bluuebunny/crossref_metadata_2025 huggingface dataset:
Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease
Authors: Marino Marco , Moriondo Valeria , Vighi Eleonora , Pignatti Elisa , Simoni Manuela
Published: September 2014

Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians.
Design of CGMP Production of18F- and68Ga-Radiopharmaceuticals
Authors: Chi Yen-Ting , Chu Pei-Chun , Chao Hao-Yu , Shieh Wei-Chen , Chen Chuck C.
Published: September 2014

Objective.Radiopharmaceutical production process must adhere to current good manufacturing process (CGMP) compliance to ensure the quality of precursor, prodrug (active pharmaceutical ingredient, API), and the final drug product that meet acceptance criteria. We aimed to develop an automated system for production of CGMP grade of PET radiopharmaceuticals.Methods.The hardware and software of the automated synthesizer that fit in the hot cell under cGMP requirement were developed. Examples of production yield and purity for68Ga-DOTATATE and18F-FDG at CGMP facility were optimized. Analytical assays and acceptance criteria for cGMP grade of68Ga-DOTATATE and18F-FDG were established.Results.CGMP facility for the production of PET radiopharmaceuticals has been established. Radio-TLC and HPLC analyses of68Ga-DOTATATE and18F-FDG showed that the radiochemical purity was 92% and 96%, respectively. The products were sterile and pyrogenic-free.Conclusion.CGMP compliance of radiopharmaceuticals has been reviewed.68Ga-DOTATATE and18F-FDG were synthesized with high radiochemical yield under CGMP process.
Detecting Local Community Structures in Networks Based on Boundary Identification
Authors: Yang Liu , Xin-sheng Ji , Caixia Liu , Ding Wang
Published: September 2014

Detecting communities within networks is of great importance to understand the structure and organizations of real‐world systems. To this end, one of the major challenges is to find the local community from a given node with limited knowledge of the global network. Most of the existing methods largely depend on the starting node and require predefined parameters to control the agglomeration procedure, which may cause disturbing inference to the results of local community detection. In this work, we propose a parameter‐free local community detecting algorithm, which uses two self‐adaptive phases in detecting the local community, thus comprehensively considering the external and internal link similarity of neighborhood nodes in each clustering iteration. Based on boundary nodes identification, our self‐adaptive method can effectively control the scale and scope of the local community. Experimental results show that our algorithm is efficient and well‐behaved in both computer‐generated and real‐world networks, greatly improving the performance of local community detection in terms of stability and accuracy.
Birhythmicity and Hard Excitation from Coupled Synthetic Feedback Loops
Authors: Chen Aimin , Liu Caixia , Wang Junwei
Published: September 2014

Synthetic biology opens up the possibility of creating circuits that would not survive in the natural world and studying their behaviors in living cells, expanding our notion of biology. Based on this, we analyze on a synthetic biological system the effect of coupling between two instability-generating mechanisms. The systems considered are two topologically equivalent synthetic networks. In addition to simple periodic oscillations and stable steady state, the system can exhibit a variety of new modes of dynamic behavior: coexistence between two stable periodic regimes (birhythmicity) and coexistence of a stable periodic regime with a stable steady state (hard excitation). Birhythmicity and hard excitation have been proved to exist in biochemical networks. Through bifurcation analysis on these two synthetic cellular networks, we analyze the function of network structure for the collapse and revival of birhythmicity and hard excitation with the variation of parameters. The results have illustrated that the bifurcation space can be divided into four subspaces for which the dynamical behaviors of the system are generically distinct. Our analysis corroborates the results obtained by numerical simulation of the dynamics.
Analysis on Steady-State Operation and Heat Loss of Chinese Integrated Pressurized Water Reactor
Authors: Fan Zhang , Dao-Gang Lu , Dan-Ting Sui , Chao Guo , Bo Yuan
Published: September 2014

Chinese integrated pressurized water reactor (CIPWR) has compact configuration and high inherent safety, which is appropriate for nuclear power plants of small and medium scale. Heat balance model has been adopted widely in thermal power calibration of PWRs because of its advantage of accuracy. In this paper, a package based on FORTRAN language is developed and added into RELAP5 to calculate the heat loss value needed in heat balance analysis. The steady-state operation of CIPWR is modelled correctly by RELAP5. The heat loss of CIPWR is calculated by the package, and the comparison of the main values of parameters needed in the heat loss calculation between RELAP5 and the package has been done. It shows that the package has high calculation accuracy and can be applied in reactor design and monitoring.
Unawareness of a Prolonged Retained Capsule Endoscopy: The Importance of Careful Follow-Up and Cooperation between Medical Institutions
Authors: Saigusa Susumu , Ohi Masaki , Imaoka Hiroki , Shimura Tadanobu , Uratani Ryo , Inoue Yasuhiro , Kusunoki Masato
Published: September 2014

