bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Thermal Transport in Zirconia and Yttria‐Stabilized Zirconia by Molecular‐Dynamics Simulation
Authors: Schelling Patrick K. , Phillpot Simon R.
Published: March 2010

We present results of molecular‐dynamics simulations of the thermal conductivity, κ, of ZrO2 and Y2O3‐stabilized ZrO2 (YSZ). For both pure ZrO2 and YSZ with low concentrations of Y2O3, we find that the high‐temperature κ is typical of a crystalline solid, with the dominant mechanism being phonon‐phonon scattering. With increasing Y2O3 concentration, however, the mechanism changes to one more typical of an amorphous system. In particular, phononlike vibrational modes with well‐defined wave vectors appear only at very low frequencies. As in amorphous materials, the vast majority of vibrational modes, while delocalized, do not propagate like ordinary phonon modes but transport energy in a diffusive manner. We also find that the few highest frequency modes are localized and do not contribute to κ.
Aqueous Solubility Diagrams for Cementitious Waste Stabilization Systems: II, End‐Member Stoichiometries of Ideal Calcium Silicate Hydrate Solid Solutions
Authors: Kulik Dmitrii A. , Kersten Michael
Published: March 2010

Solubility in the fully hydrated CaO–SiO2–H2O system can be best described using two ideal C‐S‐H‐(I) and C‐S‐H‐(II) binary solid solution phases. The most recent structural ideas about the C‐S‐H gel permit one to write stoichiometries of polymerized C‐S‐H‐(II) end‐members as hydrated precursors of the stable tobermorite and jennite minerals in the form of 5Ca(OH)2·6SiO2·5H2O and 10Ca(OH)2·6SiO2·6H2O, respectively. For thermodynamic modeling purposes, it is more convenient to express the number of basic silica and portlandite units in these stoichiometries using the coefficients nSi and nCa. Thermodynamic solid‐solution aqueous‐solution equilibrium modeling by applying the Gibbs energy minimization (GEM) approach shows the best generic fits to the available experimental solubility data at solid 0.8 < Ca/Si < 2.0 if both stoichiometry and thermodynamic constants of the end‐members are normalized to nSi= 1.0 ± 0.3. Recommended stoichiometries and thermodynamic data for the C‐S‐H end‐members provide a reliable basis for the subsequent multicomponent extension of the ideal C‐S‐H solid solution model by incorporation of end‐members for the (radio)toxic elements or trace metals.
Effect of β‐Seed Addition on the Microstructural Evolution of Silicon Nitride Ceramics
Authors: Rhee Sang‐Hoon , Lee Jae Do , Kim Doh‐Yeon
Published: March 2010

When a small amount of β‐Si3N4 seed particles is added during the preparation of Si3N4 ceramics, a bimodal microstructure is obtained by sintering at 1760°C. When the specimen is further heat‐treated at 1900°C to enhance the bimodal characteristic, the growth of large β grains is limited. The addition of a controlled amount of β seeds of uniform and large size is suggested to obtain the intended bimodal microstructure of Si3N4 ceramics.
Synthesis of Ternary Titanium Aluminum Carbides Using Self‐Propagating High‐Temperature Synthesis Technique
Authors: Łopaciński Michał , Puszynski Jan , Lis Jerzy
Published: March 2010

Different ternary carbide phases, namely Ti3AlC2, Ti3AlC, and Ti2AlC, were successfully synthesized in a self‐sustaining regime. Direct reactions among elemental powders of titanium, aluminum, and carbon are strongly exothermic, and the resulting reaction products consist of binary carbides and they are partially molten. The use of TiAl, instead of elemental titanium and aluminum, significantly reduces the combustion temperature. As a result, ternary titanium aluminum carbide phases are formed. In addition, the combustion‐synthesized products are not sintered and easy to deagglomerate. Reaction conditions and X‐ray diffraction patterns of different ternary phases formed in a self‐sustaining regime are presented.
MgSiN2 Addition as a Means of Increasing the Thermal Conductivity of β‐Silicon Nitride
Authors: Hayashi Hiroyuki , Hirao Kiyoshi , Toriyama Motohiro , Kanzaki Shuzo , Itatani Kiyoshi
Published: March 2010

Si3N4 powders with the concurrent addition of Yb2O3 and MgSiN2 were sintered at 1900°C for 2–48 h under 0.9 MPa nitrogen pressure. Microstructure, lattice oxygen content, and thermal conductivity of the sintered specimens were evaluated and compared with Si3N4, Yb2O3, and MgO addition. MgSiN2 addition was effective for improving the thermal conductivity of Si3N4 ceramics, and a material with high thermal conductivity over 140 W·(m·K)−1 could be obtained. For both specimens, lattice oxygen content was decreased with sintering time. However, the thermal conductivity of the MgSiN2‐doped specimen was slightly higher than the MgO‐doped specimen with the same oxygen content.
ORIGINAL ARTICLE: Accuracy of calculated free testosterone formulae in men
Authors: Ly Lam P. , Sartorius Gideon , Hull Laura , Leung Andrew , Swerdloff Ronald S. , Wang Christina , Handelsman David J.
Published: March 2010

Background  As reference laboratory methods for measuring free testosterone (FT) by equilibrium dialysis (ED) are laborious, costly and nonautomatable, FT levels are often calculated (cFT) rather than measured. However, the predictive accuracy of such estimates in routine use relative to laboratory measurements is not well defined. We provide a large‐scale evaluation of the predictive accuracy for different FT formulae compared with laboratory ED measurement and an analysis of clinical factors that may influence accuracy.

