bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA binding properties of the US11 protein from four primate simplexviruses
Authors: Tohme Sarah , Cukier Cyprian D , Severini Alberto 
Published: November 2011

Abstract

Background
The protein encoded by the Us11 gene of herpes simplex viruses is a dsRNA binding protein which inhibits protein kinase R activity, thereby preventing the interferon-induced shut down of protein synthesis following viral infection. Us11 protein is not essential for infectivity in vitro and in mice in herpes simplex virus type 1 (HSV1), however this virus has a second, and apparently more important, inhibitor of PKR activity, the γ134.5 protein. Recently sequenced simian simplexviruses SA8, HVP2 and B virus do not have an ORF corresponding to the γ134.5 protein, yet they have similar, or greater, infectivity as HSV1 and HSV2.

Methods
We have expressed the US11 proteins of the simplexviruses HSV1, HSV2, HVP2 and B virus and measured their abilities to bind dsRNA, in order to investigate possible differences that could complement the absence of the γ134.5 protein. We employed a filter binding technique that allows binding of the Us11 protein under condition of excess dsRNA substrate and therefore a measurement of the true Kd value of Us11-dsRNA binding.

Results and Conclusions
The results show a Kd of binding in the range of 0.89 nM to 1.82 nM, with no significant difference among the four Us11 proteins.
Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes
Authors: Kondo Hiroyo , Fujino Hidemi , Murakami Shinichiro , Nagatomo Fumiko , Roy Roland R , Ishihara Akihiko 
Published: November 2011

Abstract
Based on findings obtained using two-dimensional capillary analyses on tissue cross-sections, diabetes has been shown to be associated with a high risk for microangiopathy and capillary regression in skeletal muscles. We visualized the three-dimensional architecture of the capillary networks in the soleus muscle of non-obese Goto-Kakizaki (GK) rats with type 2 diabetes and compared them with those of control Wistar rats to provide novel information, e.g., capillary volume, on the capillary networks. In addition, we examined pro- and anti-angiogenic gene expression levels in the soleus muscle of GK rats using TaqMan probe-based real-time PCR. As expected, plasma glucose levels were higher and insulin levels lower in GK than control rats. The three-dimensional architecture of the capillary networks was regressed and capillary volume was smaller in the soleus muscle of GK compared to control rats. The mRNA expression levels of the pro-angiogenic factors HIF-1α, KDR, Flt-1, ANG-1, and Tie-2 were lower, whereas the level of the anti-angiogenic factor TSP-1 was higher in GK than control rats. These data suggest that a decrease in pro-angiogenic and increase in anti-angiogenic factors may play an important role in type 2 diabetes-induced muscle circulatory complications.
The impact of clinical data on the evaluation of tibial fracture healing
Authors: Dijkman Bernadette G , Busse Jason W , Walter Stephen D , Bhandari Mohit ,   the TRUST Investigators
Published: November 2011

AbstractBackgroundRadiographic healing is a common outcome measure in orthopedic trials and adjudication by outcome assessors is often conducted on the basis of plain films alone. The degree to which this process reflects clinical practice, in which both plain films and clinical notes are available, is uncertain. We explored the effect of adding clinical notes to radiographs in the adjudication process of a feasibility trial of tibial shaft fractures.MethodsRadiographic and clinical data from a multicenter randomized controlled trial of 51 patients with operatively treated tibial fractures formed the basis of the study data. At the completion of the trial, serial radiographs (anteroposterior and lateral) were independently evaluated for progression of fracture healing, defined as bridging of at least 3 of 4 cortices, by an adjudication committee comprised of 3 blinded orthopaedic trauma surgeons. Immediately after determination of radiographic time to healing, each surgeon was provided with clinical notes associated with each radiographic follow up visit and asked to re-visit their initial impression. Consensus was achieved for both adjudications. We calculated the percentage of time to healing consensus decisions that changed after evaluation of clinical notes. We further examined the contents of clinical notes and their relative influence on the committee's decisions.Results47 of 51 patients were determined to have healed radiographically during the trial follow-up period, and consideration of clinical notes resulted in a change of 40% (19 of 47) of time to healing consensus decisions; however, revised decisions were equally likely to support an earlier or a later time to healing. Clinical notes that resulted in a change to either a 'healed' or a 'not healed' decision contained significantly more comments of either pain resolution or deterioration, respectively, resumption of or failure to resume weightbearing, or either return or no return to work/pre-injury activities (p < 0.001).ConclusionsThe addition of clinical notes to the adjudication of radiographic fracture healing changed the outcome decision in a substantial number of cases. Orthopedic trialists should consider the addition of clinical notes to adjudication material in studies of fracture healing in order to enhance the generalizability of their results.Trial RegistrationThe TRUST trial was registered [IDNCT00667849] athttp://clinicaltrials.gov/ct2/show/NCT00667849
Osseointegration of porous titanium implants with and without electrochemically deposited DCPD coating in an ovine model
Authors: Chen Dong , Bertollo Nicky , Lau Abe , Taki Naoya , Nishino Tomofumi , Mishima Hajime , Kawamura Haruo , Walsh William R 
Published: November 2011

