bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurovascular Proximity in the Diaphragm Muscle of Adult Mice
Authors: CORREA DIEGO , SEGAL STEVEN S.
Published: January 2012

Please cite this paper as: Correa D, Segal SS(2012). Neurovascular proximity in the diaphragm muscle of adult mice. Microcirculation 19: 306–315, 2012.

Objective:  Regional blood flow to the diaphragm muscle varies with the workload of inspiration. To provide anatomical insight into coupling between muscle fiber recruitment and oxygen supply, we tested whether arterioles are physically associated with motor nerve branches of the diaphragm.

Methods:  Following vascular casting, intact diaphragm muscles of C57BL/6 and CD‐1 mice were stained for motor innervation. Arteriolar networks and nerve networks were mapped (∼2 μm resolution) to evaluate their physical proximity.

Results:  Neurovascular proximity was similar between muscle regions and mouse strains. Of total mapped nerve lengths (C57BL/6, 70 ± 15 mm; CD‐1, 87 ± 13 mm), 80 ± 14% and 67 ± 10% were ≤250 μm from the nearest arteriole and associated predominantly with arterioles ≤45 μm in diameter. Distances to the nearest arteriole encompassing 50% of total nerve length (D50) were consistently within 200 μm. With nerve networks repositioned randomly within muscle borders, D50 values nearly doubled (p < 0.05). Reference lines within anatomical boundaries reduced proximity to arterioles (p < 0.05) as they deviated from the original location of motor nerves.

Conclusion:  Across two strains of mice, motor nerves and arterioles of the diaphragm muscle are more closely associated than can be explained by chance. We hypothesize that neurovascular proximity facilitates local perfusion upon muscle fiber recruitment.
Effect of Dysprosia Additive on the Consolidation of CeO2 by Spark Plasma Sintering
Authors: Choi Kwanghoon , Reavis Richard E. , Osterberg Daniel D. , Jaques Brian J. , Butt Darryl P. , Mariani Robert D. , Burkes Douglas E. , Munir Zuhair A.
Published: January 2012

The influence of dysprosia addition on the sintering and resulting microstructure of nano‐grained CeO2 ceramics was investigated as functions of the spark plasma sintering parameters. The addition of Dy2O3 (forming a solid solution) resulted in an increase in relative density and a decrease in grain size in sintered samples. The relative density of samples with Dy2O3 content of 6 and 10 mol% was over 95% when sintered at 1050°C under 500 MPa for holding times as short as 5 min. The application of high pressure facilitated the consolidation to relatively high densities with minimal grain growth. Heating rate and holding time, however, had insignificant effect on density but a measurable effect on grain size.
Evidence on the Dual Nature of Aluminum in the Calcium‐Silicate‐Hydrates Based on Atomistic Simulations
Authors: Abdolhosseini Qomi Mohammad Javad , Ulm Franz‐Josef , Pellenq Roland J.‐M.
Published: January 2012

Hydration of tri‐calcium silicate (C3S) and di‐calcium silicate (C2S) precipitates calcium‐silicate‐hydrate (CSH) which is the bonding phase responsible for the strength of cementitious materials. Substitution of part of C3S and C2S with aluminum‐containing additives alters the chemical composition of hydration products by precipitating calcium‐aluminate‐silicate‐hydrate (CASH). Incorporation of aluminum in the molecular building blocks of CSH entails structural and chemo‐mechanical consequences. These alterations can be measured through solid state nuclear magnetic resonance (NMR) experiments. By conducting a wide spectrum of atomistic simulation methods on thousands of aluminum‐containing molecular CASH structures, an overall molecular approach for determination of CASH nanostructure is presented. Through detailed analysis of different order parameters, it is found that aluminum can exhibit a tetra‐/penta‐/octahedral behavior which is fully consistent with the recent NMR observations. This corresponds to the formation of a class of complex three‐dimensional alumino‐silicate skeletons with partial healing effect in the CASH nanostructure potentially increasing durability and strength of hydration products. We explored the variation of mechanical observables by increasing aluminum content in CASH structures of varying calcium to silicon ratio. Finally, deformation of CSHs and CASHs of different chemical formula in a multi‐scale fashion unravels the effect of chemical composition on the strength and kinematics of deformation in this particular type of composites.
Strong ZrB2–SiC–WC Ceramics at 1600°C
Authors: Zou Ji , Zhang Guo‐Jun , Hu Chun‐Feng , Nishimura Toshiyuki , Sakka Yoshio , Vleugels Jef , Van der Biest Omer
Published: January 2012

High temperature flexural strength of ZrB2–20 vol% SiC ceramics (ZS) up to 1600°C in high purity argon atmosphere was significantly improved by adding 5 vol% WC, but degraded when 5 vol% ZrC was added. ZrB2–20SiC–5WC ceramic (ZSW) has a very high strength (mean ± SD) of 675 ± 33 MPa at 1600°C, and also an elastic and transgranular fracture mode was observed. According to the analysis of the fracture modes and crack origins in ZSW ceramics, the improvement in strength above 1000°C was attributed to the removal of the oxide impurities from grain boundaries.
Structural Transitions and Microwave Dielectric Properties of Ba2−2xSr2xSmSbO6 Double Perovskites
Authors: Zhou Yuanyuan , Tian Cailan , Meng Siqin , Yue Zhenxing , Li Longtu
Published: January 2012

