations where there is a strong family history of bleeding, long‐term prophylaxis is administered in selected cases. Short intervals of prophylaxis can also be given before some surgeries or during pregnancy. The benefits of prophylaxis must be balanced by the risk of side effects. Therefore, it is essential to delineate its management in a specialized comprehensive care environment. In haemophilia, decades of clinical experience and numerous retrospective and, recently, prospective studies clearly demonstrate that prophylactic treatment is superior to on‐demand treatment, regardless of whether the outcome is the number of joint‐ or life‐threatening bleeds, arthropathy evaluated by X‐ray or MRI, or quality of life measured by generic or haemophilia‐specific instruments. Optimal prophylactic treatment should be started early in life (primary prophylaxis) but various options exist for the dose and dose interval. These depend on the objective of treatment in the individual patient, which, in turn, is dependent on resources in the health care system.
Factor VIII and von Willebrand factor – too sweet for their own good
Authors: LENTING P. J. , PEGON J. N. , CHRISTOPHE O. D. , DENIS C. V.
Published: June 2010

Summary.  Although factor VIII (FVIII) and von Willebrand factor (VWF) are products of two distinct genes, they circulate in plasma as a tight non‐covalent complex. Moreover, they both play a critical role in the haemostatic process, a fact that is illustrated by the severe bleeding tendency associated with the functional absence of either protein. FVIII is an essential cofactor for coagulation factor IX, while VWF is pertinent to the recruitment of platelets to the injured vessel wall under conditions of rapid flow. FVIII and VWF have in common that they are heavily glycosylated: full‐length FVIII contains 20 N‐linked and at least seven O‐linked glycans, while VWF contains 12 N‐linked and 10 O‐linked glycans. Three decades of research have revealed that the carbohydrate structures of FVIII and VWF contribute to many of the steps that can be distinguished in the life‐cycle of these proteins, including biosynthesis/secretion, function and clearance. In this review, several of these aspects will be discussed. In addition, the interaction of the FVIII/VWF complex with two families of carbohydrate‐binding proteins, i.e. Galectins and Siglecs, and their potential physiological relevance will be discussed.
Low dose secondary prophylaxis reduces joint bleeding in severe and moderate haemophilic children: a pilot study in China
Authors: WU R. , LUKE K.‐H. , POON M.‐C. , WU X. , ZHANG N. , ZHAO L. , SU Y. , ZHANG J.
Published: June 2010

Summary.  The most common bleeding in haemophilic patients is in joints, and joint disability is the most common complications in these patients receiving inadequate treatment. Limited by economy and inadequate treatment, developing countries face huge challenge to reduce disability and improve quality of life (QoL) of haemophilic children. The aim of this study was to investigate the effect of low dose secondary prophylaxis in China. Children with moderate and severe haemophilia from the Beijing Children Hospital, Beijing, China, and with established joint disease, were followed for a 12‐week observation period followed by a 12‐week low dose secondary prophylaxis‐study period (for haemophilia A, factor VIII concentrate 10 IU kg−1 twice weekly; for haemophilia B, factor IX concentrate 20 IU kg−1 weekly). The reduction of joint bleeding, improvement of joint function and QoL during prophylaxis were analysed. In total 34 children (median age 7.8 years) were analyzable. The number of joint bleeds decreased from a total of 337 (individual range 3–24, mean 9.9) during the observation period to 57 (range 0–6, mean 1.7) during the study period with an overall of reduction 83%. Joint function improved in 66.7% of disease joints, with 23.2% of which were considered good to moderate. School attendance improved in all subjects, sports participation and daily activity improved moderately. Low dose secondary prophylaxis significantly reduces frequency of joint bleeding; with moderate improvement in joint function, school attendance, sport participation and daily activities. Low dose secondary prophylaxis is therefore, cost‐effective as applied to developing countries such as China, although there are still unresolved issues.
Biogeography in the life and literature of John Muir: a ceaseless search for pattern
Authors: McDowall R. M.
Published: June 2010

John Muir has long been known as a significant figure in the history of conservation, including for promoting the recognition of the Yosemite Valley in the Sierra Nevada Mountains of California as a national park by the American people and government. Muir is known particularly for his pivotal involvement in the establishment of the Sierra Club, one of North America’s leading conservation associations. His place in the history of biogeography has been largely unrecognized, although a reading of his books shows that there is a rich seam of innovative historical and ecological biogeographical ideas resulting from his many years living in the Sierras. Added to Muir’s interests in the Sierra Mountains and the Sierra Club were his explorations of the mountain ranges and forests of Alaska, as well as his near world‐wide travels to Europe, Asia, Africa, South America and the Pacific. The literature on biogeography has remained very largely isolated from Muir’s writing, a dissociation that the present paper seeks to remedy.
Genetic and serological analyses of elongation factor EF‐Tu of paulownia witches’‐broom phytoplasma (16SrI‐D)
Authors: Wang J. , Zhu X.‐P. , Gao R. , Lin C.‐L. , Li Y. , Xu Q.‐C. , Piao C.‐G. , Li X.‐D. , Li H.‐F. , Tian G.‐Z.
Published: June 2010

