bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complex
Authors: Morita Daisuke , Yamamoto Yukie , Mizutani Tatsuaki , Ishikawa Takeshi , Suzuki Juri , Igarashi Tatsuhiko , Mori Naoki , Shiina Takashi , Inoko Hidetoshi , Fujita Hiroaki , Iwai Kazuhiro , Tanaka Yoshimasa , Mikami Bunzo , Sugita Masahiko 
Published: January 2016

AbstractThe covalent conjugation of a 14-carbon saturated fatty acid (myristic acid) to the amino-terminal glycine residue is critical for some viral proteins to function. This protein lipidation modification, termed N-myristoylation, is targeted by host cytotoxic T lymphocytes (CTLs) that specifically recognize N-myristoylated short peptides; however, the molecular mechanisms underlying lipopeptide antigen (Ag) presentation remain elusive. Here we show that a primate major histocompatibility complex (MHC) class I-encoded protein is capable of binding N-myristoylated 5-mer peptides and presenting them to specific CTLs. A high-resolution X-ray crystallographic analysis of the MHC class I:lipopeptide complex reveals an Ag-binding groove that is elaborately constructed to bind N-myristoylated short peptides rather than prototypic 9-mer peptides. The identification of lipopeptide-specific, MHC class I-restricted CTLs indicates that the widely accepted concept of MHC class I-mediated presentation of long peptides to CTLs may need some modifications to incorporate a novel MHC class I function of lipopeptide Ag presentation.
Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore
Authors: Wong Edward S Y , Shekar Sandhya , Met-Domestici Marie , Chan Claire , Sze Melody , Yap Yoon Sim , Rozen Steven G , Tan Min-Han , Ang Peter , Ngeow Joanne , Lee Ann S G 
Published: January 2016

AbstractGenetic testing for germline mutations in breast cancer predisposition genes can potentially identify individuals at a high risk of developing breast and/or ovarian cancer. There is a paucity of such mutational information for Asians. Panel testing of 25 cancer susceptibility genes and BRCA1/2 deletion/duplication analysis was performed for 220 Asian breast cancer patients or their family members referred for genetics risk assessment. All 220 participants had at least one high-risk feature: having a family history of breast and/or ovarian cancer in first- and/or second-degree relatives; having breast and ovarian cancer in the same individual or bilateral breast cancer; having early-onset breast cancer or ovarian cancer (⩽40 years of age). We identified 67 pathogenic variants in 66 (30.0%) patients. Of these, 19 (28.3%) occurred in BRCA1, 16 (23.9%) in BRCA2, 7 (10.4%) in PALB2, 6 (9.0%) in TP53, 2 (3.0%) in PTEN, 2 (3.0%) in CDH1 and 15 (22.4%) in other predisposition genes. Notably, 47.8% of pathogenic variants were in non-BRCA1/2 genes. Of the 66 patients with pathogenic mutations, 63.6% (42/66) were under the age of 40 years. Family history of breast and/or ovarian cancer is enriched in patients with BRCA1/2 pathogenic variants but less predictive for non-BRCA1/2 related pathogenic variations. We detected a median of three variants of unknown significance (VUS) per gene (range 0–21). Custom gene panel testing is feasible and useful for the detection of pathogenic mutations and should be done in the setting of a formal clinical cancer genetics service given the rate of VUS.
Non-coding RNAs profiling in head and neck cancers
Authors: Salyakina Daria , Tsinoremas Nicholas F 
Published: January 2016