A 50-year-old man with anemia was referred to our hospital to undergo capsule endoscopy (CE), which revealed small intestinal ulcers. After 5 months of CE, he returned because of recurrent anemia without abdominal symptoms. Abdominal X-ray and computed tomography showed capsule retention in the small intestine at the pelvic cavity. The capsule remained at the same place for 7 days. We performed capsule retrieval by laparoscopy-assisted surgery with resection of the involved small intestine, including an ileal stricture. Resected specimen showed double ulcers with different morphologies, an ulcer scar with stricture, and a wide ulcer at the proximal side of the others. Each ulcer had different histopathological findings such as the degree of fibrosis and monocyte infiltration. These differences led us to consider that the proximal ulcer may have been secondarily induced by capsule retention. Our experience indicated that careful follow-up and the cooperation between medical institutions after CE examination should be undertaken for patients with incomplete examination, unknown excretion of the capsule, and/or ulcerative lesions despite the lack of abdominal symptoms. Additionally, a retained CE remaining over long periods and at the same place in the small intestine may lead to secondary ulceration.
Dynamics ofMycobacteriumandbovine tuberculosisin a Human-Buffalo Population
Authors: Hassan A. S. , Garba S. M. , Gumel A. B. , Lubuma J. M.-S.
Published: September 2014

A new model for the transmission dynamics ofMycobacterium tuberculosisand bovine tuberculosis in a community, consisting of humans and African buffalos, is presented. The buffalo-only component of the model exhibits the phenomenon of backward bifurcation, which arises due to the reinfection of exposed and recovered buffalos, when the associated reproduction number is less than unity. This model has a unique endemic equilibrium, which is globally asymptotically stable for a special case, when the reproduction number exceeds unity. Uncertainty and sensitivity analyses, using data relevant to the dynamics of the two diseases in the Kruger National Park, show that the distribution of the associated reproduction number is less than unity (hence, the diseases would not persist in the community). Crucial parameters that influence the dynamics of the two diseases are also identified. Both the buffalo-only and the buffalo-human model exhibit the same qualitative dynamics with respect to the local and global asymptotic stability of their respective disease-free equilibrium, as well as with respect to the backward bifurcation phenomenon. Numerical simulations of the buffalo-human model show that the cumulative number ofMycobacterium tuberculosiscases in humans (buffalos) decreases with increasing number of bovine tuberculosis infections in humans (buffalo).
An Immunization Strategy Based on Propagation Mechanism
Authors: Zhu Yixin , Zhang Fengli , Guo Wenqiang
Published: September 2014

With the ubiquity of smart phones, wearable equipment, and wireless sensors, the topologies of networks composed by them change along with time. The immunization strategies in which network immune nodes are chosen by analyzing the static aggregation network topologies have been challenged. The studies about interaction propagations between two pathogens show that the interaction can change propagation threshold and the final epidemic size of each other, which provides a new thinking of immunization method. The eradication or inhibition of the virus can be achieved through the spread of its opposite party. Here, we put forward an immunization strategy whose implementation does not depend on the analysis of network topology. The immunization agents are randomly placed on a few of individuals of network and spread out from these individuals on network in a propagation method. The immunization agents prevent virus infecting their habitat nodes with certain immune success rate. The analysis and simulation of evolution equation of the model show that immune propagation has a significant impact on the spread threshold and steady-state density of virus on a finite size of BA networks. Simulations on some real-world networks also suggest that the immunization strategy is feasible and effective.
Tracing the Roots of Cancer Evolution
Authors: Jiang Yanwen , Elemento Olivier
Published: September 2014

Summary: By comparing the genomes of progenitor cells and mature cells of lymphoid and myeloid lineages in patients with chronic lymphocytic leukemia (CLL), Damm and colleagues confirmed that CLL originates from preleukemic CD34+ progenitor cells and identified early CLL mutations that are associated with these progenitor cells. Moreover, they discovered that deregulation of B-cell receptor signaling may be one of the hallmarks of CLL, particularly in tumors with EGR2 mutations. Cancer Discov; 4(9); 995–7. ©2014 AACR.

See related article by Damm et al., p. 1088
Common Genetic Variants Contribute to Primary Hypertriglyceridemia Without Differences Between Familial Combined Hyperlipidemia and Isolated Hypertriglyceridemia
Authors: De Castro-Orós Isabel , Cenarro Ana , Tejedor María Teresa , Baila-Rueda Lucía , Mateo-Gallego Rocío , Lamiquiz-Moneo Itziar , Pocoví Miguel , Civeira Fernando
Published: September 2014

Background—

The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined.

Methods and Results—

This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of
APOE
,
APOA5
,
GALNTN2
, and
GCKR
variants were positively correlated with plasma triglycerides, whereas minor alleles of
ADIPOR2
,
ANGPTL3
,
LPL
, and
TRIB1
polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in
LPL
, rs662799 and rs3135506 in
APOA5
, and rs1260326 in
GCKR
explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables.
LPL
,
GCKR
, and
APOA5
polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in
APOE
and rs1800795 in
IL6
; rs2808607 in
CYP7A1
and rs3812316 and rs17145738 in
MLXIPL
were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL.