Structures and microwave dielectric properties of Ba2−2xSr2xSmSbO6 (x = 0–1) ceramics were studied in this article. The phase transitions were analyzed using X‐ray powder diffraction, transmission electron microscopy, and Raman spectroscopy. All structures are proved to be ordered double perovskites, and a series of composition‐induced phase transitions are confirmed in the Ba2−2xSr2xSmSbO6 system via the sequence: Fm‐3m → I2/m → P21/n. Dielectric properties of the ceramics were measured at microwave frequencies (9–11 GHz). With the increase of x, the dielectric constant (εr) varies gradually from 20.7 to 16.0, the quality factor (Q × f) decreases first from 86 500 GHz to a minimum value at x = 0.4 and then increases slightly to 93 000 GHz, and the temperature coefficient of resonant frequency (τf) decreases from +25 to −50 ppm/°C. The relationships between composition, structure, and microwave dielectric properties in Ba2−2xSr2xSmSbO6 were discussed from the phase transition consideration.
Crystallographic Orientation Relationships Between SrTiO3 and Ruddlesden‐Popper Phase
Authors: Nien Chih‐Hung , Lu Hong‐Yang
Published: January 2012

The crystalline phase mixture and microstructure of SrO‐excess SrTiO3 powder sintered at 1350°C/4 h is analyzed using X‐ray diffractometry (XRD), and scanning and transmission electron microscopy (SEM and TEM). Second phases represented by Ruddlesden–Popper Sr3Ti2O7 (RP2) and Sr4Ti3O10 (RP3) coexist with SrTiO3 (ST), consistent with the SrO–TiO2 phase equilibrium diagram. Some ST grains contain inter‐grown RP2 lamellae that permits analysis of the ST‐RP2 interface. The ST‐RP2 boundary shared by (001)ST and (001)RP2, although containing a lattice mismatch, is accommodated by long‐range elastic strain. The crystallographic orientation relationships of ST and RP2 at the interface are determined by selected area diffraction patterns (SADP) and described by transformation matrices. The crystallographic shear structure across the ST–RP boundary exhibiting the characteristic α‐fringe pattern can be represented by a fault vector R = 1/2(111)ST.
Directionally Solidified Al2O3–Er3Al5O12–ZrO2 Eutectic Ceramics with Interpenetrating or Nanofibrillar Microstructure: Residual Stress Analysis
Authors: Mesa María Cristina , Oliete Patricia B. , Larrea Ángel , Orera Víctor M.
Published: January 2012

Directionally solidified Al2O3–Er3Al5O12–ZrO2 eutectic ceramic rods were fabricated by the laser‐assisted float zone method at growth rates from 25 to 1200 mm/h. The microstructure of the eutectic rods was studied as a function of the solidification rate and the three eutectic phases present in the material were identified by X‐ray and electron diffraction. The size of the eutectic phases measured in the plane perpendicular to the growth direction decreased when the growth rate increased. The microstructure showed a geometrical pattern morphology at low growth rates, an irregular faceted and interpenetrating morphology at medium rates, and a nanofibrillar morphology in samples solidified at 1200 mm/h. The fibrous pattern consisted of Al2O3 trifold shaped nano‐fibers surrounded by a jacket of Er‐stabilized ZrO2 (t < 50 nm) and embedded in a matrix of Er3Al5O12 of ~150 nm width. The residual stress in the alumina phase due to the thermal contraction mismatch between phases was determined by piezospectroscopy. It decreased with solidification rate from 262 MPa compressive at room temperature in the sample with the coarsest microstructure to 135 MPa in the sample solidified at 1200 mm/h. A linear behavior of the thermoelastic stresses was found in the 110–370 K temperature range. The stress relief temperature at which the stresses become zero markedly decreased with the interphase spacing. The decrease was attributed to thermal activation of diffusional creep in the nanometric ZrO2 phase.
The Wisdom of the Crowd in Combinatorial Problems
Authors: Yi Sheng Kung Michael , Steyvers Mark , Lee Michael D. , Dry Matthew J.
Published: January 2012

The “wisdom of the crowd” phenomenon refers to the finding that the aggregate of a set of proposed solutions from a group of individuals performs better than the majority of individual solutions. Most often, wisdom of the crowd effects have been investigated for problems that require single numerical estimates. We investigate whether the effect can also be observed for problems where the answer requires the coordination of multiple pieces of information. We focus on combinatorial problems such as the planar Euclidean traveling salesperson problem, minimum spanning tree problem, and a spanning tree memory task. We develop aggregation methods that combine common solution fragments into a global solution and demonstrate that these aggregate solutions outperform the majority of individual solutions. These case studies suggest that the wisdom of the crowd phenomenon might be broadly applicable to problem‐solving and decision‐making situations that go beyond the estimation of single numbers.
Middle Cerebellar Peduncles and Pontine T2 Hypointensities in ARSACS
Authors: Shimazaki Haruo , Takiyama Yoshihisa , Honda Junko , Sakoe Kumi , Namekawa Michito , Tsugawa Jun , Tsuboi Yoshio , Suzuki Chieko , Baba Masayuki , Nakano Imaharu
Published: January 2012

BACKGROUND AND PURPOSE

Magnetic resonance imaging (MRI) of autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) cases in Quebec and Europe was reported to show linear hypointensities in T2‐weighted and Fluid Attenuated Inversion Recovery (FLAIR) images of the pons. We attempted to clarify the characteristics of the brain MRI findings in ARSACS cases.

