bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and retinoic acid regulation of the zebrafish nr2f orphan nuclear receptor genes
Authors: Love Crystal E. , Prince Victoria E.
Published: July 2012

Background: The vertebrate nuclear receptor subfamily 2, group f (nr2f) genes encode orphan receptors that have the capacity to act as negative regulators of retinoic acid (RA) signaling. Results: We describe embryonic and larval expression of four of the six zebrafish nr2f genes, nr2f1a, nr2f1b, nr2f2, and nr2f5. These genes show highly regulated patterns of expression within the central nervous system, including in the developing hindbrain, as well as in the mesoderm and endoderm. We also investigated the role of RA and fibroblast growth factor (Fgf) signaling in regulating early nr2f gene expression. RA is not required for nr2f expression in the hindbrain; however, exogenous RA can repress this expression. Conversely, we find that RA positively regulates nr2f1a expression in trunk endoderm and mesoderm. Fgf signaling is not required for nr2f expression onset in the hindbrain; however, it may play a role in maintaining rhombomere‐specific expression. Conclusions: We report detailed expression analysis of four nr2f genes in all three germ layers. The onset of nr2f expression in the hindbrain does not require RA or Fgf signals. Our finding that RA positively regulates nr2f1a expression in the trunk supports the possibility that Nr2fs function in a negative feedback loop to modulate RA signaling in this region. Developmental Dynamics 241:1603–1615, 2012. © 2012 Wiley Periodicals, Inc.
Spatiotemporal regulation of keratin 5 and 17 in the axolotl limb
Authors: Moriyasu Miyuki , Makanae Aki , Satoh Akira
Published: July 2012

Background: Amphibians have greater regeneration capability than higher vertebrates. They can regenerate their limbs after an amputation. As a limb is regenerated, a regeneration‐specific epithelium called the apical epithelial cap (AEC) is induced. The AEC is an essential structure for limb regeneration. Despite the importance of the AEC, molecular marker genes have not been well studied at the molecular level. Results: In the present study, keratin5 (KRT5) and KRT17 were investigated in an axolotl‐regenerating limb. KRT5 and KRT17 were expressed in a regenerating limb but down‐regulated in a differentiating limb. KRT5 showed characteristic regulation in a regenerating blastema. KRT5 was suppressed in the basal layer of the AEC. This KRT5 suppression was correlated to the blastema differentiation and nerve presence. Simple skin wounding could also upregulate both KRT5 and KRT17 gene expression. But these genes were suppressed within a shorter time than in limb regeneration. Conclusions: The KRT5 and KRT17 gene profile can be a useful marker gene to investigate AEC in limb regeneration. Developmental Dynamics 241:1616–1624, 2012. © 2012 Wiley Periodicals, Inc.
Characterization and functional study of a cluster of four highly conserved orphan adhesion‐GPCR in mouse
Authors: Prömel Simone , Waller‐Evans Helen , Dixon John , Zahn Dirk , Colledge William H. , Doran Joanne , Carlton Mark B.L. , Grosse Johannes , Schöneberg Torsten , Russ Andreas P. , Langenhan Tobias
Published: July 2012

Background: Adhesion G protein‐coupled receptors (aGPCR) constitute a structurally and functionally diverse class of seven‐transmembrane receptor proteins. Although for some of the members important roles in immunology, neurology, as well as developmental biology have been suggested, most receptors have been poorly characterized. Results: We have studied evolution, expression, and function of an entire receptor group containing four uncharacterized aGPCR: Gpr110, Gpr111, Gpr115, and Gpr116. We show that the genomic loci of these four receptors are clustered tightly together in mouse and human genomes and that this cluster likely derives from a single common ancestor gene. Using transcriptional profiling on wild‐type and knockout/LacZ reporter knockin mice strains, we have obtained detailed expression maps that show ubiquitous expression of Gpr116, co‐expression of Gpr111 and Gpr115 in developing skin, and expression of Gpr110 in adult kidney. Loss of Gpr110, Gpr111, or Gpr115 function did not result in detectable defects, indicating that genes of this aGPCR group might function redundantly. Conclusions: The aGPCR cluster Gpr110, Gpr111, Gpr115, and Gpr116 developed from one common ancestor in vertebrates. Expression suggests a role in epithelia, and one can speculate about a possible redundant function of GPR111 and GPR115. Developmental Dynamics 241:1591–1602, 2012. © 2012 Wiley Periodicals, Inc.
Influence of peer context on the relationship between body dissatisfaction and eating pathology in women and men
Authors: Forney K. Jean , Holland Lauren A. , Keel Pamela K.
Published: July 2012

Objective:

This study examined the influence of peer context on the relationship between body dissatisfaction and eating pathology in women and men.

Method:

Secondary analyses were conducted using survey data from a large community sample of women and men (N = 2,060).

Results:

The frequency of friend comments on weight and diet moderated the relationship between body dissatisfaction and eating pathology such that more frequent comments strengthened the relationship between body dissatisfaction and eating pathology in women. This effect was not significant in analyses of men. Instead, friend comments were directly related to eating pathology in men.