Conclusions—

Common genetic variants found in
LPL
,
APOA5
, and
GCKR
are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.
Serranus magnificus Macleay 1882, a junior synonym of Epinephelus lanceolatus (Bloch 1790) (Teleostei: Serranidae)
Authors: GILL ANTHONY C.
Published: September 2014

William John Macleay (1882) described Serranus magnificus from the holotype collected by Andrew Goldie in Port Moresby, Papua New Guinea. The holotype was originally in the Macleay Museum, but was subsequently transferred to the Australian Museum (AMS) in 1907, along with around 500 additional lots of mostly Goldie New Guinea and “Chevert” expedition fishes (AMS series I.9039–I.9198, I.9200–I.9241, I.9457–I.9476, I.9620–I.9726, I.9739–I.9802 and I.13356–I.13456), and was duly registered there (registration number I.9460). The specimen was subsequently misplaced, and could not be located by J.E. Randall and P.C. Heemstra for their revision of Indo-Pacific Epinephelinae (Heemstra & Randall 1991). They were unable to associate the name with any known species, and listed the species as a nomen dubium (also indicated as such by Heemstra & Randall 1993). This is surprising as Macleay’s description mostly agrees with Epinephelus lanceolatus (Bloch 1790), with the exception of the number of anal-fin rays (III,9 versus III,8). His description is reproduced here (Macleay 1882, p. 229):
Enhancement of surface enhanced raman scattering from arrays of hybrid Au–Ag nanoparticles via localised surface plasmon resonance
Authors: Liu J. , Cai H. , Kong L. , Zhu X.
Published: September 2014

The enhancement of surface enhanced raman scattering of the hybrid Au–Ag triangular nanostructure arrays via localised surface plasmon resonance is systematically investigated. The hybrid nanostructure can prevent the pure silver nanoparticles from oxidation and the stability of Au–Ag nanoparticles compared with non-coated Ag nanoparticles has been verified. Discrete dipole approximation calculated results show the size of the nanoparticle has an important effect on localised surface plasmon resonance of the hybrid nanostructure. Nanosphere lithography is used to fabricate the hybrid nanoparticle arrays with different sizes of nanoparticle. Both theoretical calculations and experimental results show that with an increase in size of the nanoparticle, positions of localised surface plasmon resonance peak are less strongly redshifted and peak of the surface enhanced Raman scattering of the arrays is obviously strengthened. A maximum intensity of the surface enhanced raman scattering can be achieved when the localised surface plasmon resonance wavelength of the hybrid Au–Ag nanoparticle arrays well match the laser excitation wavelength.
Heat shock proteins HSP70 and MRJ cooperatively regulate cell adhesion and migration through urokinase receptor
Authors: Lin Yuli , Peng Nana , Zhuang Hongqin , Zhang Di , Wang Yao , Hua Zi-Chun
Published: September 2014

Background

The urokinase-type plasminogen activator receptor (uPAR) is an important regulator of ECM proteolysis, cell-ECM interactions and cell signaling. uPAR and heat shock proteins HSP70 and MRJ (DNAJB6) have been implicated in tumor growth and metastasis. We have reported recently that MRJ (DNAJB6, a heat shock protein) can interact with uPAR and enhance cell adhesion. Here, we identified another heat shock protein HSP70 as a novel uPAR-interacting protein.

Methods

We performed co-immunoprecipitation in human embryonic kidney (HEK) 293 and colon cancer HCT116 cells as well as immunofluorence assays in HEK293 cells stably transfected with uPAR to investigate the association of suPAR with HSP70/MRJ. To understand the biological functions of the triple complex of suPAR/HSP70/MRJ, we determined whether HSP70 and/or MRJ regulated uPAR-mediated cell invasion, migration, adhesion to vitronectin and MAPK pathway in two pair of human tumor cells (uPAR negative HEK293 cells vs HEK293 cells stably transfected with uPAR and HCT116 cells stably transfected with antisense-uPAR vs HCT116 mock cells transfected with vector only) using transwell assay, wound healing assay, quantitative RT-PCR analyzing mmp2 and mmp9 transcription levels, cell adhesion assay and Western blotting assay.

Results

HSP70 and MRJ formed a triple complex with uPAR and over-expression of MRJ enhanced the interaction between HSP70 and uPAR, while knockdown of MRJ decreased soluble uPAR in HCT116 cells (P < 0.05) and reduced the formation of the triple complex, suggesting that MRJ may act as an uPAR-specific adaptor protein to link uPAR to HSP70. Further experiments showed that knockdown of HSP70 and/or MRJ by siRNA inhibited uPAR-mediated cell adhesion to vitronectin as well as suppressed cell invasion and migration. Knockdown of HSP70 and/or MRJ inhibited expression of invasion related genes mmp2 and mmp9. Finally, HSP70 and/or MRJ up-regulated phosphorylation levels of ERK1/2 and FAK suggesting MAPK pathway was involved. All the biological function experiments in cell level showed an additive effect when HSP70 and MRJ were regulated simultaneously indicating their collaborated regulation effects on uPAR.