This study determined the tuf gene sequence of the phytoplasma specific to paulownia witches’‐broom from Nanyang, China (hereby designated PaWB‐Ny). The PaWB‐Ny tuf gene was 1185 nucleotides in length and confirmed that the phytoplasma belongs to subgroup 16SrI‐D of aster yellows. Three characteristic GTP‐binding protein motifs were identified based on the peptide deduced from the tuf gene sequence. Results suggested that the elongation factor EF‐Tu was localized in the cytoplasm and lacked hydrophobic transmembrane domains. Antibodies against PaWB‐Ny EF‐Tu were prepared by rabbit immunization with glutathione‐S‐transferase (GST)‐tagged EF‐Tu fusion protein expressed in Escherichia coli. EF‐Tu exhibited a molecular weight of ∼43 kDa and was detected in PaWB‐infected paulownia plants by western blot analysis. Indirect enzyme‐linked immunosorbent assays (ELISA) and dot blotting analyses were performed with freezing and thawing treatments during antigen preparation. Dilution of extracts to an appropriate scale significantly reduced non‐specific reactions. The resultant PaWB EF‐Tu antibody reacted with antigens from plants infected with periwinkle virescence and chinaberry tree witches’‐broom phytoplasmas, but not those infected with jujube witches’‐broom or bishopwood witches’‐broom phytoplasma. The EF‐Tu was characteristically localized within the phytoplasmal cytoplasm of infected plant phloem tissues.
Association of allergic sensitization with infectious diseases burden in Roma and non‐Roma children
Authors: Michos Athanasios , Terzidis Agis , Kanariou Maria , Kalampoki Vasiliki , Koilia Christina , Giannaki Maria , Liatsis Manolis , Pangalis Anastasia , Petridou Eleni
Published: June 2010

To cite this article: Michos A, Terzidis A, Kanariou M, Kalampoki V, Koilia C, Giannaki M, Liatsis M, Pangalis A, Petridou E. Association of allergic sensitization with infectious diseases burden in Roma and non‐Roma children. Pediatr Allergy Immunol 2011; 22: 243–248.

The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non‐Roma children who live in the same area. Analyses included 98 Roma and 118 non‐Roma children. Serum IgG antibodies for 13 foodborne‐ airborne‐ and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food‐ and aero‐allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV‐1, CMV, and Hepatitis B (p < 0.0001). Non‐Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non‐Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non‐Roma children (OR: 1.38, 95% CI: 1.08–1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11–1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non‐Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32–6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non‐Roma children.
A neuronal substrate for a state‐dependent modulation of sensory inputs in the brainstem
Authors: Ray Didier Le , Juvin Laurent , Boutin Tanguy , Auclair François , Dubuc Réjean
Published: June 2010

Central networks modulate sensory transmission during motor behavior. Sensory inputs may thus have distinct impacts according to the state of activity of the central networks. Using an in‐vitro isolated lamprey brainstem preparation, we investigated whether a brainstem locomotor center, the mesencephalic locomotor region (MLR), modulates sensory transmission. The synaptic responses of brainstem reticulospinal (RS) cells to electrical stimulation of the sensory trigeminal nerve were recorded before and after electrical stimulation of the MLR. The RS cell synaptic responses were significantly reduced by MLR stimulation and the reduction of the response increased with the stimulation intensity of the MLR. Bath perfusion of atropine prevented the depression of sensory transmission, indicating that muscarinic receptor activation is involved. Previous studies have shown that, upon stimulation of the MLR, behavioral activity switches from a resting state to an active‐locomotor state. Therefore, our results suggest that a state‐dependent modulation of sensory transmission to RS cells occurs in the behavioral context of locomotion and that muscarinic inputs from the MLR are involved.
Imbalance of the autonomic nervous system at night in women with gestational diabetes
Authors: Pöyhönen‐Alho M. , Viitasalo M. , Nicholls M. G. , Lindström B.‐M. , Väänänen H. , Kaaja R.
Published: June 2010

Diabet. Med. 27, 988–994 (2010)

Aims  Autonomic nervous system dysfunction is observed in Type 2 diabetes. As gestational diabetes is a potent risk factor of later Type 2 diabetes, we set out to determine whether autonomic nervous system imbalance could already be observed in women with this condition. Because activity of the sympathetic nervous system tends to be relatively stable in the nocturnal hours, we performed the study at night.