Discussion:

Both women and men may benefit from peer‐led interventions, with the greatest potential benefits for women with high body dissatisfaction, consistent with results from selective peer‐led prevention programs in sororities. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: Evidence of interoceptive dysregulation
Authors: Strigo Irina A. , Matthews Scott C. , Simmons Alan N. , Oberndorfer Tyson , Klabunde Megan , Reinhardt Lindsay E. , Kaye Walter H.
Published: July 2012

Objective:

Recent evidence raises the possibility that symptoms of anorexia nervosa (AN) could be related to impaired interoception. Pain is an interoceptive process with well‐characterized neuroanatomical pathways that may overlap to a large degree with neural systems that may be dysregulated in individuals with AN, such as the insula.

Method:

Functional magnetic resonance imaging (fMRI) was used to assess neural substrates of pain anticipation and processing in 10 healthy control women (CW) and 12 individuals recovered from AN (REC AN) in order to avoid the confounding effects of malnutrition. Painful heat stimuli were applied while different colors signaled the intensity of the upcoming stimuli.

Results:

REC AN compared with CW showed greater activation within right anterior insula (rAI), dorsolateral prefrontal cortex (dlPFC) and cingulate during pain anticipation, and greater activation within dlPFC and decreased activation within posterior insula during painful stimulation. Greater anticipatory rAI activation correlated positively with alexithymic feelings in REC AN participants.

Discussion:

REC AN showed a mismatch between anticipation and objective responses, suggesting altered integration and, possibly, disconnection between reported and actual interoceptive state. Alexithymia assessment provided additional evidence of an altered ability to accurately perceive bodily signals in women recovered from AN. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Therapeutic alliance in two treatments for adolescent anorexia nervosa
Authors: Forsberg Sarah , LoTempio Elizabeth , Bryson Susan , Fitzpatrick Kathleen Kara , Le Grange Daniel , Lock James
Published: July 2012

Objective:

The aim of this study was to examine the relationship between therapeutic alliance and treatment outcome (remission status) in family‐based treatment (FBT) and adolescent‐focused therapy (AFT) for adolescents with anorexia nervosa (AN).

Method:

Independent observers rated audiotapes of early therapy sessions using the Working Alliance Inventory‐Observer Version (WAI‐o). Outcome was defined using established cut‐points for full and partial remission. To control for effects of early symptom improvement, changes in weight‐ and eating‐related psychopathology prior to the alliance session were calculated and entered as a covariate in each analysis.

Results:

Participants in AFT had significantly higher alliance scores; however, overall scores were high in both therapies. The alliance was not a predictor of full remission for either treatment, though it was a non‐specific predictor for partial remission.

Discussion:

Therapeutic alliance is achievable in adolescents with AN in both AFT and FBT, but demonstrated no relationship to full remission of the disorder. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Specialization in habitat use by coral reef damselfishes and their susceptibility to habitat loss
Authors: Pratchett Morgan S. , Coker Darren J. , Jones Geoffrey P. , Munday Philip L.
Published: July 2012

While it is generally assumed that specialist species are more vulnerable to disturbance compared with generalist counterparts, this has rarely been tested in coastal marine ecosystems, which are increasingly subject to a wide range of natural and anthropogenic disturbances. Habitat specialists are expected to be more vulnerable to habitat loss because habitat availability exerts a greater limitation on population size, but it is also possible that specialist species may escape effects of disturbance if they use habitats that are generally resilient to disturbance. This study quantified specificity in use of different coral species by six coral‐dwelling damselfishes (Chromis viridis, C. atripectoralis, Dascyllus aruanus, D. reticulatus, Pomacentrus moluccensis, and P. amboinensis) and related habitat specialization to proportional declines in their abundance following habitat degradation caused by outbreaks of the coral eating starfish, Acanthaster planci. The coral species preferred by most coral‐dwelling damselfishes (e.g., Pocillopora damicornis) were frequently consumed by coral eating crown‐of‐thorns starfish, such that highly specialized damselfishes were disproportionately affected by coral depletion, despite using a narrower range of different coral species. Vulnerability of damselfishes to this disturbance was strongly correlated with both their reliance on corals and their degree of habitat specialization. Ongoing disturbances to coral reef ecosystems are expected, therefore, to lead to fundamental shifts in the community structure of fish communities where generalists are favored over highly specialist species.
Zinc Complexes of a Bioinspired Binucleating Ligand Platform – Equilibria in Solution and Structures in the Solid State
Authors: Wöckel Simone , Gałęzowska Joanna , Dechert Sebastian , Meyer‐Klaucke Wolfram , Nordlander Ebbe , Meyer Franc
Published: July 2012