Abstract

Background
Uncemented fixation of components in joint arthroplasty is achieved primarily through de novo bone formation at the bone-implant interface and establishment of a biological and mechanical interlock. In order to enhance bone-implant integration osteoconductive coatings and the methods of application thereof are continuously being developed and applied to highly porous and roughened implant substrates. In this study the effects of an electrochemically-deposited dicalcium phosphate dihydrate (DCPD) coating of a porous substrate on implant osseointegration was assessed using a standard uncemented implant fixation model in sheep.

Methods
Plasma sprayed titanium implants with and without a DCPD coating were inserted into defects drilled into the cancellous and cortical sites of the femur and tibia. Cancellous implants were inserted in a press-fit scenario whilst cortical implants were inserted in a line-to-line fit. Specimens were retrieved at 1, 2, 4, 8 and 12 weeks postoperatively. Interfacial shear-strength of the cortical sites was assessed using a push-out test, whilst bone ingrowth, ongrowth and remodelling were investigated using histologic and histomorphometric endpoints.

Results
DCPD coating significantly improved cancellous bone ingrowth at 4 weeks but had no significant effect on mechanical stability in cortical bone up to 12 weeks postoperatively. Whilst a significant reduction in cancellous bone ongrowth was observed from 4 to 12 weeks for the DCPD coating, no other statistically significant differences in ongrowth or ingrowth in either the cancellous or cortical sites were observed between TiPS and DCPD groups.

Conclusion
The application of a DCPD coating to porous titanium substrates may improve the extent of cancellous bone ingrowth in the early postoperative phase following uncemented arthroplasty.
Network analysis of microRNAs and their regulation in human ovarian cancer
Authors: Schmeier Sebastian , Schaefer Ulf , Essack Magbubah , Bajic Vladimir B 
Published: November 2011

Abstract

Background
MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.

Results
We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.

Conclusions
We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our understanding of the molecular mechanisms underlying human cancer development and OC in particular.
Transcription factor NF-Y is involved in differentiation of R7 photoreceptor cell in Drosophila
Authors: Yoshioka Yasuhide , Ly Luong Linh , Yamaguchi Masamitsu 
Published: November 2011

Summary
The CCAAT motif-binding factor NF-Y consists of three different subunits, NF-YA, NF-YB and NF-YC. Knockdown of Drosophila NF-YA (dNF-YA) in eye discs with GMR-GAL4 and UAS-dNF-YAIR resulted in a rough eye phenotype and monitoring of differentiation of photoreceptor cells by LacZ expression in seven up-LacZ and deadpan-lacZ enhancer trap lines revealed associated loss of R7 photoreceptor signals. In line with differentiation of R7 being regulated by the sevenless (sev) gene and the MAPK cascade, the rough eye phenotype and loss of R7 signals in dNF-YA-knockdown flies were rescued by expression of the sev gene, or the D-raf gene, a downstream component of the MAPK cascade. The sev gene promoter contains two dNF-Y-binding consensus sequences which play positive roles in promoter activity. In chromatin immunoprecipitation assays with anti-dNF-YA antibody and S2 cells, the sev gene promoter region containing the NF-Y consensus was effectively amplified in immunoprecipitates from transgenic flies by polymerase chain reaction, indicating that dNF-Y is necessary for appropriate sev expression and involved in R7 photoreceptor cell development.
Cane toads lack physiological enhancements for dispersal at the invasive front in Northern Australia
Authors: Tracy Christopher R. , Christian Keith A. , Baldwin John , Phillips Ben L. 
Published: November 2011