Methods  The accuracy of five different cFT formulae (two equilibrium binding, three empirical) based on immunoassays of total testosterone (TT) and SHBG was evaluated by comparing those estimates with FT measurement by ED in 2159 serum samples from men at a single research laboratory over several years.

Results  cFT formulae show systematic discrepancies from the two equilibrium‐binding formulae. One empirical formula overestimated FT relative to ED measurements, whereas two newer empirical cFT formulae were more concordant. These discrepancies persisted after correction for serum albumin and were not influenced by obesity, ethnicity or gonadal status.

Conclusions  Commonly used cFT formulae significantly overestimate FT relative to laboratory measurement by ED in male serum samples. The accuracy of the formulae is not influenced by correction for serum albumin, obesity, ethnicity or gonadal status. Such inaccuracy relative to the reference method renders some cFT estimates unreliable for evaluating androgen deficiency as recommended by clinical best practice guidelines.
HDAC2 expression and variable number of repeats in exon 1 of the HDAC2 gene in corticotroph adenomas
Authors: Evang J. Arild , Borota Olivera Casar , Melum Espen , Holm Ruth , Ramm‐Pettersen Jon , Bollerslev Jens , Berg Jens P.
Published: March 2010

Objectives  Alterations in protein expression of histone deacetylase 2 (HDAC2) have been demonstrated in various neoplasms, and lack of nuclear expression of HDAC2 has previously been shown in some human and canine corticotroph adenomas. This study aimed to examine HDAC2 expression in a Norwegian cohort of corticotroph adenomas, screen for exonic HDAC2 gene variants in the adenomas and correlate the results with clinical data.

Patients and design  Forty‐four patients with verified Cushing’s disease or Nelson’s syndrome, positive ACTH staining and tissue available for immunohistochemistry and/or DNA sequencing were included. Ninety‐four controls were chosen from the Norwegian Bone Marrow Registry.

Results  Histone deacetylase 2 expression examined by immunohistochemistry was strongly reduced in 3/30 adenomas. There were no association between HDAC2 expression and clinical variables. A previously unidentified insertion of three bases in a region coding for a polyserine cluster in exon 1 of the HDAC2 gene was identified in 6/32 adenomas. No other mutations in HDAC2 exons were found. Examination of DNA extracted from peripheral blood confirmed germ‐line origin of the exon 1 insertion. The same insertion was also found in 28/94 of the controls (i.e., not significantly different from the patients).

Conclusions  Strongly reduced HDAC2 protein expression was confirmed in a small portion of corticotroph tumours. Mutations in HDAC2 exons are unlikely to play an important role in the development of corticotroph adenomas.
Clinical efficacy and safety of the factor VIII/von Willebrand factor concentrate BIOSTATE® in patients with von Willebrand’s disease: a prospective multi‐centre study
Authors: DUNKLEY S. , BAKER R. I. , PIDCOCK M. , PRICE J. , SELDON M. , SMITH M. , STREET A. , MAHER D. , BARRESE G. , STONE C. , LLOYD J.
Published: March 2010

Summary.  von Willebrand’s disease (VWD) is an inherited bleeding disorder characterized by deficient levels of or dysfunctional von Willebrand factor (VWF). This phase II/III open‐label, multicentre study evaluated the efficacy and safety of BIOSTATE®, a high purity plasma‐derived double‐virus inactivated FVIII/VWF concentrate, when used in non‐surgical bleeds, surgical procedures and prophylactic therapy in VWD patients for whom desmopressin treatment was deemed ineffective, inadequate or contraindicated. Twenty three patients (7 type 1, 9 type 2 and 7 type 3; 12 male, 11 female), who received FVIII/VWF concentrate as part of their VWD management, were recruited prospectively between December 2004 and May 2007 from eight centres in Australia and New Zealand. BIOSTATE dosing was based on pre‐treatment FVIII:C and/or VWF:RCo plasma levels and a predetermined dosing guide. Haemostatic efficacy of BIOSTATE was rated as excellent or good for all major and minor surgery events, long‐term prophylaxis, and for four of the six assessable non‐surgical bleeding events. Blood transfusions were required by two major surgery patients as well as one patient with a non‐surgical bleed. The median overall exposure to BIOSTATE across all groups was 8 days, greater in the prophylactic group (range 53–197) compared with major surgery (3–24), minor surgery (1–8) and non‐surgical bleeds (1–10). BIOSTATE was shown to be efficacious and well tolerated when treating patients with VWD. This study also provides important insights into dosing regimens with BIOSTATE and the role of monitoring therapy with FVIII:C and VWF:RCo.
Psychosocial correlates of physical activity in adolescents with haemophilia
Authors: BUXBAUM N. P. , PONCE M. , SAIDI P. , MICHAELS L. A.
Published: March 2010

Summary.  Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11–18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10–16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self‐image and similar levels of anxiety as peers without a bleeding disorder. Self‐efficacy scores were lower than for controls suggesting increased sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support‐seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical activity in patients with haemophilia is needed to more effectively encourage healthy behaviours.
Computer‐assisted pathological immunohistochemistry scoring is more time‐effective than conventional scoring, but provides no analytical advantage
Authors: Ong Chee Wee , Kim Lay Gek , Kong Hui Hui , Low Lai Yee , Wang Ting Ting , Supriya Srivastava , Kathiresan Manickam , Soong Richie , Salto‐Tellez Manuel
Published: March 2010