The zinc(II) coordination chemistry of the bioinspired bis(tetradentate) ligand 3,5‐bis{bis[2‐(1‐methylimidazolyl)methyl]aminomethyl}pyrazole (L) was studied in detail both in solution and in the solid state. Six different species were determined in aqueous solution by means of potentiometry within the pH range 2–11, namely mononuclear [ZnH2L]4+, dinuclear [Zn2L]4+, [Zn2H–1L]3+ and [Zn2H–2L]2+, as well as tetranuclear [Zn4H–5L2]3+ and [Zn4H–6L2]2+. Complexes representing the protonation state of four of these species could be isolated and structurally characterized by X‐ray diffraction, namely [ZnH2L(MeCN)](ClO4)4 (1), [Zn2H–1L](SO3CF3)3 (4), [Zn2H–1L(MeOHOMe)](ClO4)2 (5a), [Zn2H–1L(OMe)](ClO4)2 (5b), and [(Zn2H–1L)2(μ‐O)(μ‐OH)](ClO4)3 (6). In addition, a bis(pyrazolato)‐bridged complex, [(ZnH–1L)2](ClO4)2 (2), was obtained and structurally characterized, and it was found to exhibit ligand dynamics in solution. Both 5a and 5b are likely present in solution, which requires significant plasticity of the Zn···Zn distance (4.21 Å in 5a vs. 3.38 Å in 5b). Interconversion of 5a and 5b is proposed to be a facile process, supporting the idea that the Zn–O2H3–Zn moiety is a functionally relevant hydrolytic zinc–aqua structure in oligozinc metalloenzymes. The tetranuclear complex 6 that features two {Zn2H–1L} subunits connected by a central μ‐oxido‐μ‐hydroxido moiety is unprecedented in zinc(II) chemistry. Combining X‐ray crystallography with potentiometry, ESI mass spectrometry, as well as NMR and EXAFS spectroscopy has provided a comprehensive picture of the multitude of species present in this rather complex system.
Occurrence of polyfunctional thiols in sorghum beer ‘ikigage’ made with Vernonia amygdalina ‘umubirizi’
Authors: Lyumugabe Francois , Gros Jacques , Thonart Philippe , Collin Sonia
Published: July 2012

Several polyfunctional thiols have been previously identified in beers made from barley and hops. These compounds have not been investigated in beers brewed with ‘non‐Western’ raw materials. Here we have performed a thiol‐specific extraction with p‐hydroxymercuribenzoic acid on a traditional ikigage sorghum beer from Rwandese peasants (use of Vernonia amygdalina just for yeast propagation), and on two pilot beers with addition (or not) of V. amygdalina in the boiling kettle, instead of hops. Gas chromatography–olfactometry, gas chromatography–mass spectrometry and gas chromatography with pulsed flame photometric detection analyses of the extracts enabled us to identify 14 polyfunctional thiols. The well‐known hop constituent 3‐methyl‐2‐buten‐1‐thiol emerged as a key flavour in the unhopped beers containing V. amygdalina (flavour dilution > 262 144). The addition of V. amygdalina during boiling also resulted in the presence of 1‐butanethiol, but the production of 2‐sulfanylethanol and 2‐sulfanylethyl acetate was inhibited. Complementary data are required to understand how V. amygdalina leaves are able to impact upon the Ehrlich pathway leading to cysteine and homocysteine‐derived thiols. Copyright © 2012 John Wiley & Sons, Ltd.
Preparation and characteristic odour of optically active 3‐hydroxy‐2‐octanone
Authors: Liu Yong‐guo , Chen Kai , Li Chen , Zhang Shuo , Chen Haitao , Tian Hong‐yu , Sun Bao‐guo
Published: July 2012

The preparation of optically active 3‐hydroxy‐2‐octanone was examined by Sharpless asymmetric dihydroxylation of a silyl enol ether derived from 2‐octanone. (R)‐3‐Hydroxy‐2‐octanone was obtained in 68% yield and 87.8% ee when AD‐mix‐β was used as an oxidant, while the (S)‐enantiomer was produced in 69% yield and 77.3% ee from AD‐mix‐α. The characteristic odour of the optically active products was evaluated by chiral gas chromatography–olfactometry. (R)‐3‐Hydroxy‐2‐octanone has a mushroom‐like, fresh grass odour, while the (S)‐enantiomer presents a mushroom‐like, earthy note. Aroma extract dilution analysis was applied to determine the flavour dilution factors of the two enantiomers. The flavour dilution factor of the (R)‐enantiomer was 1024, which is much higher than that of (S)‐enantiomer (256). They obviously differ in odour intensity. Copyright © 2012 John Wiley & Sons, Ltd.
Application of the VORTFIND algorithm for the identification of vortical flow features around complex three‐dimensional geometries
Authors: Phillips Alexander Brian , Turnock Stephen Richard
Published: July 2012