METHODS

Eight Japanese early‐onset ataxia patients with ARSACS confirmed molecularly were investigated. We performed neurological examination, SACS gene analysis, and MRI in the patients.

RESULTS

Hypointensity lesions in the middle cerebellar peduncles in addition to the pons were observed in T2‐weighted and FLAIR images in all eight cases. Although superior cerebellar atrophy was seen in all cases, this MRI finding might not be specific for ARSACS. Upper cervical cord and medulla oblongata atrophy was not observed in 3 of the 7 patients examined.

CONCLUSION

Not only pontine but also middle cerebellar peduncle hypointensity lesions observed in T2‐weighted and FLAIR images could be specific findings for ARSACS even in cases with variable clinical phenotypes.
The Optic Radiation and the Cerebellar Peduncles in Adolescents with First‐Admission Schizophrenia —A Diffusion Tensor Imaging Study
Authors: Henze Romy , Brunner Romuald , Thiemann Ulf , Parzer Peter , Klein Jan , Resch Franz , Stieltjes Bram
Published: January 2012

BACKGROUND AND PURPOSE

Previous studies have found gray matter alterations in the cerebellum and in the visual system in both adults and adolescents with schizophrenia. The present study was conducted to investigate whether white matter tracts associated with these regions are also affected in the early stages of the disorder.

METHODS

Using a 1.5 Tesla magnetic resonance imaging (MRI) scanner and fiber tracking, the optic radiations and the middle cerebellar peduncles were examined in 13 adolescents with first‐admission schizophrenia and 13 healthy controls matched for age, gender, school type, and handedness.

RESULTS

Patients with schizophrenia displayed significantly decreased fractional anisotropy in the optic radiations, but no differences in the middle cerebellar peduncles compared to healthy controls.

CONCLUSIONS

Our findings of altered fiber integrity in the optic radiations in adolescents with schizophrenia are in line with gray matter alterations in the visual cortices previously reported in the same sample and are in accordance with other studies that found decreased fractional anisotropy in these regions. These findings support the view that the visual system plays an important role in the pathogenesis of schizophrenia and may enhance our understanding of associations between the visual cortex and symptoms of the disorder.
Fatalities Temporally Associated with the Ingestion of Ibogaine
Authors: Alper Kenneth R. , Stajić Marina , Gill James R.
Published: January 2012

Abstract:  Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5–76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine.
A Population Genetic Database of Cat Breeds Developed in Coordination with a Domestic Cat STR Multiplex*
Authors: Menotti‐Raymond Marilyn , David Victor A. , Weir Bruce S. , O’Brien Stephen J.
Published: January 2012

Abstract:  A simple tandem repeat (STR) PCR‐based typing system developed for the genetic individualization of domestic cat samples has been used to generate a population genetic database of domestic cat breeds. A panel of 10 tetranucleotide STR loci and a gender‐identifying sequence tagged site (STS) were co‐amplified in genomic DNA of 1043 individuals representing 38 cat breeds. The STR panel exhibits relatively high heterozygosity in cat breeds, with an average 10‐locus heterozygosity of 0.71, which represents an average of 38 breed‐specific heterozygosities for the 10‐member panel. When the entire set of breed individuals was analyzed as a single population, a heterozygosity of 0.87 was observed. Heterozygosities obtained for the 10 loci range from 0.72 to 0.96. The power for genetic individualization of domestic cat samples of the multiplex is high, with a probability of match (pm) of 6.2E‐14, using a conservative θ = 0.05.
Is There a Relationship Between Bladder Outlet Obstruction due to Benign Prostatic Hyperplasia and Pulmonary Thromboembolism?
Authors: Rosenfeld Hannah E. , Byard Roger W.
Published: January 2012

Abstract:  Benign prostatic hyperplasia with chronic bladder outlet obstruction has been associated with deep venous thrombosis (DVT) and fatal pulmonary thromboembolism (PTE). To evaluate this further, 60 autopsy cases of men with PTE were compared with 60 age‐matched controls. The criteria for outlet obstruction were macroscopic prostatic enlargement with bladder trabeculation and benign prostatic hyperplasia on microscopy. Ten of the 60 men (16.7%) with fatal PTE had evidence of bladder outlet obstruction (age 57–78 years; mean 71.4 years). Of the 60 controls, 12 had evidence of bladder outlet obstruction (20%) (age 67–86 years; mean 75.5 years). No significant relationship could be demonstrated between bladder outlet obstruction and fatal PTE cases (p = 0.8). Given reports of this association, however, it is possible that bladder distension with venous compression may act as a risk modifier in certain individuals in association with other significant comorbidities, but this risk appears low.
Lower Extremity Deep Venous Thrombosis with Fatal Pulmonary Thromboembolism Caused by Benign Pelvic Space‐Occupying Lesions—An Overview
Authors: Rosenfeld Hannah , Byard Roger W.
Published: January 2012