Research design and methods  We studied 41 women with gestational diabetes, 22 healthy pregnant controls and 14 non‐pregnant controls. We assayed plasma noradrenaline at 24.00, 04.00 and 07.00 h and performed an overnight Holter recording for heart rate variability analysis. In addition, we assayed plasma adrenomedullin, a cardiovascular protective hormone.

Results  Compared with non‐pregnant controls, plasma noradrenaline levels were increased at 04.00 and 07.00 h in the gestational diabetic (P = 0.003) and pregnant control (P = 0.002) groups, with no difference between them. Heart rate variability, very‐low‐frequency and low‐frequency power were lower in pregnant groups compared to the non‐pregnant controls. Heart rate variability remained unchanged between specified sampling times in the gestational diabetic group, in contrast to fluctuation seen in the control groups.

Conclusions  Gestational diabetes, compared with normal pregnancy, seems not to be a state of overall sympathetic nervous system activation. At the heart level, however, an inhibitory effect on autonomic nervous system modulation was seen. Plasma noradrenaline and heart rate variability correlated well, supporting the use of this function in future studies of overall sympathetic activity during pregnancy.
Gibberellin‐associated cisgenes modify growth, stature and wood properties in Populus
Authors: Han Katherine M. , Dharmawardhana Palitha , Arias Reneé S. , Ma Cathleen , Busov Victor , Strauss Steven H.
Published: June 2010

We studied the effects on plant growth from insertion of five cisgenes that encode proteins involved in gibberellin metabolism or signalling. Intact genomic copies of PtGA20ox7, PtGA2ox2,Pt RGL1_1, PtRGL1_2 and PtGAI1 genes from the genome‐sequenced Populus trichocarpa clone Nisqually‐1 were transformed into Populus tremula × alba (clone INRA 717‐1B4), and growth, morphology and xylem cell size characterized in the greenhouse. Each cisgene encompassed 1–2 kb of 5′ and 1 kb of 3′ flanking DNA, as well as all native exons and introns. Large numbers of independent insertion events per cisgene (19–38), including empty vector controls, were studied. Three of the cisgenic modifications had significant effects on plant growth rate, morphology or wood properties. The PtGA20ox7 cisgene increased rate of shoot regeneration in vitro, accelerated early growth, and variation in growth rate was correlated with PtGA20ox7 gene expression. PtRGL1_1 and PtGA2ox2 caused reduced growth, while PtRGL1_2 gave rise to plants that grew normally but had significantly longer xylem fibres. RT‐PCR studies suggested that the lack of growth inhibition observed in PtRGL1_2 cisgenic plants was a result of co‐suppression. PtGAI1 slowed regeneration rate and both PtGAI1 and PtGA20ox7 gave rise to increased variance among events for early diameter and volume index, respectively. Our work suggests that cisgenic insertion of additional copies of native genes involved in growth regulation may provide tools to help modify plant architecture, expand the genetic variance in plant architecture available to breeders and accelerate transfer of alleles between difficult‐to‐cross species.
Unintentional covert motor activations predict behavioral effects: Multilevel modeling of trial‐level electrophysiological motor activations
Authors: Zayas Vivian , Greenwald Anthony G. , Osterhout Lee
Published: June 2010

The present experiment measured an EEG indicator of motor cortex activation, the lateralized readiness potential (LRP), while participants performed a speeded category classification task. The LRP data showed that visually masked words triggered covert motor activations. These prime‐induced motor activations preceded motor activations by subsequent (to‐be‐classified) visible target words. Multilevel statistical analyses of trial‐level effects, applied here for the first time with electrophysiological data, revealed that accuracy and latency of classifying target words was affected by both (a) covert motor activations caused by visually masked primes and (b) spontaneous fluctuations in covert motor activations. Spontaneous covert motor fluctuations were unobserved with standard subject‐level (multi‐trial) analyses of grand‐averaged LRPs, highlighting the utility of multilevel modeling of trial‐level effects.
Fixed‐dose combinations for cough and common cold in India: an assessment of availability and rationality
Authors: Roy Vandana , Malhotra Rohit , Tayal Vandana , Bansal Abhishek , Gupta Kripa Shankar
Published: June 2010

This study was conducted to determine the number and composition of the various cough and cold formulations available in the Indian market and to study their pharmacological rationale over a period of 7 years. Data for the study was collected from an annual Drug Compendium entitled ‘THE DRUG TODAY’ of the years 2001, 2004, and 2007. Medications were assessed for total number, different formulations, and number of constituents present in each formulation, their pharmacological group and amount of each constituent per dose. Rationality of available preparations was assessed on a seven‐point scoring criteria. There are over thirteen hundred drug products for cough and cold in the Indian market, which is an increase of 71.2% from the year 2001. More than 90% of the preparations were fixed‐dose combinations (FDCs). Majority of the cough and cold preparations had 3–4 constituents. Many preparations contained more than one constituent of the same pharmacological group. Some preparations had constituents with opposing action. A wide variation in the amount of each constituent present per dose in different formulations was observed. The number of banned drug combinations for cough and cold showed an increase from 9 in 2001 to 27 in 2007. Rationality assessment of the FDC preparations revealed that most of the preparations were irrational and had no documented benefit in the treatment of common cold. Availability of such a large number of irrational FDCs for cough and cold requires serious review of the legal provisions in India for drug manufacturing and marketing.
Retrospective Study: Incidence of ionized hypocalcemia in septic dogs and its association with morbidity and mortality: 58 cases (2006–2007)
Authors: Luschini Maureen A. , Fletcher Daniel J. , Schoeffler Gretchen L.
Published: June 2010

