bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological characteristics of freezing of gait in autopsy‐confirmed Parkinson's disease
Authors: Virmani Tuhin , Moskowitz Carol B. , Vonsattel Jean‐Paul , Fahn Stanley 
Published: August 2015

ABSTRACTBackgroundTwenty‐five percent to sixty percent of Parkinson's disease (PD) patients reportedly have freezing of gait, leading to impaired mobility, falls, and decreased quality of life. Several factors have been associated with gait freezing in PD patients. We analyze for these factors in autopsy‐proven PD patients.MethodsWe performed a chart review of 58 patients with pathologically confirmed PD based on substantia nigra Lewy bodies. Freezing of gait was defined as a score of 1 or more on Item 14 of the Unified Parkinson's Disease Rating Scale or if documented on examination. Serial office notes and scales were used to determine onset and progression of motor and non‐motor symptoms.ResultsPatients had been followed up for an average of 20 visits over 9 y. The mean onset of gait freezing was 9.3 y from initial motor symptoms. Patients with earlier gait freezing more commonly had initial gait difficulties and developed postural instability, dyskinesias, memory impairment, hallucinations, and vivid dreams earlier during the disease course. Early onset of hallucinations was correlated with more rapid progression of gait freezing. Maximal equivalent levodopa dose was not correlated with earlier onset or progression of gait freezing. Progressive and more severe gait freezing trended toward higher‐severity Lewy body disease on postmortem examination.ConclusionsEarly onset and rapid progression of freezing of gait in this cohort were correlated with early cognitive impairment and hallucinations that are potential clinical hallmarks of cortical Lewy bodies. The gradual worsening and severity of gait freezing correlated with the density of cortical Lewy body–containing neurons. © 2015 International Parkinson and Movement Disorder Society
Cdk8 deletion in the ApcMin murine tumour model represses EZH2 activity and accelerates tumourigenesis
Authors: McCleland Mark L , Soukup Tim M , Liu Scot D , Esensten Jonathan H , de Sousa e Melo Felipe , Yaylaoglu Murat , Warming Soren , Roose‐Girma Merone , Firestein Ron 
Published: August 2015

AbstractCDK8 is a dissociable kinase module of the Mediator complex and has been shown to play an important role in transcriptional regulation in organisms as diverse as yeast and humans. Recent studies suggest that CDK8 functions as an oncoprotein in melanoma and colon cancer. Importantly, these studies were conducted using in vitro cell line models and the role of CDK8 in tumourigenesis in vivo has not been explored. We have generated a mouse with a Cdk8 conditional knockout allele and examined the consequences of Cdk8 loss on normal tissue homeostasis and tumour development in vivo. Cdk8 deletion in the young adult mouse did not induce any gross or histopathological abnormalities, implying that Cdk8 is largely dispensable for somatic cellular homeostasis. In contrast, Cdk8 deletion in the ApcMin intestinal tumour model shortened the animals' survival and increased tumour burden. Although Cdk8 deletion did not affect tumour initiation, intestinal tumour size and growth rate were significantly increased in Cdk8‐null animals. Transcriptome analysis performed on Cdk8‐null intestinal cells revealed up‐regulation of genes that are governed by the Polycomb group (PcG) complex. In support of these findings, Cdk8‐null intestinal cells and tumours displayed a reduction in histone H3K27 trimethylation, both globally and at the promoters of a number of PcG‐regulated genes involved in oncogenic signalling. Together, our findings uncover a tumour suppressor function for CDK8 in vivo and suggest that the role of CDK8 activity in driving oncogenesis is context‐specific. Sequencing data were deposited at GEO (Accession No. GSE71385). Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Loss of RUNX3 expression promotes cancer‐associated bone destruction by regulating CCL5, CCL19 and CXCL11 in non‐small cell lung cancer
Authors: Kim Hyun‐Jeong , Park Junhee , Lee Sun Kyoung , Kim Ki Rim , Park Kwang‐Kyun , Chung Won‐Yoon 
Published: August 2015