Conclusions

These findings may offer a novel insight into the interactions between uPAR and HSP70/MRJ and their functions in cell adhesion and migration may provide more understanding of the roles in regulating cancer metastasis.
Self-rated and observer-rated measures of well-being and distress in adolescence: an exploratory study
Authors: Vescovelli Francesca , Albieri Elisa , Ruini Chiara
Published: September 2014

The evaluation of eudaimonic well-being in adolescence is hampered by the lack of specific assessment tools. Moreover, with younger populations, the assessment of positive functioning may be biased by self-report data only, and may be more accurate by adding significant adults’ evaluations. The objective of this research was to measure adolescents’ well-being and prosocial behaviours using self-rated and observer-rated instruments, and their pattern of associations. The sample included 150 Italian high school adolescents. Observed-evaluation was performed by their school teachers using the Strengths and Difficulties Questionnaire. Adolescents completed Ryff’s Psychological Well-being Scales and Symptom Questionnaire. Pearson’ r correlations and Linear regression were performed. Self-rated dimensions of psychological well-being significantly correlated with all observer-rated dimensions, but Strengths and Difficulties Emotional symptom scale. Multiple linear regression showed that the self-rated dimensions Environmental Mastery and Personal Growth, and surprisingly not Positive Relations, are related to the observer-rated dimension Prosocial Behaviour. Adolescents with higher levels of well-being in specific dimensions tend to be perceived as less problematic by their teachers. However, some dimensions of positive functioning present discrepancies between self and observer-rated instruments. Thus, the conjunct use of self-reports and observer-rated tools for a more comprehensive assessment of students’ eudaimonic well-being is recommended.
The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma
Authors: van Roosmalen Ingrid A M , Reis Carlos R , Setroikromo Rita , Yuvaraj Saravanan , Joseph Justin V , Tepper Pieter G , Kruyt Frank A E , Quax Wim J
Published: September 2014

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related apoptosis-inducing ligand (TRAIL WT) or the DR5-specific TRAIL D269H/E195R variant as a potential new strategy to eradicate GBM cells using TRAIL-resistant and -sensitive GBM cells. GBM cell lines were investigated for their sensitivity to TRAIL, DMC and combination of both agents. Cell viability was measured by MTS assay and apoptosis was assessed by Annexin V/PI and acridine orange staining. Caspase activation and protein expression levels were analysed with Western blotting. Death Receptor (DR) cell surface expression levels were quantified by flow cytometry. DR5 expression was increased in U87 cells by ectopic expression using a retroviral plasmid and survivin expression was silenced using specific siRNAs. We demonstrate that A172 expresses mainly DR5 on the cell surface and that these cells show increased sensitivity for the DR5-specific rhTRAIL D269H/E195R variant. In contrast, U87 cells show low DR cell surface levels and is insensitive via both DR4 and DR5. We determined that DMC treatment displays a dose-dependent reduction in cell viability against a number of GBM cells, associated with ER stress induction, as shown by the up-regulation of glucose-regulated protein 78 (GRP78) and CCAAT/-enhancer-binding protein homologous protein (CHOP) in A172 and U87 cells. The dramatic decrease in cell viability is not accompanied by a correspondent increase in Annexin V/PI or caspase activation typically seen in apoptotic or/and necrotic cells within 24h of treatment. Although DMC did not affect DR5 expression in the GBM cells, it increased TRAIL-induced caspase-8 activation in both TRAIL-sensitive and -resistant cells, indicating that DMC potentiates initiator caspase activation in these cells. In A172 cells, sub-toxic concentrations of DMC greatly potentiated TRAIL-induced apoptosis. Furthermore, DMC strongly reduced survivin expression in A172 and U87 cells and silencing of this anti-apoptotic protein partially sensitized cells to TRAIL-induced apoptosis. Our findings corroborate that DMC is a promising agent against GBM, and uncovers a potential synergistic cooperation with TRAIL in this highly malignant cancer.
OsSUV3 transgenic rice maintains higher endogenous levels of plant hormones that mitigates adverse effects of salinity and sustains crop productivity
Authors: Sahoo Ranjan Kumar , Ansari Mohammad Wahid , Tuteja Renu , Tuteja Narendra
Published: September 2014

Background

The SUV3 (suppressor of Var 3) gene encodes a DNA and RNA helicase, which is localized in the mitochondria. Plant SUV3 has not yet been characterized in detail. However, the Arabidopsis ortholog of SUV3 (AT4G14790) has been shown to be involved in embryo sac development. Previously, we have reported that rice SUV3 functions as DNA and RNA helicase and provides salinity stress tolerance by maintaining photosynthesis and antioxidant machinery. Here, we report further analysis of the transgenic OsSUV3 rice plants under salt stress.