Objective
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To determine the incidence rate and prognostic significance of ionized hypocalcemia (iHCa) among septic dogs.

Design
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Retrospective study

Setting
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Veterinary teaching hospital

Animals
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Fifty‐eight septic dogs that were presented to Cornell University Hospital for Animals between January 2006 and December 2007.

Procedure
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Cases were diagnosed with sepsis if they exhibited 2 or more criteria of the systemic inflammatory response syndrome with a concurrent documented infectious focus. Cases were excluded if diagnosed with a concurrent illness reportedly associated with calcium derangements. Lowest, mean, and highest blood ionized calcium concentrations were recorded and statistically analyzed for an association with morbidity, as measured by duration of hospitalization and number of blood product transfusions, and outcome. In addition, the incidence rate of iHCa was recorded.

Results
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Of the 58 cases included in this study, iHCa was documented in 4 of 6 (67%) patients that died, 5 of 19 (26%) euthanized patients and 5 of 33 (15%) patients that survived to discharge, with an overall incidence of 24%. Dogs that died during hospitalization had more severe iHCa than patients that were discharged or euthanized as well as significantly lower mean ionized calcium concentrations than patients who were discharged. Severity of iHCa was also associated with a longer duration of hospitalization. The highest ionized calcium concentration was not associated with outcome.

Conclusion and Clinical Relevance
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This study is the first to document the incidence of iHCa among septic dogs. Because both low mean ionized calcium and the lowest documented ionized calcium concentration are associated with poor outcome, it is likely that both the severity and duration of hypocalcemia are important in these patients. Further prospective studies investigating the prognostic significance, etiology and treatment of iHCa among septic veterinary patients are needed to better understand its role in sepsis.
N‐arachidonyl‐glycine modulates synaptic transmission in superficial dorsal horn
Authors: Jeong Hyo‐Jin , Vandenberg Robert J , Vaughan Christopher W
Published: June 2010

BACKGROUND AND PURPOSE The arachidonyl‐amino acid N‐arachidonyl‐glycine (NAGly) is an endogenous lipid, generated within the spinal cord and producing spinally mediated analgesia via non‐cannabinoid mechanisms. In this study we examined the actions of NAGly on neurons within the superficial dorsal horn, a key site for the actions of many analgesic agents.

EXPERIMENTAL APPROACH Whole cell patch clamp recordings were made from lamina II neurons in rat spinal cord slices to examine the effect of NAGly on glycinergic and NMDA‐mediated synaptic transmission.

KEY RESULTS N‐arachidonyl‐glycine prolonged the decay of glycine, but not β‐alanine induced inward currents and decreased the amplitude of currents induced by both glycine and β‐alanine. NAGly and ALX‐1393 (inhibitor of the glycine transporter, GLYT2), but not the GLYT1 inhibitor, ALX‐5407, produced a strychnine‐sensitive inward current. ALX‐5407 and ALX‐1393, but not NAGly prolonged the decay phase of glycine receptor‐mediated miniature inhibitory postsynaptic currents (IPSCs). NAGly prolonged the decay phase of evoked IPSCs, although to a lesser extent than ALX‐5407 and ALX‐1393. In the presence of ALX‐1393, NAGly shortened the decay phase of evoked IPSCs. ALX‐5407 increased and NAGly decreased the amplitude of evoked NMDA‐mediated excitatory postsynaptic currents.

CONCLUSIONS AND IMPLICATIONS Our results suggest that NAGly enhanced inhibitory glycinergic synaptic transmission within the superficial dorsal horn by blocking glycine uptake via GLYT2. In addition, NAGly decreased excitatory NMDA‐mediated synaptic transmission. Together, these findings provide a cellular explanation for the spinal analgesic actions of NAGly.
Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders
Authors: Fenger‐Eriksen Christian , Moore Gary W. , Rangarajan Savita , Ingerslev Jørgen , Sørensen Benny
Published: June 2010

BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline.

STUDY DESIGN AND METHODS: Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo‐optical Clauss methods, one mechanical Clauss method, a prothrombin‐derived method, and viscoelastic measurement through thromboelastometry.

RESULTS: Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo‐optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin.

CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss.
Temporal variation in breeding and cone size selection by three species of crossbills Loxia spp. in a native Scots pinewood
Authors: Summers Ron W. , Dawson Robert J. G. , Proctor Robert
Published: June 2010

The breeding biology and cone size selection of crossbills was studied mainly during 1995 to 2002 at Abernethy Forest, Scotland, an ancient native Scots pine Pinus sylvestris wood, where only a single crossbill species, the Scottish crossbill Loxia scotica, was assumed to occur and to be adapted to feed on seeds in Scots pine cones. However, three crossbill species (common Loxia curvirostra, Scottish and parrot crossbills Loxia pytyopsittacus) nested in some years, with the parrot crossbill being the most abundant. Most nests were in old large pines, with the three crossbill species not differing in their use of tree size or stand density for nesting. The mean clutch and brood sizes were 3.8 and 2.9, and their mean survivals were 86 and 74%, respectively, with no significant differences among species. The timing of breeding differed between species, with parrot crossbills breeding earliest (median date 21 March, including second attempts) and common crossbills breeding last (median date 21 April), probably in response to the differing accessibility of Scots pine seeds to these species. The difference in the time of breeding may reduce mixed mating. Crossbills foraged preferentially on trees with small cones when the cones were closed. Small cones had thinner scales than large cones, suggesting that the preference for small cones was related to higher feeding rates on these cones when cones are closed. Such a preference was also found for captive crossbills with the Scottish crossbill showing a more pronounced preference for smaller cones than the larger‐billed parrot crossbill. However, crossbills selected larger cones within trees and trees with larger cones once the cones opened in April. Such a shift occurred presumably because variation in scale thickness has little impact on seed accessibility once cones open, and larger cones have larger and more seeds. The greater ability of parrot crossbills to exploit seeds in closed Scots pine cones allowed parrot crossbills to start breeding earlier and to have young when seeds were most accessible. Only after the cones opened were the smaller‐billed common crossbills able to easily access seeds and to start breeding. The time of breeding of Scottish crossbills was intermediate between common and parrot crossbills, and they probably had an intermediate ability to exploit Scots pine cones. The reason why there were few Scottish crossbills nesting in Abernethy Forest remains a puzzle, considering that native pine wood is assumed to be the ancestral habitat to which the Scottish crossbill is adapted. The breeding season for all crossbills ended in June, when most of the seed from a given cone cohort was shed. This is when starved broods were found, not associated with bad weather.
Fitness consequences of timing of breeding in birds: date effects in the course of a reproductive episode
Authors: Grüebler Martin U , Naef‐Daenzer Beat
Published: June 2010

In seasonal environments, avian reproductive performance almost generally declines in the course of the season. Quantifying the associated fitness consequences of timing of breeding, i.e. of date‐related factors, is important for understanding the evolution of temporal patterns in avian life‐histories and for predicting consequences of climate change. The seasonal decline can also be caused by an effect of parental quality: individuals with high phenotypic quality may breed early. The results of existing experimental studies investigating whether date or quality effects cause the seasonal decline are inconsistent, indicating that both mechanisms might be involved. However, it remains unclear to what extent the confounding effect of quality occurs and what the fitness consequences of timing per se over a whole breeding episode are. In a cross‐fostering experiment using the barn swallows’ second broods we evaluated the causes for the seasonal decline in reproductive performance for three distinct periods of a reproductive attempt, the early nestling period, the late nestling period and the post‐fledging period, and we assessed the overall fitness consequences of timing per se. A seasonal decline in juvenile feather growth rate was mainly due to date effects in the late nestling period, although we determined quality effects during early nestling development. Date effects on survival were present in the post‐fledging period, but not in the nestling period. The decline in feather length due to date effects in the nestling period accounted for 9% of the seasonal decline in post‐fledging survival, whereas date effects arising only in the post‐fledging period caused 91% of the decline. These results suggest that date effects increase in the course of a reproductive episode. Thus, the benefits of an early timing of breeding can be quantified only when considering also the post‐fledging period. We suggest that the timing of breeding evolved through a trade‐off between date‐related benefits and quality‐related costs of early breeding.
Extensive color polymorphism in the southeast Asian oriental dwarf kingfisher Ceyx erithaca: a result of gene flow during population divergence?
Authors: Lim Haw Chuan , Sheldon Frederick H. , Moyle Robert G.
Published: June 2010