AbstractThe majority of studies on human cancers published to date focus on coding genes. More recently, however, non-coding RNAs (ncRNAs) are gaining growing recognition as important regulatory components. Here we characterise the ncRNA landscape in 442 head and neck squamous cell carcinomas (HNSCs) from the cancer genome atlas (TCGA). HNSCs represent an intriguing case to study the potential role of ncRNA as a function of viral presence, especially as HPV is potentially oncogenic. Thus, we identify HPV16-positive (HPV16+) and HPV-negative (HPV−) tumours and study the expression of ncRNAs on both groups. Overall, the ncRNAs comprise 36% of all differentially expressed genes, with antisense RNAs being the most represented ncRNA type (12.6%). Protein-coding genes appear to be more frequently downregulated in tumours compared with controls, whereas ncRNAs show significant upregulation in tumours, especially in HPV16+ tumours. Overall, expression of pseudogenes, antisense and short RNAs is elevated in HPV16+ tumours, while the remaining long non-coding RNA types are more active in all HNSC tumours independent of HPV status. In addition, we identify putative regulatory targets of differentially expressed ncRNAs. Among these ‘targets’ we find several well-established oncogenes, tumour suppressors, cytokines, growth factors and cell differentiation genes, which indicates the potential involvement of ncRNA in the control of these key regulators as a direct consequence of HPV oncogenic activity. In conclusion, our findings establish the ncRNAs as crucial transcriptional components in HNSCs. Our results display the great potential for the study of ncRNAs and the role they have in human cancers.
Genomic medicine in the military
Authors: De Castro Mauricio , Biesecker Leslie G , Turner Clesson , Brenner Ruth , Witkop Catherine , Mehlman Maxwell , Bradburne Chris , Green Robert C 
Published: January 2016

AbstractThe announcement of the Precision Medicine Initiative was an important step towards establishing the use of genomic information as part of the wider practice of medicine. The US military has been exploring the role that genomic information will have in health care for service members (SMs) and its integration into the continuum of military medicine. An important part of the process is establishing robust protections to protect SMs from genetic discrimination in the era of exome/genome sequencing.
Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines
Authors: Noor Dzul Azri Mohamed , Jeyapalan Jennie N , Alhazmi Safiah , Carr Matthew , Squibb Benjamin , Wallace Claire , Tan Christopher , Cusack Martin , Hughes Jaime , Reader Tom , Shipley Janet , Sheer Denise , Scotting Paul J 
Published: January 2016

AbstractSilencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome-wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes.
Fatigue in Parkinson’s disease: report from a multidisciplinary symposium
Authors: Friedman Joseph H , Beck James C , Chou Kelvin L , Clark Gracia , Fagundes Christopher P , Goetz Christopher G , Herlofson Karen , Kluger Benzi , Krupp Lauren B , Lang Anthony E , Lou Jao-Shin , Marsh Laura , Newbould Anne , Weintraub Daniel 
Published: January 2016

AbstractFatigue is a severe problem for many people living with Parkinson’s disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson’s Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer—disorders in which fatigue figures prominently too. We conclude with focused recommendations to enhance our understanding and treatment of this prominent problem in PD.
Different PD-MCI criteria and risk of dementia in Parkinson’s disease: 4-year longitudinal study
Authors: Wood Kyla-Louise , Myall Daniel J , Livingston Leslie , Melzer Tracy R , Pitcher Toni L , MacAskill Michael R , Geurtsen Gert J , Anderson Tim J , Dalrymple-Alford John C 
Published: January 2016

AbstractThe Movement Disorder Society Task Force (MDS-TF) has proposed diagnostic criteria for mild cognitive impairment in Parkinson’s disease (PD-MCI). We hypothesized that the risk of dementia (PDD) varies across the different cutoff schemes allowed. A longitudinal study followed 121 non-demented PD patients for up to 4.5 years. In Part One, unique groups of patients were identified as PD-MCI at baseline using the MDS-TF requirement of two impaired cognitive test scores, with both scores classified as impaired at either (i) 2 s.d., (ii) 1.5 s.d. or (iii) 1 s.d. below normative data; relative risk (RR) of PDD was assessed at each criterion. In Part Two, the whole sample was reassessed and (i) RR of PDD determined when two impairments at 1.5 s.d. existed within a single cognitive domain, followed by (ii) RR of PDD in the unique group whose two impairments at 1.5 s.d. did not exist within a single domain (i.e., only across two domains). Twenty-one percent of patients converted to PDD. Part One showed that the 1.5 s.d. criterion at baseline is optimal to maximize progression to PDD over 4 years. Part Two, however, showed that the 1.5 s.d. cutoff produced a high RR of PDD only when two impairments were identified within a single cognitive domain (7.2, 95% confidence interval (CI)=3.4–16.6, P<0.0001; 51% converted). The RR when the 1.5 s.d. impairments occurred only across two different domains, was nonsignificant (1.7, CI=0.5–7.4, P=0.13; 11% converted) and similar to using a 1 s.d. criterion (1.9, CI=0.3–4.3, P=0.13; 8% converted). If the intent of a PD-MCI diagnosis is to detect increased risk of PDD in the next 4 years, optimal criteria should identify at least two impairments at 1.5 s.d. within a single cognitive domain.
The Mesoscopic Electrochemistry of Molecular Junctions
Authors: Bueno Paulo R. , Benites Tiago A. , Davis Jason J. 
Published: January 2016