Ong C W, Kim L G, Kong H H, Low L Y, Wang T T, Supriya S, Kathiresan M, Soong R & Salto‐Tellez M  (2010) Histopathology56, 523–529

Computer‐assisted pathological immunohistochemistry scoring is more time‐effective than conventional scoring, but provides no analytical advantage

Aims:  Interpretation of immunohistochemistry is primarily done through human visual scoring while computer‐assisted scoring is relatively uncommon. This study aimed to examine (i) the level of agreement between human visual and computer‐assisted pathological scoring of immunoreactivity expression in colorectal cancers, (ii) whether computer‐assisted scoring affects the prognostic significance of biomarkers, and (iii) whether computer‐assisted pathological scoring provides any time‐saving or reproducibility advantages.

Methods and results:  Tissue microarray blocks were constructed from the primary colorectal adenocarcinoma specimens of 486 patients. Scoring of the six markers [cytokeratin (CK) 7, CK20, cyclooxygenase‐2, Ki67, p27 and p53] was done independently by a qualified pathologist, a trained scientist and the Ariol SL‐50 (Applied Imaging). Univariate analysis showed that human visual and computer‐assisted scoring were strongly correlated (all κ values >0.8). Both human visual and computer‐assisted pathological scoring identified the same set of biomarkers with significant association with survival. Computer‐assisted pathological scoring was shown to be a time‐effective means of scoring larger numbers of slides (for high‐throughput studies).

Conclusions:  Our results suggest that computer‐assisted pathological scoring can be a viable alternative to pathologist scoring in a manner that is more practical and time‐effective, but, interestingly, providing no analytical advantage.
The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy
Authors: Van Oort Inge M , Bruins H Maxim , Kiemeney Lambertus A L M , Knipscheer Ben C , Witjes J Alfred , Hulsbergen‐van de Kaa Christina A
Published: March 2010

van Oort I M, Bruins H M, Kiemeney L A L M, Knipscheer B C, Witjes J A & Hulsbergen‐van de Kaa C A (2010) Histopathology56, 464–471

The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy

Aims:  To evaluate the prognostic role of the length of a positive surgical margin (+SM) for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostatic cancer.

Methods and results:  Consecutive RP specimens (n = 267) with +SM were analysed. All RP specimens were sectioned at 4‐mm intervals and completely embedded. Data were analysed using Kaplan–Meier survival analysis and proportional hazards models.

In 267 patients the length of +SM ranged from 0.4 to 174.5 mm (median 11.2 mm) and correlated with preoperative prostate specific antigen (PSA) (P < 0.001), pathological stage (P < 0.001), tumour volume (P = 0.001), number of +SM (P < 0.001), Gleason grade at +SM (P < 0.001) and Gleason score (P = 0.015). Patients with detectable postoperative PSA levels (n = 34) or adjuvant therapy (n = 59) were excluded from BCR analysis. In the remaining 174 patients the 5‐year risk of BCR was 29%; in patients with +SM ≤10 mm and >10 mm this was 21% and 39%, respectively. On multivariable analysis BCR was associated with an increasing length of +SM (≤10 mm versus >10 mm; hazard ratio 2.15; 95% confidence interval 1.12, 4.15; P = 0.022).

Conclusions:  The length of +SM is an independent prognostic factor for BCR in patients with undetectable PSA after RP.
Papillary lesions of the breast—accuracy of core biopsy
Authors: Tse Gary M , Tan Puay‐Hoon , Lacambra Maribel D , Jara‐Lazaro Ana Richelia , Chan Siu‐Ki , Lui Philip C , Ma Tony K F , Vong Joaquim S , Ng David C H , Shi Hui‐Juan , Lam Wynnie W
Published: March 2010

Tse G M, Tan P‐H, Lacambra M D, Jara‐Lazaro A R, Chan S‐K, Lui P C, Ma T K F, Vong J S, Ng D C H, Shi H‐J & Lam W W (2010) Histopathology56, 481–488

Papillary lesions of the breast—accuracy of core biopsy

Aims:  To assess the accuracy of diagnosing papillary breast lesions in core needle biopsy.

Methods and results:  One hundred biopsy specimens of papillary breast lesions were reviewed and compared with the final excisional diagnoses. The discordant biopsy specimens were stained for oestrogen receptor (ER), cytokeratin (CK) 14 and p63, and these specimens were reclassified based on these results. The overall core biopsy accuracy, false‐positive and false‐negative rate were 79%, 5% and 16%, respectively. A benign core biopsy specimen diagnosis gave a false‐negative rate of 10%, and malignant core biopsy specimen diagnosis did not give any false‐positive results. Using homogeneous ER (epithelial), positive CK14 (epithelial) and p63 (myoepithelial) immunoreactivity as benign criteria, the discordant rate was reduced by 30% and 69% when using all three or two of these three criteria for diagnosis. However, false‐positive and ‐negative cases could not be totally eliminated.