Extensive plumage color polymorphism in the oriental dwarf kingfisher Ceyx erithaca has long intrigued ornithologists of the Indo–Malayan region. A large proportion of birds in Sumatra, Peninsular Malaysia and Borneo have plumages intermediate between the northerly black form and the southerly rufous form. We used molecular genetic techniques to investigate whether the pattern is likely caused by selection, contemporary hybridization or past introgression of genes. These data consist of DNA sequences of a mitochondrial gene (ND2) and five nuclear intronic loci. Phylogenetic analyses indicated that birds from continental southeast Asia (excluding the Thai–Malay Peninsula) are well differentiated from those from insular southeast Asia. This genetic distinction correlates well with a fixed difference in mantle coloration. Northern birds have black mantles and are consistently dark; southern birds, though highly variable in parts of the plumage, consistently possess a rusty brown mantle. Multivariate analyses of morphometric data also support clustering birds in the two groups defined by mantle coloration. Coalescent analyses suggest that gene flow occurred after initial population splitting. We hypothesized that the dynamic geography of the Indo–Malayan Archipelago, as driven by eustatic sea‐level changes related to glacial cycles, is responsible for extensive secondary contact, and gene flow, between the two color forms. Such periodic contacts, after initial separation of the populations, may be equally common in other geographically dynamic regions of the world.
Variable reproductive effort for two ptarmigan species in response to spring weather in a northern alpine ecosystem
Authors: Wilson Scott , Martin Kathy
Published: June 2010

Predicting how animal populations respond to climate change requires knowledge of how species traits influence the response of individuals to variation in anuual weather. Over a four‐year study with two warm and two cold years, we examined how sympatric rock ptarmigan Lagopus muta and white‐tailed ptarmigan L. leucura in the southern Yukon Territory respond to spring weather in terms of breeding phenology and the allocation of reproductive effort. The onset of breeding was approximately synchronous; for each one‐degree rise in spring temperature, mean breeding dates of rock and white‐tailed ptarmigan advanced by about 2.7 and 4 days respectively. Although onset of breeding was similar, the two species differed in their reproductive effort. As breeding was delayed, average first clutch sizes of rock ptarmigan declined from 9.4 to 5.8 eggs over the breeding period, while those of white‐tailed ptarmigan only declined from an average of 7.8 to 6.8. Rock ptarmigan were also less likely to re‐nest if their first clutch was lost to predators and as a consequence they had shorter breeding seasons. White‐tailed ptarmigan produced about 25% more offspring annually than rock ptarmigan and contributed more young through re‐nesting. While white‐tailed ptarmigan had higher annual reproductive output, adult rock ptarmigan had a 20–25% higher annual survival rate, which may indicate a reproduction–survival trade‐off for the two species. These results show that even within the same location, closely related species can differ in how they allocate effort as environmental conditions fluctuate.
Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans
Authors: Saccone N. L. , Schwantes‐An T.‐H. , Wang J. C. , Grucza R. A. , Breslau N. , Hatsukami D. , Johnson E. O. , Rice J. P. , Goate A. M. , Bierut L. J.
Published: June 2010

Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5–CHRNA3–CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect the risk of nicotine dependence in a new sample of African Americans (AAs) (N = 710). We also analyzed this AA sample together with a European American (EA) sample (N = 2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine‐dependent smokers and controls are non‐dependent smokers. Variants in or near CHRND–CHRNG, CHRNA7 and CHRNA10 show modest association with nicotine dependence risk in the AA sample. In addition, CHRNA4, CHRNB3–CHRNA6 and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor single nucleotide polymorphisms (SNPs) that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni‐corrected significance in the AA sample alone. The trait variation explained by three key associated SNPs in CHRNA5–CHRNA3–CHRNB4 is 1.9% in EAs and also 1.9% in AAs; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations.
Community‐acquired pneumonia in children: what’s old? What’s new?
Authors: Don Massimiliano , Canciani Mario , Korppi Matti
Published: June 2010

Community‐acquired pneumonia (CAP) still remains a significant cause for childhood morbidity worldwide. Streptococcus pneumoniae is the most important causative agent at all ages. Respiratory syncytial virus is common in young children, and Mycoplasma pneumoniae in schoolchildren. Paediatric CAP is universally treated with antibiotics; amoxicillin is the drug of choice for presumably pneumococcal and a macrolide for presumably atypical bacterial cases. Because of globally increased resistances, macrolides are not safety for pneumococcal CAP. At present, available prospective research data on the epidemiology of paediatric CAP in western countries are from 1970s to 1980s; correspondingly, data on bacterial aetiology are mainly from 1980s to 1990s. Current concepts on pneumococcal aetiology are mostly based on poorly validated antibody assays. Most data on clinical characteristics in children’s CAP, as well as on antibiotic treatment come from developing countries, thus not being directly applicable in western communities. Recent viral studies have revealed the role of rhinoviruses, metapneumovirus and bocavirus in the aetiology of paediatric CAP. This review critically summarizes the available data on epidemiology, aetiology, clinical presentation, treatment and outcome of CAP in children, with special focus on the newest microbial findings, the age and applicability of the data and the need of new studies.
Default Risk in Corporate Yield Spreads
Authors: Dionne Georges , Gauthier Geneviève , Hammami Khemais , Maurice Mathieu , Simonato Jean‐Guy
Published: June 2010