Findings

The transgenic OsSUV3 overexpressing rice T1 lines showed significantly higher endogenous content of plant hormones viz., gibberellic acid (GA3), zeatin (Z) and indole-3-acetic acid (IAA) in leaf, stem and root as compared to wild-type (WT), vector control (VC) and antisense (AS) plants under salt (200 mM NaCl) stress condition. A similar trend of endogenous plant hormones profile was also reflected in the T2 generation of OsSUV3 transgenic rice under defined parameters and stress condition.

Conclusions

In response to stress, OsSUV3 rice plants maintained plant hormone levels that regulate the expression of several stress-induced genes and reduce adverse effects of salt on plant growth and development and therefore sustains crop productivity.
VISPA: a computational pipeline for the identification and analysis of genomic vector integration sites
Authors: Calabria Andrea , Leo Simone , Benedicenti Fabrizio , Cesana Daniela , Spinozzi Giulio , Orsini Massimilano , Merella Stefania , Stupka Elia , Zanetti Gianluigi , Montini Eugenio
Published: September 2014

The analysis of the genomic distribution of viral vector genomic integration sites is a key step in hematopoietic stem cell-based gene therapy applications, allowing to assess both the safety and the efficacy of the treatment and to study the basic aspects of hematopoiesis and stem cell biology. Identifying vector integration sites requires ad-hoc bioinformatics tools with stringent requirements in terms of computational efficiency, flexibility, and usability. We developed VISPA (Vector Integration Site Parallel Analysis), a pipeline for automated integration site identification and annotation based on a distributed environment with a simple Galaxy web interface. VISPA was successfully used for the bioinformatics analysis of the follow-up of two lentiviral vector-based hematopoietic stem-cell gene therapy clinical trials. Our pipeline provides a reliable and efficient tool to assess the safety and efficacy of integrating vectors in clinical settings.
Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy
Authors: Goldstein Lee E , McKee Ann C , Stanton Patric K
Published: September 2014

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath.
Tibia bone properties at different time course of ovariectomized rats
Authors: Noor Zairin , Kania Nia , Setiawan Bambang
Published: September 2014

Background

The model of bilaterally ovariectomized rats mimics the accelerated bone loss observed in postmenopausal women due to estrogen deficiency. Although calcium is main mineral in bone, previous study in human showed there is hypermineralization and higher calcium level in hydroxyapatite crystal structure from osteoporosis patients. This study was aimed to investigate the effect of time course ovariectomized on tibia bone turn over markers, mineral elements, hydroxyapatite crystale, mesostructure, and histomorphometry.

Methods

A total of 30 Wistar female rats were randomly assigned into three groups (n = 10 each): control group, ovariectomy group follow up for one month and two month. All animals procedures was according to Animal Ethics Guidelines and approval by ethic committee of the Medical Faculty, Lambung Mangkurat University which obtained prior the study. Expression of osteocalcin (OC) and C-telopeptyde collagen type I (CTX) was analyzed by ELISA method. Tibia bone mineral element was measured using X-Ray Fluorescence. Hydroxyapatite crystale structure was analyzed using X-Ray Diffracttion. Mesostructure was determined using Scanning Electron Microscope. Histomorphometry was analyzed using BoneJ software analyzer. ANOVA test was used to analyze the different level of serum bone turnover markers and bone mineral elements.

Results

Serum OC and CTX were significantly decrease in one month and two month after ovariectomized groups compared to sham-operated group (P < 0.05). The levels Ca, P, Fe, Cu, Zn, Ni, Ca/P, and Cu/Zn were not significantly different in all groups (P > 0.05). The structure of hydroxyapatite crystal in one month and two month after ovariectomized groups were different compared with sham-operated control group. Mesostructure of tibia bone after one and two month ovariectomized procedure significantly different than that in sham-operated rats. The level of trabecular volume were lower significantly on OVX-1 and OVX-2 groups compared with sham group (P < 0.05). The trabecular thickness and spacing were increase significantly on OVX-1 and OVX-2 groups compared with sham group (P < 0.05). The trabecular number were significantly decrease OVX-1 and OVX-2 groups than that sham group (P < 0.05).

Conclusion

We found that two month after ovariectomized decrease serum osteocalcin but not change bone mineral elements in rats. Also, we found the difference of lattice parameter of hydroxyapatite crystale structure and trabecular properties which determined bone mesostructure.
Editorial: The contribution of myeloid-derived suppression to inflammatory disease
Authors: Smith Ava Rhule , Reynolds Joseph M
Published: September 2014

Discussion on the role of Ly6Chigh myeloid cells in suppressing inflammation during colitis.
Medication management following first-episode psychosis in young people: a developmental approach
Authors: Richards Jo
Published: September 2014

Young adults and adolescents who experience a first episode of psychosis are faced with important issues and choices concerning their future mental health. Individual and family psychological treatments and psychosocial supportive measures are now well recognised interventions for this group of individuals. This article considers the complexity surrounding medication management after the initial recovery from psychosis. The discussion focuses particularly on the medical treatments, developmental considerations and roles of psychiatrists in improving outcomes for this group of patients.