AbstractNon‐small cell lung cancer (NSCLC) frequently metastasizes to bone, which is associated with significant morbidity and a dismal prognosis. RUNX3 functions as a tumour suppressor in lung cancer and loss of expression occurs more frequently in invasive lung adenocarcinoma than in pre‐invasive lesions. Here, we show that RUNX3 and RUNX3‐regulated chemokines are linked to NSCLC‐mediated bone resorption. Notably, the receptor activator of nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, an index of osteoclastogenic stimulation, was significantly increased in human osteoblastic cells treated with conditioned media derived from RUNX3‐knockdown NSCLC cells. We aimed to identify RUNX3‐regulated factors that modify the osteoblastic RANKL/OPG ratio and found that RUNX3 knockdown led to CCL5 up‐regulation and down‐regulation of CCL19 and CXCL11 in NSCLC cells. Tumour size was noticeably increased and more severe osteolytic lesions were induced in the calvaria and tibiae of mice that received RUNX3‐knockdown cells. In response to RUNX3 knockdown, serum and tissue levels of CCL5 increased, whereas CCL19 and CXCL11 decreased. Furthermore, CCL5 increased the proliferation, migration, and invasion of lung cancer cells in a dose‐dependent manner; however, CCL19 and CXCL11 did not show any significant effects. The RANKL/OPG ratio in osteoblastic cells was increased by CCL5 but reduced by CCL19 and CXCL11. CCL5 promoted osteoclast differentiation, but CCL19 and CXCL11 reduced osteoclastogenesis in RANKL‐treated bone marrow macrophages. These findings suggest that RUNX3 and related chemokines are useful markers for the prediction and/or treatment of NSCLC‐induced bone destruction. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Eosinophilia and Fever with Levetiracetam: A Case Report
Authors: Flannery Alexander H. , Willey Maria D. , Thompson Bastin Melissa L. , Buch Ketan P. , Bensadoun Eric S. 
Published: August 2015

Levetiracetam is considered by many clinicians to be one of the most benign antiepileptic medications available. We report the case of a 24‐year‐old man presenting with seizures for which he was started on levetiracetam. Despite an extensive work‐up and treatment of possible infectious and noninfectious issues, the patient remained intermittently febrile. When a marked peripheral eosinophilia was noted, the patient's levetiracetam was discontinued and phenytoin prescribed. The fever resolved within 24 hours, and the patient's eosinophilia count returned to normal limits following discharge back to his long‐term care facility. We estimate the probability of this reaction related to levetiracetam as probable based on a score of 7 on the Naranjo scale. Clinicians should be aware of the possibility that levetiracetam may be an offending agent in a patient with unexplained fever and eosinophilia. These may be early signs of the progression to a more serious drug hypersensitivity reaction, such as drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome.
GATA1 directly mediates interactions with closely spaced pseudopalindromic but not distantly spaced double GATA sites on DNA
Authors: Wilkinson‐White Lorna , Lester Krystal L. , Ripin Nina , Jacques David A. , Mitchell Guss J. , Matthews Jacqueline M. 
Published: August 2015

AbstractThe transcription factor GATA1 helps regulate the expression of thousands of genes involved in blood development, by binding to single or double GATA sites on DNA. An important part of gene activation is chromatin looping, the bringing together of DNA elements that lie up to many thousands of basepairs apart in the genome. It was recently suggested, based on studies of the closely related protein GATA3, that GATA‐mediated looping may involve interactions of each of two zinc fingers (ZF) with distantly spaced DNA elements. Here we present a structure of the GATA1 ZF region bound to pseudopalindromic double GATA site DNA, which is structurally equivalent to a recently‐solved GATA3‐DNA complex. However, extensive analysis of GATA1‐DNA binding indicates that although the N‐terminal ZF (NF) can modulate GATA1‐DNA binding, under physiological conditions the NF binds DNA so poorly that it cannot play a direct role in DNA‐looping. Rather, the ability of the NF to stabilize transcriptional complexes through protein–protein interactions, and thereby recruit looping factors such as Ldb1, provides a more compelling model for GATA‐mediated looping.
Structure mediation in substrate binding and post‐translational processing of penicillin acylases: Information from mutant structures of Kluyvera citrophila penicillin G acylase
Authors: Chand Deepak , Varshney NishantKumar , Ramasamy Sureshkumar , Panigrahi Priyabrata , Brannigan James A. , Wilkinson Anthony J. , Suresh C. G. 
Published: August 2015