Abstract:  Venous stasis predisposes to thrombosis. One hundred and sixty cases of fatal pulmonary thromboembolism were reviewed to determine how many cases had deep venous thromboses associated with venous blood flow reduction caused by external pressure from benign pelvic masses. Three cases were identified, representing 2% of cases overall (3/160): a 44‐year‐old woman with a large uterine leiomyoma (1048 g); a 74‐year‐old man with prostatomegaly and bladder distension (containing 1 L of urine); and a 70‐year‐old man with prostatomegaly and bladder distension (containing 3 L of urine). Although a rare cause of fatal deep venous thrombosis and pulmonary thromboembolism, space‐occupying pelvic lesions can lead to extrinsic pressure on adjacent veins reducing blood flow and causing stasis and thrombosis. Individuals with large pelvic masses may, therefore, be at increased risk of pulmonary thromboembolism from deep venous thrombosis, particularly in the presence of concurrent risk factors such as immobility, thrombophilias, malignancy, and significant cardiopulmonary disease.
Impact of childhood life events and trauma on the course of depressive and anxiety disorders
Authors: Hovens J. G. F. M. , Giltay E. J. , Wiersma J. E. , Spinhoven P. , Penninx B. W. J. H. , Zitman F. G.
Published: January 2012

Hovens JGFM, Giltay EJ, Wiersma JE, Spinhoven P, Penninx BWJH, Zitman FG. Impact of childhood life events and trauma on the course of depressive and anxiety disorders.

Objective:  Data on the impact of childhood life events and childhood trauma on the clinical course of depressive and anxiety disorders are limited.

Method:  Longitudinal data were collected from 1209 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events and trauma at baseline were assessed with a semi‐structured interview and the clinical course after 2 years with a DSM‐IV‐based diagnostic interview and Life Chart Interview.

Results:  At baseline, 18.4% reported at least one childhood life event and 57.8% any childhood trauma. Childhood life events were not predictive of any measures of course trajectory. Emotional neglect, psychological and physical abuse, but not sexual abuse, were associated with persistence of both depressive and comorbid anxiety and depressive disorder at follow‐up. Emotional neglect and psychological abuse were associated with a higher occurrence of a chronic course. Poor course outcomes were mediated mainly through a higher baseline severity of depressive symptoms.

Conclusion:  Childhood trauma, but not childhood life events, was associated with an increased persistence of comorbidity and chronicity in adults with anxiety and/or depressive disorders. More unfavourable clinical characteristics at baseline mediate the relationship between childhood trauma and a poorer course of depressive and anxiety disorders.
Loss of E‐cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma
Authors: ELZAGHEID ADAM , BUHMEIDA ABDELBASET , LAATO MATTI , EL‐FAITORI OMRAN , SYRJÄNEN KARI , COLLAN YRJÖ , PYRHÖNEN SEPPO
Published: January 2012

Elzagheid A, Buhmeida A, Laato M, El‐Faitori O, Syrjänen K, Collan Y, Pyrhönen S. Loss of E‐cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma. APMIS 2012; 120: 539–48.

The traditional staging system is currently inadequate for identifying those patients with colorectal carcinoma (CRC) who carry a high risk for poor outcome. In this study, the expression of E‐cadherin was evaluated in CRC to determine its correlation with clinico‐pathological variables, and association with disease outcome in patients with long‐term follow‐up. The present series consisted of tissue samples obtained from 230 patients with stage I, II, III, or IV CRC treated during 1981–1990 at Turku University Hospital. Archival paraffin‐embedded samples were used to build up tissue microarray blocks, and E‐cadherin expression was assessed by immunohistochemistry using an automated staining system. Different grading systems were tested for expression of E‐cadherin. Fifty‐nine percent of all tumors were positive for E‐Cadherin. There was no significant correlation between E‐cadherin expression and gender (p < 0.83), localization (p < 0.45), tumor invasion (p < 0.32), or histologic grade (p < 0.41). However, loss of E‐cadherin expression was significantly associated with older age (p < 0.03) and lymph node involvement (p < 0.02), and with borderline significance with advanced stage (p < 0.09) and tumor metastasis (p < 0.09). In univariate (Kaplan–Meier) survival analysis, positive E‐cadherin significantly (p = 0.009) predicted longer disease‐free survival (DFS), and the same was true with disease‐specific survival (DSS) as well (p = 0.007). In multivariate (Cox) survival analysis, E‐cadherin retained its significance as independent predictor of DFS (HR = 1.56; 95% CI 1.01–2.42, p = 0.043), but not DSS. A sub‐group analysis revealed that E‐cadherin expression also predicts DFS (p < 0.01) and DSS (p < 0.04) in stage II CRC. Our results implicate the usefulness of E‐cadherin expression in predicting disease recurrence and long‐term survival in CRC.
Dual‐energy X‐ray absorptiometry and biochemical markers of bone turnover after autologous stem cell transplantation in myeloma
Authors: Laroche Michel , Lemaire Olivia , Bourin Philippe , Corre Jill , Gadelorge Mélanie , Roussel Muriel , Attal Michel
Published: January 2012

Objectives:  To evaluate the effect of high‐dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) on bone turnover and bone mineral density in a cohort of 39 consecutive patients with multiple myeloma (MM).

Methods:  Phosphorus and calcium parameters, bone turnover markers, and bone mineral density were studied. Timepoints were diagnosis (T1), just before ASCT (T2), 6 months (T3) after ASCT, and 1 yr (T4) after ASCT.