Learning Objectives

•

Understand the potential benefits and risks of maintenance antipsychotics for young people recovering from first-episode psychosis.

•

Have an improved knowledge of psychological and developmental concepts that can underpin young people's decision-making regarding maintenance medication for mental illness.

•

Be able to develop a range of (age-appropriate) strategies to assist medication decision-making.
NRP1-mediated Sema3A signals coordinate laminar formation in the developing chick optic tectum
Authors: Watanabe Yuji , Sakuma Chie , Yaginuma Hiroyuki
Published: September 2014

The optic tectum comprises multiple layers, which are formed by radial and tangential migration during development. Here, we report that Neuropilin 1 (NRP1)-mediated Sema3A signals are involved in the process of tectal laminar formation, which is elaborated by tangential migration. In the developing chick tectum, NRP1, a receptor for Sema3A, is expressed in microtubule-associated protein 2 (MAP2)-positive intermediate layers IV and V. Sema3A itself is a diffusible guidance factor and is expressed in the overlying layer VI. Using stable fluorescent labeling of tectal cells, we show that MAP2-positive intermediate layers are formed by the neurons that have been dispersed by tangential migration along the tectal efferent axons. When Sema3A was mis-expressed during laminar formation, local Sema3A repelled the tangential migrants, thus eliminating MAP2-positive neurons that expressed NRP1. Furthermore, in the absence of the MAP2-positive neurons, tectal layers were disorganized into an undulated form, indicating that MAP2-positive intermediate layers are required for proper laminar formation. These results suggest that NRP1-mediated Sema3A signals provide repulsive signals for MAP2-positive neurons to segregate tectal layers, which is important in order to coordinate laminar organization of the optic tectum.
The lipid-transfer protein Nir2 enhances epithelial-mesenchymal transition and facilitates breast cancer metastasis
Authors: Keinan Omer , Kedan Amir , Gavert Nancy , Selitrennik Michael , Kim SoHui , Karn Thomas , Becker Sven , Lev Sima
Published: September 2014

The involvement of Epithelial-mesenchymal transition (EMT) in breast cancer metastasis has been demonstrated by many studies. However, the intracellular proteins and signaling pathways that regulate EMT have not been fully identified. Here we show that the lipid-transfer protein Nir2 enhances EMT in mammary epithelial and breast cancer cells. Nir2 overexpression induces down-regulation of epithelial markers and concomitant up-regulation of mesenchymal markers, while silencing of Nir2 by shRNA has opposite effects. Additionally, Nir2 expression is increased during EMT and affects cell morphology, while Nir2 depletion attenuates growth factor-induced cell migration. These effects of Nir2 on EMT-associated processes are mainly mediated through the PI3K/AKT and the ERK1/2 pathways. Nir2 depletion also inhibits cell invasion in vitro and lung metastasis in animal models. Immunohistochemical analysis of breast cancer tissue samples reveals a correlation between high Nir2 expression and tumor grade, and Kaplan–Meier survival curves correlate Nir2 expression with poor disease outcome. These results suggest that Nir2 not only enhances EMT in vitro and breast cancer metastasis in animal models, but also contributes to breast cancer progression in human patients.
Application of Ionic Liquid-based Nanofluids Containing Gold Nanoparticles in an Electrochemical Sensor for Uric Acid
Authors: Ding Sufang , Lü Xue , Liu Jie , Xü Ranran
Published: September 2014

Under ultrasonic dispersing, an ionic liquid-based nanofluid was prepared by extraction–reduction method using 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6]) as medium, poly(vinylpyrrolidone) as an extractant and a dispersant, and gold nanoparticles (AuNPs) as nanoparticles. A new electrochemical sensor for detecting uric acid (UA) was fabricated by immobilizing the ionic liquid-based nanofluids containing AuNPs on a glassy carbon electrode surface. This sensor exhibited good selectivity, reproducibility, and sensitivity for the direct determination of UA in real human urine samples.
Low-temperature Sintering of Yttria-stabilized Zirconia Using Bismuth–Vanadium Oxide as a Sintering Aid at 800 °C
Authors: Nagao Masahiro , Kobayashi Kazuyo , Hibino Takashi
Published: September 2014

The effect of the addition of copper-doped bismuth–vanadium oxide to yttria-stabilized zirconia (YSZ) on the sinterability and electrical conductivity, especially in reducing atmospheres, has been investigated. When Bi2Cu0.1V0.9O5.35 was used as a sintering aid, the sintering temperature could be reduced to 800 °C, whereas the conventional sintering process requires temperatures above 1300 °C. Although the conductivity of YSZ with 1.5 mol % Bi2Cu0.1V0.9O5.35 was slightly lower than that of pure YSZ sintered at 1300 °C, no PO2 dependence was observed under reducing conditions (e.g., PO2 = 10−5–10−24 atm), which indicates that the electrolyte is applicable to solid-oxide fuel cells.
The immunobiology of cobalt
Authors: Lawrence H. , Deehan D. , Holland J. , Kirby J. , Tyson-Capper A.
Published: September 2014

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression.

