Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems

EPA Science Inventory

Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate of human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a pr...

Recent advances in understanding the role of nutrition in human genome evolution.

PubMed

Ye, Kaixiong; Gu, Zhenglong

2011-11-01

Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics.

Differences between sliding semi-landmark methods in geometric morphometrics, with an application to human craniofacial and dental variation

PubMed Central

Ivan Perez, S; Bernal, Valeria; Gonzalez, Paula N

2006-01-01

Over the last decade, geometric morphometric methods have been applied increasingly to the study of human form. When too few landmarks are available, outlines can be digitized as series of discrete points. The individual points must be slid along a tangential direction so as to remove tangential variation, because contours should be homologous from subject to subject whereas their individual points need not. This variation can be removed by minimizing either bending energy (BE) or Procrustes distance (D) with respect to a mean reference form. Because these two criteria make different assumptions, it becomes necessary to study how these differences modify the results obtained. We performed bootstrapped-based Goodall's F-test, Foote's measurement, principal component (PC) and discriminant function analyses on human molars and craniometric data to compare the results obtained by the two criteria. Results show that: (1) F-scores and P-values were similar for both criteria; (2) results of Foote's measurement show that both criteria yield different estimates of within- and between-sample variation; (3) there is low correlation between the first PC axes obtained by D and BE; (4) the percentage of correct classification is similar for BE and D, but the ordination of groups along discriminant scores differs between them. The differences between criteria can alter the results when morphological variation in the sample is small, as in the analysis of modern human populations. PMID:16761977

A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans

PubMed Central

Liu, Fan; van der Lijn, Fedde; Schurmann, Claudia; Zhu, Gu; Chakravarty, M. Mallar; Hysi, Pirro G.; Wollstein, Andreas; Lao, Oscar; de Bruijne, Marleen; Ikram, M. Arfan; van der Lugt, Aad; Rivadeneira, Fernando; Uitterlinden, André G.; Hofman, Albert; Niessen, Wiro J.; Homuth, Georg; de Zubicaray, Greig; McMahon, Katie L.; Thompson, Paul M.; Daboul, Amro; Puls, Ralf; Hegenscheid, Katrin; Bevan, Liisa; Pausova, Zdenka; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Wicking, Carol; Boehringer, Stefan; Spector, Timothy D.; Paus, Tomáš; Martin, Nicholas G.; Biffar, Reiner; Kayser, Manfred

2012-01-01

Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes—PRDM16, PAX3, TP63, C5orf50, and COL17A1—in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications. PMID:23028347

Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

PubMed

Hitomi, Yuki; Tokunaga, Katsushi

2017-01-01

Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

Nucleic acid probes in diagnostic medicine

NASA Technical Reports Server (NTRS)

Oberry, Phillip A.

1991-01-01

The need for improved diagnostic procedures is outlined and variations in probe technology are briefly reviewed. A discussion of the application of probe technology to the diagnosis of disease in animals and humans is presented. A comparison of probe versus nonprobe diagnostics and isotopic versus nonisotopic probes is made and the current state of sequence amplification is described. The current market status of nucleic acid probes is reviewed with respect to their diagnostic application in human and veterinary medicine. Representative product examples are described and information on probes being developed that offer promise as future products is discussed.

Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk.

PubMed

Murach, Michelle M; Kang, Yun-Seok; Goldman, Samuel D; Schafman, Michelle A; Schlecht, Stephen H; Moorhouse, Kevin; Bolte, John H; Agnew, Amanda M

2017-09-01

The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p < 0.001) by rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax.

Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk

PubMed Central

Murach, Michelle M.; Kang, Yun-Seok; Goldman, Samuel D.; Schafman, Michelle A.; Schlecht, Stephen H.; Moorhouse, Kevin; Bolte, John H.; Agnew, Amanda M.

2018-01-01

The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p<0.001) by rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax. PMID:28547660

Application of toxicogenomic profiling to evaluate effects of benzene and formaldehyde: from yeast to human

PubMed Central

McHale, Cliona M.; Smith, Martyn T.; Zhang, Luoping

2014-01-01

Genetic variation underlies a significant proportion of the individual variation in human susceptibility to toxicants. The primary current approaches to identify gene–environment (GxE) associations, genome-wide association studies (GWAS) and candidate gene association studies, require large exposed and control populations and an understanding of toxicity genes and pathways, respectively. This limits their application in the study of GxE associations for the leukemogens benzene and formaldehyde, whose toxicity has long been a focus of our research. As an alternative approach, we applied innovative in vitro functional genomics testing systems, including unbiased functional screening assays in yeast and a near-haploid human bone marrow cell line (KBM7). Through comparative genomic and computational analyses of the resulting data, we have identified human genes and pathways that may modulate susceptibility to benzene and formaldehyde. We have validated the roles of several genes in mammalian cell models. In populations occupationally exposed to low levels of benzene, we applied peripheral blood mononuclear cell transcriptomics and chromosome-wide aneuploidy studies (CWAS) in lymphocytes. In this review of the literature, we describe our comprehensive toxicogenomic approach and the potential mechanisms of toxicity and susceptibility genes identified for benzene and formaldehyde, as well as related studies conducted by other researchers. PMID:24571325

Fabrication of biomimetically-patterned surfaces and their application to probing plant-bacteria interactions

USDA-ARS?s Scientific Manuscript database

Understanding of plant-bacterial interactions is of critical importance for developing effective control measures against infectious diseases caused by foodborne human pathogens. However, limitations of existing scientific tools to access and evaluate natural plant tissues, and the large variations ...

Space languages

NASA Technical Reports Server (NTRS)

Hays, Dan

1987-01-01

Applications of linguistic principles to potential problems of human and machine communication in space settings are discussed. Variations in language among speakers of different backgrounds and change in language forms resulting from new experiences or reduced contact with other groups need to be considered in the design of intelligent machine systems.

Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing.

PubMed

Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens; Gniadecki, Robert; Dybkaer, Karen; Rosenberg, Jacob; Langhoff, Jill Levin; Cruz, David Flores Santa; Fonager, Jannik; Izarzugaza, Jose M G; Gupta, Ramneek; Sicheritz-Ponten, Thomas; Brunak, Søren; Willerslev, Eske; Nielsen, Lars Peter; Hansen, Anders Johannes

2015-08-19

Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.

Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes.

PubMed

Brahma, Rajeev Kungur; McCleary, Ryan J R; Kini, R Manjunatha; Doley, Robin

2015-01-01

Snake venoms are cocktails of protein toxins that play important roles in capture and digestion of prey. Significant qualitative and quantitative variation in snake venom composition has been observed among and within species. Understanding these variations in protein components is instrumental in interpreting clinical symptoms during human envenomation and in searching for novel venom proteins with potential therapeutic applications. In the last decade, transcriptomic analyses of venom glands have helped in understanding the composition of various snake venoms in great detail. Here we review transcriptomic analysis as a powerful tool for understanding venom profile, variation and evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Land cover variation and West Nile virus prevalence: Patterns, processes, and implications for disease control

USGS Publications Warehouse

Ezenwa, V.O.; Milheim, L.E.; Coffey, M.F.; Godsey, M.S.; King, R.J.; Guptill, S.C.

2007-01-01

Identifying links between environmental variables and infectious disease risk is essential to understanding how human-induced environmental changes will effect the dynamics of human and wildlife diseases. Although land cover change has often been tied to spatial variation in disease occurrence, the underlying factors driving the correlations are often unknown, limiting the applicability of these results for disease prevention and control. In this study, we described associations between land cover composition and West Nile virus (WNV) infection prevalence, and investigated three potential processes accounting for observed patterns: (1) variation in vector density; (2) variation in amplification host abundance; and (3) variation in host community composition. Interestingly, we found that WNV infection rates among Culex mosquitoes declined with increasing wetland cover, but wetland area was not significantly associated with either vector density or amplification host abundance. By contrast, wetland area was strongly correlated with host community composition, and model comparisons suggested that this factor accounted, at least partially, for the observed effect of wetland area on WNV infection risk. Our results suggest that preserving large wetland areas, and by extension, intact wetland bird communities, may represent a valuable ecosystem-based approach for controlling WNV outbreaks. ?? Mary Ann Liebert, Inc.

Experimental evaluation of a system for human life detection under debris

NASA Astrophysics Data System (ADS)

Joju, Reshma; Konica, Pimplapure Ramya T.; Alex, Zachariah C.

2017-11-01

It is difficult to for the human beings to be found under debris or behind the walls in case of military applications. Due to which several rescue techniques such as robotic systems, optical devices, and acoustic devices were used. But if victim was unconscious then these rescue system failed. We conducted an experimental analysis on whether the microwaves could detect heart beat and breathing signals of human beings trapped under collapsed debris. For our analysis we used RADAR based on by Doppler shift effect. We calculated the minimum speed that the RADAR could detect. We checked the frequency variation by placing the RADAR at a fixed position and placing the object in motion at different distances. We checked the frequency variation by using objects of different materials as debris behind which the motion was made. The graphs of different analysis were plotted.

Maxillary and Mandibular First Premolars Showing Three-Cusp Pattern: An Unusual Presentation

PubMed Central

Kotrashetti, Vijayalakshmi; Nayak, Aarati; Patil, Viraj; Kulkarni, Mayuri; Somannavar, Pradeep

2013-01-01

Dental anatomy is the study of morphology of various teeth in human dentitions. The application of dental anatomy in clinical practice is important, and dentist should have a thorough knowledge regarding the morphology of the teeth. At times as a result of genetic variation, environmental factors, diet of an individual and race, variations in the morphology of the teeth can be observed. These variations have been extensively studied by the researcher in the field of anthropology to define a particular race. The most commonly observed changes include peg-shaped laterals, shovel-shaped incisors, and extra cusp on molar. Common variations documented with regard to maxillary and mandibular first premolars are the variation in the number of roots. But the variations with respect to crown morphology are few. We report a first documented unusual presentation of maxillary and mandibular first premolars with three-cusps pattern in a female patient. PMID:23476817

Assessment of Variation in Microbial Community Amplicon Sequencing by the Microbiome Quality Control (MBQC) Project Consortium

EPA Science Inventory

Precision medicine has been made possible by the translation of ‘omics to the clinic, and human microbiome studies must likewise transition to applications in public health. This will require especially robust measurements and assimilation of data from multiple population-scale c...

Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

PubMed

Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

2016-01-01

The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Environmental and biomedical applications of natural metal stable isotope variations

USGS Publications Warehouse

Bullen, T.D.; Walczyk, T.

2009-01-01

etal stable isotopes are now being used to trace metal contaminants in the environment and as indicators of human systemic function where metals play a role. Stable isotope abundance variations provide information about metal sources and the processes affecting metals in complex natural systems, complementing information gained from surrogate tracers, such as metal abundance ratios or biochemical markers of metal metabolism. The science is still in its infancy, but the results of initial studies confirm that metal stable isotopes can provide a powerful tool for forensic and biomedical investigations.

Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics.

PubMed

ElRakaiby, Marwa; Dutilh, Bas E; Rizkallah, Mariam R; Boleij, Annemarie; Cole, Jason N; Aziz, Ramy K

2014-07-01

The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.

Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics

PubMed Central

ElRakaiby, Marwa; Dutilh, Bas E.; Rizkallah, Mariam R.; Boleij, Annemarie; Cole, Jason N.

2014-01-01

Abstract The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug–microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed. PMID:24785449

Visualisation of Massive Military Datasets: Human Factors, Applications, and Technologies

DTIC Science & Technology

2001-05-01

we have been confronted with data of new kinds at a rate faster than our human brains can manage to turn into information. “Visualisation” means the...because variation of these kinds do not have the qaulities of textons. Figure 2.5 A trivial Icon Map in which there is a data attribute, shown as...information management is to ensure that the right information is available to the right person, at the right time, and shown in such a way that the person

VarioML framework for comprehensive variation data representation and exchange.

PubMed

Byrne, Myles; Fokkema, Ivo Fac; Lancaster, Owen; Adamusiak, Tomasz; Ahonen-Bishopp, Anni; Atlan, David; Béroud, Christophe; Cornell, Michael; Dalgleish, Raymond; Devereau, Andrew; Patrinos, George P; Swertz, Morris A; Taschner, Peter Em; Thorisson, Gudmundur A; Vihinen, Mauno; Brookes, Anthony J; Muilu, Juha

2012-10-03

Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.

VarioML framework for comprehensive variation data representation and exchange

PubMed Central

2012-01-01

Background Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. Results The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. Conclusions VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity. PMID:23031277

Telerobotic surgery: applications on human patients and training with virtual reality.

PubMed

Rovetta, A; Bejczy, A K; Sala, R

1997-01-01

This paper deals with the developed researches and applications on telerobotic surgery, devoted to human patients and with training by virtual reality. The researches have been developed in cooperation between Telerobotics Laboratory, Department of Mechanics, Politecnico di Milano, Italy, and Automation and Control Section, Jet Propulsion Laboratory, Pasadena, USA. The researches carried to a telesurgery robotic operation on a dummy on 7th July 1993, by means of satellites communications, to a prostatic biopsy on a human patient on 1st September 1995 with optical fibers, to results on time delay effects, to results on virtual reality applications for training on laparoscopy and surgery. The search implied time delay when the control input originated in Politecnico di Milano, Italy. The results were satisfactory, but also pointed out the need for specific new control transformations to ease the operator's or surgeon's visual/mental workload for hand-eye coordination. In the same research, dummy force commands from JPL to Milan were sent, and were echoed immediately back to JPL, measuring the round-trip time of the command signal. This, to some degree, simulates a contact force feedback situation. The results were very surprising; despite the fact that the ISDN calls are closed and "private" calls, the round-trip time exhibited great variations not only between calls but also within the same call. The results proved that telerobotics and telecontrol may be applied to surgery. Time latency variations are caused by features of communication network, of sending and receiving end computer software. The problem and its solution is also an architectural issue, and considerable improvements are possible. Virtual reality in the application of the research is a strong support to training on virtual objects and not on living beings.