Accurate prediction of the hydrodynamic forces and moments acting on a manoeuvring marine vehicle using Reynolds averaged Navier–Stokes simulations requires sufficient mesh resolution to capture off‐body vortical structures. Because the path of these structures is not known a priori, a vortex identification and capture strategy is required alongside an iterative mesh adaption process. An improved version of the VORTFIND algorithm, which can identify multiple vortices of variable strength and rotational direction using a K‐means algorithm is described. The algorithm is applied to velocity fields generated from Reynolds averaged Navier–Stokes simulations to increase the mesh resolution in the vortex core region, ensuring sufficient mesh density to capture the downstream propagation of the vortex for a submarine hull at drift and ship propeller–rudder interaction.Copyright © 2012 John Wiley & Sons, Ltd.
Prospective Calculation of Identification Power for Individual Genes in Analyses Controlling the False Discovery Rate
Authors: Crager Michael R.
Published: July 2012

Recent work on prospective power and sample size calculations for analyses of high‐dimension gene expression data that control the false discovery rate (FDR) focuses on the average power over all the truly nonnull hypotheses, or equivalently, the expected proportion of nonnull hypotheses rejected. Using another characterization of power, we adapt Efron's ([2007] Ann Stat 35:1351–1377) empirical Bayes approach to post hoc power calculation to develop a method for prospective calculation of the “identification power” for individual genes. This is the probability that a gene with a given true degree of association with clinical outcome or state will be included in a set within which the FDR is controlled at a specified level. An example calculation using proportional hazards regression highlights the effects of large numbers of genes with little or no association on the identification power for individual genes with substantial association.
Development of a framework for recovery in older people with mental disorder
Authors: Daley Stephanie , Newton David , Slade Mike , Murray Joanna , Banerjee Sube
Published: July 2012

Objective

To evaluate whether a conceptual framework of recovery developed for working age adults holds value for users of older people's mental health services, including those with dementia.

Method

Thirty‐eight qualitative interviews were undertaken with service users and carers from an older people's mental health service in South London and were analysed using grounded theory methods.

Results

Components of recovery, which appear to be meaningful to older people with mental disorder include the following: (i) the impact of illness, (ii) the significance of personal responsibility, and (iii) specific coping strategies. Unlike their younger peers, older people did not aspire to a new and revised sense of identity, nor did they seek peer support from others with lived experience of mental illness. Three components of recovery were identified as being distinct to older people: the significance of an established and enduring sense of identity; coping strategies, which provide continuity and reinforce identity; and the associated impact of physical illness. Finally, two additional components of recovery were identified for people with dementia: (i) the changing experience over time and (ii) support from others.

Conclusion

Mental health policy is increasingly framed in terms of ‘recovery’. This paper provides empirical evidence of how it applies to users of older people's mental health services. Practice implications include the need to focus on the maintenance of identity, and embed the values of empowerment, agency and self‐management within service delivery. Copyright © 2012 John Wiley & Sons, Ltd.
An Abbreviated Screening Instrument for Autism Spectrum Disorders
Authors: Smith Nicola J. , Sheldrick R. Christopher , Perrin Ellen C.
Published: July 2012

The reliability and validity of the Parent's Observations of Social Interactions (POSI), a new, seven‐item screening instrument for autism spectrum disorders (ASD), is examined in two substudies. In Study 1, parents of 217 children (18–48 months) evaluated at a developmental clinic completed intake questionnaires that included the POSI and the Modified Checklist for Autism in Toddlers (M‐CHAT) checklist. POSI and M‐CHAT scores were compared to clinical evaluation results to assess reliability and validity. In Study 2, parents of 232 children (16–36 months) from both primary care and subspecialty settings completed the POSI, the M‐CHAT, and a report of their child's diagnoses. POSI and M‐CHAT scores were compared to reported diagnoses to assess reliability and validity. In both studies, the POSI demonstrated adequate internal reliability (Cronbach α = 0.83 and 0.86, respectively). In Study 1, POSI sensitivity (89%) was higher than that for the M‐CHAT (71%; p < .05); specificities were not significantly different (POSI: 54%, M‐CHAT: 62%). In Study 2, sensitivity (83%) compared favorably to that for the M‐CHAT (50%), although specificity was lower (75 vs. 84%). Despite its brevity, the POSI demonstrated good internal reliability and comparable sensitivity/specificity to the M‐CHAT checklist in two independent populations. If results are reproduced in larger, more diverse samples, the POSI may provide an efficient method for ASD screening in young children.
Osteopetrosis rescue upon RANKL administration to Rankl−/− mice: A new therapy for human RANKL-dependent ARO
Authors: Lo Iacono Nadia , Blair Harry C , Poliani Pietro L , Marrella Veronica , Ficara Francesca , Cassani Barbara , Facchetti Fabio , Fontana Elena , Guerrini Matteo M , Traggiai Elisabetta , Schena Francesca , Paulis Marianna , Mantero Stefano , Inforzato Antonio , Valaperta Serenella , Pangrazio Alessandra , Crisafulli Laura , Maina Virginia , Kostenuik Paul , Vezzoni Paolo , Villa Anna , Sobacchi Cristina
Published: July 2012