AbstractPenicillin acylases are industrially important enzymes for the production of 6‐APA, which is used extensively in the synthesis of secondary antibiotics. The enzyme translates into an inactive single chain precursor that subsequently gets processed by the removal of a spacer peptide connecting the chains of the mature active heterodimer. We have cloned the penicillin G acylase from Kluyvera citrophila (KcPGA) and prepared two mutants by site‐directed mutagenesis. Replacement of N‐terminal serine of the β‐subunit with cysteine (Serβ1Cys) resulted in a fully processed but inactive enzyme. The second mutant in which this serine is replaced by glycine (Serβ1Gly) remained in the unprocessed and inactive form. The crystals of both mutants belonged to space group P1 with four molecules in the asymmetric unit. The three‐dimensional structures of these mutants were refined at resolutions 2.8 and 2.5 Å, respectively. Comparison of these structures with similar structures of Escherichia coli PGA (EcPGA) revealed various conformational changes that lead to autocatalytic processing and consequent removal of the spacer peptide. The large displacements of residues such as Arg168 and Arg477 toward the N‐terminal cleavage site of the spacer peptide or the conformational changes of Arg145 and Phe146 near the active site in these structures suggested probable steps in the processing dynamics. A comparison between the structures of the processed Serβ1Cys mutant and that of the processed form of EcPGA showed conformational differences in residues Argα145, Pheα146, and Pheβ24 at the substrate binding pocket. Three conformational transitions of Argα145 and Pheα146 residues were seen when processed and unprocessed forms of KcPGA were compared with the substrate bound structure of EcPGA. Structure mediation in activity difference between KcPGA and EcPGA toward acyl homoserine lactone (AHL) is elucidated.
Evidence that the conservation reserve program slowed population declines of pheasants on a changing landscape in Nebraska, USA
Authors: Hiller Tim L. , Taylor J. Scott , Lusk Jeffrey J. , Powell Larkin A. , Tyre Andrew J. 
Published: August 2015

ABSTRACTNebraska's agricultural landscape underwent dramatic changes during the last half of the 20th century. Since 1986, the Conservation Reserve Program (CRP) has led to an increase in grassland cover, but pheasant (Phasianus colchicus) populations have been decreasing for decades. We hypothesized that if the CRP positively affected pheasant populations in Nebraska, USA, we should see effects reflected in pheasant population trend data. Thus, we examined one of the longest‐running population time‐series data sets in Nebraska, the rural mail‐carrier survey. We averaged pheasant counts annually over the entire state during 1951–2007. We fit 4 simple demographic models to the statewide population abundance index and used information‐theoretic methods to select the model with the most support. We found strong evidence that a logistic model with a 2‐period decline (transition year of 1986 based on optimization) in carrying capacity described the data better than all other models (e.g., AICc wi = 0.99). This model indicated an annual decline in our population index of approximately 15% until 1986, but then a slower annual decline of approximately 5% after 1986. The transition year (1986) corresponded with the date of implementation of the CRP. No other known effect occurred near the transition year and there is no evidence that other potential factors (e.g., disease, changes in predator communities) contributed to large‐scale population declines during our study. The introduction of the CRP may have positively affected pheasant populations, but the effects are so far insufficient to reverse the decline of pheasants in Nebraska. © 2015 The Wildlife Society.
Characterization of shape and dimensional accuracy of incrementally formed titanium sheet parts with intermediate curvatures between two feature types
Authors: Behera Amar Kumar , Lu Bin , Ou Hengan 
Published: August 2015

Abstract
Single point incremental forming (SPIF) is a relatively new manufacturing process that has been recently used to form medical grade titanium sheets for implant devices. However, one limitation of the SPIF process may be characterized by dimensional inaccuracies of the final part as compared with the original designed part model. Elimination of these inaccuracies is critical to forming medical implants to meet required tolerances. Prior work on accuracy characterization has shown that feature behavior is important in predicting accuracy. In this study, a set of basic geometric shapes consisting of ruled and freeform features were formed using SPIF to characterize the dimensional inaccuracies of grade 1 titanium sheet parts. Response surface functions using multivariate adaptive regression splines (MARS) are then generated to model the deviations at individual vertices of the STL model of the part as a function of geometric shape parameters such as curvature, depth, distance to feature borders, wall angle, etc. The generated response functions are further used to predict dimensional deviations in a specific clinical implant case where the curvatures in the part lie between that of ruled features and freeform features. It is shown that a mixed-MARS response surface model using a weighted average of the ruled and freeform surface models can be used for such a case to improve the mean prediction accuracy within ±0.5 mm. The predicted deviations show a reasonable match with the actual formed shape for the implant case and are used to generate optimized tool paths for minimized shape and dimensional inaccuracy. Further, an implant part is then made using the accuracy characterization functions for improved accuracy. The results show an improvement in shape and dimensional accuracy of incrementally formed titanium medical implants.
Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus
Authors: Li Zan , Qi XiaoLe , Ren XianGang , Cui Lei , Wang XiaoMei , Zhu Ping 
Published: August 2015