Learning-based stochastic object models for characterizing anatomical variations

NASA Astrophysics Data System (ADS)

Dolly, Steven R.; Lou, Yang; Anastasio, Mark A.; Li, Hua

2018-03-01

It is widely known that the optimization of imaging systems based on objective, task-based measures of image quality via computer-simulation requires the use of a stochastic object model (SOM). However, the development of computationally tractable SOMs that can accurately model the statistical variations in human anatomy within a specified ensemble of patients remains a challenging task. Previously reported numerical anatomic models lack the ability to accurately model inter-patient and inter-organ variations in human anatomy among a broad patient population, mainly because they are established on image data corresponding to a few of patients and individual anatomic organs. This may introduce phantom-specific bias into computer-simulation studies, where the study result is heavily dependent on which phantom is used. In certain applications, however, databases of high-quality volumetric images and organ contours are available that can facilitate this SOM development. In this work, a novel and tractable methodology for learning a SOM and generating numerical phantoms from a set of volumetric training images is developed. The proposed methodology learns geometric attribute distributions (GAD) of human anatomic organs from a broad patient population, which characterize both centroid relationships between neighboring organs and anatomic shape similarity of individual organs among patients. By randomly sampling the learned centroid and shape GADs with the constraints of the respective principal attribute variations learned from the training data, an ensemble of stochastic objects can be created. The randomness in organ shape and position reflects the learned variability of human anatomy. To demonstrate the methodology, a SOM of an adult male pelvis is computed and examples of corresponding numerical phantoms are created.

[Study on the experimental application of floating-reference method to noninvasive blood glucose sensing].

PubMed

Yu, Hui; Qi, Dan; Li, Heng-da; Xu, Ke-xin; Yuan, Wei-jie

2012-03-01

Weak signal, low instrument signal-to-noise ratio, continuous variation of human physiological environment and the interferences from other components in blood make it difficult to extract the blood glucose information from near infrared spectrum in noninvasive blood glucose measurement. The floating-reference method, which analyses the effect of glucose concentration variation on absorption coefficient and scattering coefficient, gets spectrum at the reference point and the measurement point where the light intensity variations from absorption and scattering are counteractive and biggest respectively. By using the spectrum from reference point as reference, floating-reference method can reduce the interferences from variation of physiological environment and experiment circumstance. In the present paper, the effectiveness of floating-reference method working on improving prediction precision and stability was assessed through application experiments. The comparison was made between models whose data were processed with and without floating-reference method. The results showed that the root mean square error of prediction (RMSEP) decreased by 34.7% maximally. The floating-reference method could reduce the influences of changes of samples' state, instrument noises and drift, and improve the models' prediction precision and stability effectively.

Energy harvesting from arterial blood pressure for powering embedded micro sensors in human brain

NASA Astrophysics Data System (ADS)

Nanda, Aditya; Karami, M. Amin

2017-03-01

This manuscript investigates energy harvesting from arterial blood pressure via the piezoelectric effect for the purpose of powering embedded micro-sensors in the human brain. One of the major hurdles in recording and measuring electrical data in the human nervous system is the lack of implantable and long term interfaces that record neural activity for extended periods of time. Recently, some authors have proposed micro sensors implanted deep in the brain that measure local electrical and physiological data which are then communicated to an external interrogator. This paper proposes a way of powering such interfaces. The geometry of the proposed harvester consists of a piezoelectric, circular, curved bimorph that fits into the blood vessel (specifically, the Carotid artery) and undergoes bending motion because of blood pressure variation. In addition, the harvester thickness is constrained such that it does not modify arterial wall dynamics. This transforms the problem into a known strain problem and the integral form of Gauss's law is used to obtain an equation relating arterial wall motion to the induced voltage. The theoretical model is validated by means of a Multiphysics 3D-FEA simulation comparing the harvested power at different load resistances. The peak harvested power achieved for the Carotid artery (proximal to Brain), with PZT-5H, was 11.7 μW. The peak power for the Aorta was 203.4 μW. Further, the variation of harvested power with variation in the harvester width and thickness, arterial contractility, and pulse rate is investigated. Moreover, potential application of the harvester as a chronic, implantable and real-time Blood pressure sensor is considered. Energy harvested via this mechanism will also have applications in long-term, implantable Brain Micro-stimulation.

Integrating multi-scale data to create a virtual physiological mouse heart.

PubMed

Land, Sander; Niederer, Steven A; Louch, William E; Sejersted, Ole M; Smith, Nicolas P

2013-04-06

While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human- and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle.

Integrating multi-scale data to create a virtual physiological mouse heart

PubMed Central

Land, Sander; Niederer, Steven A.; Louch, William E.; Sejersted, Ole M.; Smith, Nicolas P.

2013-01-01

While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human- and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle. PMID:24427525

Culture, morality and individual differences: comparability and incomparability across species.

PubMed

Saucier, Gerard

2018-04-19

Major routes to identifying individual differences (in diverse species) include studies of behaviour patterns as represented in language and neurophysiology. But results from these approaches appear not to converge on some major dimensions. Identifying dimensions of human variation least applicable to non-human species may help to partition human-specific individual differences of recent evolutionary origin from those shared across species. Human culture includes learned, enforced social-norm systems that are symbolically reinforced and referenced in displays signalling adherence. At a key juncture in human evolution bullying aggression and deception-based cheating apparently became censured in the language of a moral community, enabling mutual observation coordinated in gossip, associated with external sanctions. That still-conserved cultural paradigm moralistically regulates selfish advantage-taking, with shared semantics and explicit rules. Ethics and moral codes remain critical and universal components of human culture and have a stronger imprint in language than most aspects of the currently popular Big-Five taxonomy, a model that sets out five major lines of individual-differences variation in human personality. In other species (e.g. chimpanzees), human observers might see apparent individual differences in morality-relevant traits, but not because the animals have human-analogue sanctioning systems. Removing the moral dimension of personality and other human-specific manifestations (e.g. religion) may aid in identifying those other bases of individual differences more ubiquitous across species.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues.

PubMed

Florea, Liliana; Song, Li; Salzberg, Steven L

2013-01-01

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina's Human Body Map project (>2.5 billion reads).  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed ('switched') between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository ( http://zenodo.org/record/7068; doi: 10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.

Traditional and modern plant breeding methods with examples in rice (Oryza sativa L.).

PubMed

Breseghello, Flavio; Coelho, Alexandre Siqueira Guedes

2013-09-04

Plant breeding can be broadly defined as alterations caused in plants as a result of their use by humans, ranging from unintentional changes resulting from the advent of agriculture to the application of molecular tools for precision breeding. The vast diversity of breeding methods can be simplified into three categories: (i) plant breeding based on observed variation by selection of plants based on natural variants appearing in nature or within traditional varieties; (ii) plant breeding based on controlled mating by selection of plants presenting recombination of desirable genes from different parents; and (iii) plant breeding based on monitored recombination by selection of specific genes or marker profiles, using molecular tools for tracking within-genome variation. The continuous application of traditional breeding methods in a given species could lead to the narrowing of the gene pool from which cultivars are drawn, rendering crops vulnerable to biotic and abiotic stresses and hampering future progress. Several methods have been devised for introducing exotic variation into elite germplasm without undesirable effects. Cases in rice are given to illustrate the potential and limitations of different breeding approaches.

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

PubMed

Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

2016-01-01

This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations. © 2015 Anatomical Society.

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications.

PubMed

Yoshida, Yoshinori; Yamanaka, Shinya

2017-06-09

Induced pluripotent stem cells (iPSCs) are reprogrammed cells that have features similar to embryonic stem cells, such as the capacity of self-renewal and differentiation into many types of cells, including cardiac myocytes. Although initially the reprogramming efficiency was low, several improvements in reprogramming methods have achieved robust and efficient generation of iPSCs without genomic insertion of transgenes. iPSCs display clonal variations in epigenetic and genomic profiles and cellular behavior in differentiation. iPSC-derived cardiac myocytes (iPSC cardiac myocytes) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models, and are useful for drug discovery and toxicology testing. In addition, iPSC cardiac myocytes can help with patient stratification in regard to drug responsiveness. Furthermore, they can be used as source cells for cardiac regeneration in animal models. Here, we review recent progress in iPSC technology and its applications to cardiac diseases. © 2017 American Heart Association, Inc.

Toxicogenomics and clinical toxicology: an example of the connection between basic and applied sciences.

PubMed

Ferrer-Dufol, Ana; Menao-Guillen, Sebastian

2009-04-10

The relationship between basic research and its potential clinical applications is often a difficult subject. Clinical toxicology has always been very dependent on experimental research whose usefulness has been impaired by the existence of huge differences in the toxicity expression of different substances, inter- and intra-species which make it difficult to predict clinical effects in humans. The new methods in molecular biology developed in the last decades are furnishing very useful tools to study some of the more relevant molecules implied in toxicokinetic and toxicodynamic processes. We aim to show some meaningful examples of how recent research developments with genes and proteins have clear applications to understand significant clinical matters, such as inter-individual variations in susceptibility to chemicals, and other phenomena related to the way some substances act to induce variations in the expression and functionality of these targets.

Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.

PubMed

Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

2015-01-01

The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

ENGINES: exploring single nucleotide variation in entire human genomes.

PubMed

Amigo, Jorge; Salas, Antonio; Phillips, Christopher

2011-04-19

Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data. We have developed a genetic variant site explorer able to retrieve data for Single Nucleotide Variation (SNVs), population by population, from entire genomes without compromising future scalability and agility. ENGINES (ENtire Genome INterface for Exploring SNVs) uses data from the 1000 Genomes Phase I to demonstrate its capacity to handle large amounts of genetic variation (>7.3 billion genotypes and 28 million SNVs), as well as deriving summary statistics of interest for medical and population genetics applications. The whole dataset is pre-processed and summarized into a data mart accessible through a web interface. The query system allows the combination and comparison of each available population sample, while searching by rs-number list, chromosome region, or genes of interest. Frequency and FST filters are available to further refine queries, while results can be visually compared with other large-scale Single Nucleotide Polymorphism (SNP) repositories such as HapMap or Perlegen. ENGINES is capable of accessing large-scale variation data repositories in a fast and comprehensive manner. It allows quick browsing of whole genome variation, while providing statistical information for each variant site such as allele frequency, heterozygosity or FST values for genetic differentiation. Access to the data mart generating scripts and to the web interface is granted from http://spsmart.cesga.es/engines.php. © 2011 Amigo et al; licensee BioMed Central Ltd.

Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

PubMed

Tang, Tao; Stevenson, R Jan; Infante, Dana M

2016-10-15

Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments introduced a tradeoff with assessment consistency when metrics differed across site groups, but they justified the convenient and consistent use of ecoregions. Copyright © 2016 Elsevier B.V. All rights reserved.

Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

PubMed

Butler, Erin E; Dominy, Nathaniel J

2016-04-01

The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here. © 2015 Anatomical Society.

Anatomy, Medical Education, and Human Ancestral Variation

ERIC Educational Resources Information Center

Strkalj, Goran; Spocter, Muhammad A.; Wilkinson, A. Tracey

2011-01-01

It is argued in this article that the human body both in health and disease cannot be fully understood without adequately accounting for the different levels of human variation. The article focuses on variation due to ancestry, arguing that the inclusion of information pertaining to ancestry in human anatomy teaching materials and courses should…

Understanding 3D human torso shape via manifold clustering

NASA Astrophysics Data System (ADS)

Li, Sheng; Li, Peng; Fu, Yun

2013-05-01

Discovering the variations in human torso shape plays a key role in many design-oriented applications, such as suit designing. With recent advances in 3D surface imaging technologies, people can obtain 3D human torso data that provide more information than traditional measurements. However, how to find different human shapes from 3D torso data is still an open problem. In this paper, we propose to use spectral clustering approach on torso manifold to address this problem. We first represent high-dimensional torso data in a low-dimensional space using manifold learning algorithm. Then the spectral clustering method is performed to get several disjoint clusters. Experimental results show that the clusters discovered by our approach can describe the discrepancies in both genders and human shapes, and our approach achieves better performance than the compared clustering method.

Multiphoton microscopic imaging of human normal and cancerous oesophagus tissue.

PubMed

Chen, W S; Wang, Y; Liu, N R; Zhang, J X; Chen, R

2014-01-01

In this paper, microstructures of human oesophageal submucosa are evaluated using multiphoton microscopy, based on two-photon excited fluorescence and second harmonic generation. The content and distribution of collagen, elastic fibers and cancer cells in normal and cancerous submucosa layer have been distinctly obtained and briefly discussed. The variation of these components is very relevant to the pathology in oesophagus, especially in early oesophageal cancer. Our results further indicate that the multiphoton microscopy technique has the potential application in vivo in clinical diagnosis and monitoring of early oesophageal cancer. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Variation in dielectric properties due to pathological changes in human liver.

PubMed

Peyman, Azadeh; Kos, Bor; Djokić, Mihajlo; Trotovšek, Blaž; Limbaeck-Stokin, Clara; Serša, Gregor; Miklavčič, Damijan

2015-12-01

Dielectric properties of freshly excised human liver tissues (in vitro) with several pathological conditions including cancer were obtained in frequency range 100 MHz-5 GHz. Differences in dielectric behavior of normal and pathological tissues at microwave frequencies are discussed based on histological information for each tissue. Data presented are useful for many medical applications, in particular nanosecond pulsed electroporation techniques. Knowledge of dielectric properties is vital for mathematical calculations of local electric field distribution inside electroporated tissues and can be used to optimize the process of electroporation for treatment planning procedures. © 2015 Wiley Periodicals, Inc.