In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations in the receptor activator of NF-κB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl−/− mice, which closely resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial. © 2012 American Society for Bone and Mineral Research.
Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes
Authors: Sinnesael Mieke , Claessens Frank , Laurent Michaël , Dubois Vanessa , Boonen Steven , Deboel Ludo , Vanderschueren Dirk
Published: July 2012

Androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling has been mainly attributed to osteoblasts. Although osteocytes have emerged as key regulators of bone remodeling, the influence of sex steroids on these cells has been poorly studied. We aimed to investigate the role of AR signaling, specifically in osteocytes using the Cre/LoxP system in male mice (driven by dentin matrix protein 1 [ocy-ARKOs]). Osteocyte fractions of control (AR(ex2)/Y) and ocy-ARKO (ARflox(ex2)/Y; DMP1-cre) mice isolated through sequential collagenase digestion showed increasing AR expression toward the mature osteocyte fraction of control males compared with the more immature fractions, whereas this was reduced by >80% in ocy-ARKO osteocytes. The skeletal phenotype of mutant mice was further assessed by histomorphometry and quantitative micro-computed tomography at 12 and 32 weeks of age. Ocy-ARKOs had significantly lower trabecular bone volume and number in femora and tibias at 32 weeks as well as decreased trabecular number in the L5 vertebra at 12 weeks. Biomechanical testing showed that ocy-ARKO femora were also stiffer and required a lower ultimate force to induce failure at 32 weeks. However, femoral cortical structure was not significantly different at any time point. The absence of AR in osteocyte also did not appear to affect trabecular bone formation nor its response to mechanical loading. In conclusion, selective inactivation of the AR in osteocytes of male mice accelerates age-related deterioration of skeletal integrity. These findings provide evidence for a direct role of androgens in the maintenance of trabecular bone through actions of the AR in osteocytes. © 2012 American Society for Bone and Mineral Research.
Antiresorptives overlapping ongoing teriparatide treatment result in additional increases in bone mineral density
Authors: Muschitz Christian , Kocijan Roland , Fahrleitner-Pammer Astrid , Lung Solveig , Resch Heinrich
Published: July 2012

During teriparatide (TPTD) treatment, high levels of bone formation are accompanied by an increase in bone resorption. The aim of this work was to test if coadministration of raloxifene (RAL) or alendronate (ALN) following 9 months of ongoing TPTD therapy would reopen the anabolic window, thereby exerting additional benefit on bone mineral density (BMD). Postmenopausal women (n = 125) with severe osteoporosis on TPTD treatment for 9 months were randomized into three open-label groups for a further 9 months: ALN (70 mg/week) in addition to TPTD; RAL (60 mg/d) in addition to TPTD; or no medication in addition to TPTD. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), and areal and volumetric BMD at the lumbar spine and hip were assessed. During the combination period, P1NP concentrations did not change on TPTD monotherapy (693% ± 371%, p < 0.0001) and decreased in the ALN (360% ± 153%, p < 0.0001) and RAL (482% ± 243%, p < 0.0001) combination groups; whereas CTX did not change on TPTD monotherapy (283% ± 215%, p < 0.0001), decreased to the starting level in the ALN combination group (17% ± 72%, p = 0.39), and remained elevated in the RAL combination group (179% ± 341%, p < 0.0001). The increase in lumbar spine BMD was 5% ± 6.3% in the ALN and 6% ± 5.2% in the RAL combination groups compared with 2.8% ± 9.3% in the TPTD monotherapy group (p = 0.085 and p = 0.033, respectively). The increase of trabecular lumbar spine BMD for both the ALN and RAL combination groups was superior to TPTD monotherapy. Total hip BMD changes were 4% ± 5.3% for the ALN combination group and 1.4% ± 5.1% for the TPTD monotherapy (p = 0.032), and 1.4% ± 3.4% (p = 0.02) for the RAL combination group. With the exception of no differences in the trabecular compartment of femoral neck, volumetric BMD changes in the ALN combination group for all other comparisons were significantly superior to the two other groups. Our data suggest that ALN when added to TPTD 9 months after initiation of TPTD monotherapy results in a more robust increase in BMD, probably due to a reopening of the anabolic window. The clinical relevance of the BMD increase is unknown. © 2013 American Society for Bone and Mineral Research
Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta
Authors: Sinder Benjamin P , Eddy Mary M , Ominsky Michael S , Caird Michelle S , Marini Joan C , Kozloff Kenneth M
Published: July 2012

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly→Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. © 2013 American Society for Bone and Mineral Research
High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study
Authors: Ardawi Mohammed-Salleh M , Rouzi Abdulrahim A , Al-Sibiani Sharifa A , Al-Senani Nawal S , Qari Mohammed H , Mousa Shaker A
Published: July 2012

Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 ± 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women. © 2012 American Society for Bone and Mineral Research.
Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population-based cohort study
Authors: Chen Yu-Chun , Wu Jau-Ching , Liu Laura , Huang Wen-Cheng , Cheng Henrich , Chen Tzeng-Ji , Thien Peck-Foong , Lo Su-Shun
Published: July 2012