Abstract
Infectious bursal disease virus (IBDV) poses a significant threat to the poultry industry. Viral protein 2 (VP2), the major structural protein of IBDV, has been subjected to frequent mutations that have imparted tremendous genetic diversity to the virus. To determine how amino acid mutations may affect the virulence of IBDV, we built a structural model of VP2 of a very virulent strain of IBDV identified in China, vvIBDV Gx, and performed a molecular dynamics simulation of the interaction between virulence sites. The study showed that the amino acid substitutions that distinguish vvIBDV from attenuated IBDV (H253Q and T284A) favor a hydrophobic and flexible conformation of β-barrel loops in VP2, which could promote interactions between the virus and potential IBDV-specific receptors. Population sequence analysis revealed that the IBDV strains prevalent in East Asia show a significant signal of positive selection at virulence sites 253 and 284. In addition, a signal of co-evolution between sites 253 and 284 was identified. These results suggest that changes in the virulence of IBDV may result from both the interaction and the co-evolution of multiple amino acid substitutions at virulence sites.
Effects of deep cryogenic treatment on mechanical and tribological properties of AISI D3 tool steel
Authors: Khun Nay Win , Liu Erjia , Tan Adrian Wei Yee , Senthilkumar D. , Albert Bensely , Mohan Lal D. 
Published: August 2015

Abstract
In this study, the effects of deep cryogenic treatment (DCT) on the mechanical and tribological properties of AISI D3 tool steel were investigated together with a systematic correlation between their hardness and wear resistance. It was found that conventionally heat treated AISI D3 tool steel samples were significantly hardened via an additional DCT, which was attributed to the more retained austenite elimination, more homogenized carbide distribution and more reduction in carbide size in the samples. As a result, the hardened AISI D3 samples exhibited reductions in their friction and wear during rubbing against alumina and 100Cr6 steel balls under different normal loads due to the effectively hindered removal of surface materials. The results clearly showed that the DCT was an effective way to improve the mechanical and tribological properties of the AISI D3 tool steel samples as the tribological performance of the tool steel samples was significantly influenced by their hardness.
Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence
Authors: DeVilbiss Elizabeth A. , Gardner Renee M. , Newschaffer Craig J. , Lee Brian K. 
Published: August 2015

AbstractEmerging evidence from epidemiological studies supports the notion that maternal folate status regulated by dietary and genetic factors early in pregnancy may influence the risk of autism spectrum disorders (ASD). In this review, we provide an overview of what is known about the role of folate in the aetiology of neurodevelopmental disorders; summarise relevant biological, genetic and epigenetic mechanisms; and synthesise the evidence from human observational studies and randomised controlled trials that have examined the relationship between maternal folate and ASD or related traits. Much of the existing literature on this topic is subject to limitations such as potential confounding by healthy behaviours and other dietary factors, and exposure assessed within limited exposure windows. As the existing evidence is inconclusive, further research remains to be conducted in order to verify this hypothesis. Complete assessment of maternal functional folate status through the pre- and peri-conceptional periods requires biological measurement of folate, vitamin B12and homocysteine and genetic variants involved in one-carbon metabolism and epigenetic mechanisms. In addition to more complete assessment of maternal functional folate status, careful consideration of potential confounding is warranted.
Reduction in sodium intake is independently associated with improved blood pressure control in people with chronic kidney disease in primary care
Authors: Nerbass Fabiana B. , Pecoits-Filho Roberto , McIntyre Natasha J. , Shardlow Adam , McIntyre Christopher W. , Taal Maarten W. 
Published: August 2015