Conclusions:  Immunohistochemistry is helpful in core biopsy diagnosis of papillary breast lesions, but some cases remained misdiagnosed.
Ribosomal versus non‐ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+T cells
Authors: Philip Mary , Schietinger Andrea , Schreiber Hans
Published: March 2010

Proteins released from dying cells can be taken up and presented by antigen‐presenting cells (APC) to T cells. While the presentation of such self antigens may lead to beneficial anti‐tumour responses, in autoimmune disease it leads to pathological immune responses. The sub‐set of self proteins targeted in autoimmune disease is circumscribed, and certain cellular components such as ribonucleoprotein (RNP) complexes are often targeted. Although explanations for this antigen selectivity have been proposed, there has been little direct testing of these hypotheses. We and others previously showed that ribosomal proteins, targeted in autoimmune disease, are also targets of anti‐tumour T‐cell responses. We asked whether particular properties of ribosomal proteins such as incorporation into RNP complexes or sub‐cellular localization enhance ribosomal protein presentation by APC to CD4+T cells. Ribosomal protein antigens within purified intact ribosomes or free of the ribosomes were equally well taken up and presented by APC, demonstrating that inclusion of ribosomal proteins into an RNP complex does not confer an advantage. However, antigens localized to ribosomes within apoptotic cells were less efficiently taken up and presented by APC than the same antigens localized diffusely throughout the cell. This suggests that presentation of ribosomal proteins is somehow down‐regulated, possibly to facilitate presentation of other less‐abundant intracellular proteins. Consequently, the explanation for the frequent targeting of ribosomal proteins by both autoimmune and anti‐tumour T‐cell responses is not at the level of uptake from apoptotic cells and must be sought elsewhere.
The potential of CD4 T‐cell memory
Authors: McKinstry K. Kai , Strutt Tara M. , Swain Susan L.
Published: March 2010

While many aspects of memory T‐cell immunobiology have been characterized, we suggest that we know only a fraction of the effector functions that CD4 T cells can bring to bear during secondary challenges. Exploring the full impact of memory CD4 T‐cell responses is key to the development of improved vaccines against many prominent pathogens, including influenza viruses, and also to a better understanding of the mechanisms of autoimmunity. Here we discuss factors regulating the generation of memory CD4 T cells during the activation of naïve cells and how the nature of the transition from highly activated effector to resting memory upon the resolution of primary responses might impact memory CD4 T‐cell heterogeneity in vivo. We stress that memory CD4 T cells have unique functional attributes beyond the secretion of T helper (Th) subset‐associated cytokines that can shape highly effective secondary responses through novel mechanisms. These include the recruitment of innate inflammatory responses at early phases of secondary responses as well as the action of enhanced direct effector functions at later phases, in addition to well‐established helper roles for CD8 T‐cell and B‐cell responses.
Comparing adolescents’ adjustment and family resilience in divorced families depending on the types of primary caregiver
Authors: Shin Sung H , Choi Heeseung , Kim Mi J , Kim Yoon H
Published: March 2010

Aims.  This study compared three different types of primary caregiver in divorced families: father, mother and grandparent(s) and aimed to (1) compare adolescents’ perception of their level of adjustment and family resilience and (2) identify the family resilience predictors of adolescents’ adjustment.

Background.  The Resiliency Model of Family Stress, Adjustment and Adaptation guided this study.

Design.  Survey.

Method.  Adolescents in divorced families in Korea (n = 178) completed self‐administered questionnaires. Family resilience was measured by Family Hardiness Index, Family Crisis Oriented Personal Evaluation Scale, Parent‐Adolescent Communication Inventory, Social Support Appraisal Scale, Belief about Parental Divorce and Self‐Esteem Scale. Korean‐Child Behaviour Checklist was used to assess adolescents’ adjustment. Descriptive statistics, chi‐square test, anova, ancova and multiple regression analysis were used for data analysis.

Results.  The level of adolescents’ adjustment was not statistically different among the three groups. However, statistically significant differences were found in family hardiness, family communication and problem‐solving/coping skill‐seeking help among the family resilience measurements. Adolescents living with mothers reported the highest scores in family hardiness and family communication. The grandparent(s) group sought and accepted help outside of the family more often than did the other groups. Regardless of the types of primary caregiver, a common significant predictor for adolescents’ adjustment was their positive belief about parental divorce; whereas high self‐esteem and low level of seeking help were additional predictors for the father group and grandparent(s) group, respectively.

Conclusions.  Adolescents’ belief about parental divorce is a major predictor for adolescents’ adjustment to divorced family life. Nursing services that maximise the family resilience predictors found in this study would enhance adolescents’ adjustment in divorced families.

Relevance to clinical practice.  This study provides empirical evidence for nursing care of adolescents who live with differing primary caregivers in divorced families and enhances nurses’ understanding of family resilience predictors that influence adolescents’ adjustment in divorced families.
CobB regulates Escherichia coli chemotaxis by deacetylating the response regulator CheY
Authors: Li Ru , Gu Jing , Chen Yuan‐Yuan , Xiao Chuan‐Le , Wang Li‐Wei , Zhang Zhi‐Ping , Bi Li‐Jun , Wei Hong‐Ping , Wang Xu‐De , Deng Jiao‐Yu , Zhang Xian‐En
Published: March 2010