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age- and sex-matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed-up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person-years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person-years; 95% CI, 12.0–16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89–3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90–3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. © 2013 American Society for Bone and Mineral Research.
Natural bond critical point analysis: Quantitative relationships between natural bond orbital‐based and QTAIM‐based topological descriptors of chemical bonding
Authors: Weinhold Frank
Published: July 2012

We have developed a “Natural Bond Critical Point” (NBCP) module for the natural bond orbital (NBO) program that allows mutual analysis of NBO‐basedversusBader‐type quantum theory of atoms in molecules (QTAIM) topological descriptors of chemical bonding interactions. Conventional QTAIM bond path and bond critical point (BCP) descriptors deduced from total electron density ρ(r) can thereby be compared with analogous “natural” (NBCP) descriptors for idealized densities ρNAIM(r) composed solely from NBO‐based “natural atoms in molecules” (NAIM) at the terminal nuclei. Standard ρ(rBCP) and ∇2ρ(rBCP) descriptors can also be decomposed into unique contributions from individual NBOs or other localized, semilocalized, or delocalized orbital components. These results allow one to recognize many relationships between QTAIM and NBO analyses, showing why close correlations are often found between NBO‐basedversusρ(rBCP)‐based characterizations of chemical bonding interactions, despite strongly divergent conceptions of “the atom in the molecule.” © 2012 Wiley Periodicals, Inc.
Extraction of zinc(II) from ammoniacal solution into hydrophobic ionic liquids
Authors: Hu Jiugang , Chen Qiyuan , Hu Huiping , Ma Qian , Yin Zhoulan , Hu Fengchun
Published: July 2012

BACKGROUND: Separation and recovery of zinc from ammoniacal solutions with solvent extraction is very important in the hydrometallurgical industry. Ionic liquids (ILs) have considerable potential for the separation of metal ions. The extraction behaviour of zinc from ammoniacal solution into three hydrophobic ILs was investigated using β‐diketone as the extractant.

RESULTS: The extraction efficiency of zinc for three ILs reached a maximum at pH 7.5 and subsequently decreased with increase of pH and it also decreases with increase of the total ammonia concentration. The overall extraction process is exothermic. The extractability decreases in the IL order: [BMIM]NTf2 > [OMIM]PF6 > [OMIM]NTf2. The results of X‐ray absorption spectra indicate that the coordination number of the extracted zinc complexes decreases with increase in the hydrophobicity of the ILs. The results of five recycling experiments indicate that the three hydrophobic ILs are more stable than [BMIM]PF6 for the extraction of zinc in ammoniacal solutions.

CONCLUSION: Hydrophobic ILs combined with β‐diketone can be used to extract zinc from ammoniacal solutions. The extraction of zinc is dependent on the zinc species in ammoniacal solutions and the hydrophobicity of ILs. Moreover, the latter affects both the extractability of extraction systems and the structure of the extracted complexes. © 2012 Society of Chemical Industry
Aminooxy‐functionalized DOTA for radiolabeling of oxidized antibodies: evaluation of site‐specific 111In‐labeled trastuzumab
Authors: Bejot Romain , Goggi Julian , Moonshi Shebbrin S. , Padmanabhan Parasuraman , Bhakoo Kishore K.
Published: July 2012

Antibody‐targeted nuclear imaging or radiotherapy rely on chemical modification of the polypeptide backbone that may hamper the antigen binding and hence the targeting ability. In this study, we examine a strategy for covalent modification and radiolabeling of monoclonal antibodies utilizing the oligosaccharide moieties on the molecule: the 111In‐radiolabeling of the monoclonal antibody trastuzumab (Herceptin®, Roche, Basel, Switzerland), which targets the breast cancer‐related ErbB2/human epidermal growth factor‐2 (HER2) protein. The site‐specific radiolabeled antibody was obtained through mild oxidation of the antibody Fc region with periodate and its conjugation with an aminooxy‐functionalized tetraazacyclododecanetetraacetic acid (DOTA) chelator. It was further evaluated both in vitro with HER2 expressing cells and in vivo with tumor‐bearing mice by single photon emission computed tomography (SPECT), and compared with the DOTA‐N‐hydroxysuccinimide methodology.

Such radiolabeled trastuzumab did not show significant difference in stability when compared with lysine‐conjugated antibodies (>95%, 3 days postinjection). They also maintain their immunoreactivity (>90% immunoreactive fraction) and affinity both in vitro (Kd ~ 4–5 nM) and in vivo (12.9 %ID/g in MDA‐MB‐361 tumors).