AbstractDecreasing sodium intake has been associated with improvements in blood pressure (BP) and proteinuria, two important risk factors for CVD and chronic kidney disease (CKD) progression. We aimed to investigate the role of sodium intake by examining the effect of changes in sodium intake over 1 year on BP and proteinuria in people with early stage CKD. From thirty-two general practices, 1607 patients with previous estimated glomerular filtration rate of 59–30 ml/min per 1·73 m2 and mean age of 72·9 (sd 9·0) years were recruited. Clinical assessment, urine and serum biochemistry testing were performed at baseline and after 1 year. Sodium intake was estimated from early morning urine specimens using an equation validated for this study population. We found that compared with people who increased their sodium intake from ≤100 to >100 mmol/d over 1 year, people who decreased their intake from >100 to ≤100 mmol/d evidenced a greater decrease in all BP variables (Δmean arterial pressure (ΔMAP)=–7·44 (sd 10·1) v. –0·23 (sd 10·4) mmHg; P<0·001) as well as in pulse wave velocity (ΔPWV=–0·47 (sd 1·3) v. 0·08 (sd 1·88) m/s; P<0·05). Albuminuria improved only in albuminuric patients who decreased their sodium intake. BP improved in people who maintained low sodium intake at both times and in those with persistent high intake, but the number of anti-hypertensive increased only in the higher sodium intake group, and PWV improved only in participants with lower sodium intake. Decreasing sodium intake was an independent determinant of ΔMAP. Although more evidence is needed, our results support the benefits of reducing and maintaining sodium intake below 100 mmol/d (2·3–2·4 g/d) in people with early stages of CKD.
Palaeoscolecids from the Balang Fauna of the Qiandongian (Cambrian Series 2), Guizhou, China
Authors: PENG JIN , HUANG DIYING , ZHAO YUANLONG , SUN HAIJING 
Published: August 2015

AbstractWronascolexis a taxon of palaeoscolecids. It is commonly represented by isolated button-like microfossils or compressed individuals, which are found worldwide in strata ranging from the Cambrian Series 2 to Series 3. The earliest representative ofWronascolexis known from the Sinsk Formation of the lower Cambrian of the Siberian Platform. Other species occur in Burgess Shale-type biotas of Cambrian age from Australia, Spain and North America. New palaeoscolecid material from the Balang Fauna of the Cambrian Series 2 of eastern Guizhou represents a new species ofWronascolex,W. geyiensissp. nov., and extends the geographic and stratigraphic distribution ofWronascolex, as well as providing additional evidence for understanding its morphology based upon correlation of body configuration and cuticular ornaments.
Spore tetrads, possible indicators of intense climatic regimes: case study from an early Permian stratum of Singrauli Coalfield, Son-Mahanadi Basin, India
Authors: SAXENA ANJU , SINGH KAMAL JEET , MURTHY SRIKANTA , CHANDRA SHAILA , GOSWAMI SHREERUP 
Published: August 2015

AbstractA large number of naked, fossil spore tetrads assignable to the dispersed microspore genera Indotriradites, Microbaculispora and Microfoveolatispora are reported for the first time from an early Permian stratum (Lower Barakar Formation) of Singrauli Coalfield, Son-Mahanadi Basin, Central India. This is also the first record of tetrads from any Artinskian strata in the world. There is no evidence of any kind of sporangia or related plant parts in the present investigation that could ascertain the affinity of these tetrads; however, the presence of a trilete mark in the spores of the tetrads demonstrates their alliance at least with the pteridophyte group. The present study suggests possible factors affecting the sporogenesis process in the past, considering other available global records pertaining to fossil spore tetrads. The results of significant physiological and biochemical analyses performed on the anthers of modern plants related to reproductive biology, in order to understand the conditions and changes responsible for the formation of tetrads, are also considered. We analysed the globally occurring fossil tetrads and the palaeoclimates prevailing during their deposition. A correlation between extreme climatic conditions, specific pH values inside microsporangium and the formation of tetrad is envisaged. It is deduced that extreme climatic conditions (extreme cold/extreme hot) might have triggered some sort of malfunctioning in the sporogenesis process that altered the specific pH values inside the microsporangium. Any restraint of the activity of the callase enzyme, responsible for dissolution of callose walls laid between the individual spores, may therefore have apprehended the dissociation of tetrads into individual spores.