The silent information regulator (Sir2) family proteins are NAD+‐dependent deacetylases. Although a few substrates have been identified, functions of the bacteria Sir2‐like protein (CobB) still remain unclear. Here the role of CobB on Escherichia coli chemotaxis was investigated. We used Western blotting and mass spectrometry to show that the response regulator CheY is a substrate of CobB. Surface plasmon resonance (SPR) indicated that acetylation affects the interaction between CheY and the flagellar switch protein FliM. The presence of intact flagella in knockout strains ΔcobB, Δacs, Δ(cobB) Δ(acs), Δ(cheA) Δ(cheZ), Δ(cheA) Δ(cheZ) Δ(cobB) and Δ(cheA) Δ(cheZ) Δ(acs) was confirmed by electron microscopy. Genetic analysis of these knockout strains showed that: (i) the ΔcobB mutant exhibited reduced responses to chemotactic stimuli in chemotactic assays, whereas the Δacs mutant was indistinguishable from the parental strain, (ii) CheY from the ΔcobB mutant showed a higher level of acetylation, indicating that CobB can mediate the deacetylation of CheY in vivo, and (iii) deletion of cobB reversed the phenotype of Δ(cheA) Δ(cheZ). Our findings suggest that CobB regulates E. coli chemotaxis by deacetylating CheY. Thus a new function of bacterial cobB was identified and also new insights of regulation of bacterial chemotaxis were provided.
Reversible Nε‐lysine acetylation regulates the activity of acyl‐CoA synthetases involved in anaerobic benzoate catabolism in Rhodopseudomonas palustris
Authors: Crosby Heidi A. , Heiniger Erin K. , Harwood Caroline S. , Escalante‐Semerena Jorge C.
Published: March 2010

Rhodopseudomonas palustris grows photoheterotrophically on aromatic compounds available in aquatic environments rich in plant‐derived lignin. Benzoate degradation is regulated at the transcriptional level in R. palustris in response to anoxia and the presence of benzoate and/or benzoyl‐CoA (Bz‐CoA). Here, we report evidence that anaerobic benzoate catabolism in this bacterium is also regulated at the post‐translational level. In this pathway, benzoate is activated to Bz‐CoA by the AMP‐forming Bz‐CoA synthetase (BadA) enzyme. Mass spectrometry and mutational analysis data indicate that residue Lys512 is critical to BadA activity. Acetylation of Lys512 inactivated BadA; deacetylation reactivated BadA. Likewise, 4‐hydroxybenzoyl‐CoA (HbaA) and cyclohexanecarboxyl‐CoA (AliA) synthetases were also reversibly acetylated. We identified one acetyltransferase that modified BadA, Hba and AliA in vitro. The acetyltransferase enzyme is homologous to the protein acetyltransferase (Pat) enzyme of Salmonella enterica sv Typhimurium LT2, thus we refer to it as RpPat. RpPat also modified acetyl‐CoA (Ac‐CoA) synthetase (Acs) from R. palustris. In vivo data indicate that at least two deacetylases reactivate BadAAc. One is SrtN (encoded by srtN, formerly rpa2524), a sirtuin‐type NAD+‐dependent deacetylase (O‐acetyl‐ADPribose‐forming); the other deacetylase is LdaA (encoded by ldaA, for lysine deacetylase A; formerly rpa0954), an acetate‐forming protein deacetylase. LdaA reactivated HbaAc and AliAAcin vitro.
Breakthrough cerebral toxoplasmosis in a patient receiving atovaquone prophylaxis after a hematopoietic stem cell transplantation
Authors: Megged Orli , Shalit Itamar , Yaniv Isaac , Stein Jerry , Fisher Salvador , Levy Itzhak
Published: March 2010

Abstract:  We describe a case of breakthrough cerebral toxoplasmosis during atovaquone therapy in a child who was intolerant of conventional prophylactic regimens after hematopoietic stem cell transplantation. The available data on the efficacy of atovaquone prophylaxis in Toxoplasma sero‐positive stem cell transplant recipients remain limited, and other strategies, such as preemptive strategy using toxoplasma PCR or TMP–SMX desensitization should be considered in this setting.
Long‐term outcome of pediatric renal transplantation: The Norwegian experience in three eras 1970–2006
Authors: Tangeraas Trine , Bjerre Anna , Lien Bjorn , Kyte Anders , Monn Eirik , Cvancarova Milada , Leivestad Torbjørn , Reisæter Anna Varberg
Published: March 2010

Abstract:  During the years 1970–2006, 251 renal transplantations were performed in 178 children in Norway. The proportion of LD was 84%. Transplantations were performed preemptively in 52%. Pretransplant dialysis time was median three months. Structural abnormalities and hereditary renal disorders constituted 69% of end‐stage renal diseases, 29% were caused by glomerulopathies and other acquired disorders and 2% of unknown cause. Patient survival rates were 94.2, 93.5, and 84.4% at five, 10, and 20 yr, respectively. The most frequent cause of death was infections followed by cardiovascular events. For recipients of living donor grafts (n = 149), survival of first transplant was 82, 68.8, and 45.1% at five, 10, and 20 yr, respectively, and was significantly higher than for recipients of deceased donor organs (n = 29; log rank, p = 0.008). The only significant predictor for better transplant survival when modeled with multiple regression analysis adjusted for pretransplant dialysis, diagnosis, donor age, sex and immunosuppressive era, was the use of LD compared with DD (HR = 2.1, 95% CI [1.1–4.0], p = 0.02). The acute rejection rate declined significantly from 61.5% in 1970–1982 to 14.5% in 2000–2006 (log rank, p = 0.002). It remains to be seen whether the reduction in acute rejection rate and present immunosuppressive therapy will have a positive impact on long‐term graft survival in years to come.
Analysis of the CC chemokine receptor 5Δ32 polymorphism in pediatric liver transplant recipients
Authors: Fischer‐Maas Louise , Schneppenheim Reinhard , Oyen Florian , Grabhorn Enke , Richter Andrea , Fischer Lutz , Ganschow Rainer
Published: March 2010