AbstractWithin the context of an electron dynamic (time-dependent) perspective and a voltage driving force acting to redistribute electrons between metallic and addressable molecular states, we define here the associated electron admittance and conductance. We specifically present a mesoscopic approach to resolving the electron transfer rate associated with the electrochemistry of a redox active film tethered to metallic leads and immersed in electrolyte. The methodology is centred on aligning the lifetime of the process of electron exchange with associated resistance and capacitance quantities. Notably, however, these are no longer those empirically known as charge transfer resistance and pseudo-capacitance, but are those derived instead from a consideration of the quantum states contained in molecular films and their accessibility through a scattering region existing between them and the metallic probe. The averaged lifetime (τr) associated with the redox site occupancy is specifically dependent on scattering associated with the quantum channels linking them to the underlying metallic continuum and associated with both a quantum resistance (Rq) and an electrochemical (redox) capacitance (Cr). These are related to electron transfer rate throughk = 1/τr = (RqCr)−1. The proposed mesoscopic approach is consistent with Marcus’s (electron transfer rate) theory and experimental measurements obtained by capacitance spectroscopy.
Prevalence and care index of early childhood caries in mainland China: evidence from epidemiological surveys during 1987–2013
Authors: Zhang Xiaonan , Yang Sheng , Liao Zhaoying , Xu Ling , Li Conghua , Zeng Huan , Song Jinlin , Zhang Lei 
Published: January 2016

AbstractEarly childhood caries (ECC) is the most common chronic disease in young children. Its reported prevalence varies greatly across China. This systematic review aimed to explore the epidemiological characteristics of ECC in mainland China from 1987 to 2013. In total, 102 articles were included. The pooled national prevalence and care index (ft/dmft%) for ECC were 65.5% and 3.6%, respectively. The overall ECC prevalence declined from 77.9% during 1987–1994 to 56.4% during 2010–2013. The pooled ECC prevalence for children aged 1–6 years was 0.3%, 17.3%, 40.2%, 54.4%, 66.1% and 70.7%, respectively. There was no significant difference in prevalence between boys (59.1%) and girls (58.9%); and the care index was also similar (8.1% versus 7.7%). Slightly higher ECC prevalence was observed in rural areas (63.5%) compared with urban areas (59.5%) (RR = 1.08, 95% CI: 1.02–1.14); but a much higher care index was reported in urban children (6.0%) than their rural counterparts (1.6%) (RR = 3.68, 95% CI: 2.54–5.35). The 2006–2013 map of ECC prevalence among 5-year-olds showed wide geographic variations across China. Four adjacent provinces, including Sichuan, Chongqing, Hubei and Shaanxi, constituted the areas with the lowest ECC prevalence in mainland China.
Scalable topographies to support proliferation and Oct4 expression by human induced pluripotent stem cells
Authors: Reimer Andreas , Vasilevich Aliaksei , Hulshof Frits , Viswanathan Priyalakshmi , van Blitterswijk Clemens A. , de Boer Jan , Watt Fiona M. 
Published: January 2016