SummaryMany invasive species have evolved behavioural and morphological characteristics that facilitate their dispersal into new areas, but it is unclear how selection on this level of the phenotype filters through to the underlying physiology. Cane toads have been dispersing westward across northern tropical Australia for more than 70 years. Previous studies of cane toads at the invasive front have identified several behavioural, morphological and locomotory characteristics that have evolved to facilitate dispersal of toads. We assessed a range of physiological characteristics associated with locomotory abilities in toads from the long-established, east coast of Australia, from the invasive front, and from a site in between these locations. We measured time to exhaustion and respiratory gases of toads exercising on a treadmill, time to recovery from exhaustion, blood properties (lactate, haematocrit, haemoglobin, red blood cell count, blood cell volume), and muscle properties associated with locomotion (activities of the enzymes citrate synthase and lactate dehydrogenase, and pH buffering capacity). None of the measured physiological parameters supported the hypothesis that toads from the invasive front possess physiological adaptations that facilitate dispersal compared to toads from areas colonised in the past. The strongest difference among the three groups of toads, time to exhaustion, showed exactly the opposite trend; toads from the long-established populations in the east coast had the longest time to exhaustion. Successful colonisers can employ many characteristics to facilitate their dispersal, so the extent to which behaviour, morphology and physiology co-evolve remains an interesting question. However, in the present case at least, behavioural adaptations do not appear to have altered the organism's underlying physiology.
High-Yield Synthesis of Dendrimers through Alternate Multiaddition Reactions with Commercially Available Reagents
Authors: Aoki Ken’ichi , Ichimura Kunihiro 
Published: November 2011

Abstract
An alternate multiaddition (AMA) process consisting of Michael addition and urethane formation is proposed to achieve the quantity synthesis of dendrimers without by-product formation and any weight loss by using commercially available compounds. α-Thioglycerol (TG) was added to pentaerythritol tetraacrylate (PETA) to give the corresponding octaol, but the subsequent reaction with 1,1-bis(acryloyloxymethyl)ethyl isocyanate (BEI) resulted in incomplete urethane formation because of the steric effect of the secondary OH groups. The replacement of BEI with 2-isocyanatoethyl acrylate (AOI) improved the efficiency of the addition of NCO to the secondary OH groups, but an excess amount of AOI was required. Subsequently, we employed the combination of PETA, 2-sulfanylethanol (SE), and BEI. The addition of SE to PETA produced readily the tetraol, which was reacted with BEI to afford dendritic octaacrylate (Ac8b). The repetition of the two addition reactions gave dendritic octaol and hexadecylacrylate (Ac16b), respectively, in large scales. The base-catalyzed Michael addition of 2-naphthalenethiol to acrylate residues of Ac8a and Ac16b gave naphthylthio-terminated dendrimers N8b and N16b, respectively, which were purified by column chromatography. GPC as well as UV-spectroscopic analysis of N8b and N16b revealed that N8b is reasonably monodispersed whereas the purity of N16b is slightly reduced.
Diphenyl Diselenide-Assisted α-Phenylthiolation of Carbonyl Compounds with Diphenyl Disulfide
Authors: Anbou Hiroaki , Umeda Rui , Nishiyama Yutaka 
Published: November 2011

Abstract
For the cesium carbonate-catalyzed α-phenylthiolation of carbonyl compounds with diphenyl disulfide, the yields of the α-phenylthio carbonyl compounds were dramatically improved by the addition of a catalytic amount of diphenyl diselenide.
Synthesis and Optical Properties of Pyridino End-Capped Oligothiophenes
Authors: Hwang Yong-Mook , Ohshita Joji , Mizumo Tomonobu , Yoshida Hiroto , Kunugi Yoshihito , Sugioka Takashi 
Published: November 2011