Abstract: In adult liver graft recipients, it has been shown that certain chemokine polymorphisms (CCR5Δ32) may correspond to ischemic type biliary lesions leading to chronic graft dysfunction. The aim of our present study was to assess the importance of CCR5Δ32 polymorphism in a cohort of pediatric liver graft recipients with regard to acute or chronic graft dysfunction. A total of 137 children post‐liver transplantation have been included for genetic analysis (CCR5Δ32 polymorphism), and the incidence of acute and chronic graft dysfunction was analyzed. The most common diagnosis leading to LTx was biliary atresia (56.2%), the median age was 14 months, and 33.5% of the patients received a living‐related graft. In all, 110 of the subjects were found to have the CCR5 wild type, 25 children were heterozygous for CCR5Δ32, and two patients were homozygous. Of 137, 44 (32.1%) developed acute graft rejection, nine out of 137 (6.6%) chronic graft dysfunction (vanishing bile duct syndrome), and 84 (61.3%) children had neither acute nor chronic graft rejection. There was no significant correlation between acute graft rejection or chronic graft dysfunction and the CCR5Δ32 allele in the study population. We conclude that CCR5Δ32 polymorphism may not play a role in acute or chronic liver graft dysfunction in children.
Combined liver‐kidney transplantation in children: Indications and outcome
Authors: Sutherland Scott M. , Alexander Steven R. , Sarwal Minnie M. , Berquist William E. , Concepcion Waldo
Published: March 2010

Abstract: Although it remains a relatively infrequent procedure in children, CLKT has become a viable option for a select group of pediatric patients with severe liver and kidney disease. Most are performed for rare primary diseases such as PH1, but a selected few are performed in the setting of concomitant hepatic and renal failure of uncertain etiology and prognosis. This article reviews the indications for and outcomes following CLKT in children. While it focuses on the specific primary diseases which impact liver and kidney function simultaneously, it addresses the indications based on concomitant hepatic and renal failure, such as seen in the hepatorenal syndrome, as well.
Novel insect‐tree associations resulting from accidental and intentional biological ‘invasions’: a meta‐analysis of effects on insect fitness
Authors: Bertheau Coralie , Brockerhoff Eckehard G. , Roux‐Morabito Géraldine , Lieutier François , Jactel Hervé
Published: March 2010

Ecology Letters (2010) 13: 506–515

The translocation of species beyond their native range is a major threat to biodiversity. Invasions by tree‐feeding insects attacking native trees and the colonization of introduced trees by native insects result in new insect–tree relationships. To date there is uncertainty about the key factors that influence the outcome of these novel interactions. We report the results of a meta‐analysis of 346 pairwise comparisons of forest insect fitness on novel and ancient host tree species from 31 publications. Host specificity of insects and phylogenetic relatedness between ancient and novel host trees emerged as key factors influencing insect fitness. Overall, fitness was significantly lower on novel host species than on ancient hosts. However, in some cases, fitness increased on novel hosts, mainly in polyphagous insects or when close relatives of ancient host trees were colonized. Our synthesis enables greatly improved impact prediction and risk assessment of biological invasions.
Prevalence of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy
Authors: Batura Deepak , Rao G. Gopal , Nielsen Peder Bo
Published: March 2010

Study Type – Prevalence (non‐consecutive cohort) Level of Evidence 3b

OBJECTIVE To determine the prevalence of antimicrobial resistance in intestinal flora of patients undergoing transrectal ultrasonography (TRUS)‐guided prostate biopsies (TGB) and to examine if this information is useful in selecting appropriate antimicrobial agents for prophylaxis and treatment of biopsy‐associated infections.

PATIENTS AND METHODS In 2007 and 2008, rectal swabs were cultured from patients before undergoing TGB. Antimicrobial sensitivity of coliforms to amikacin, ciprofloxacin and coamoxiclav was determined. Laboratory records were used to identify patients who had bacteraemia or significant bacteriuria within 30 days of the TGB and the antimicrobial sensitivity pattern of these organisms were compared to those from the rectal swab.

RESULTS Of 592 patients who had TGB, 445 (75.1%) had a rectal swab beforehand; 0.2%,10.6% and 13.3% of the coliforms were resistant to amikacin, ciprofloxacin and coamoxiclav, respectively. After TGB, six patients presented with urinary tract infections (UTI) and two with bacteraemia. All the infections were caused by coliforms except one UTI which was caused by ciprofloxacin‐sensitive Pseudomonas aeruginosa. The blood culture isolates were sensitive to amikacin but resistant to ciprofloxacin and coamoxiclav. All the coliforms in the urine were resistant to ciprofloxacin but sensitive to coamoxiclav. Urine isolates were not tested for amikacin sensitivity. There was a strong correlation between the antimicrobial sensitivity of the coliforms from the rectal swabs and those cultured from urine or blood in both patients for amikacin, six of eight for ciprofloxacin and seven of eight for coamoxiclav.