An important research question examined in the credit risk literature focuses on the proportion of corporate yield spreads attributed to default risk. This topic is reexamined in light of the different issues associated with the computation of default probabilities obtained from historical default data. We find that the estimated default risk proportion in corporate yield spreads is sensitive to the ex ante estimated term structure of default probabilities used as inputs. This proportion can become a large fraction of the spread when sensitivity analyses are made with respect to the period over which the probabilities are estimated and the recovery rates.
Combined effects of climate and land‐use change on the future of humid tropical forests
Authors: Asner Gregory P. , Loarie Scott R. , Heyder Ursula
Published: June 2010

New deforestation and selective logging data and climate change projections suggest that biodiversity refugia in humid tropical forests may change more extensively than previously reported. However, the relative impacts from climate change and land use vary by region. In the Amazon, a combination of climate change and land use renders up to 81% of the region susceptible to rapid vegetation change. In the Congo, logging and climate change could negatively affect the biodiversity in 35–74% of the basin. Climate‐driven changes may play a smaller role in Asia‐Oceania compared to that of Latin America or Africa, but land use renders 60–77% of Asia‐Oceania susceptible to major biodiversity changes. By 2100, only 18–45% of the biome will remain intact. The results provide new input on the geography of projected climate change relative to ongoing land‐use change to better determine where biological conservation might be most effective in this century.
The distribution of close conjugate algebraic numbers
Authors: Beresnevich Victor , Bernik Vasili , Götze Friedrich
Published: June 2010

We investigate the distribution of real algebraic numbers of a fixed degree that have a close conjugate number, with the distance between the conjugate numbers being given as a function of their height. The main result establishes the ubiquity of such algebraic numbers in the real line and implies a sharp quantitative bound on their number. Although the main result is rather general, it implies new estimates on the least possible distance between conjugate algebraic numbers, which improve recent bounds obtained by Bugeaud and Mignotte. So far, the results à la Bugeaud and Mignotte have relied on finding explicit families of polynomials with clusters of roots. Here we suggest a different approach in which irreducible polynomials are implicitly tailored so that their derivatives assume certain values. We consider some applications of our main theorem, including generalisations of a theorem of Baker and Schmidt and a theorem of Bernik, Kleinbock and Margulis in the metric theory of Diophantine approximation.
Some complements to the Lazard isomorphism
Authors: Huber Annette , Kings Guido , Naumann Niko
Published: June 2010

Lazard showed in his seminal work (Groupes analytiques p-adiques, Publ. Math. Inst. Hautes Études Sci. 26 (1965), 389–603) that for rational coefficients, continuous group cohomology of p-adic Lie groups is isomorphic to Lie algebra cohomology. We refine this result in two directions: first, we extend Lazard’s isomorphism to integral coefficients under certain conditions; and second, we show that for algebraic groups over finite extensions K/ℚp, his isomorphism can be generalized to K-analytic cochains andK-Lie algebra cohomology.
Methylglyoxal‐induced imbalance in the ratio of vascular endothelial growth factor to angiopoietin 2 secreted by retinal pigment epithelial cells leads to endothelial dysfunction
Authors: Bento C. F. , Fernandes R. , Matafome P. , Sena C. , Seiça R. , Pereira P.
Published: June 2010

Progressive microvascular complications are a main feature of diabetes and are associated with impairment of the angiogenic response. Methylglyoxal (MGO) has been implicated in the molecular events that lead to endothelial dysfunction in diabetes. In this study, we hypothesize that increased levels of MGO disrupt the ratio of vascular endothelial growth factor (VEGF) to angiopoietin 2 (Ang 2) secreted by retinal pigment epithelial (RPE) cells, which provides a key destabilizing signal that leads to apoptosis and decreased proliferation of retinal endothelial cells. Indeed, we show that MGO increases the levels of Ang 2 and dramatically decreases the levels of VEGF secreted by RPE cells in response to hypoxia. Downregulation of VEGF is likely to be related to decreased hypoxia‐inducible factor‐1α (HIF‐1α) protein levels and HIF‐1 transcriptional activity. Data further show that MGO‐induced imbalance in the VEGF/Ang II ratio significantly changes the levels of BAX and Bcl‐2 in endothelial cells. Moreover, this imbalance is accompanied by an increase in the activity of caspase‐3 and decreased proliferation of endothelial cells. Data obtained in cell culture systems are consistent with observations in retinas of diabetic animals, where increased availability of MGO is associated with changes in distribution and levels of HIF‐1α, VEGF and Ang 2 and increased microvascular permeability. In conclusion, the MGO‐induced imbalance in the VEGF/Ang 2 ratio secreted by retinal epithelial cells activates apoptosis and decreases proliferation of retinal endothelial cells, which are likely to contribute to endothelial dysfunction in diabetic retinopathy.
An Exact
Three-Dimensional Beam Element With Nonuniform Cross
Section
Authors: Jafari M. , Mahjoob M.
J.
Published: June 2010