Development of a mathematical model of the human cardiovascular system: An educational perspective

NASA Astrophysics Data System (ADS)

Johnson, Bruce Allen

A mathematical model of the human cardiovascular system will be a useful educational tool in biological sciences and bioengineering classrooms. The goal of this project is to develop a mathematical model of the human cardiovascular system that responds appropriately to variations of significant physical variables. Model development is based on standard fluid statics and dynamics principles, pressure-volume characteristics of the cardiac cycle, and compliant behavior of blood vessels. Cardiac cycle phases provide the physical and logical model structure, and Boolean algebra links model sections. The model is implemented using VisSim, a highly intuitive and easily learned block diagram modeling software package. Comparisons of model predictions of key variables to published values suggest that the model reasonably approximates expected behavior of those variables. The model responds plausibly to variations of independent variables. Projected usefulness of the model as an educational tool is threefold: independent variables which determine heart function may be easily varied to observe cause and effect; the model is used in an interactive setting; and the relationship of governing equations to model behavior is readily viewable and intuitive. Future use of this model in classrooms may give a more reasonable indication of its value as an educational tool.* *This dissertation includes a CD that is multimedia (contains text and other applications that are not available in a printed format). The CD requires the following applications: CorelPhotoHouse, CorelWordPerfect, VisSinViewer (included on CD), Internet access.

Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, G.; Lundgren, E.; Ekre, H.P.

Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition ofmore » the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity.« less

Size variation in Middle Pleistocene humans.

PubMed

Arsuaga, J L; Carretero, J M; Lorenzo, C; Gracia, A; Martínez, I; Bermúdez de Castro, J M; Carbonell, E

1997-08-22

It has been suggested that European Middle Pleistocene humans, Neandertals, and prehistoric modern humans had a greater sexual dimorphism than modern humans. Analysis of body size variation and cranial capacity variation in the large sample from the Sima de los Huesos site in Spain showed instead that the sexual dimorphism is comparable in Middle Pleistocene and modern populations.

Joseph S. Weiner and the foundation of post-WW II human biology in the United Kingdom.

PubMed

Little, Michael A; Collins, Kenneth J

2012-01-01

Both the United States and the United Kingdom experienced a transformation in the science of physical anthropology from the period before World War II until the post-war period. In the United States, Sherwood L. Washburn is credited with being a leading figure in this transformation. In the United Kingdom, two individuals were instrumental in bringing about a similar change in the profession. These were Joseph S. Weiner at the University of Oxford and Nigel Barnicot at the University of London, with Weiner playing the principal role as leader in what Washburn called the "New Physical Anthropology," that is, the application of evolutionary theory, the de-emphasis on race classification, and the application of the scientific method and experimental approaches to problem solving. Weiner's contributions to physical anthropology were broad-based--climatic and work physiology, paleoanthropology, and human variation--in what became known as human biology in the U.K. and human adaptability internationally. This biographical essay provides evidence for the significant influence of J.S. Weiner on the post-war development of human biology (biological or physical anthropology) inthe U.K. Copyright © 2012 Wiley Periodicals, Inc.

Bridging two scholarly islands enriches both: COI DNA barcodes for species identification versus human mitochondrial variation for the study of migrations and pathologies.

PubMed

Thaler, David S; Stoeckle, Mark Y

2016-10-01

DNA barcodes for species identification and the analysis of human mitochondrial variation have developed as independent fields even though both are based on sequences from animal mitochondria. This study finds questions within each field that can be addressed by reference to the other. DNA barcodes are based on a 648-bp segment of the mitochondrially encoded cytochrome oxidase I. From most species, this segment is the only sequence available. It is impossible to know whether it fairly represents overall mitochondrial variation. For modern humans, the entire mitochondrial genome is available from thousands of healthy individuals. SNPs in the human mitochondrial genome are evenly distributed across all protein-encoding regions arguing that COI DNA barcode is representative. Barcode variation among related species is largely based on synonymous codons. Data on human mitochondrial variation support the interpretation that most - possibly all - synonymous substitutions in mitochondria are selectively neutral. DNA barcodes confirm reports of a low variance in modern humans compared to nonhuman primates. In addition, DNA barcodes allow the comparison of modern human variance to many other extant animal species. Birds are a well-curated group in which DNA barcodes are coupled with census and geographic data. Putting modern human variation in the context of intraspecies variation among birds shows humans to be a single breeding population of average variance.

Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale.

PubMed

Liu, Siyang; Huang, Shujia; Rao, Junhua; Ye, Weijian; Krogh, Anders; Wang, Jun

2015-01-01

Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.

CRISPR/Cas9 Genome Editing: A Promising Tool for Therapeutic Applications of Induced Pluripotent Stem Cells.

PubMed

Zhang, Yanli; Sastre, Danuta; Wang, Feng

2018-01-01

Induced pluripotent stem cells hold tremendous potential for biological and therapeutic applications. The development of efficient technologies for targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) system is recently recognized as a powerful tool for editing DNA at specific loci. The ease of use of the CRISPR-Cas9 technology will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. More recently, this system was modified to repress (CRISPR interference, CRISPRi) or activate (CRISPR activation, CRISPRa) gene expression without alterations in the DNA, which amplified the scope of applications of CRISPR systems for stem cell biology. Here, we highlight latest advances of CRISPR-associated applications in human pluripotent stem cells. The challenges and future prospects of CRISPR-based systems for human research are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Host genetic variation impacts microbiome composition across human body sites.

PubMed

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

PubMed

Shtrichman, R; Germanguz, I; Itskovitz-Eldor, J

2013-06-01

Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.

The impact of next-generation sequencing on genomics

PubMed Central

Zhang, Jun; Chiodini, Rod; Badr, Ahmed; Zhang, Genfa

2011-01-01

This article reviews basic concepts, general applications, and the potential impact of next-generation sequencing (NGS) technologies on genomics, with particular reference to currently available and possible future platforms and bioinformatics. NGS technologies have demonstrated the capacity to sequence DNA at unprecedented speed, thereby enabling previously unimaginable scientific achievements and novel biological applications. But, the massive data produced by NGS also presents a significant challenge for data storage, analyses, and management solutions. Advanced bioinformatic tools are essential for the successful application of NGS technology. As evidenced throughout this review, NGS technologies will have a striking impact on genomic research and the entire biological field. With its ability to tackle the unsolved challenges unconquered by previous genomic technologies, NGS is likely to unravel the complexity of the human genome in terms of genetic variations, some of which may be confined to susceptible loci for some common human conditions. The impact of NGS technologies on genomics will be far reaching and likely change the field for years to come. PMID:21477781

Association of common genetic variants with human skin color variation in Indian populations.

PubMed

Sarkar, Anujit; Nandineni, Madhusudan R

2018-01-01

Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ∼31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ∼19% of the variation observed in the samples. These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. © 2017 Wiley Periodicals, Inc.

Spatial variation of the Universal Thermal Climate Index in Lublin in specified weather scenarios / Zróżnicowanie przestrzenne wskaźnika UTCI w Lublinie w określonych scenariuszach pogodowych

NASA Astrophysics Data System (ADS)

Dobek, Mateusz; Demczuk, Piotr; Nowosad, Marek

2013-06-01

Due to the diversified land relief and presence of numerous gorge dissections intensively used by man largely for recreational purposes, Lublin is a valuable study area in terms of bioclimatology. The results of modelling of the variation of the bioclimatic conditions of Lublin provide information useful e.g. in the economy and spatial planning. The determined features of the city's bioclimate can be a significant element in the selection of locations for new residential and recreational investments. Knowledge on the spatial variation of biometeorological situations positively and negatively influencing the human organism can also find application in activities concerning the improvement of life quality and health protection, as well as in tourism and recreation. The objective of the paper is to present the spatial variation of biometeorological conditions in Lublin based on the example of specified weather scenarios.

Diet composition as a source of variation in experimental animal models of cancer cachexia.

PubMed

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R; Mazurak, Vera

2016-05-01

A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. The search revealed a number of nutrient intervention studies (n = 44), with the majority including n-3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair-feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre-clinical studies and aid the interpretation and translation of results to humans with cancer.

Diet composition as a source of variation in experimental animal models of cancer cachexia

PubMed Central

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R.

2015-01-01

Abstract Background A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. Methods A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. Results The search revealed a number of nutrient intervention studies (n = 44), with the majority including n‐3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair‐feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. Conclusion The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre‐clinical studies and aid the interpretation and translation of results to humans with cancer. PMID:27493865

[The ways in which variations in space and atmospheric factors act upon the biosphere and humans].

PubMed

Chernogor, L F

2010-01-01

The system analysis is validated to be an efficient means for studying the channels through which variations in space and tropospheric weather affect the biosphere (humans). The basics of the system analysis paradigm are presented. The causes of variations in space and tropospheric weather are determined, and the interrelations between them are demonstrated. The ways in which these variations affect the biosphere (humans) are discussed. Aperiodic and quasi-periodic disturbances in the physical fields that influence the biosphere (humans) are intercompared.

A novel scheme for the validation of an automated classification method for epileptic spikes by comparison with multiple observers.

PubMed

Sharma, Niraj K; Pedreira, Carlos; Centeno, Maria; Chaudhary, Umair J; Wehner, Tim; França, Lucas G S; Yadee, Tinonkorn; Murta, Teresa; Leite, Marco; Vos, Sjoerd B; Ourselin, Sebastien; Diehl, Beate; Lemieux, Louis

2017-07-01

To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data. Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs. First, we determined whether WC-human agreement variability falls within inter-reviewer agreement variability by calculating the variation of information for each classifier pair and quantifying the overlap between all WC-reviewer and all reviewer-reviewer pairs. Second, we compared WC and EEG reviewers' spike identification and individual spike class labels visually and quantitatively. The overlap between all WC-human pairs and all human pairs was >80% for 3/5 patients and >58% for the other 2 patients demonstrating WC falling within inter-human variation. The average sensitivity of spike marking for WC was 91% and >87% for all three EEG reviewers. Finally, there was a strong visual and quantitative similarity between WC and EEG reviewers. WC performance is indistinguishable to that of EEG reviewers' suggesting it could be a valid clinical tool for the assessment of IEDs. WC can be used to provide quantitative analysis of epileptic spikes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Variation of ecosystem services and human activities: A case study in the Yanhe Watershed of China

NASA Astrophysics Data System (ADS)

Su, Chang-hong; Fu, Bo-Jie; He, Chan-Sheng; Lü, Yi-He

2012-10-01

The concept of 'ecosystem service' provides cohesive views on mechanisms by which nature contributes to human well-being. Fast social and economic development calls for research on interactions between human and natural systems. We took the Yanhe Watershed as our study area, and valued the variation of ecosystem services and human activities of 2000 and 2008. Five ecosystem services were selected i.e. net primary production (NPP), carbon sequestration and oxygen production (CSOP), water conservation, soil conservation, and grain production. Human activity was represented by a composite human activity index (HAI) that integrates human population density, farmland ratio, influence of residential sites and road network. Analysis results of the five ecosystem services and human activity (HAI) are as follows: (i) NPP, CSOP, water conservation, and soil conservation increased from 2000 to 2008, while grain production declined. HAI decreased from 2000 to 2008. Spatially, NPP, CSOP, and water conservation in 2000 and 2008 roughly demonstrated a pattern of decline from south to north, while grain production shows an endocentric increasing spatial pattern. Soil conservation showed a spatial pattern of high in the south and low in the north in 2000 and a different pattern of high in the west and low in the east in 2008 respectively. HAI is proportional to the administrative level and economic development. Variation of NPP/CSOP between 2000 and 2008 show an increasing spatial pattern from northwest to southeast. In contrast, the variation of soil conservation shows an increasing pattern from southeast to northwest. Variation of water conservation shows a fanning out decreasing pattern. Variation of grain production doesn't show conspicuous spatial pattern. (ii) Variation of water conservation and of soil conservation is significantly positively correlated at 0.01 level. Both variations of water conservation and soil conservation are negatively correlated with variation of HAI at 0.01 level. Variations of NPP/CSOP are negatively correlated with variations of soil conservation and grain production at 0.05 level. (iii) Strong tradeoffs exist between regulation services and provision service, while synergies exist within regulation services. Driving effect of human activities on ecosystem services and tradeoffs and synergies among ecosystem service are also discussed.

Three-dimensional (3D) geometric morphometric analysis of human premolars to assess sexual dimorphism and biological ancestry in Australian populations.

PubMed

Yong, Robin; Ranjitkar, Sarbin; Lekkas, Dimitra; Halazonetis, Demetrios; Evans, Alistair; Brook, Alan; Townsend, Grant

2018-06-01

This study aimed to investigate size and shape variation of human premolars between Indigenous Australians and Australians of European ancestry, and to assess whether sex and ancestry could be differentiated between these groups using 3D geometric morphometrics. Seventy dental casts from each group, equally subdivided by sex, were scanned using a structured-light scanner. The 3D meshes of upper and lower premolars were processed using geometric morphometric methods. Seventy-two landmarks were recorded for upper premolars and 50 landmarks for lower premolars. For each tooth type, two-way ANOVA was used to assess group differences in centroid size. Shape variations were explored using principal component analysis and visualized using 3D morphing. Two-way Procrustes ANOVA was applied to test group differences for ancestry and sex, and a "leave-one-out" discriminant function was applied to assess group assignment. Centroid size and shape did not display significant difference between the sexes. Centroid size was larger in Indigenous Australians for upper premolars and lower second premolars compared to the Australians of European ancestry. Significant shape variation was noted between the two ancestral groups for upper premolars and the lower first premolar. Correct group assignment of individual teeth to their ancestral groups ranged between 80.0 and 92.8% for upper premolars and 60.0 and 75.7% for lower premolars. Our findings provide evidence of significant size and shape variation in human premolars between the two ancestral groups. High classification rates based on shape analysis of upper premolars highlight potential application of geometric morphometrics in anthropological, bioarcheological and forensic contexts. © 2018 Wiley Periodicals, Inc.

Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data.

PubMed

Cole, Charles; Krampis, Konstantinos; Karagiannis, Konstantinos; Almeida, Jonas S; Faison, William J; Motwani, Mona; Wan, Quan; Golikov, Anton; Pan, Yang; Simonyan, Vahan; Mazumder, Raja

2014-01-27

Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available from the CSR website (http://hive.biochemistry.gwu.edu/dna.cgi?cmd=csr). Availability of thousands of sequenced samples from patients provides a rich repository of sequence information that can be utilized to identify individual level SNVs and their effect on the human proteome beyond what the dbSNP database provides.

Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data

PubMed Central

2014-01-01

Background Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. Results To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available from the CSR website (http://hive.biochemistry.gwu.edu/dna.cgi?cmd=csr). Conclusions Availability of thousands of sequenced samples from patients provides a rich repository of sequence information that can be utilized to identify individual level SNVs and their effect on the human proteome beyond what the dbSNP database provides. PMID:24467687

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening.

PubMed

Tyson, Jess; Majerus, Tamsin Mo; Walker, Susan; Armour, John Al

2009-09-28

Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

Quadruplex MAPH: improvement of throughput in high-resolution copy number screening

PubMed Central

Tyson, Jess; Majerus, Tamsin MO; Walker, Susan; Armour, John AL

2009-01-01

Background Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Results Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. Conclusion QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms. PMID:19785739

Top-down Proteomics in Health and Disease: Challenges and Opportunities

PubMed Central

Gregorich, Zachery R.; Ge, Ying

2014-01-01

Proteomics is essential for deciphering how molecules interact as a system and for understanding the functions of cellular systems in human disease; however, the unique characteristics of the human proteome, which include a high dynamic range of protein expression and extreme complexity due to a plethora of post-translational modifications (PTMs) and sequence variations, make such analyses challenging. An emerging “top-down” mass spectrometry (MS)-based proteomics approach, which provides a “bird’s eye” view of all proteoforms, has unique advantages for the assessment of PTMs and sequence variations. Recently, a number of studies have showcased the potential of top-down proteomics for unraveling of disease mechanisms and discovery of new biomarkers. Nevertheless, the top-down approach still faces significant challenges in terms of protein solubility, separation, and the detection of large intact proteins, as well as the under-developed data analysis tools. Consequently, new technological developments are urgently needed to advance the field of top-down proteomics. Herein, we intend to provide an overview of the recent applications of top-down proteomics in biomedical research. Moreover, we will outline the challenges and opportunities facing top-down proteomics strategies aimed at understanding and diagnosing human diseases. PMID:24723472

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

PubMed

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Estimation of time-dependent Hurst exponents with variational smoothing and application to forecasting foreign exchange rates

NASA Astrophysics Data System (ADS)

Garcin, Matthieu

2017-10-01

Hurst exponents depict the long memory of a time series. For human-dependent phenomena, as in finance, this feature may vary in the time. It justifies modelling dynamics by multifractional Brownian motions, which are consistent with time-dependent Hurst exponents. We improve the existing literature on estimating time-dependent Hurst exponents by proposing a smooth estimate obtained by variational calculus. This method is very general and not restricted to the sole Hurst framework. It is globally more accurate and easier than other existing non-parametric estimation techniques. Besides, in the field of Hurst exponents, it makes it possible to make forecasts based on the estimated multifractional Brownian motion. The application to high-frequency foreign exchange markets (GBP, CHF, SEK, USD, CAD, AUD, JPY, CNY and SGD, all against EUR) shows significantly good forecasts. When the Hurst exponent is higher than 0.5, what depicts a long-memory feature, the accuracy is higher.

Child Development and Structural Variation in the Human Genome

ERIC Educational Resources Information Center

Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

2013-01-01

Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

α satellite DNA variation and function of the human centromere

PubMed Central

Sullivan, Lori L.; Chew, Kimberline

2017-01-01

ABSTRACT Genomic variation is a source of functional diversity that is typically studied in genic and non-coding regulatory regions. However, the extent of variation within noncoding portions of the human genome, particularly highly repetitive regions, and the functional consequences are not well understood. Satellite DNA, including α satellite DNA found at human centromeres, comprises up to 10% of the genome, but is difficult to study because its repetitive nature hinders contiguous sequence assemblies. We recently described variation within α satellite DNA that affects centromere function. On human chromosome 17 (HSA17), we showed that size and sequence polymorphisms within primary array D17Z1 are associated with chromosome aneuploidy and defective centromere architecture. However, HSA17 can counteract this instability by assembling the centromere at a second, “backup” array lacking variation. Here, we discuss our findings in a broader context of human centromere assembly, and highlight areas of future study to uncover links between genomic and epigenetic features of human centromeres. PMID:28406740

[Single nucleotide polymorphism and its application in allogeneic hematopoietic stem cell transplantation--review].

PubMed

Li, Su-Xia

2004-12-01

Single nucleotide polymorphism (SNP) is the third genetic marker after restriction fragment length polymorphism (RFLP) and short tandem repeat. It represents the most density genetic variability in the human genome and has been widely used in gene location, cloning, and research of heredity variation, as well as parenthood identification in forensic medicine. As steady heredity polymorphism, single nucleotide polymorphism is becoming the focus of attention in monitoring chimerism and minimal residual disease in the patients after allogeneic hematopoietic stem cell transplantation. The article reviews SNP heredity characterization, analysis techniques and its applications in allogeneic stem cell transplantation and other fields.

Efficient and robust pupil size and blink estimation from near-field video sequences for human-machine interaction.

PubMed

Chen, Siyuan; Epps, Julien

2014-12-01

Monitoring pupil and blink dynamics has applications in cognitive load measurement during human-machine interaction. However, accurate, efficient, and robust pupil size and blink estimation pose significant challenges to the efficacy of real-time applications due to the variability of eye images, hence to date, require manual intervention for fine tuning of parameters. In this paper, a novel self-tuning threshold method, which is applicable to any infrared-illuminated eye images without a tuning parameter, is proposed for segmenting the pupil from the background images recorded by a low cost webcam placed near the eye. A convex hull and a dual-ellipse fitting method are also proposed to select pupil boundary points and to detect the eyelid occlusion state. Experimental results on a realistic video dataset show that the measurement accuracy using the proposed methods is higher than that of widely used manually tuned parameter methods or fixed parameter methods. Importantly, it demonstrates convenience and robustness for an accurate and fast estimate of eye activity in the presence of variations due to different users, task types, load, and environments. Cognitive load measurement in human-machine interaction can benefit from this computationally efficient implementation without requiring a threshold calibration beforehand. Thus, one can envisage a mini IR camera embedded in a lightweight glasses frame, like Google Glass, for convenient applications of real-time adaptive aiding and task management in the future.

Internet Communication Disorder and the structure of the human brain: initial insights on WeChat addiction.

PubMed

Montag, Christian; Zhao, Zhiying; Sindermann, Cornelia; Xu, Lei; Fu, Meina; Li, Jialin; Zheng, Xiaoxiao; Li, Keshuang; Kendrick, Keith M; Dai, Jing; Becker, Benjamin

2018-02-01

WeChat represents one of the most popular smartphone-based applications for communication. Although the application provides several useful features that simplify daily life, a growing number of users spend excessive amounts of time on the application. This may lead to interferences with everyday life and even to addictive patterns of use. In the context of the ongoing discussion on Internet Communication Disorder (ICD), the present study aimed to better characterize the addictive potential of communication applications, using WeChat as an example, by examining associations between individual variations in tendencies towards WeChat addiction and brain structural variations in fronto-striatal-limbic brain regions. To this end levels of addictive tendencies, frequency of use and structural MRI data were assessed in n = 61 healthy participants. Higher tendencies towards WeChat addiction were associated with smaller gray matter volumes of the subgenual anterior cingulate cortex, a key region for monitoring and regulatory control in neural networks underlying addictive behaviors. Moreover, a higher frequency of the paying function was associated with smaller nucleus accumbens volumes. Findings were robust after controlling for levels of anxiety and depression. The present results are in line with previous findings in substance and behavioral addictions, and suggest a similar neurobiological basis in ICD.

Exploiting sequence similarity to validate the sensitivity of SNP arrays in detecting fine-scaled copy number variations.

PubMed

Wong, Gerard; Leckie, Christopher; Gorringe, Kylie L; Haviv, Izhak; Campbell, Ian G; Kowalczyk, Adam

2010-04-15

High-density single nucleotide polymorphism (SNP) genotyping arrays are efficient and cost effective platforms for the detection of copy number variation (CNV). To ensure accuracy in probe synthesis and to minimize production costs, short oligonucleotide probe sequences are used. The use of short probe sequences limits the specificity of binding targets in the human genome. The specificity of these short probeset sequences has yet to be fully analysed against a normal reference human genome. Sequence similarity can artificially elevate or suppress copy number measurements, and hence reduce the reliability of affected probe readings. For the purpose of detecting narrow CNVs reliably down to the width of a single probeset, sequence similarity is an important issue that needs to be addressed. We surveyed the Affymetrix Human Mapping SNP arrays for probeset sequence similarity against the reference human genome. Utilizing sequence similarity results, we identified a collection of fine-scaled putative CNVs between gender from autosomal probesets whose sequence matches various loci on the sex chromosomes. To detect these variations, we utilized our statistical approach, Detecting REcurrent Copy number change using rank-order Statistics (DRECS), and showed that its performance was superior and more stable than the t-test in detecting CNVs. Through the application of DRECS on the HapMap population datasets with multi-matching probesets filtered, we identified biologically relevant SNPs in aberrant regions across populations with known association to physical traits, such as height, covered by the span of a single probe. This provided empirical confirmation of the existence of naturally occurring narrow CNVs as well as the sensitivity of the Affymetrix SNP array technology in detecting them. The MATLAB implementation of DRECS is available at http://ww2.cs.mu.oz.au/ approximately gwong/DRECS/index.html.

Intrapopulational body size variation and cranial capacity variation in Middle Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).

PubMed

Lorenzo, C; Carretero, J M; Arsuaga, J L; Gracia, A; Martínez, I

1998-05-01

A sexual dimorphism more marked than in living humans has been claimed for European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In this paper, body size and cranial capacity variation are studied in the Sima de los Huesos Middle Pleistocene sample. This is the largest sample of non-modern humans found to date from one single site, and with all skeletal elements represented. Since the techniques available to estimate the degree of sexual dimorphism in small palaeontological samples are all unsatisfactory, we have used the bootstraping method to asses the magnitude of the variation in the Sima de los Huesos sample compared to modern human intrapopulational variation. We analyze size variation without attempting to sex the specimens a priori. Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella; calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral midshaft perimeter shows an unusual high variation (only when it is expressed by the maximum ratio, not by the coefficient of variation). In spite of that the cranial capacity range at Sima de los Huesos almost spans the rest of the European and African Middle Pleistocene range. The maximum ratio is in the central part of the distribution of modern human samples. Thus, the hypothesis of a greater sexual dimorphism in Middle Pleistocene populations than in modern populations is not supported by either cranial or postcranial evidence from Sima de los Huesos.

Evolutionary Determinants of Genetic Variation in Susceptibility to Infectious Diseases in Humans

PubMed Central

Baker, Christi; Antonovics, Janis

2012-01-01

Although genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles. These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. The strongest predictors of levels of genetic variation in susceptibility were disease characteristics negatively associated with immune effectiveness. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful. These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology. PMID:22242158

Precision wildlife medicine: applications of the human-centred precision medicine revolution to species conservation.

PubMed

Whilde, Jenny; Martindale, Mark Q; Duffy, David J

2017-05-01

The current species extinction crisis is being exacerbated by an increased rate of emergence of epizootic disease. Human-induced factors including habitat degradation, loss of biodiversity and wildlife population reductions resulting in reduced genetic variation are accelerating disease emergence. Novel, efficient and effective approaches are required to combat these epizootic events. Here, we present the case for the application of human precision medicine approaches to wildlife medicine in order to enhance species conservation efforts. We consider how the precision medicine revolution, coupled with the advances made in genomics, may provide a powerful and feasible approach to identifying and treating wildlife diseases in a targeted, effective and streamlined manner. A number of case studies of threatened species are presented which demonstrate the applicability of precision medicine to wildlife conservation, including sea turtles, amphibians and Tasmanian devils. These examples show how species conservation could be improved by using precision medicine techniques to determine novel treatments and management strategies for the specific medical conditions hampering efforts to restore population levels. Additionally, a precision medicine approach to wildlife health has in turn the potential to provide deeper insights into human health and the possibility of stemming and alleviating the impacts of zoonotic diseases. The integration of the currently emerging Precision Medicine Initiative with the concepts of EcoHealth (aiming for sustainable health of people, animals and ecosystems through transdisciplinary action research) and One Health (recognizing the intimate connection of humans, animal and ecosystem health and addressing a wide range of risks at the animal-human-ecosystem interface through a coordinated, collaborative, interdisciplinary approach) has great potential to deliver a deeper and broader interdisciplinary-based understanding of both wildlife and human diseases. © 2016 John Wiley & Sons Ltd.

Statistical Analysis of Variation in the Human Plasma Proteome

DOE PAGES

Corzett, Todd H.; Fodor, Imola K.; Choi, Megan W.; ...

2010-01-01

Quantifying the variation in the human plasma proteome is an essential prerequisite for disease-specific biomarker detection. We report here on the longitudinal and individual variation in human plasma characterized by two-dimensional difference gel electrophoresis (2-D DIGE) using plasma samples from eleven healthy subjects collected three times over a two week period. Fixed-effects modeling was used to remove dye and gel variability. Mixed-effects modeling was then used to quantitate the sources of proteomic variation. The subject-to-subject variation represented the largest variance component, while the time-within-subject variation was comparable to the experimental variation found in a previous technical variability study where onemore » human plasma sample was processed eight times in parallel and each was then analyzed by 2-D DIGE in triplicate. Here, 21 protein spots had larger than 50% CV, suggesting that these proteins may not be appropriate as biomarkers and should be carefully scrutinized in future studies. Seventy-eight protein spots showing differential protein levels between different individuals or individual collections were identified by mass spectrometry and further characterized using hierarchical clustering. The results present a first step toward understanding the complexity of longitudinal and individual variation in the human plasma proteome, and provide a baseline for improved biomarker discovery.« less

Statistical analysis of variation in the human plasma proteome.