Results:  No bone mineral loss was shown on dual‐energy X‐ray absorptiometry (DXA) at T1 (lumbar Z‐score −0.02, femoral neck Z‐score 0.77) or during follow‐up. Chronic vitamin D deficiency (25OHD3 11.7 ± 7.7 ng/mL at T1) and relative hyperparathyroidism from T2 to T4 were observed. In spite of this moderate hyperparathyroidism, serum C‐telopeptide of type I collagen (CTX) decreased significantly between T1 and T4. Bone alkaline phosphatase levels were low at diagnosis and showed no significant change after ASCT, unlike DKK1 levels that were high at diagnosis and decreased 6 months after ASCT in patients not previously treated with bisphosphonates.

Conclusion:  Bone demineralization is moderate in multiple myeloma. ASCT induces a decrease in bone resorption but no changes in bone formation, remaining low despite the decrease in DKK1. Bone mineral loss, evaluated by DXA, is moderate in multiple myeloma. High‐dose chemotherapy followed by ASCT leads to decreased bone resorption but osteoblastic bone formation remains low, in spite of reduced circulating DKK1.
Hypoxia improves expansion potential of human cord blood–derived hematopoietic stem cells and marrow repopulation efficiency
Authors: Roy Sushmita , Tripathy Manjul , Mathur Nitin , Jain Asish , Mukhopadhyay Asok
Published: January 2012

Objectives:  In bone marrow, hematopoietic stem cells (HSCs) reside in the most hypoxic endosteum niche, whereas the proliferating progenitors are located near the relatively oxygen‐rich vascular region. High oxygen tension is potentially detrimental to HSCs. The objective of this investigation was to compare cellular, functional, and molecular responses of human umbilical cord blood (UCB)‐derived hematopoietic stem and progenitor cells in culture under hypoxic and normoxic conditions.

Methods:  CD133‐enriched UCB cells were cultured in growth factor containing serum‐free and serum‐supplemented medium under 5% O2 (hypoxia) or 21% O2 (normoxia) for 10 d. The phenotypes of expanded cells were analyzed by flow cytometry and the engraftability by SCID‐repopulation assay. The expression of hypoxia‐inducible factor (HIF)‐1α and some of its target genes was analyzed by real‐time RT‐PCR.

Results:  In hypoxic culture, CD34+ CD38− cells were expanded about 27‐fold, which was significantly (P < 0.01) higher than that obtained in normoxic culture. Serum‐free culture did not support the growth of cells in the presence of 21% O2. Myeloid colony‐forming potential of cells was significantly (P < 0.05) increased in 5% O2 compared with 21% O2 culture. SCID‐repopulation efficiency seems to be better preserved in the cells cultured under hypoxic conditions. Hypoxia significantly (P < 0.05) induced the expression of HIF‐1α, vascular endothelial growth factor (VEGF), and ABCG2 genes and also upregulated CXCR4 receptor expression.

Conclusions:  Low oxygen tension enhanced the proliferation of UCB‐derived HSC/progenitor cells and maintenance of SCID‐repopulating cells than normoxia. These expanded cells are expected to be beneficial in the patients who lack human leukocyte antigen (HLA)‐matched donors.
Development of an ELISA method for testing VWF ristocetin cofactor activity with improved sensitivity and reliability in the diagnosis of von Willebrand disease
Authors: Zhao Yiming , Gu Ying , Ji Shundong , Yang Jianfeng , Yu Ziqian , Ruan Changgeng
Published: January 2012

Objectives:  Current methods in assessing von Willebrand factor (VWF) ristocetin cofactor activity for Von Willebrand’s disease (VWD) diagnosis include platelet agglutination by aggregometer or macroscopic slide examination, which are both time‐consuming with suboptimal interassay and intra‐assay variation. The purpose of this study is to establish a sensitive assay to detect VWF:RCo activity and evaluate its performance in VWD diagnosis.

Methods:  We have established a sensitive VWF:RCo–ELISA method using a monoclonal antibody, SZ‐151, to immobilize the recombinant fragment of platelet glycoprotein Ib (rfGPIbα). VWF was captured by rfGPIbα in the presence of ristocetin, and then detected by HRP‐conjugated rabbit anti‐human VWF IgG. We tested the VWF:RCo level by this VWF:RCo–ELISA in 25 patients with different types of VWD and 36 healthy donors, and compared this method to a previously reported ELISA using 2D4 coating antibody.

Results:  The sensitivity of VWF:RCo–ELISA was greatly improved with this assay (0.008 IU/dL compared to 0.031 IU/dL by 2D4 antibody). The interassay and intra‐assay coefficient variation were 8% and 12%, respectively. The mean values (ranges) of VWF:RCo in patients with type 1, type 2A, type 2B, type 2M, and type 3 of VWD and control group are 31.8 (22.3–56.9), 4.8 (0.6–11.8), 8.6 (1.6–19.7), 3.9 (1.0–6.8), 1.0 (0.5–1.6), and 91.5 (47.3–169.2) IU/dL, respectively. The corresponding ratios (ranges) of VWF:RCo/VWF:Ag are 0.83 (0.70–1.16), 0.27 (0.08–0.58), 0.31 (0.15–0.40), 0.18 (0.14–0.21), 0.52 (0.13–1.19), and 0.92 (0.62–1.26).