In this paper, the exact stiffness matrix of curved beams with nonuniform cross section is derived using direct method. The considered element has two nodes and 12 degrees of freedom, with three forces and three moments applied at each node. The noncoincidence effect of shear center and center of area is also considered in this element. The deformations of the beam are due to bending, torsion, tensile, and shear loads. The line passing through center of area is a general three-dimensional curve and the cross section properties may change arbitrarily along it. The method is extended to deal with distributed loads on the curved beams. The stiffness matrix of some selected types of beams is determined by this method. The results are compared (where possible) with previously published results, simple beam finite element analysis and analytic solution. It is shown that the determined stiffness matrix is exact and that any type of beam can be analyzed by this method.
Groove Formation Modeling in Fabricating Hollow Fiber Membrane for Nerve Regeneration
Authors: Yin Jun , Coutris Nicole , Huang Yong
Published: June 2010

Hollow fiber membrane (HFM) is one of the most popular membranes used for different industrial applications. Under some controlled fabrication conditions, axially aligned grooves can be formed on the HFM inner surface during typical immersion precipitation-based phase inversion fabrication processes. Such grooved HFMs are finding promising medical applications for nerve repair and regeneration. For better nerve regeneration performance, the HFM groove morphology should be carefully controlled. Toward this goal, this study has modeled the HFM groove number based on the shrinkage-induced buckling model in HFM fabrication. HFM has been modeled as a three-layer long fiber membrane. The HFM inner layer has been treated as a thin-walled elastic cylindrical shell and buckles due to the shrinkage of the compliant intermediate layer during solidification. The groove geometry, especially the groove number, has been reasonably predicted compared with the experimental measurements. This study has laid a mathematical foundation for HFM circumferential instability modeling, which is of recent interest in membrane fabrication.
Nonlinear Dynamic Behavior Analysis of Microelectrostatic Actuator Based on a Continuous Model Under Electrostatic Loading
Authors: Chen Cha’o-Kuang , Liu Chin-Chia , Lai Hsin-Yi
Published: June 2010

Analyzing the dynamic behavior of microelectrostatic devices is problematic due to the complexity of the interactions between the electrostatic coupling effect, the fringing field effect, the residual stress, the tensile stress, and the nonlinear electrostatic force. In this study, this problem is resolved by modeling the electrostatic system using a continuous model and solving the resulting governing equation of motion using a hybrid scheme comprising the differential transformation method and the finite difference method. The feasibility of the proposed approach is demonstrated by modeling the dynamic responses of two fixed-fixed microbeams when actuated by a dc voltage. It is shown that the numerical results for the pull-in voltage deviate by no more than 1.74% from those presented in the literature. The hybrid scheme is then applied to examine the nonlinear behavior of one clamped microbeam actuated by a combined dc/ac scheme. The beam displacement is analyzed as a function of both the magnitude and the frequency of the ac voltage. Finally, the actuating conditions, which ensure the stability of the microbeam, are identified by reference to phase portraits and Poincaré maps. Overall, the results presented in this study show that the hybrid differential transformation and finite difference method provides a suitable means of analyzing a wide variety of common electrostatically actuated microstructures.
Competing for Transport
Authors: Foley John F.
Published: June 2010

Competition between nitrate and auxin for binding to the nitrate transporter protein NRT1.1 regulates the growth of lateral roots in plants.
A Postreceptor Intervention
Authors: Adler Elizabeth M.
Published: June 2010

Modulation of 5-HT
1A
receptor–associated Gα
i2
activity has antidepressant-like effects in mice.
MiR-33 in Cholesterol Control
Authors: Kiberstis Paula A.
Published: June 2010

A small noncoding RNA helps regulate cholesterol levels in mice.
(R)evolution of Complex Regulatory Systems
Authors: Linding Rune
Published: June 2010

Understanding the implications of the changes in signaling systems requires analysis in both cellular and evolutionary time scales.
Oligochlorophens Are Potent Inhibitors of
Bacillus anthracis
Authors: Foss Marie H. , Weibel Douglas B.
Published: June 2010

Bacterial cytoskeletal proteins are an emerging set of targets for antibiotic development. This paper describes oligochlorophen analogs based on the monomer 4-chloro-2,6-dimethylphenol as antimicrobial agents against
Bacillus anthracis
. The most potent analogs have a MIC of 160 to 320 nM against
B. anthracis
and may target the cytoskeletal protein FtsZ.
B. anthracis
develops resistance to the oligochlorophens at a rate of 4.34 × 10
−10
per generation, which is ∼10-fold lower than that of commercial antibiotics used to treat this human pathogen.