AbstractIt is well established that topographical features modulate cell behaviour, including cell morphology, proliferation and differentiation. To define the effects of topography on human induced pluripotent stem cells (iPSC), we plated cells on a topographical library containing over 1000 different features in medium lacking animal products (xeno-free). Using high content imaging, we determined the effect of each topography on cell proliferation and expression of the pluripotency marker Oct4 24 h after seeding. Features that maintained Oct4 expression also supported proliferation and cell-cell adhesion at 24 h and by 4 days colonies of Oct4-positive, Sox2-positive cells had formed. Computational analysis revealed that small feature size was the most important determinant of pluripotency, followed by high wave number and high feature density. Using this information we correctly predicted whether any given topography within our library would support the pluripotent state at 24 h. This approach not only facilitates the design of substrates for optimal human iPSC expansion, but also, potentially, identification of topographies with other desirable characteristics, such as promoting differentiation.
Vitamin D status predicts reproductive fitness in a wild sheep population
Authors: Handel Ian , Watt Kathryn A. , Pilkington Jill G. , Pemberton Josephine M. , Macrae Alastair , Scott Philip , McNeilly Tom N. , Berry Jacqueline L. , Clements Dylan N. , Nussey Daniel H. , Mellanby Richard J. 
Published: January 2016

AbstractVitamin D deficiency has been associated with the development of many human diseases and with poor reproductive performance in laboratory rodents. We currently have no idea how natural selection directly acts on variation in vitamin D metabolism due to a total lack of studies in wild animals. Here, we measured serum 25 hydroxyvitamin D (25(OH)D) concentrations in female Soay sheep that were part of a long-term field study on St Kilda. We found that total 25(OH)D was strongly influenced by age and that light coloured sheep had higher 25(OH)D3 (but not 25(OH)D2) concentrations than dark sheep. The coat colour polymorphism in Soay sheep is controlled by a single locus, suggesting vitamin D status is heritable in this population. We also observed a very strong relationship between total 25(OH)D concentrations in summer and a ewe’s fecundity the following spring. This resulted in a positive association between total 25(OH)D and the number of lambs produced that survived their first year of life, an important component of female reproductive fitness. Our study provides the first insight into naturally-occurring variation in vitamin D metabolites and offers the first evidence that vitamin D status is both heritable and under natural selection in the wild.
Large molecular systems landscape uncovers T cell trapping in human skin cancer
Authors: Hillert Reyk , Gieseler Anne , Krusche Andreas , Humme Daniel , Röwert-Huber Hans-Joachim , Sterry Wolfram , Walden Peter , Schubert Walter 
Published: January 2016

AbstractImmune surveillance of tumour cells is an important function of CD8 T lymphocytes, which has failed in cancer for reasons still unknown in many respect but mainly related to cellular processes in the tumour microenvironment. Applying imaging cycler microscopy to analyse the immune contexture in a human skin cancer we could identify and map 7,000 distinct cell surface-associated multi-protein assemblies. The resulting combinatorial geometry-based high-functional resolution led to discovery of a mechanism of T cell trapping in the epidermis, which involves SPIKE, a network of suprabasal keratinocyte projections piercing and interconnecting CD8 T cells. It appears initiated by clusters of infrabasal T and dendritic cells connected via cell projections across a fractured basal lamina to suprabasal keratinocytes and T lymphocytes.
Temperature based Restricted Boltzmann Machines
Authors: Li Guoqi , Deng Lei , Xu Yi , Wen Changyun , Wang Wei , Pei Jing , Shi Luping 
Published: January 2016