Conclusion:  The VWF:RCo–ELISA using monoclonal anti‐rfGPIbα antibody SZ‐151 showed improved sensitivity and reliability in detecting VWF:RCo activity, and its clinical application would facilitate the diagnosis and classification of VWD.
An ErbB receptor–mediated AP‐1 regulatory network is modulated by STAT3 and c‐MYC during calcium‐dependent keratinocyte differentiation
Authors: Saeki Yuko , Nagashima Takeshi , Kimura Shuhei , Okada‐Hatakeyama Mariko
Published: January 2012

Abstract:  A calcium gradient in skin epidermis is known to regulate epidermal differentiation. In cultures of human epidermal keratinocytes (NHEK), induction of calcium‐dependent differentiation is associated with phosphorylation of ErbB receptors, including the epidermal growth factor receptor (EGFR). The activation of EGFR triggers the induction of activator protein 1 (AP‐1) proteins necessary for keratinocyte terminal differentiation. Interestingly, an in vitro long‐term calcium treatment revealed the activation of different ErbB receptors with different timings, which is consistent with the differential localization of each receptor in the skin layers in vivo. In the current study, the regulatory relationship between ErbB receptor activation and induction of AP‐1 proteins in calcium‐dependent keratinocyte differentiation was analysed. For this purpose, we used a mathematical method to predict molecular regulations from time‐course proteomic data of 30 target components. The predicted network showed that the ErbB receptor might regulate AP‐1 protein expression via two pathways: positive regulation by c‐MYC and negative regulation by signal transducer and activator of transcription 3 (STAT3) pathways. Experimental validation analysis revealed that ErbB receptor inhibition resulted in defective induction of AP‐1 proteins and suppressed terminal differentiation of keratinocytes. Inhibition of STAT3, however, affected expression of a partial set of AP‐1 proteins and resulted in premature differentiation. Studies using RNAi to diminish expression of each ErbB receptor and the AP‐1 proteins strongly suggested that STAT3 established a balance that maintains the appropriate set of AP‐1 proteins and participates in a complex network for regulating keratinocyte differentiation.
Can the intermediate disturbance hypothesis and information on species traits predict anuran responses to fire?
Authors: Westgate Martin J. , Driscoll Don A. , Lindenmayer David B.
Published: January 2012

Fire is a common form of recurrent disturbance in many ecosystems, but ecological theory has a poor record of predicting animal responses to fire, at both species and assemblage levels. As a consequence, there is limited information to guide fire regime management for biodiversity conservation. We investigated a key research gap in the fire ecology literature; that is, the response of an anuran assemblage to variation in the fire return interval. We tested two hypotheses using a spatially‐explicit fire database collected over a 40 year period: 1) species richness would peak at intermediate levels of disturbance. 2) Species with traits which enabled them to escape fire – burrowing or canopy dwelling – would be better able to survive fires, resulting in higher levels of occurrence in frequently burned sites. We found no evidence for either a reduction in species richness at locations with short fire return intervals, or a peak in species richness at intermediate levels of disturbance. Although we found some support for individual species responses to fire return intervals, these were inconsistent with the interpretation of burrowing or climbing being functional traits for fire‐avoidance. Instead burrowing and climbing species may be more likely to be disadvantaged by frequent fire than surface dwelling frogs. More generally, our results show that many species in our study system have persisted despite a range of fire frequencies, and therefore that active management of fire regimes for anuran persistence may be unnecessary. The responses of anurans to fire in this location are unlikely to be predictable using simple life‐history traits. Future work should focus on understanding the mechanistic underpinnings of fire responses, by integrating information on animal behavior and species’ ecological requirements.
The relationship between larval size and fitness in the tapeworm Schistocephalus solidus: bigger is better?
Authors: Benesh Daniel P. , Weinreich Friederike , Kalbe Martin
Published: January 2012

In organisms with complex life cycles, fitness often increases with body size at the transition from larva to adult. The translation of larval size into fitness, however, can depend on the source of size variation, with size, per se, not always increasing adult success. In parasitic worms, many factors influence larval growth, but little is known about the consequences of this growth variation. We examined how the size of the tapeworm Schistocephalus solidus in its copepod first intermediate host affects infection success and growth in the stickleback second host. Moreover, we assessed whether the conspicuous growth variation caused by copepod size is fitness‐relevant. Using larvae of the same age, we found that larger worms had a substantially higher infection probability and they tended to still be slightly larger after several months of growth in fish. However, big larvae from bigger copepods did not have higher fitness, suggesting that being large relative to the host, but not necessarily large in general, is important. These findings clarify some aspects of the life history strategy of S. solidus (e.g. why there is a flat ontogenetic reaction norm across copepod stages), but also raise questions (e.g. why growth costs have been hard to document). More generally, our results indicate that larval size can correlate with fitness in helminths, but that not all size variation is predictive of success in the next host.
Fish stocking creates an ecological trap for an avian predator via effects on prey availability
Authors: Kloskowski Janusz
Published: January 2012