PubMed

Corzett, Todd H; Fodor, Imola K; Choi, Megan W; Walsworth, Vicki L; Turteltaub, Kenneth W; McCutchen-Maloney, Sandra L; Chromy, Brett A

2010-01-01

Quantifying the variation in the human plasma proteome is an essential prerequisite for disease-specific biomarker detection. We report here on the longitudinal and individual variation in human plasma characterized by two-dimensional difference gel electrophoresis (2-D DIGE) using plasma samples from eleven healthy subjects collected three times over a two week period. Fixed-effects modeling was used to remove dye and gel variability. Mixed-effects modeling was then used to quantitate the sources of proteomic variation. The subject-to-subject variation represented the largest variance component, while the time-within-subject variation was comparable to the experimental variation found in a previous technical variability study where one human plasma sample was processed eight times in parallel and each was then analyzed by 2-D DIGE in triplicate. Here, 21 protein spots had larger than 50% CV, suggesting that these proteins may not be appropriate as biomarkers and should be carefully scrutinized in future studies. Seventy-eight protein spots showing differential protein levels between different individuals or individual collections were identified by mass spectrometry and further characterized using hierarchical clustering. The results present a first step toward understanding the complexity of longitudinal and individual variation in the human plasma proteome, and provide a baseline for improved biomarker discovery.

The optimal modified variational iteration method for the Lane-Emden equations with Neumann and Robin boundary conditions

NASA Astrophysics Data System (ADS)

Singh, Randhir; Das, Nilima; Kumar, Jitendra

2017-06-01

An effective analytical technique is proposed for the solution of the Lane-Emden equations. The proposed technique is based on the variational iteration method (VIM) and the convergence control parameter h . In order to avoid solving a sequence of nonlinear algebraic or complicated integrals for the derivation of unknown constant, the boundary conditions are used before designing the recursive scheme for solution. The series solutions are found which converges rapidly to the exact solution. Convergence analysis and error bounds are discussed. Accuracy, applicability of the method is examined by solving three singular problems: i) nonlinear Poisson-Boltzmann equation, ii) distribution of heat sources in the human head, iii) second-kind Lane-Emden equation.

Characterizing noise in nonhuman vocalizations: Acoustic analysis and human perception of barks by coyotes and dogs

NASA Astrophysics Data System (ADS)

Riede, Tobias; Mitchell, Brian R.; Tokuda, Isao; Owren, Michael J.

2005-07-01

Measuring noise as a component of mammalian vocalizations is of interest because of its potential relevance to the communicative function. However, methods for characterizing and quantifying noise are less well established than methods applicable to harmonically structured aspects of signals. Using barks of coyotes and domestic dogs, we compared six acoustic measures and studied how they are related to human perception of noisiness. Measures of harmonic-to-noise-ratio (HNR), percent voicing, and shimmer were found to be the best predictors of perceptual rating by human listeners. Both acoustics and perception indicated that noisiness was similar across coyote and dog barks, but within each species there was significant variation among the individual vocalizers. The advantages and disadvantages of the various measures are discussed.

Abundant raw material for cis-regulatory evolution in humans

NASA Technical Reports Server (NTRS)

Rockman, Matthew V.; Wray, Gregory A.

2002-01-01

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

Neuromorphic Vibrotactile Stimulation of Fingertips for Encoding Object Stiffness in Telepresence Sensory Substitution and Augmentation Applications

PubMed Central

Sorgini, Francesca; Massari, Luca; D’Abbraccio, Jessica; Petrovic, Petar B.; Carrozza, Maria Chiara; Newell, Fiona N.

2018-01-01

We present a tactile telepresence system for real-time transmission of information about object stiffness to the human fingertips. Experimental tests were performed across two laboratories (Italy and Ireland). In the Italian laboratory, a mechatronic sensing platform indented different rubber samples. Information about rubber stiffness was converted into on-off events using a neuronal spiking model and sent to a vibrotactile glove in the Irish laboratory. Participants discriminated the variation of the stiffness of stimuli according to a two-alternative forced choice protocol. Stiffness discrimination was based on the variation of the temporal pattern of spikes generated during the indentation of the rubber samples. The results suggest that vibrotactile stimulation can effectively simulate surface stiffness when using neuronal spiking models to trigger vibrations in the haptic interface. Specifically, fractional variations of stiffness down to 0.67 were significantly discriminated with the developed neuromorphic haptic interface. This is a performance comparable, though slightly worse, to the threshold obtained in a benchmark experiment evaluating the same set of stimuli naturally with the own hand. Our paper presents a bioinspired method for delivering sensory feedback about object properties to human skin based on contingency–mimetic neuronal models, and can be useful for the design of high performance haptic devices. PMID:29342076

Size variation in early human mandibles and molars from Klasies River, South Africa: comparison with other middle and late Pleistocene assemblages and with modern humans.

PubMed

Royer, Danielle F; Lockwood, Charles A; Scott, Jeremiah E; Grine, Frederick E

2009-10-01

Previous studies of the Middle Stone Age human remains from Klasies River have concluded that they exhibited more sexual dimorphism than extant populations, but these claims have not been assessed statistically. We evaluate these claims by comparing size variation in the best-represented elements at the site, namely the mandibular corpora and M(2)s, to that in samples from three recent human populations using resampling methods. We also examine size variation in these same elements from seven additional middle and late Pleistocene sites: Skhūl, Dolní Vestonice, Sima de los Huesos, Arago, Krapina, Shanidar, and Vindija. Our results demonstrate that size variation in the Klasies assemblage was greater than in recent humans, consistent with arguments that the Klasies people were more dimorphic than living humans. Variation in the Skhūl, Dolní Vestonice, and Sima de los Huesos mandibular samples is also higher than in the recent human samples, indicating that the Klasies sample was not unusual among middle and late Pleistocene hominins. In contrast, the Neandertal samples (Krapina, Shanidar, and Vindija) do not evince relatively high mandibular and molar variation, which may indicate that the level of dimorphism in Neandertals was similar to that observed in extant humans. These results suggest that the reduced levels of dimorphism in Neandertals and living humans may have developed independently, though larger fossil samples are needed to test this hypothesis.

Flexible Sensors for Pressure Therapy: Effect of Substrate Curvature and Stiffness on Sensor Performance.

PubMed

Khodasevych, Iryna; Parmar, Suresh; Troynikov, Olga

2017-10-20

Flexible pressure sensors are increasingly being used in medical and non-medical applications, and particularly in innovative health monitoring. Their efficacy in medical applications such as compression therapy depends on the accuracy and repeatability of their output, which in turn depend on factors such as sensor type, shape, pressure range, and conformability of the sensor to the body surface. Numerous researchers have examined the effects of sensor type and shape, but little information is available on the effect of human body parameters such as support surfaces' curvature and the stiffness of soft tissues on pressure sensing performance. We investigated the effects of body parameters on the performance of pressure sensors using a custom-made human-leg-like test setup. Pressure sensing parameters such as accuracy, drift and repeatability were determined in both static (eight hours continuous pressure) and dynamic (10 cycles of pressure application of 30 s duration) testing conditions. The testing was performed with a focus on compression therapy application for venous leg ulcer treatments, and was conducted in a low-pressure range of 20-70 mmHg. Commercially available sensors manufactured by Peratech and Sensitronics were used under various loading conditions to determine the influence of stiffness and curvature. Flat rigid, flat soft silicone and three cylindrical silicone surfaces of radii of curvature of 3.5 cm, 5.5 cm and 6.5 cm were used as substrates under the sensors. The Peratech sensor averaged 94% accuracy for both static and dynamic measurements on all substrates; the Sensitronics sensor averaged 88% accuracy. The Peratech sensor displayed moderate variations and the Sensitronics sensor large variations in output pressure readings depending on the underlying test surface, both of which were reduced markedly by individual pressure calibration for surface type. Sensor choice and need for calibration to surface type are important considerations for their application in healthcare monitoring.

Flexible Sensors for Pressure Therapy: Effect of Substrate Curvature and Stiffness on Sensor Performance

PubMed Central

Khodasevych, Iryna; Parmar, Suresh

2017-01-01

Flexible pressure sensors are increasingly being used in medical and non-medical applications, and particularly in innovative health monitoring. Their efficacy in medical applications such as compression therapy depends on the accuracy and repeatability of their output, which in turn depend on factors such as sensor type, shape, pressure range, and conformability of the sensor to the body surface. Numerous researchers have examined the effects of sensor type and shape, but little information is available on the effect of human body parameters such as support surfaces’ curvature and the stiffness of soft tissues on pressure sensing performance. We investigated the effects of body parameters on the performance of pressure sensors using a custom-made human-leg-like test setup. Pressure sensing parameters such as accuracy, drift and repeatability were determined in both static (eight hours continuous pressure) and dynamic (10 cycles of pressure application of 30 s duration) testing conditions. The testing was performed with a focus on compression therapy application for venous leg ulcer treatments, and was conducted in a low-pressure range of 20–70 mmHg. Commercially available sensors manufactured by Peratech and Sensitronics were used under various loading conditions to determine the influence of stiffness and curvature. Flat rigid, flat soft silicone and three cylindrical silicone surfaces of radii of curvature of 3.5 cm, 5.5 cm and 6.5 cm were used as substrates under the sensors. The Peratech sensor averaged 94% accuracy for both static and dynamic measurements on all substrates; the Sensitronics sensor averaged 88% accuracy. The Peratech sensor displayed moderate variations and the Sensitronics sensor large variations in output pressure readings depending on the underlying test surface, both of which were reduced markedly by individual pressure calibration for surface type. Sensor choice and need for calibration to surface type are important considerations for their application in healthcare monitoring. PMID:29053605

Systematic review of the concentrations of oligosaccharides in human milk

PubMed Central

Thurl, Stephan; Munzert, Manfred; Boehm, Günther; Matthews, Catherine; Stahl, Bernd

2017-01-01

Context Oligosaccharides are the third largest solid component in human milk. These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. The structures of more than 100 oligosaccharides in human milk have been elucidated so far. Objective The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. Data Sources A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. Study Selection The initial search resulted in 1363 hits. After the elimination of duplicates, the literature was screened. The application of strict inclusion criteria resulted in 21 articles selected. Data Extraction Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. Results Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. In addition, large interlaboratory variations in the data were observed. Conclusions Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. PMID:29053807

Systematic review of the concentrations of oligosaccharides in human milk.

PubMed

Thurl, Stephan; Munzert, Manfred; Boehm, Günther; Matthews, Catherine; Stahl, Bernd

2017-11-01

Oligosaccharides are the third largest solid component in human milk. These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. The structures of more than 100 oligosaccharides in human milk have been elucidated so far. The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. The initial search resulted in 1363 hits. After the elimination of duplicates, the literature was screened. The application of strict inclusion criteria resulted in 21 articles selected. Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. In addition, large interlaboratory variations in the data were observed. Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

Differential Entropy Preserves Variational Information of Near-Infrared Spectroscopy Time Series Associated With Working Memory.

PubMed

Keshmiri, Soheil; Sumioka, Hidenubo; Yamazaki, Ryuji; Ishiguro, Hiroshi

2018-01-01

Neuroscience research shows a growing interest in the application of Near-Infrared Spectroscopy (NIRS) in analysis and decoding of the brain activity of human subjects. Given the correlation that is observed between the Blood Oxygen Dependent Level (BOLD) responses that are exhibited by the time series data of functional Magnetic Resonance Imaging (fMRI) and the hemoglobin oxy/deoxy-genation that is captured by NIRS, linear models play a central role in these applications. This, in turn, results in adaptation of the feature extraction strategies that are well-suited for discretization of data that exhibit a high degree of linearity, namely, slope and the mean as well as their combination, to summarize the informational contents of the NIRS time series. In this article, we demonstrate that these features are inefficient in capturing the variational information of NIRS data, limiting the reliability and the adequacy of the conclusion on their results. Alternatively, we propose the linear estimate of differential entropy of these time series as a natural representation of such information. We provide evidence for our claim through comparative analysis of the application of these features on NIRS data pertinent to several working memory tasks as well as naturalistic conversational stimuli.

Deep Networks Can Resemble Human Feed-forward Vision in Invariant Object Recognition

PubMed Central

Kheradpisheh, Saeed Reza; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

2016-01-01

Deep convolutional neural networks (DCNNs) have attracted much attention recently, and have shown to be able to recognize thousands of object categories in natural image databases. Their architecture is somewhat similar to that of the human visual system: both use restricted receptive fields, and a hierarchy of layers which progressively extract more and more abstracted features. Yet it is unknown whether DCNNs match human performance at the task of view-invariant object recognition, whether they make similar errors and use similar representations for this task, and whether the answers depend on the magnitude of the viewpoint variations. To investigate these issues, we benchmarked eight state-of-the-art DCNNs, the HMAX model, and a baseline shallow model and compared their results to those of humans with backward masking. Unlike in all previous DCNN studies, we carefully controlled the magnitude of the viewpoint variations to demonstrate that shallow nets can outperform deep nets and humans when variations are weak. When facing larger variations, however, more layers were needed to match human performance and error distributions, and to have representations that are consistent with human behavior. A very deep net with 18 layers even outperformed humans at the highest variation level, using the most human-like representations. PMID:27601096

Evolutionary contributions to the study of human fertility.

PubMed

Sear, Rebecca

2015-01-01

Demography, lacking an overarching theoretical framework of its own, has drawn on theories in many other social sciences to inform its analyses. The aim of this paper is to bring to the demographic community's attention research in the evolutionary sciences on fertility, and to demonstrate that evolutionary theory can be another useful tool in the demographer's toolkit. I first dispel some myths which impede the incorporation of evolutionary theory into demography: I make it clear that evolutionary explanations do not assume that all human behaviour is hardwired and functions to maximize genetic fitness; that they are able to explain variation in human behaviour; and that they are not necessarily alternatives to social science explanations. I then describe the diversity of work on fertility by evolutionary researchers, particularly human evolutionary ecologists and cultural evolutionists, and illustrate the usefulness of the evolutionary approach with examples of its application to age at first birth and the fertility transition.