These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement.

Cite this article: Bone Joint J 2014; 96-B:1172–7.
An anatomical study of the entry point in the greater trochanter for intramedullary nailing
Authors: Farhang K. , Desai R. , Wilber J. H. , Cooperman D. R. , Liu R. W.
Published: September 2014

Malpositioning of the trochanteric entry point during the introduction of an intramedullary nail may cause iatrogenic fracture or malreduction. Although the optimal point of insertion in the coronal plane has been well described, positioning in the sagittal plane is poorly defined.

The paired femora from 374 cadavers were placed both in the anatomical position and in internal rotation to neutralise femoral anteversion. A marker was placed at the apparent apex of the greater trochanter, and the lateral and anterior offsets from the axis of the femoral shaft were measured on anteroposterior and lateral photographs. Greater trochanteric morphology and trochanteric overhang were graded.

The mean anterior offset of the apex of the trochanter relative to the axis of the femoral shaft was 5.1 mm (sd 4.0) and 4.6 mm (sd 4.2) for the anatomical and neutralised positions, respectively. The mean lateral offset of the apex was 7.1 mm (sd 4.6) and 6.4 mm (sd 4.6), respectively.

Placement of the entry position at the apex of the greater trochanter in the anteroposterior view does not reliably centre an intramedullary nail in the sagittal plane. Based on our findings, the site of insertion should be about 5 mm posterior to the apex of the trochanter to allow for its anterior offset.

Cite this article: Bone Joint J 2014;96-B:1274–81.
Indústria e inovação em Portugal: análise do Community Innovation Survey 2008
Authors: Gama Rui , Fernandes Ricardo
Published: September 2014

Num contexto marcado, quer por rápidas mudanças tecnológicas e sociais quer por uma crescente integração e interdependência das atividades económicas à escala global, a inovação é considerada como o principal motor do desenvolvimento socioeconómico. O Community Innovation Survey 2008 assume-se como uma fonte para que se possa avaliar as atividades e processos de inovação em Portugal, ao nível do produto, do processo e da inovação organizacional e de marketing, bem como dos seus condicionantes, resultados e fragilidades/potencialidades. Tendo por base a análise do contexto socioeconómico português, torna-se essencial perceber como é que a inovação tem sido incorporada neste início de século nas estratégias das empresas e quais os reflexos observados na mudança de comportamentos e padrões territoriais.
Territórios em mudança e os incêndios na interface urbano-florestal. Estudo de caso em Baião
Authors: Fidalgo Emanuel Sardo
Published: September 2014

A presença do elemento humano no seu quotidiano, quer em situações de trabalho ou de lazer, acarreta sempre riscos. Portugal, geograficamente integrado na bacia do Mediterrâneo, possui características favoráveis à deflagração e propagação de incêndios florestais, nomeadamente no estio. Apesar de não serem um fenómeno recente, os incêndios florestais na interface urbano florestal (IUF) têm ganho realce por quanto os seus danos são cada vez maiores, resultado do aumento das áreas com tais características. Atualmente, as dinâmicas territoriais, demográficas e sociais verificadas, nomeadamente nas áreas rurais de montanha do noroeste, resultam num cenário que agravou a ocorrência de incêndios na IUF.
A paisagem urbana de Pombal - dinâmica geográfica, representações simbólicas e apropriações ideológicas
Authors: Fernandes João Luís J.
Published: September 2014

As paisagens, uma síntese entre elementos patrimoniais tradicionais e inovadores que vão deixando marca no espaço geográfico, constituem importantes objetos de análise. Geossímbolos como algumas edificações, a toponímia, a estatuária ou outros elementos espaciais de celebração constroem paisagens nem sempre consensuais e, porque reflectem relações de poder, são territórios em muitos casos contestados. Embora seja uma cidade de baixa densidade e escassa polarização, Pombal é um complexo nem sempre bem articulado de elementos patrimoniais, de geossímbolos que expressam narrativas locais contíguos aos que afirmam outras escalas. O enquadramento rural, os ciclos de emigração e de industrialização e a mais recente e ténue deriva pós-moderna, quase sempre de celebração e nostalgia do passado, acrescentaram heterogeneidade patrimonial a este espaço urbano.
Três décadas de incêndios florestais em Portugal: incidência regional e principais fatores responsáveis
Authors: Nunes Adélia , Lourenço Luciano , Bento-Gonçalves António , Vieira António
Published: September 2014