AbstractRestricted Boltzmann machines (RBMs), which apply graphical models to learning probability distribution over a set of inputs, have attracted much attention recently since being proposed as building blocks of multi-layer learning systems called deep belief networks (DBNs). Note that temperature is a key factor of the Boltzmann distribution that RBMs originate from. However, none of existing schemes have considered the impact of temperature in the graphical model of DBNs. In this work, we propose temperature based restricted Boltzmann machines (TRBMs) which reveals that temperature is an essential parameter controlling the selectivity of the firing neurons in the hidden layers. We theoretically prove that the effect of temperature can be adjusted by setting the parameter of the sharpness of the logistic function in the proposed TRBMs. The performance of RBMs can be improved by adjusting the temperature parameter of TRBMs. This work provides a comprehensive insights into the deep belief networks and deep learning architectures from a physical point of view.
Parathyroidectomy Associates with Reduced Mortality in Taiwanese Dialysis Patients with Hyperparathyroidism: Evidence for the Controversy of Current Guidelines
Authors: Ho Li-Chun , Hung Shih-Yuan , Wang Hsi-Hao , Kuo Te-Hui , Chang Yu-Tzu , Tseng Chin-Chung , Wu Jia-Ling , Li Chung-Yi , Wang Jung-Der , Tsai Yau-Sheng , Sung Junne-Ming ,   Tainan RENal Disease Study (TRENDS) group, Sung Junne-Ming , Wang Jung-Der , Li Chung-Yi , Tseng Chin-Chung , Chang Yu-Tzu , Kuo Te-Hui , Wang Hsi-Hao , Ho Li-Chun , Wu Jia-Ling , Hsieh Chih-Cheng , Yen Miao-Fen , Wu Hung-Lien , Chen Ping-Yu , Li Wen-Huang , Chang Wei-Ting 
Published: January 2016

AbstractParathyroidectomy is recommended by the clinical guidelines for dialysis patients with unremitting secondary hyperparathyroidism (SHPT). However, the survival advantage of parathyroidectomy is debated because of the selection bias in previous studies. To minimize potential bias in the present nationwide cohort study, we enrolled only dialysis patients who had undergone radionuclide parathyroid scanning to ensure all patients had severe SHPT. The parathyroidectomized patients were matched with the controls based on propensity score for parathyroidectomy. Mortality hazard was estimated using multivariate Cox proportional hazard models adjusting for comorbidities before scanning (model 1) or over the whole study period (model 2). Our results showed that among the 2786 enrolled patients, 1707 underwent parathyroidectomy and the other 1079 were controls. The crude mortality rates were lower in the parathyroidectomized patients than in the controls. In adjusted analyses for the population matched on propensity score, parathyroidectomy was associated with a significant 20% to 25% lower risk for all-cause mortality (model 1: hazard ratio 0.76, 95% confidence interval 0.61 to 0.94; model 2: hazard ratio 0.80, 95% confidence internal 0.64 to 0.98). We concluded that parathyroidectomy was associated with a reduced long-term mortality risk in dialysis patients with severe SHPT.
Genetic affinities of the Jewish populations of India
Authors: Chaubey Gyaneshwer , Singh Manvendra , Rai Niraj , Kariappa Mini , Singh Kamayani , Singh Ashish , Pratap Singh Deepankar , Tamang Rakesh , Selvi Rani Deepa , Reddy Alla G. , Kumar Singh Vijay , Singh Lalji , Thangaraj Kumarasamy 
Published: January 2016

AbstractDue to the lack of written records or inscription, the origin and affiliation of Indian Jewish populations with other world populations remain contentious. Previous genetic studies have found evidence for a minor shared ancestry of Indian Jewish with Middle Eastern (Jewish) populations. However, these studies (relied on limited individuals), haven’t explored the detailed temporal and spatial admixture process of Indian Jewish populations with the local Indian populations. Here, using large sample size with combination of high resolution biparental (autosomal) and uniparental markers (Y chromosome and mitochondrial DNA), we reconstructed genetic history of Indian Jewish by investigating the patterns of genetic diversity. Consistent with the previous observations, we detected minor Middle Eastern specific ancestry component among Indian Jewish communities, but virtually negligible in their local neighbouring Indian populations. The temporal test of admixture suggested that the first admixture of migrant Jewish populations from Middle East to South India (Cochin) occurred during fifth century. Overall, we concluded that the Jewish migration and admixture in India left a record in their genomes, which can link them to the ‘Jewish Diaspora’.