CONCLUSIONS Our study shows that in the coliforms in the bowel flora of our local population there is a relatively high level of resistance to ciprofloxacin and coamoxiclav, and very low level of resistance to amikacin. As there was a strong correlation between the antimicrobial sensitivity of organisms causing infections after TGB and those isolated from the rectal swabs, we conclude that rectal swab cultures before TGB provide useful evidence for selecting appropriate antimicrobials for prophylaxis and treatment of TGB‐associated infections.
Role of the extracellular transmembrane domain interface in gating and pharmacology of a heteromeric neuronal nicotinic receptor
Authors: Aldea Marcos , Castillo Mar , Mulet José , Sala Salvador , Criado Manuel , Sala Francisco
Published: March 2010

J. Neurochem.(2010)113, 1036–1045.

Nicotinic acetylcholine receptors (nAChRs) transmit the agonist signal to the channel gate through a number of extracellular domains. We have previously shown that particular details of the process of coupling binding to gating could be quantitative and qualitatively different in muscle and neuronal type nAChRs. We have extended previous studies on homomeric α7 nAChRs to heteromeric α3β4 nAChRs, by mutating residues located at loops 2 and 7, and M2–M3 linker of both α3 and β4 subunits which, in order to monitor surface expression, were modified to bind α‐bungarotoxin, and expressed inXenopusoocytes. We show that, in general, mutations in these domains of both α3 and β4 subunits affect the gating function, although the effects are slightly larger if they are inserted in the α3 subunit. However, the involvement of a previously reported intrasubunit interaction in coupling (Gln48‐Ile130) seems to be restricted to the β4 subunit. We also show that mutations at these domains, particularly loop 2 of the α3 subunit, change the pharmacological profile of α3β4 nAChRs, decreasing nicotine’s and increasing cytisine’s effectiveness relative to acetylcholine. It is concluded that, unlike muscle nAChRs, the non‐α subunits play a relevant role in the coupling process of neuronal α3β4 nAChRs.
Recent advances in vertebrate aging research 2009
Authors: Austad Steven
Published: March 2010

Among the notable trends seen in this year’s highlights in mammalian aging research is an awakening of interest in the assessment of age‐related measures of mouse health in addition to the traditional focus on longevity. One finding of note is that overexpression of telomerase extended life and improved several indices of health in mice that had previously been genetically rendered cancer resistant. In another study, resveratrol supplementation led to amelioration of several degenerative conditions without affecting mouse lifespan. A primate dietary restriction (DR) study found that restriction led to major improvements in glucoregulatory status along with provocative but less striking effects on survival. Visceral fat removal in rats improved their survival, although not as dramatically as DR. An unexpected result showing the power of genetic background effects was that DR shortened the lifespan of long‐lived mice bearing Prop1df, whereas a previous report in a different background had found DR to extend the lifespan of Prop1df mice. Treatment with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, enhanced the survival of even elderly mice and improved their vaccine response. Genetic inhibition of a TOR target made female, but not male, mice live longer. This year saw the mTOR network firmly established as a major modulator of mammalian lifespan.
Reduced EBF expression underlies loss of B‐cell potential of hematopoietic progenitors with age
Authors: Lescale Chloé , Dias Sheila , Maës Jérôme , Cumano Ana , Szabo Paul , Charron Dominique , Weksler Marc E. , Dosquet Christine , Vieira Paulo , Goodhardt Michele
Published: March 2010

Aging is accompanied by a reduction in the generation of B lymphocytes leading to impaired immune responses. In this study, we have investigated whether the decline in B lymphopoiesis is due to age‐related defects in the hematopoietic stem cell compartment. The ability of hematopoietic stem cells from old mice to generate B cells, as measured in vitro, is decreased 2–5‐fold, while myeloid potential remains unchanged. This age‐related decrease in B‐cell potential is more marked in common lymphoid progenitors (CLP) and was associated with reduced expression of the B‐lineage specifying factors, EBF and Pax5. Notably, retrovirus‐mediated expression of EBF complemented the age‐related loss of B‐cell potential in CLP isolated from old mice. Furthermore, transduction of CLP from old mice with a constitutively active form of STAT5 restored both EBF and Pax5 expression and increased B‐cell potential. These results are consistent with a mechanism, whereby reduced expression of EBF with age decreases the frequency with which multipotent hematopoietic progenitors commit to a B‐cell fate, without altering their potential to generate myeloid cells.
Ionizing radiation‐induced long‐term expression of senescence markers in mice is independent of p53 and immune status
Authors: Le Oanh N. L. , Rodier Francis , Fontaine Francois , Coppe Jean‐Philippe , Campisi Judith , DeGregori James , Laverdière Caroline , Kokta Victor , Haddad Elie , Beauséjour Christian M.
Published: March 2010

Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR‐induced senescence markers could persist long‐term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16INK4a expression, two hallmarks of cellular senescence and aging. BrdU‐labeling experiments revealed that IR‐induced damaged cells are preferentially eliminated, at least partially, in a tissue‐dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild‐type and Rag2−/− γC−/− mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long‐term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.
The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cells
Authors: Bendix Laila , Horn Peer Bendix , Jensen Uffe Birk , Rubelj Ivica , Kolvraa Steen
Published: March 2010