Our results confirm that the formation of a hydrolytically stable oxime linker between a chelating agent and the oxidized N‐glycan residues, away from the variable antigen‐binding sites, is an attractive approach for site‐specific conjugation of antibodies and accessing radiopharmaceuticals and immunotherapeutics. Copyright © 2012 John Wiley & Sons, Ltd.
Substance P enhances collagen remodeling and MMP‐3 expression by human tenocytes
Authors: Fong Gloria , Backman Ludvig J. , Hart David A. , Danielson Patrik , McCormack Bob , Scott Alex
Published: July 2012

The loss of collagen organization is considered a hallmark histopathologic feature of tendinosis. At the cellular level, tenocytes have been shown to produce signal substances that were once thought to be restricted to neurons. One of the main neuropeptides implicated in tendinosis, substance P (SP), is known to influence collagen organization, particularly after injury. The aim of this study was to examine the influence of SP on collagen remodeling by primary human tendon cells cultured in vitro in three‐dimensional collagen lattices. We found that SP stimulation led to an increased rate of collagen remodeling mediated via the neurokinin‐1 receptor (NK‐1 R), the preferred cell receptor for SP. Gene expression analysis showed that SP stimulation resulted in significant increases in MMP3, COL3A1 and ACTA2 mRNA levels in the collagen lattices. Furthermore, cyclic tensile loading of tendon cell cultures along with the administration of exogenous SP had an additive effect on MMP3 expression. Immunoblotting confirmed that SP increased MMP3 protein levels via the NK‐1 R. This study indicates that SP, mediated via NK‐1 R, increases collagen remodeling and leads to increased MMP3 mRNA and protein expression that is further enhanced by cyclic mechanical loading. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:91–98, 2012
A novel piece of Minoan art in Italy: the first spectroscopic study of the wall paintings from Phaistos
Authors: Zoppi Angela , Lofrumento Cristiana , Ricci Marilena , Cantisani Emma , Fratini Tiziana , Castellucci Emilio Mario
Published: July 2012

Some fragments of wall paintings of Phaistos (Crete), belonging to the Bronze Age, from the Archaeological National Museum of Florence, were analysed to investigate the material composition of their pictorial layers and to explore the pictorial technology. These samples belong to the oldest surviving examples of decorative polychrome painting on plaster from Crete and constitute a further document in the frame of the already known evidences of painted materials from the palatial sites. The wall painting fragments were studied to define the composition of the paint layers and of the plaster used as substrate, and to classify the painting method. The coloured strata were investigated through micro‐Raman analyses by acquiring the vibrational spectra on different points selected for every hue, whereas for the plaster, different techniques were employed such as optical microscopy, X‐ray diffraction and Fourier transform infrared spectroscopy. In accordance with similar Aegean Bronze painted plasters, the obtained results show a rather homogenous colour palette mostly made of mineral pigments, which recur in the different tones in all the fragments. The absence of organic binders and the possibility to differentiate calcite grains present in the painting layers from that present in the plaster underneath were indicative of fresco–secco technique. On the whole, the obtained results could be considered as valuable archaeological indicators for the contribution they could offer to the comprehension of the painting techniques and the materials used in Crete during the Medium Minoan period. Copyright © 2012 John Wiley & Sons, Ltd.
Probing thermal behaviour of microbial transglutaminase with fluorescence and in silico methods
Authors: Aprodu Iuliana , Stănciuc Nicoleta , Banu Iuliana , Bahrim Gabriela
Published: July 2012

BACKGROUND: Knowledge of transglutaminase behaviour at thermal treatment allows efficient applications in food processing. The heat‐induced conformational changes of microbial transglutaminase were studied by fluorescence spectroscopy and a molecular modelling approach.

RESULTS: The experimental results indicate the unfolding of transglutaminase in a single‐phase reaction, at temperatures over 60 °C. The incidence of conformational changes is also supported by the increase of both intrinsic and 1‐anilino‐8‐naphthalene sulfonate fluorescence intensity with temperature. Changes in the secondary and tertiary structure of transglutaminase were outlined after running molecular dynamics simulations at temperatures ranging from 25 °C to 80 °C.

CONCLUSION: The motif's particularities varied with the temperature, suggesting structural rearrangements of the protein, mainly in helices. The largest deviation from the structure equilibrated at 25 °C was observed at 80 °C. © 2012 Society of Chemical Industry
Mercury in fruiting bodies of dark honey fungus (Armillaria solidipes) and beneath substratum soils collected from spatially distant areas
Authors: Falandysz Jerzy , Mazur Aneta , Kojta Anna K , Jarzyńska Grażyna , Drewnowska Małgorzata , Dryżałowska Anna , Nnorom Innocent C
Published: July 2012

BACKGROUND: This paper reports data on bioconcentration potential and baseline mercury concentrations of fruiting bodies of dark honey fungus (Armillaria solidipes) Peck and soil substrate layer (0–10 cm) from 12 spatially distant sites across Poland. Mercury content of caps, stipes and soil samples were determined using validated analytical procedure including cold‐vapor atomic absorption spectroscopy after thermal decomposition of the sample matrix and further amalgamation and desorption of mercury from gold wool.