Personalized skincare: from molecular basis to clinical and commercial applications.

PubMed

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare.

Personalized skincare: from molecular basis to clinical and commercial applications

PubMed Central

Markiewicz, Ewa; Idowu, Olusola Clement

2018-01-01

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare. PMID:29692619

ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins

PubMed Central

Krassowski, Michal; Paczkowska, Marta; Cullion, Kim; Huang, Tina; Dzneladze, Irakli; Ouellette, B F Francis; Yamada, Joseph T; Fradet-Turcotte, Amelie

2018-01-01

Abstract Interpretation of genetic variation is needed for deciphering genotype-phenotype associations, mechanisms of inherited disease, and cancer driver mutations. Millions of single nucleotide variants (SNVs) in human genomes are known and thousands are associated with disease. An estimated 21% of disease-associated amino acid substitutions corresponding to missense SNVs are located in protein sites of post-translational modifications (PTMs), chemical modifications of amino acids that extend protein function. ActiveDriverDB is a comprehensive human proteo-genomics database that annotates disease mutations and population variants through the lens of PTMs. We integrated >385,000 published PTM sites with ∼3.6 million substitutions from The Cancer Genome Atlas (TCGA), the ClinVar database of disease genes, and human genome sequencing projects. The database includes site-specific interaction networks of proteins, upstream enzymes such as kinases, and drugs targeting these enzymes. We also predicted network-rewiring impact of mutations by analyzing gains and losses of kinase-bound sequence motifs. ActiveDriverDB provides detailed visualization, filtering, browsing and searching options for studying PTM-associated mutations. Users can upload mutation datasets interactively and use our application programming interface in pipelines. Integrative analysis of mutations and PTMs may help decipher molecular mechanisms of phenotypes and disease, as exemplified by case studies of TP53, BRCA2 and VHL. The open-source database is available at https://www.ActiveDriverDB.org. PMID:29126202

Scanning the human genome at kilobase resolution.

PubMed

Chen, Jun; Kim, Yeong C; Jung, Yong-Chul; Xuan, Zhenyu; Dworkin, Geoff; Zhang, Yanming; Zhang, Michael Q; Wang, San Ming

2008-05-01

Normal genome variation and pathogenic genome alteration frequently affect small regions in the genome. Identifying those genomic changes remains a technical challenge. We report here the development of the DGS (Ditag Genome Scanning) technique for high-resolution analysis of genome structure. The basic features of DGS include (1) use of high-frequent restriction enzymes to fractionate the genome into small fragments; (2) collection of two tags from two ends of a given DNA fragment to form a ditag to represent the fragment; (3) application of the 454 sequencing system to reach a comprehensive ditag sequence collection; (4) determination of the genome origin of ditags by mapping to reference ditags from known genome sequences; (5) use of ditag sequences directly as the sense and antisense PCR primers to amplify the original DNA fragment. To study the relationship between ditags and genome structure, we performed a computational study by using the human genome reference sequences as a model, and analyzed the ditags experimentally collected from the well-characterized normal human DNA GM15510 and the leukemic human DNA of Kasumi-1 cells. Our studies show that DGS provides a kilobase resolution for studying genome structure with high specificity and high genome coverage. DGS can be applied to validate genome assembly, to compare genome similarity and variation in normal populations, and to identify genomic abnormality including insertion, inversion, deletion, translocation, and amplification in pathological genomes such as cancer genomes.

Minimal Absent Words in Four Human Genome Assemblies

PubMed Central

Garcia, Sara P.; Pinho, Armando J.

2011-01-01

Minimal absent words have been computed in genomes of organisms from all domains of life. Here, we aim to contribute to the catalogue of human genomic variation by investigating the variation in number and content of minimal absent words within a species, using four human genome assemblies. We compare the reference human genome GRCh37 assembly, the HuRef assembly of the genome of Craig Venter, the NA12878 assembly from cell line GM12878, and the YH assembly of the genome of a Han Chinese individual. We find the variation in number and content of minimal absent words between assemblies more significant for large and very large minimal absent words, where the biases of sequencing and assembly methodologies become more pronounced. Moreover, we find generally greater similarity between the human genome assemblies sequenced with capillary-based technologies (GRCh37 and HuRef) than between the human genome assemblies sequenced with massively parallel technologies (NA12878 and YH). Finally, as expected, we find the overall variation in number and content of minimal absent words within a species to be generally smaller than the variation between species. PMID:22220210

An analytical approach to separate climate and human contributions to basin streamflow variability

NASA Astrophysics Data System (ADS)

Li, Changbin; Wang, Liuming; Wanrui, Wang; Qi, Jiaguo; Linshan, Yang; Zhang, Yuan; Lei, Wu; Cui, Xia; Wang, Peng

2018-04-01

Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change (ΔQc) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

Observing Consistency in Online Communication Patterns for User Re-Identification.

PubMed

Adeyemi, Ikuesan Richard; Razak, Shukor Abd; Salleh, Mazleena; Venter, Hein S

2016-01-01

Comprehension of the statistical and structural mechanisms governing human dynamics in online interaction plays a pivotal role in online user identification, online profile development, and recommender systems. However, building a characteristic model of human dynamics on the Internet involves a complete analysis of the variations in human activity patterns, which is a complex process. This complexity is inherent in human dynamics and has not been extensively studied to reveal the structural composition of human behavior. A typical method of anatomizing such a complex system is viewing all independent interconnectivity that constitutes the complexity. An examination of the various dimensions of human communication pattern in online interactions is presented in this paper. The study employed reliable server-side web data from 31 known users to explore characteristics of human-driven communications. Various machine-learning techniques were explored. The results revealed that each individual exhibited a relatively consistent, unique behavioral signature and that the logistic regression model and model tree can be used to accurately distinguish online users. These results are applicable to one-to-one online user identification processes, insider misuse investigation processes, and online profiling in various areas.

[The prospect of application of toxicogenetics/pharmcogenetics theory and methods in forensic practice].

PubMed

Shen, Dan-na; Yi, Xu-fu; Chen, Xiao-gang; Xu, Tong-li; Cui, Li-juan

2007-10-01

Individual response to drugs, toxicants, environmental chemicals and allergens varies with genotype. Some respond well to these substances without significant consequences, while others may respond strongly with severe consequences and even death. Toxicogenetics and toxicogenomics as well as pharmacogenetics explain the genetic basis for the variations of individual response to toxicants by sequencing the human genome and large-scale identification of genome polymorphism. The new disciplines will provide a new route for forensic specialists to determine the cause of death.

Applications of the 1000 Genomes Project resources

PubMed Central

Zheng-Bradley, Xiangqun

2017-01-01

Abstract The 1000 Genomes Project created a valuable, worldwide reference for human genetic variation. Common uses of the 1000 Genomes dataset include genotype imputation supporting Genome-wide Association Studies, mapping expression Quantitative Trait Loci, filtering non-pathogenic variants from exome, whole genome and cancer genome sequencing projects, and genetic analysis of population structure and molecular evolution. In this article, we will highlight some of the multiple ways that the 1000 Genomes data can be and has been utilized for genetic studies. PMID:27436001

A framework for the use of agent based modeling to simulate inter- and intraindividual variation in human behaviors

EPA Science Inventory

Simulation of human behavior in exposure modeling is a complex task. Traditionally, inter-individual variation in human activity has been modeled by drawing from a pool of single day time-activity diaries such as the US EPA Consolidated Human Activity Database (CHAD). Here, an ag...

Cultural variation is part of human nature : Literary universals, context-sensitivity, and "shakespeare in the bush".

PubMed

Sugiyama, Michelle Scalise

2003-12-01

In 1966, Laura Bohannan wrote her classic essay challenging the supposition that great literary works speak to universal human concerns and conditions and, by extension, that human nature is the same everywhere. Her evidence: the Tiv of West Africa interpret Hamlet differently from Westerners. While Bohannan's essay implies that cognitive universality and cultural variation are mutually exclusive phenomena, adaptationist theory suggests otherwise. Adaptive problems ("the human condition") and cognitive adaptations ("human nature") are constant across cultures. What differs between cultures is habitat: owing to environmental variation, the means and information relevant to solving adaptive problems differ from place to place. Thus, we find differences between cultures not because human minds differ in design but largely because human habitats differ in resources and history. On this view, we would expect world literature to express both human universals and cultural particularities. Specifically, we should expect to find literary universality at the macro level (e.g., adaptive problems, cognitive adaptations) and literary variation at the micro level (e.g., local solutions to adaptive problems).

CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells

PubMed Central

Kim, Eun Ji; Kang, Ki Ho; Ju, Ji Hyeon

2017-01-01

Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology—and particularly clustered regularly interspaced short palindromic repeats (CRISPR)—will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed. PMID:28049282

CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells.

PubMed

Kim, Eun Ji; Kang, Ki Ho; Ju, Ji Hyeon

2017-01-01

Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology-and particularly clustered regularly interspaced short palindromic repeats (CRISPR)-will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.

The fractal based analysis of human face and DNA variations during aging.

PubMed

Namazi, Hamidreza; Akrami, Amin; Hussaini, Jamal; Silva, Osmar N; Wong, Albert; Kulish, Vladimir V

2017-01-16

Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also dependent on his gen. In this paper, for the first time we analyze the variations of human DNA and face simultaneously. We do this job by analyzing the fractal dimension of DNA walk and face during human aging. The results of this study show the human DNA and face get more complex by aging. These complexities are mapped on fractal exponents of DNA walk and human face. The method discussed in this paper can be further developed in order to investigate the direct influence of DNA mutation on the face variations during aging, and accordingly making a model between human face fractality and the complexity of DNA walk.

Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach.

PubMed

Giardine, Belinda; Borg, Joseph; Higgs, Douglas R; Peterson, Kenneth R; Philipsen, Sjaak; Maglott, Donna; Singleton, Belinda K; Anstee, David J; Basak, A Nazli; Clark, Barnaby; Costa, Flavia C; Faustino, Paula; Fedosyuk, Halyna; Felice, Alex E; Francina, Alain; Galanello, Renzo; Gallivan, Monica V E; Georgitsi, Marianthi; Gibbons, Richard J; Giordano, Piero C; Harteveld, Cornelis L; Hoyer, James D; Jarvis, Martin; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N; Papadopoulos, Petros; Pavlovic, Sonja; Perseu, Lucia; Radmilovic, Milena; Riemer, Cathy; Satta, Stefania; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John S; Wiemann, Claudia; Zukic, Branka; Chui, David H K; Wajcman, Henri; Hardison, Ross C; Patrinos, George P

2011-03-20

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.

The Relevance of HLA Sequencing in Population Genetics Studies

PubMed Central

Sanchez-Mazas, Alicia

2014-01-01

Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for HLA polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the HLA genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of HLA sequence data will be available in the next years for different populations, with the potential to change our understanding of HLA variation in humans. In this review, we first explain how HLA sequencing allows a better assessment of the HLA diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing HLA sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both HLA and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the HLA molecular diversity observed today. PMID:25126587

[Establishment of enzyme-linked immunosorbent assay (ELISA) for measuring human urinary uromodulin and application of the method in patients with IgA nephropathy].

PubMed

Liu, Ying; Chen, Yu-qing; Zhou, Jing-jing; Han, Jia; Liang, Yu; Li, Xue-ying; Zhang, Hong

2012-04-18

To establish a method of enzyme-linked immunosorbent assay (ELISA) to measure urinary uromodulin and explore the urinary uromudulin level in IgA nephropathy. The rabbit anti-human uromodulin polyclonal antibodies were coated on plates to capture uromodulin and the mouse anti-human uromodulin monoclonal antibody was used as detecting antibody to set up ELISA procedure. The precision and repeatability of this ELISA method were evaluated, and then this method was compared with the commercialized Tamm-Horsfall Glycoprotein ELISA Kit by examining urinary uromodulin levels in 55 individuals. Finally, the urinary uromodulin level in 166 IgA nephropathy patients were detected as well as 48 normal controls with this established method. The detecting range of uromodulin was 0.78-12.5 μg/L by this method. The coefficient of variation within-run was 7.5%, and between-run of coefficient of variation was 7.9%. Correlation of this method and comercialized kit was good (r=0.615, P<0.001). The urinary uromodulin/urinary creatinine ratio in IgA nephropathy was significantly lower than that in normal controls. The established ELISA method is sensitive and repeatable, and can be used in further studies.

The relevance of HLA sequencing in population genetics studies.

PubMed

Sanchez-Mazas, Alicia; Meyer, Diogo

2014-01-01

Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for HLA polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the HLA genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of HLA sequence data will be available in the next years for different populations, with the potential to change our understanding of HLA variation in humans. In this review, we first explain how HLA sequencing allows a better assessment of the HLA diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing HLA sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both HLA and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the HLA molecular diversity observed today.

Evaluation of Stony Coral Indicators for Coral Reef ...

EPA Pesticide Factsheets

Colonies of reef-building stony corals at 57 stations around St. Croix, U.S. Virgin Islands were characterized by species, size and percentage of living tissue. Taxonomic, biological and physical indicators of coral condition were derived from these measurements and assessed for their response to gradients of human disturbance. The purpose of the study was to identify indicators that could be used for regulatory assessments under authority of the Clean Water Act--this requires that indicators distinguish anthropogenic disturbances from natural variation. Stony coral indicators were tested for correlation with human disturbance across gradients located on three different sides of the island. At the most intensely disturbed location, five of eight primary indicators were highly correlated with distance from the source of disturbance: Coral taxa richness, average colony size, the coefficient of variation of colony size (an indicator of colony size heterogeneity), total topographic coral surface area, and live coral surface area. An additional set of exploratory indicators related to rarity, reproductive and spawning mode, and taxonomic identity were also screened for association with disturbance at the same location. For the other two locations, there were no significant changes in indicator values and therefore no discernible effects of human activity. Coral indicators demonstrated sufficient precision to detect levels of change that would be applicable in a regio

Host Genetic Control of the Microbiome in Humans and Maize or Relating Host Genetic Variation to the Microbiome (2011 JGI User Meeting)

ScienceCinema

Ley, Ruth E. [Cornell Univ., Ithaca, NY (United States). Cornell Center for Comparative and Population Genomics, Dept. of Microbiology and Dept. of Molecular Biology and Genetics

2018-06-27

The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy and Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Ruth Ley of Cornell University gives a presentation on "Relating Host Genetic Variation to the Microbiome" at the 6th annual Genomics of Energy and Environment Meeting on March 23, 2011.