Abstract
Oligothiophenes end-capped with fused pyridino units were synthesized by means of the Stille coupling and their optical properties were studied. These compounds show absorption maxima and edges at 324–374 nm and 3.10–2.76 eV, respectively, depending on the oligothiophene chain lengths. DFT calculations indicate that both the HOMO and LUMO levels are lowered by the introduction of the pyridino units.
Increased length of inpatient stay and poor clinical coding: audit of patients with diabetes
Authors: Daultrey Harriet , Gooday Erine , Dhatariya Ketan 
Published: November 2011

Objectives People with diabetes stay in hospital for longer than those without diabetes for similar conditions. Clinical coding is poor across all specialties. Inpatients with diabetes often have unrecognized foot problems. We wanted to look at the relationships between these factors. Design A single day audit, looking at the prevalence of diabetes in all adult inpatients. Also looking at their feet to find out how many were high-risk or had existing problems. Setting A 998-bed university teaching hospital. Participants All adult inpatients. Main outcome measures (a) To see if patients with diabetes and foot problems were in hospital for longer than the national average length of stay compared with national data; (b) to see if there were people in hospital with acute foot problems who were not known to the specialist diabetic foot team; and (c) to assess the accuracy of clinical coding. Results We identified 110 people with diabetes. However, discharge coding data for inpatients on that day showed 119 people with diabetes. Length of stay (LOS) was substantially higher for those with diabetes compared to those without (± SD) at 22.39 (22.26) days, vs. 11.68 (6.46) ( P < 0.001). Finally, clinical coding was poor with some people who had been identified as having diabetes on the audit, who were not coded as such on discharge. Conclusion Clinical coding – which is dependent on discharge summaries – poorly reflects diagnoses. Additionally, length of stay is significantly longer than previous estimates. The discrepancy between coding and diagnosis needs addressing by increasing the levels of awareness and education of coders and physicians. We suggest that our data be used by healthcare planners when deciding on future tariffs.
Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome
Authors: Trementino Laura , Appolloni Gloria , Concettoni Carolina , Cardinaletti Marina , Boscaro Marco , Arnaldi Giorgio 
Published: November 2011

ObjectiveGlucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the fourGR(NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile.Patients and methodsSixty-one patients with CS and 71 sex- and age-matched HC were genotyped.ResultsBclI variant was markedly higher in patients with CS compared with HC (62 vs 41%,P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed.In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found.In contrast, A3669GGRcarriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%,P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl,P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl,P=0.01). The negative association between diabetes and A3669GGRpolymorphism remained significant when data were adjusted for potential confounding factors.ConclusionsThe A3669G polymorphism of theGRgene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes.
Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study
Authors: Jakob F , Oertel H , Langdahl B , Ljunggren O , Barrett A , Karras D , Walsh J B , Fahrleitner-Pammer A , Rajzbaum G , Barker C , Lems W F , Marin F 
Published: November 2011

ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months.DesignProspective, multinational, and observational study.MethodsData on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model.ResultsOf the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to <18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed.ConclusionsPostmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.
Association of hypogonadism with vitamin D status: the European Male Ageing Study
Authors: Lee David M , Tajar Abdelouahid , Pye Stephen R , Boonen Steven , Vanderschueren Dirk , Bouillon Roger , O'Neill Terence W , Bartfai Gyorgy , Casanueva Felipe F , Finn Joseph D , Forti Gianni , Giwercman Aleksander , Han Thang S , Huhtaniemi Ilpo T , Kula Krzysztof , Lean Michael E J , Pendleton Neil , Punab Margus , Wu Frederick C W , _ _ 
Published: November 2011

ObjectiveInterrelationships between hormones of the hypothalamic–pituitary–testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men.Design and methodsCross-sectional survey of 3369 community-dwelling men aged 40–79 years in eight European centres. Testosterone (T), oestradiol (E2) and dihydrotestosterone were measured by gas chromatography–mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression.ResultsIn univariate analyses, free T levels were lower (P=0.02) and E2and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E2and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52,P=0.03) and secondary hypogonadism (RRR=1.16,P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001).ConclusionsSecondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.