In anthropogenic landscapes animals may be lured into low‐quality habitats where they survive or reproduce poorly (‘ecological traps’). I investigated breeding habitat selection in relation to intra‐seasonal changes in food availability and reproductive output in red‐necked grebes Podiceps grisegena, a size‐limited predator, of common carp Cyprinus carpio ponds. Carp farms constitute highly heterogeneous habitat mosaics due to separate stocking of different age/size fish. Pond features significant for grebe settling decisions, i.e. hydroperiod and emergent vegetation cover, had no obvious effects on prey abundance for chicks and on fledging success. Breeding grebes avoided ponds containing fish too large for them to ingest but exhibited little preference between ponds with medium‐sized one‐year‐old carp that could be exploited by pre‐laying birds, and ponds designated for young‐of‐the‐year carp, where only invertebrates and amphibians were available as prey in early spring. Red‐necked grebes settling on ponds with medium‐sized fish failed to predict future shifts in interactions with carp stocks; carp exceeded the prey‐size threshold of chicks and adversely affected their non‐fish prey levels. The resulting food shortage led to severe egg‐to‐fledging mortality rates compared to fishless ponds or those containing young‐of‐the‐year fish. This study shows that waterbirds vulnerable to competition from fish can risk maladaptive habitat selection due to unrecognised spatial and temporal variation in food resources caused by fish stocking practices. Ecological traps created by perturbations to trophic interactions may be common but difficult to detect because altered dynamics of trophic resources can affect wildlife indirectly. As with other types of ecological traps, manipulation of habitat features identified as attractive cues for settling animals, but not related to critical food resources, may help to reduce perceptual pitfalls. For example, wetland management to mitigate trap effects driven by commercially stocked fish should preserve abundant emergent vegetation in habitats with weak fish impact and extend their hydroperiod.
Water deficiency induces evolutionary tradeoff between stress tolerance and chemical defense allocation that may help explain range limits in plants
Authors: Siemens David H. , Duvall‐Jisha John , Jacobs Jay , Manthey Joseph , Haugen Riston , Matzner Steve
Published: January 2012

What causes range limits is a central question in evolutionary ecology. Transplant studies indicate that areas just across range boundaries are often stressful. The recent Defense constraint (DC) hypothesis for plants states that the evolution of tolerance to stressful environments across a range boundary is constrained by allocation to chemical defense because of antagonistic crosstalk between abiotic and biotic stress signaling pathways that otherwise could be co‐opted for range expansion. Abscisic acid (ABA) drought stress tolerance and jasmonic acid/ethylene (JA/ET) defense signaling pathways, for example, are known to be antagonistic to one another in Arabidopsis and other species. To test the DC hypothesis, we examined quantitative genetic variation and co‐variation among marker‐inferred inbred lines and sib‐families of Boechera stricta, a close wild relative of Arabidopsis. The dynamics of the defense‐stress tolerance tradeoff was examined across 1) years that differed in precipitation, 2) drought and ABA treatments, and 3) a NPK nutrient supply gradient. In support of the DC hypothesis, we observed the tradeoff a) in the dry year, and b) in response to water deficiency, which c) was affected by ABA treatments, but the interaction between ABA and glucosinolate (GS) toxin levels was not significant. In contrast to the effects of water deficiency, d) the effect of lower NPK supply to cause the tradeoff was only marginally significant. Because an ABA‐mediated stress response is intrinsic to water deficient conditions and because of the known involvement of JA/ET in GS regulation, we suggest that these results provide circumstantial evidence implicating both of these pathways in the tradeoff and thus in the development of range limits.
Spatial and phylogenetic structure drive frugivory in Tyrannidae birds across the range of Brazilian Araucaria forests
Authors: Brum Fernanda T. , Kindel Andreas , Hartz Sandra M. , Duarte Leandro D. S.
Published: January 2012

We aimed to verify if frugivory in Tyrannidae birds (tyrants flycatchers) is influenced by environmental conditions, spatial filters, phylogenetic structure and food availability in Brazilian Araucaria forests. We used range maps to describe Tyrannidae species composition of 33 cells (0.25°× 0.25°) distributed along the Araucaria forest distribution range. Araucaria forests occur in southern and southeastern Brazil and northeastern Argentina, from 30°S to 20°S and at elevations above 500 m a.s.l. We compiled the feeding habits of each species from literature to calculate the proportion of frugivorous Tyrannidae in each cell. After that, we evaluated separately the influence of environmental descriptors, spatial filters (PCNM), phylogenetic structure (PCPS) and resource availability (proportion of zoochorous species) on the proportion of frugivorous birds using model selection based on AIC. Then we built a path model to evaluate the direct and indirect influences of different set of variables on frugivory. The path model showed that phylogenetic structure and spatial filters were the main factors determining the variation in frugivory in Araucaria forest sites. The environmental variable had no direct effect on frugivory, but presented an indirect effect via phylogenetic structure. Furthermore, zoochory was not selected as an important variable determining any other and was not included in the model. Our results showed that the influence of environment on frugivory by Tyrannidae birds was indirect via spatial and phylogenetic structure, that zoochory was not an important factor determining frugivory and that phylogenetic niche conservatism in feeding habits plays a role in determining the structure of Tyrannidae bird communities in Brazilian Araucaria forests.
Likelihood based population viability analysis in the presence of observation error
Authors: Nadeem Khurram , Lele Subhash R.
Published: January 2012