Multi-texture local ternary pattern for face recognition

NASA Astrophysics Data System (ADS)

Essa, Almabrok; Asari, Vijayan

2017-05-01

In imagery and pattern analysis domain a variety of descriptors have been proposed and employed for different computer vision applications like face detection and recognition. Many of them are affected under different conditions during the image acquisition process such as variations in illumination and presence of noise, because they totally rely on the image intensity values to encode the image information. To overcome these problems, a novel technique named Multi-Texture Local Ternary Pattern (MTLTP) is proposed in this paper. MTLTP combines the edges and corners based on the local ternary pattern strategy to extract the local texture features of the input image. Then returns a spatial histogram feature vector which is the descriptor for each image that we use to recognize a human being. Experimental results using a k-nearest neighbors classifier (k-NN) on two publicly available datasets justify our algorithm for efficient face recognition in the presence of extreme variations of illumination/lighting environments and slight variation of pose conditions.

A Python package for parsing, validating, mapping and formatting sequence variants using HGVS nomenclature.

PubMed

Hart, Reece K; Rico, Rudolph; Hare, Emily; Garcia, John; Westbrook, Jody; Fusaro, Vincent A

2015-01-15

Biological sequence variants are commonly represented in scientific literature, clinical reports and databases of variation using the mutation nomenclature guidelines endorsed by the Human Genome Variation Society (HGVS). Despite the widespread use of the standard, no freely available and comprehensive programming libraries are available. Here we report an open-source and easy-to-use Python library that facilitates the parsing, manipulation, formatting and validation of variants according to the HGVS specification. The current implementation focuses on the subset of the HGVS recommendations that precisely describe sequence-level variation relevant to the application of high-throughput sequencing to clinical diagnostics. The package is released under the Apache 2.0 open-source license. Source code, documentation and issue tracking are available at http://bitbucket.org/hgvs/hgvs/. Python packages are available at PyPI (https://pypi.python.org/pypi/hgvs). Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa

PubMed Central

Roemhild, Roderich; Barbosa, Camilo; Beardmore, Robert E; Jansen, Gunther; Schulenburg, Hinrich

2015-01-01

Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human pathogen Pseudomonas aeruginosa PA14 and two pairs of clinically relevant antibiotics (doripenem/ciprofloxacin and cefsulodin/gentamicin). Our results consistently show that the sequential application of two antibiotics decelerates resistance evolution relative to monotherapy. Sequential treatment enhanced population extinction although we applied antibiotics at sublethal dosage. In both experiments, we identified an order effect of the antibiotics used in the sequential protocol, leading to significant variation in the long-term efficacy of the tested protocols. These variations appear to be caused by asymmetric evolutionary constraints, whereby adaptation to one drug slowed down adaptation to the other drug, but not vice versa. An understanding of such asymmetric constraints may help future development of evolutionary robust treatments against infectious disease. PMID:26640520

A Python package for parsing, validating, mapping and formatting sequence variants using HGVS nomenclature

PubMed Central

Hart, Reece K.; Rico, Rudolph; Hare, Emily; Garcia, John; Westbrook, Jody; Fusaro, Vincent A.

2015-01-01

Summary: Biological sequence variants are commonly represented in scientific literature, clinical reports and databases of variation using the mutation nomenclature guidelines endorsed by the Human Genome Variation Society (HGVS). Despite the widespread use of the standard, no freely available and comprehensive programming libraries are available. Here we report an open-source and easy-to-use Python library that facilitates the parsing, manipulation, formatting and validation of variants according to the HGVS specification. The current implementation focuses on the subset of the HGVS recommendations that precisely describe sequence-level variation relevant to the application of high-throughput sequencing to clinical diagnostics. Availability and implementation: The package is released under the Apache 2.0 open-source license. Source code, documentation and issue tracking are available at http://bitbucket.org/hgvs/hgvs/. Python packages are available at PyPI (https://pypi.python.org/pypi/hgvs). Contact: reecehart@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25273102

Endogenous CO monitoring in exhalation with tunable diode lasers: applications to clinical and biomedical diagnostics

NASA Astrophysics Data System (ADS)

Stepanov, Eugene V.; Zyrianov, Pavel V.; Miliaev, Valerii A.; Shulagin, Yurii A.; D'yachenko, Alexander I.

1999-07-01

Middle IR tunable diode lasers were applied to studies of pulmonary excretion of endogenous carbon monoxide (CO). Variations of the CO content level in exhaled air of healthy nonsmokers were investigated for different environmental conditions with the applied laser technique. Correlation of the obtained data with atmospheric CO contamination and elevated oxygen content were studied as well as diurnal variations of the endogenous CO in exhalation was observed. Criteria for correct conditions of the endogenous CO detection in breath could be derive don this basis. Developed laser approach and methods were applied for the analysis of the excreted CO level in different diseases like bronchial asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, anemia and hepatitis. Laser based close-to-real-time monitoring of the endogenous CO elimination with breath in the course of different dynamic tests was demonstrated to be informative in studies of blood oxygen transport and pH variations in tissues for different challenges tests in human physiology.

The Evolution of Personality Variation in Humans and Other Animals

ERIC Educational Resources Information Center

Nettle, Daniel

2006-01-01

A comprehensive evolutionary framework for understanding the maintenance of heritable behavioral variation in humans is yet to be developed. Some evolutionary psychologists have argued that heritable variation will not be found in important, fitness-relevant characteristics because of the winnowing effect of natural selection. This article…

Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

PubMed Central

McDaniell, Ryan; Lee, Bum-Kyu; Song, Lingyun; Liu, Zheng; Boyle, Alan P.; Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Kucera, Katerina S.; Battenhouse, Anna; Keefe, Damian; Collins, Francis S.; Willard, Huntington F.; Lieb, Jason D.; Furey, Terrence S.; Crawford, Gregory E.; Iyer, Vishwanath R.; Birney, Ewan

2010-01-01

The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID:20299549

Genotype-specific signal generation based on digestion of 3-way DNA junctions: application to KRAS variation detection.

PubMed

Amicarelli, Giulia; Adlerstein, Daniel; Shehi, Erlet; Wang, Fengfei; Makrigiorgos, G Mike

2006-10-01

Genotyping methods that reveal single-nucleotide differences are useful for a wide range of applications. We used digestion of 3-way DNA junctions in a novel technology, OneCutEventAmplificatioN (OCEAN) that allows sequence-specific signal generation and amplification. We combined OCEAN with peptide-nucleic-acid (PNA)-based variant enrichment to detect and simultaneously genotype v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12 sequence variants in human tissue specimens. We analyzed KRAS codon 12 sequence variants in 106 lung cancer surgical specimens. We conducted a PNA-PCR reaction that suppresses wild-type KRAS amplification and genotyped the product with a set of OCEAN reactions carried out in fluorescence microplate format. The isothermal OCEAN assay enabled a 3-way DNA junction to form between the specific target nucleic acid, a fluorescently labeled "amplifier", and an "anchor". The amplifier-anchor contact contains the recognition site for a restriction enzyme. Digestion produces a cleaved amplifier and generation of a fluorescent signal. The cleaved amplifier dissociates from the 3-way DNA junction, allowing a new amplifier to bind and propagate the reaction. The system detected and genotyped KRAS sequence variants down to approximately 0.3% variant-to-wild-type alleles. PNA-PCR/OCEAN had a concordance rate with PNA-PCR/sequencing of 93% to 98%, depending on the exact implementation. Concordance rate with restriction endonuclease-mediated selective-PCR/sequencing was 89%. OCEAN is a practical and low-cost novel technology for sequence-specific signal generation. Reliable analysis of KRAS sequence alterations in human specimens circumvents the requirement for sequencing. Application is expected in genotyping KRAS codon 12 sequence variants in surgical specimens or in bodily fluids, as well as single-base variations and sequence alterations in other genes.

Behavioural variation in 172 small-scale societies indicates that social learning is the main mode of human adaptation.

PubMed

Mathew, Sarah; Perreault, Charles

2015-07-07

The behavioural variation among human societies is vast and unmatched in the animal world. It is unclear whether this variation is due to variation in the ecological environment or to differences in cultural traditions. Underlying this debate is a more fundamental question: is the richness of humans' behavioural repertoire due to non-cultural mechanisms, such as causal reasoning, inventiveness, reaction norms, trial-and-error learning and evoked culture, or is it due to the population-level dynamics of cultural transmission? Here, we measure the relative contribution of environment and cultural history in explaining the behavioural variation of 172 Native American tribes at the time of European contact. We find that the effect of cultural history is typically larger than that of environment. Behaviours also persist over millennia within cultural lineages. This indicates that human behaviour is not predominantly determined by single-generation adaptive responses, contra theories that emphasize non-cultural mechanisms as determinants of human behaviour. Rather, the main mode of human adaptation is social learning mechanisms that operate over multiple generations. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

SU-F-T-65: AutomaticTreatment Planning for High-Dose Rate (HDR) Brachytherapy with a VaginalCylinder Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Y; Tan, J; Jiang, S

Purpose: High dose rate (HDR) brachytherapy treatment planning is conventionally performed in a manual fashion. Yet it is highly desirable to perform computerized automated planning to improve treatment planning efficiency, eliminate human errors, and reduce plan quality variation. The goal of this research is to develop an automatic treatment planning tool for HDR brachytherapy with a cylinder applicator for vaginal cancer. Methods: After inserting the cylinder applicator into the patient, a CT scan was acquired and was loaded to an in-house developed treatment planning software. The cylinder applicator was automatically segmented using image-processing techniques. CTV was generated based on user-specifiedmore » treatment depth and length. Locations of relevant points (apex point, prescription point, and vaginal surface point), central applicator channel coordinates, and dwell positions were determined according to their geometric relations with the applicator. Dwell time was computed through an inverse optimization process. The planning information was written into DICOM-RT plan and structure files to transfer the automatically generated plan to a commercial treatment planning system for plan verification and delivery. Results: We have tested the system retrospectively in nine patients treated with vaginal cylinder applicator. These cases were selected with different treatment prescriptions, lengths, depths, and cylinder diameters to represent a large patient population. Our system was able to generate treatment plans for these cases with clinically acceptable quality. Computation time varied from 3–6 min. Conclusion: We have developed a system to perform automated treatment planning for HDR brachytherapy with a cylinder applicator. Such a novel system has greatly improved treatment planning efficiency and reduced plan quality variation. It also served as a testbed to demonstrate the feasibility of automatic HDR treatment planning for more complicated cases.« less

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Normalization of mass cytometry data with bead standards

PubMed Central

Finck, Rachel; Simonds, Erin F.; Jager, Astraea; Krishnaswamy, Smita; Sachs, Karen; Fantl, Wendy; Pe’er, Dana; Nolan, Garry P.; Bendall, Sean C.

2013-01-01

Mass cytometry uses atomic mass spectrometry combined with isotopically pure reporter elements to currently measure as many as 40 parameters per single cell. As with any quantitative technology, there is a fundamental need for quality assurance and normalization protocols. In the case of mass cytometry, the signal variation over time due to changes in instrument performance combined with intervals between scheduled maintenance must be accounted for and then normalized. Here, samples were mixed with polystyrene beads embedded with metal lanthanides, allowing monitoring of mass cytometry instrument performance over multiple days of data acquisition. The protocol described here includes simultaneous measurements of beads and cells on the mass cytometer, subsequent extraction of the bead-based signature, and the application of an algorithm enabling correction of both short- and long-term signal fluctuations. The variation in the intensity of the beads that remains after normalization may also be used to determine data quality. Application of the algorithm to a one-month longitudinal analysis of a human peripheral blood sample reduced the range of median signal fluctuation from 4.9-fold to 1.3-fold. PMID:23512433

Mapping local anisotropy axis for scattering media using backscattering Mueller matrix imaging

NASA Astrophysics Data System (ADS)

He, Honghui; Sun, Minghao; Zeng, Nan; Du, E.; Guo, Yihong; He, Yonghong; Ma, Hui

2014-03-01

Mueller matrix imaging techniques can be used to detect the micro-structure variations of superficial biological tissues, including the sizes and shapes of cells, the structures in cells, and the densities of the organelles. Many tissues contain anisotropic fibrous micro-structures, such as collagen fibers, elastin fibers, and muscle fibers. Changes of these fibrous structures are potentially good indicators for some pathological variations. In this paper, we propose a quantitative analysis technique based on Mueller matrix for mapping local anisotropy axis of scattering media. By conducting both experiments on silk sample and Monte Carlo simulation based on the sphere-cylinder scattering model (SCSM), we extract anisotropy axis parameters from different backscattering Mueller matrix elements. Moreover, we testify the possible applications of these parameters for biological tissues. The preliminary experimental results of human cancerous samples show that, these parameters are capable to map the local axis of fibers. Since many pathological changes including early stage cancers affect the well aligned structures for tissues, the experimental results indicate that these parameters can be used as potential tools in clinical applications for biomedical diagnosis purposes.

A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments.