RESULTS: Mean mercury concentrations ranged from 20 ± 8 to 300 ± 70 ng g−1 dry weight (dw) in caps, from 20 ± 6 to 160 ± 40 ng g−1 dw in stipes, and in underlying soil were from 20 ± 2 to 100 ± 130 ng g−1 dw. The results showed that stipes mercury concentrations were 1.1‐ to 1.7‐fold lower than those of caps. All caps and the majority of stipes were characterized by bioconcentration factor values > 1, indicating that dark honey fungus can be characterized as a moderate mercury accumulator.

CONCLUSION: Occasional or relatively frequent eating of meals including caps of dark honey fungus is considered safe in view of the low total mercury content, and the mercury intake rates are below the current reference dose and provisionally tolerable weekly intake limits for this hazardous metal. © 2012 Society of Chemical Industry
Enzyme deactivation treatments did not decrease the beneficial role of oat food in intestinal microbiota and short‐chain fatty acids: an in vivo study
Authors: Hu Xinzhong , Xing Xiaohui , Zhen Hongmin
Published: July 2012

BACKGROUND: Steaming and roasting treatments are widely used enzyme deactivation methods in the oat food industry in China. Whether or not the enzyme deactivation treatments affect the nutritional function of oat foods is unknown. In the current study, we examined the effects of 4‐week ingestion of steamed or roasted oat foods on the intestinal bacteria and short‐chain fatty acids of rats.

RESULTS: Compared with rats taking no oat foods, rats taking normal oat foods or enzyme‐deactivated oat foods showed significantly higher (P < 0.05) counts of Lactobacillus spp. and Bifidobacterium spp. in colon, significantly lower (P < 0.05) counts of Enterococcus spp. and coliforms in colon, and significantly higher (P < 0.05) levels of butyrate and acetate in colonic digesta. In addition, rats taking infrared roasting (IR)‐treated oat foods also demonstrated significantly higher (P < 0.05) fecal Lactobacillus spp. counts and significantly lower (P < 0.05) cecal and fecal counts of E. coli, Enterococcus spp. and coliforms than rats taking no oat foods. As for the comparison between the enzyme‐undeactivated oat group and the three enzyme‐deactivated oat groups, there were no significant differences in most of the parameters (P > 0.05), though a few exceptions did exist.

CONCLUSION: Enzyme deactivation treatments did not decrease the beneficial role of oat food in the intestinal microbes and short‐chain fatty acids of rats. © 2012 Society of Chemical Industry
Kinetics of reaction between acetic acid and Ag2+ in nitric acid medium
Authors: Gao‐Liang Li , Hui He , Hongbin Tang , Xiechun Liu , Guoan Ye
Published: July 2012

The reaction kinetics between acetic acid and Ag2+ in nitric acid medium is studied by spectrophotometry. The effects of concentrations of acetic acid (HAc), H+, NO−3, and temperature on the reaction are investigated. The rate equation has been determined to be –dc(Ag2+)/dt = kc(Ag2+)c(HAc)c−1(H+), where k = (610 ± 15) (mol/L)−1 min−1 with an activation energy of about (48. 8 ± 3.5) kJ mol−1 when the reaction temperature is 25°C and the ionic strength is 4.0 mol L−1. The reduction rate of Ag2+ increases with the increase in HAc concentration and/or temperature and the decrease in HNO3 concentration. However, the effect of NO−3 concentrations within 0.5–2.5 mol L−1 on the reaction rate is negligible. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 45: 47–51, 2013
High optical performance and practicality of active plasmonic devices based on rhombohedral BiFeO3
Authors: Chu S.H. , Singh D.J. , Wang J. , Li E.‐P. , Ong K.P.
Published: July 2012

First principles calculations of electronic and optical properties of multiferroic oxide BiFeO3 are used in combination with a plasmonic device model of optical switch to show that a BiFeO3 based device can have much better performance than devices based on existing materials. This arises from the combination of octahedral tilts, ferroelectricity and G‐type antiferromagnetism in BiFeO3 leading to a strong dependence of the optical refractive indices on the orientation with respect to the polarization. A prototype of a plasmonic resonator with an R‐BFO thin film layer is used as an example and shows excellent switch and modulation responses. The proposed approach provides potential opportunities to develop high performance nanophotonic devices for optical communication.
“Click & Seed” Approach to the Biomimetic Modification of Material Surfaces
Authors: Proks Vladimír , Jaroš Josef , Pop‐Georgievski Ognen , Kučka Jan , Popelka Štěpán , Dvořák Petr , Hampl Aleš , Rypáček František
Published: July 2012

A simple, versatile, protein‐repulsive, substrate‐independent biomimetic surface modification is presented that is based on the creation of a PEO brush on a polydopamine anchoring layer and its capacity for selective follow‐up modifications with various ligands using a copper‐catalyzed alkyne‐azide cycloaddition reaction. The desired surface concentration of peptide biomimetic ligands can be controlled by adjusting the peptide concentration in the reaction mixture, then measuring the activity of 125I‐radiolabeled peptides that are immobilized on the substrates. The performance of the prepared substrates is tested in cell cultures with MEF cells and a human ECC line.

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