Population viability analysis (PVA) entails calculation of extinction risk, as defined by various extinction metrics, for a study population. These calculations strongly depend on the form of the population growth model and inclusion of demographic and/or environmental stochasticity. Form of the model and its parameters are determined based on observed population time series data. A typical population time series, consisting of estimated population sizes, inevitably has some observation error and likely has missing observations. In this paper, we present a likelihood based PVA in the presence of observation error and missing data. We illustrate the importance of incorporation of observation error in PVA by reanalyzing the population time series of song sparrowMelospiza melodiaon Mandarte Island, British Columbia, Canada from 1975–1998. Using Akaike information criterion we show that model with observation error fits the data better than the one without observation error. The extinction risks predicted by with and without observation error models are quite different. Further analysis of possible causes for observation error revealed that some component of the observation error might be due to unreported dispersal. A complete analysis of such data, thus, would require explicit spatial models and data on dispersal along with observation error. Our conclusions are, therefore, two‐fold: 1) observation errors in PVA matter and 2) integrating these errors in PVA is not always enough and can still lead to important biases in parameter estimates if other processes such as dispersal are ignored.
Shrub–tree interactions and environmental changes drive treeline dynamics in the Subarctic
Authors: Grau Oriol , Ninot Josep M. , Blanco‐Moreno José M. , van Logtestijn Richard S. P. , Cornelissen Johannes H. C. , Callaghan Terry V.
Published: January 2012

Treelines have drawn persistent research interest as they can respond markedly to climate. However, the mechanisms that determine tree seedling recruitment and the response of the forest‐tundra ecotone to environmental changes remain poorly understood. We hypothesise that treeline tree seedling performance depends on the interplay between climatic and soil nutritional changes and facilitative and competitive interactions between trees and shrubs. We conducted a seedling transplantation experiment with Betula pubescens at a subarctic treeline, in northern Sweden, which followed a full factorial design with four treatment factors relating to environmental regimes of stress and resource availability: site (forest vs treeline); temperature (+/− passive warming); shrub presence (+/−Vaccinium myrtillus removal); and nutrient availability (+/− NPK addition). During three growing seasons we assessed the establishment and performance of Betula. The experimental manipulations caused highly significant effects on seedling performance. Although Vaccinium enhanced seedling survival and reduced the effects of excessive solar radiation and insect herbivory, the seedlings growing with the shrub had a poorer performance by the end of the experimental period. Also, seedlings in the forest had a poorer performance than those at the treeline. Betula seedlings showed a very pronounced and positive response to passive warming and to nutrient addition, but such effects were more evident at the treeline site and often interacted with the presence of Vaccinium. This experiment shows that shrub–tree interactions are important drivers of subarctic treeline dynamics and that they vary with time and space. Facilitation, competition, herbivory and environmental changes at the tree seedling stage act as important filters in structuring the forest–tundra ecotone. We demonstrate that changes in this ecotone cannot be simply predicted from changing temperature patterns alone, and that complex interactions need to be considered, not only between shrubs and trees, but also with herbivores and between warming and soil nutrient availability.
Bisphosphonate‐induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
Authors: Abtahi Jahan , Agholme Fredrik , Sandberg Olof , Aspenberg Per
Published: January 2012

J Oral Pathol Med (2012) 41: 494–499

Background:  Bisphosphonate‐related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate‐related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis.

Material and methods:  Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 μg/kg per day alendronate; Groups III and IV, 200 μg/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups I–III. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH).

Results:  All animals in the alendronate plus dexamethasone groups developed large ONJ‐like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups.

Conclusion:  Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ‐like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.
Myogenic capacity of muscle progenitor cells from head and limb muscles
Authors: Grefte Sander , Kuijpers Mette A.R. , Kuijpers‐Jagtman Anne M. , Torensma Ruurd , Von den Hoff Johannes W.
Published: January 2012

Grefte S, Kuijpers MAR, Kuijpers‐Jagtman AM, Torensma R, Von den Hoff JW. Myogenic capacity of muscle progenitor cells from head and limb muscles.
 
Eur J Oral Sci 2012; 120: 38–45. © 2012 Eur J Oral Sci

The restoration of muscles in the soft palate of patients with cleft lip and/or palate is accompanied by fibrosis, which leads to speech and feeding problems. Treatment strategies that improve muscle regeneration have only been tested in limb muscles. Therefore, in the present study the myogenic potential of muscle progenitor cells (MPCs) isolated from head muscles was compared with that of limb muscles. Muscle progenitor cells were isolated from the head muscles and limb muscles of rats and cultured. The proliferation of MPCs was analysed by DNA quantification. The differentiation capacity was analysed by quantifying the numbers of fused cells, and by measuring the mRNA levels of differentiation markers. Muscle progenitor cells were stained to quantify the expression of paired box protein Pax 7 (Pax‐7), myoblast determination protein 1 (MyoD), and myogenin. Proliferation was similar in the head MPCs and the limb MPCs. Differentiating head and limb MPCs showed a comparable number of fused cells and mRNA expression levels of myosin‐1 (Myh1), myosin‐3 (Myh3), and myosin‐4 (Myh4). During proliferation and differentiation, the number of Pax‐7+, MyoD+, and myogenin+ cells in head and limb MPCs was equal. It was concluded that head and limb MPCs show similar myogenic capacities in vitro. Therefore, in vivo myogenic differences between those muscles might rely on the local microenvironment. Thus, regenerative strategies for limb muscles might also be used for head muscles.