Short telomeres are thought to trigger senescence, most likely through a single – or a group of few – critically shortened telomeres. Such short telomeres are thought to result from a combination of gradual linear shortening resulting from the end replication problem, reflecting the division history of the cell, superimposed by a more stochastic mechanism, suddenly causing a significant shortening of a single telomere. Previously, studies that have tried to explore the role of critically shortened telomeres have been hampered by methodological problems. With the method presented here, Universal STELA, we have a tool that can directly investigate the relationship between senescence and the load of short telomeres. The method is a variant of the chromosome‐specific STELA method but has the advantage that it can demonstrate short telomeres regardless of chromosome. With Universal STELA, we find a strong correlation between the load of short telomeres and cellular senescence. Further we show that the load of short telomeres is higher in senescent cells compared to proliferating cells at the same passage, offering an explanation of premature cell senescence. This new method, Universal STELA, offers some advantages compared to existing methods and can be used to explore many of the unanswered questions in telomere biology including the role that telomeres play in cancer and aging.
Records of bizarre Jurassic brachycerans in the Daohugou biota, China (Diptera, Brachycera, Archisargidae and Rhagionemestriidae)
Authors: ZHANG JUN FENG
Published: March 2010

Abstract: Four new Brachycera fossils were collected from the Daohugou biota, China. Among these, two impressions demonstrating peculiar wing venation can be designated as two new species of a new genus (Mostovskisargus portentosusgen. et sp. nov. andM. signatussp. nov.) referred to a new subfamily Mostovskisarginae (subfam. nov.) within Archisargidae. The third impression belongs to a new species (Calosargus(Pterosargus)sinicussp. nov.) referred to the subgenusPterosargusMostovski, 1997 ofCalosargusMostovski, 1997 within Archisarginae, Archisargidae. It is only the second member of the subgenusPterosargusworldwide. The fourth impression is a nearly complete fly,Jurassinemestrinus orientalisgen. et sp. nov. referable to Rhagionemestriidae. It reveals new morphological data about rhagionemestriids and extends the geographical distribution of this group beyond Europe and Central Asia during the Mesozoic. A correlation for the archisargid composition of taxa in Daohugou and Karabastau formations is discussed. The age of the fly‐bearing strata is briefly reassessed and can be more accurately limited to the Callovian–Oxfordian based on both biostratigraphical correlation and radiometric dating.
A new ichthyodectiform (Actinopterygii, Teleostei) from the Lower Cretaceous Marizal Formation, north‐east Brazil
Authors: ALVARADO‐ORTEGA JESÚS , BRITO PAULO M.
Published: March 2010

Abstract:  A new genus and species, Ogunichthys triangularis, from the Early Cretaceous Marizal Formation in the Tucano Basin, Bahia State, Brazil, can be assigned to the teleost order Ichthyodectiformes and to the suborder Ichthyodectoidei by the presence of ten synapomorphies of these clades. Ogunichthys gen. nov. cannot be placed into any of the currently recognized families within Ichthyodectoidei and differs from all other ichthyodectoid genera in the ratio between the depth of the dentary symphysis and the depth of the coronoid process, the relationships between the length of the coronoid process and the alveolar border of the dentary, and a supraoccipital crest with posterior border fringed. The new taxon occurs in Early Cretaceous (Aptian) strata of the Marizal Formation, which are related to periods during epicontinental seas extended from the Caribbean Tethys into the South American continent. Rather than representing a single continuous widespread seaway, these epicontinental seas reflect local tectonic events, sometimes including locally distinctive faunas.
Exceptionally preserved conulariids and an edrioasteroid from the Hunsrück Slate (Lower Devonian, SW Germany)
Authors: VAN ITEN HEYO , SÜDKAMP WOUTER H.
Published: March 2010

Abstract:  Nineteen partial specimens of Conularia sp., together with an articulated agelacrinitid edrioasteroid and several discinid brachiopods, occur in close association with a probable biological substrate on a small slab of silty Hunsrück Slate (Lower Devonian, Emsian) from Bundenbach, Germany. Most of the conulariids occur in V‐like pairs or in a single cluster of 12 specimens arranged in a fan‐like radial pattern. Together with the edrioasteroid and (possibly) brachiopods, the conulariids probably were attached to the substrate in life and then were buried and possibly killed by a single influx of silty mud. The apertural end of many of the conulariids is partially covered by inwardly folded short lappets, which may have closed in response to rapid (but gentle) burial. Rock matrix in the apertural region of the peridermal cavity of nearly all of the conulariids exhibits irregular, variably dense concentrations of pyrite. The concentrations occur almost exclusively within the conulariids, where they probably formed as a result of the decay of retracted conulariid soft parts. Although the concentrations lack clearly defined anatomical features that can be unambiguously homologized with particular anatomical structures of any extant taxon, their form and distribution within the conulariids are consistent with the hypothesis that conulariids were polypoid scyphozoans.
Earnings Trend and Performance Relative to Benchmarks: How Consistency Influences Their Joint Use
Authors: KOONCE LISA , LIPE MARLYS GASCHO
Published: March 2010

Archival research shows that the market reacts to earnings trend as well as to earnings performance relative to analysts' forecasts (i.e., benchmark performance). We conduct four experiments to investigate how and why investors react to these two measures when both are available over multiple time periods. Our results show that investors rely on an earnings measure only when it is consistent over time. When both measures are consistent over time, investors use them in an additive fashion, suggesting that they view them as providing different information about the firm. Further tests show that investors believe that earnings trend and benchmark performance both provide information about a firm's future prospects and management's credibility. Although judged future prospects fully explain the effect of earnings trend on investor judgments, neither judged future prospects nor management credibility completely explains the effect of benchmark performance. Our study has implications for firm managers and researchers.