Os incêndios florestais constituem, em Portugal continental, o mais relevante problema ambiental e, frequentemente, têm sido explicados pelas características climáticas e meteorológicas do nosso território, por estas afetarem tanto o desenvolvimento como a inflamabilidade dos combustíveis. Todavia, o perfil do clima português, mediterrâneo, não justifica, por si só, nem o elevado número de ignições, nem a vasta área ardida ao longo destas últimas três décadas. Com o presente trabalho, pretende-se avaliar a evolução e as tendências da distribuição regional, quer das ocorrências quer das áreas ardidas em Portugal continental, desde 1981 até 2010, bem como identificar inter-relações, ao nível do distrito, entre variáveis biofísicas, trajectórias sócio-demográficas e incidência de incêndios florestais.
Medidas de emergência para proteção do solo após incêndios florestais. Resultados preliminares de algumas experiências na serra do Gerês
Authors: Bento-Gonçalves António , Vieira António , Lourenço Luciano , Salgado José , Castro Américo , Ferreira-Leite Flora , Araújo Bruno , Nunes Adélia
Published: September 2014

Uma das consequências dos incêndios florestais é o aumento da erosão da camada superior dos solos, onde se localizam, na maioria dos solos portugueses, os únicos nutrientes existentes. Num clima com características mediterrâneas, como é o caso do português, a máxima exportação dos sedimentos acontece, normalmente, nos primeiros 4 a 6 meses depois dos incêndios. Assim, o projeto Soil Protec1 (Medidas de Emergência para Proteção de Solos após Incêndios Florestais) visa testar medidas de emergência, de baixo custo, a aplicar na proteção de solos, imediatamente após os incêndios florestais de baixa/média severidade, com base nas medições efetuadas em povoamentos de Pinus pinaster na serra do Gerês.
Incêndios florestais no distrito da Guarda. Fatores desencadeantes e consequências ambientais
Authors: Henriques Susete Dos Anjos , Lourenço Luciano
Published: September 2014

Portugal tem sido fustigado, ao longo das últimas décadas, por numerosos incêndios florestais. A área ardida tem vindo a aumentar consideravelmente, sendo o país do Sul da Europa Mediterrânea com a maior percentagem de área queimada. Ao examinarmos a distribuição geográfica das áreas ardidas, em termos de NUT’s II, verificamos que a Região Centro tem sido a mais flagelada. Descendo a uma escala de mais pormenor, observa-se que o distrito da Guarda constitui o território mais afetado pelas chamas, motivo pelo qual centramos este estudo nesse espaço. Pretende-se, pois, efetuar uma análise diacrónica da manifestação do risco dendrocaustológico no distrito da Guarda, no período compreendido entre os anos hidrológicos de 1980/81 e 2009/10, com o objetivo de perceber como se têm conjugado os fatores desencadeantes. Por outro lado, após a ocorrência de incêndios florestais, registam-se mudanças na ocupação do solo, pelo que, outro dos objetivos, passa pelo estabelecimento das formas de evolução da paisagem. Deste modo, com o presente estudo procura-se contribuir para uma melhor compreensão das diversas ações que interferem com o risco de incêndio florestal, assim como, se deseja analisar a nova paisagem que, progressivamente, vai ganhando terreno após a passagem dos incêndios florestais.
Marketing territorial e imagem: o caso da Ilha Graciosa
Authors: Espínola Paulo , Fernandes João Luís Jesus
Published: September 2014

Numa época de incertezas, aumento das mobilidades espaciais e crescente desregulação, é importante fazer uma reflexão estratégica e perspetivar o futuro dos lugares. O espaço geográfico estudado – a ilha Graciosa – é um território nacional remoto que, pela sua insularidade, apresenta alguns constrangimentos, desde logo resultantes das distâncias médias a percorrer. Contudo, a posição geográfica e a respetiva condição insular, podem apresentar as mais-valias de lugares que se associam às imagens idealizadas de felicidade e bem-estar. O objetivo principal desta comunicação passa por avaliar a capacidade de uma (possível) estratégia de marketing territorial como forma de potenciar a imagem da ilha Graciosa numa perspetiva de desenvolvimento local. Em termos metodológicos, para além da pesquisa bibliográfica e de entrevistas a agentes locais, tira-se partido de um inquérito colocado a um universo de população não açoriana.
A importância das obras de correção torrencial no controlo da erosão hídrica. Exemplos da bacia hidrográfica do rio Lis
Authors: Fernandes Sofia , Lourenço Luciano
Published: September 2014

A correção torrencial foi aplicada, em Portugal, a numerosos pequenos cursos de água com regime torrencial, caracterizados por uma intensa atividade erosiva nas cabeceiras e um forte assoreamento dos leitos nas áreas vestibulares.A importância destes processos erosivos na modelação da paisagem está bem patente ao longo do rio Lis e seus afluentes, que, por isso, foram dos mais intervencionados em termos de obras de correção torrencial.