PubMed

Bravo, Rafael; Axelrod, David E

2013-11-18

Normal colon crypts consist of stem cells, proliferating cells, and differentiated cells. Abnormal rates of proliferation and differentiation can initiate colon cancer. We have measured the variation in the number of each of these cell types in multiple crypts in normal human biopsy specimens. This has provided the opportunity to produce a calibrated computational model that simulates cell dynamics in normal human crypts, and by changing model parameter values, to simulate the initiation and treatment of colon cancer. An agent-based model of stochastic cell dynamics in human colon crypts was developed in the multi-platform open-source application NetLogo. It was assumed that each cell's probability of proliferation and probability of death is determined by its position in two gradients along the crypt axis, a divide gradient and in a die gradient. A cell's type is not intrinsic, but rather is determined by its position in the divide gradient. Cell types are dynamic, plastic, and inter-convertible. Parameter values were determined for the shape of each of the gradients, and for a cell's response to the gradients. This was done by parameter sweeps that indicated the values that reproduced the measured number and variation of each cell type, and produced quasi-stationary stochastic dynamics. The behavior of the model was verified by its ability to reproduce the experimentally observed monocolonal conversion by neutral drift, the formation of adenomas resulting from mutations either at the top or bottom of the crypt, and by the robust ability of crypts to recover from perturbation by cytotoxic agents. One use of the virtual crypt model was demonstrated by evaluating different cancer chemotherapy and radiation scheduling protocols. A virtual crypt has been developed that simulates the quasi-stationary stochastic cell dynamics of normal human colon crypts. It is unique in that it has been calibrated with measurements of human biopsy specimens, and it can simulate the variation of cell types in addition to the average number of each cell type. The utility of the model was demonstrated with in silico experiments that evaluated cancer therapy protocols. The model is available for others to conduct additional experiments.

Prioritizing Conservation of Ungulate Calving Resources in Multiple-Use Landscapes

PubMed Central

Dzialak, Matthew R.; Harju, Seth M.; Osborn, Robert G.; Wondzell, John J.; Hayden-Wing, Larry D.; Winstead, Jeffrey B.; Webb, Stephen L.

2011-01-01

Background Conserving animal populations in places where human activity is increasing is an ongoing challenge in many parts of the world. We investigated how human activity interacted with maternal status and individual variation in behavior to affect reliability of spatially-explicit models intended to guide conservation of critical ungulate calving resources. We studied Rocky Mountain elk (Cervus elaphus) that occupy a region where 2900 natural gas wells have been drilled. Methodology/Principal Findings We present novel applications of generalized additive modeling to predict maternal status based on movement, and of random-effects resource selection models to provide population and individual-based inference on the effects of maternal status and human activity. We used a 2×2 factorial design (treatment vs. control) that included elk that were either parturient or non-parturient and in areas either with or without industrial development. Generalized additive models predicted maternal status (parturiency) correctly 93% of the time based on movement. Human activity played a larger role than maternal status in shaping resource use; elk showed strong spatiotemporal patterns of selection or avoidance and marked individual variation in developed areas, but no such pattern in undeveloped areas. This difference had direct consequences for landscape-level conservation planning. When relative probability of use was calculated across the study area, there was disparity throughout 72–88% of the landscape in terms of where conservation intervention should be prioritized depending on whether models were based on behavior in developed areas or undeveloped areas. Model validation showed that models based on behavior in developed areas had poor predictive accuracy, whereas the model based on behavior in undeveloped areas had high predictive accuracy. Conclusions/Significance By directly testing for differences between developed and undeveloped areas, and by modeling resource selection in a random-effects framework that provided individual-based inference, we conclude that: 1) amplified selection or avoidance behavior and individual variation, as responses to increasing human activity, complicate conservation planning in multiple-use landscapes, and 2) resource selection behavior in places where human activity is predictable or less dynamic may provide a more reliable basis from which to prioritize conservation action. PMID:21297866

Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction.

PubMed

Sweitzer, Maggie M; Donny, Eric C; Hariri, Ahmad R

2012-06-01

Addictive disorders are heritable, but the search for candidate functional polymorphisms playing an etiological role in addiction is hindered by complexity of the phenotype and the variety of factors interacting to impact behavior. Advances in human genome sequencing and neuroimaging technology provide an unprecedented opportunity to explore the impact of functional genetic variants on variability in behaviorally relevant neural circuitry. Here, we present a model for merging these technologies to trace the links between genes, brain, and addictive behavior. We describe imaging genetics and discuss the utility of its application to addiction. We then review data pertaining to impulsivity and reward circuitry as an example of how genetic variation may lead to variation in behavioral phenotype. Finally, we present preliminary data relating the neural basis of reward processing to individual differences in nicotine dependence. Complex human behaviors such as addiction can be traced to their basic genetic building blocks by identifying intermediate behavioral phenotypes, associated neural circuitry, and underlying molecular signaling pathways. Impulsivity has been linked with variation in reward-related activation in the ventral striatum (VS), altered dopamine signaling, and functional polymorphisms of DRD2 and DAT1 genes. In smokers, changes in reward-related VS activation induced by smoking abstinence may be associated with severity of nicotine dependence. Variation in genes related to dopamine signaling may contribute to heterogeneity in VS sensitivity to reward and, ultimately, to addiction. These findings illustrate the utility of the imaging genetics approach for investigating the neurobiological basis for vulnerability to addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Behavioural variation in 172 small-scale societies indicates that social learning is the main mode of human adaptation

PubMed Central

Mathew, Sarah; Perreault, Charles

2015-01-01

The behavioural variation among human societies is vast and unmatched in the animal world. It is unclear whether this variation is due to variation in the ecological environment or to differences in cultural traditions. Underlying this debate is a more fundamental question: is the richness of humans’ behavioural repertoire due to non-cultural mechanisms, such as causal reasoning, inventiveness, reaction norms, trial-and-error learning and evoked culture, or is it due to the population-level dynamics of cultural transmission? Here, we measure the relative contribution of environment and cultural history in explaining the behavioural variation of 172 Native American tribes at the time of European contact. We find that the effect of cultural history is typically larger than that of environment. Behaviours also persist over millennia within cultural lineages. This indicates that human behaviour is not predominantly determined by single-generation adaptive responses, contra theories that emphasize non-cultural mechanisms as determinants of human behaviour. Rather, the main mode of human adaptation is social learning mechanisms that operate over multiple generations. PMID:26085589

Temperature reconstruction for the Tibetan Plateau in the past 2ka years from ice cores and human documentary record

NASA Astrophysics Data System (ADS)

Yang, X.

2011-12-01

Temperature variation in the past 2000 years on the plateau is reconstructed from Puruogangri ice core d18O, and compared before compositing with other three ice core records as the Dunde ice core (northeast Plateau), Guliya ice core (northwest Plateau) and Dasuopu ice core (south Plateau). The comparison reveals the synchroneity of large-scale climate events, and the composition highlights the warming in the 7th century and 12-13th centuries, and the cold in the 19th century. We searched for historical documentary about Tibet since A.D. 620, extracting record of human activities and social development directly determined or indirectly influenced by climate, and categorizing it into five aspects as basic resources, economic development, military strength, national coherence, and cultural and religious development, to quantify Tibetan development till A.D. 1900. Curve based upon the sum of the five aspects shows Tibetan national strength variation in the past 2000 years. The composited ice core record and Tibetan national strength variation shows consistency, especially during the Songtsen Gampo reign, medieval warm period and the 19th century cold period, thus suggesting the dominative role of climate change in Tibetan civilization before modern ages, as well as proposing the potential application of historical record in paleoclimate reconstruction on the Tibetan Plateau.

Human skin volatiles: a review.

PubMed

Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

2013-05-01

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

Normalizing and scaling of data to derive human response corridors from impact tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

2014-06-03

It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. Published by Elsevier Ltd.

The affect of tissue depth variation on craniofacial reconstructions.

PubMed

Starbuck, John M; Ward, Richard E

2007-10-25

We examined the affect of tissue depth variation on the reconstruction of facial form, through the application of the American method, utilizing published tissue depth measurements for emaciated, normal, and obese faces. In this preliminary study, three reconstructions were created on reproductions of the same skull for each set of tissue depth measurements. The resulting morphological variation was measured quantitatively using the anthropometric craniofacial variability index (CVI). This method employs 16 standard craniofacial anthropometric measurements and the results reflect "pattern variation" or facial harmony. We report no appreciable variation in the quantitative measure of the pattern facial form obtained from the three different sets of tissue depths. Facial similarity was assessed qualitatively utilizing surveys of photographs of the three reconstructions. Surveys indicated that subjects frequently perceived the reconstructions as representing different individuals. This disagreement indicates that size of the face may blind observers to similarities in facial form. This research is significant because it illustrates the confounding effect that normal human variation contributes in the successful recognition of individuals from a representational three-dimensional facial reconstruction. Research results suggest that successful identification could be increased if multiple reconstructions were created which reflect a wide range of possible outcomes for facial form. The creation of multiple facial images, from a single skull, will be facilitated as computerized versions of facial reconstruction are further developed and refined.

Contextual influences on animal decision-making: Significance for behavior-based wildlife conservation and management.

PubMed

Owen, Megan A; Swaisgood, Ronald R; Blumstein, Daniel T

2017-01-01

Survival and successful reproduction require animals to make critical decisions amidst a naturally dynamic environmental and social background (i.e. "context"). However, human activities have pervasively, and rapidly, extended contextual variation into evolutionarily novel territory, potentially rendering evolved animal decision-making mechanisms and strategies maladaptive. We suggest that explicitly focusing on animal decision-making (ADM), by integrating and applying findings from studies of sensory ecology, cognitive psychology, behavioral economics and eco-evolutionary strategies, may enhance our understanding of, and our ability to predict how, human-driven changes in the environment and population demography will influence animal populations. Fundamentally, the decisions animals make involve evolved mechanisms, and behaviors emerge from the combined action of sensory integration, cognitive mechanisms and strategic rules of thumb, and any of these processes may have a disproportionate influence on behavior. Although there is extensive literature exploring ADM, it generally reflects a canalized, discipline-specific approach that lacks a unified conceptual framework. As a result, there has been limited application of ADM theory and research findings into predictive models that can enhance management outcomes, even though it is likely that the relative resilience of species to rapid environmental change is fundamentally a result of how ADM is linked to contextual variation. Here, we focus on how context influences ADM, and highlight ideas and results that may be most applicable to conservation biology. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles.

PubMed

Robinson, James; Guethlein, Lisbeth A; Cereb, Nezih; Yang, Soo Young; Norman, Paul J; Marsh, Steven G E; Parham, Peter

2017-06-01

HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C. A minority of positions have an incidence >1% for the 'second' most frequent nucleotide, comprising 70 positions in HLA-A, 85 in HLA-B and 54 in HLA-C. The majority of these positions have three or four alternative nucleotides. These positions were subject to positive selection and correspond to binding sites for peptides and receptors. Most alleles of HLA class I (>80%) are very rare, often identified in one person or family, and they differ by point mutation from older, more common alleles. These alleles with single nucleotide polymorphisms reflect the germ-line mutation rate. Their frequency predicts the human population harbors 8-9 million HLA class I variants. The common alleles of human populations comprise 42 core alleles, which represent all selected polymorphism, and recombinants that have assorted this polymorphism.

Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles

PubMed Central

Cereb, Nezih; Yang, Soo Young; Marsh, Steven G. E.; Parham, Peter

2017-01-01

HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C. A minority of positions have an incidence >1% for the ‘second’ most frequent nucleotide, comprising 70 positions in HLA-A, 85 in HLA-B and 54 in HLA-C. The majority of these positions have three or four alternative nucleotides. These positions were subject to positive selection and correspond to binding sites for peptides and receptors. Most alleles of HLA class I (>80%) are very rare, often identified in one person or family, and they differ by point mutation from older, more common alleles. These alleles with single nucleotide polymorphisms reflect the germ-line mutation rate. Their frequency predicts the human population harbors 8–9 million HLA class I variants. The common alleles of human populations comprise 42 core alleles, which represent all selected polymorphism, and recombinants that have assorted this polymorphism. PMID:28650991

Differential Entropy Preserves Variational Information of Near-Infrared Spectroscopy Time Series Associated With Working Memory

PubMed Central

Keshmiri, Soheil; Sumioka, Hidenubo; Yamazaki, Ryuji; Ishiguro, Hiroshi

2018-01-01

Neuroscience research shows a growing interest in the application of Near-Infrared Spectroscopy (NIRS) in analysis and decoding of the brain activity of human subjects. Given the correlation that is observed between the Blood Oxygen Dependent Level (BOLD) responses that are exhibited by the time series data of functional Magnetic Resonance Imaging (fMRI) and the hemoglobin oxy/deoxy-genation that is captured by NIRS, linear models play a central role in these applications. This, in turn, results in adaptation of the feature extraction strategies that are well-suited for discretization of data that exhibit a high degree of linearity, namely, slope and the mean as well as their combination, to summarize the informational contents of the NIRS time series. In this article, we demonstrate that these features are inefficient in capturing the variational information of NIRS data, limiting the reliability and the adequacy of the conclusion on their results. Alternatively, we propose the linear estimate of differential entropy of these time series as a natural representation of such information. We provide evidence for our claim through comparative analysis of the application of these features on NIRS data pertinent to several working memory tasks as well as naturalistic conversational stimuli. PMID:29922144

Optimised detection of mitochondrial DNA strand breaks.

PubMed

Hanna, Rebecca; Crowther, Jonathan M; Bulsara, Pallav A; Wang, Xuying; Moore, David J; Birch-Machin, Mark A

2018-05-04

Intrinsic and extrinsic factors that induce cellular oxidative stress damage tissue integrity and promote ageing, resulting in accumulative strand breaks to the mitochondrial DNA (mtDNA) genome. Limited repair mechanisms and close proximity to superoxide generation make mtDNA a prominent biomarker of oxidative damage. Using human DNA we describe an optimised long-range qPCR methodology that sensitively detects mtDNA strand breaks relative to a suite of short mitochondrial and nuclear DNA housekeeping amplicons, which control for any variation in mtDNA copy number. An application is demonstrated by detecting 16-36-fold mtDNA damage in human skin cells induced by hydrogen peroxide and solar simulated radiation. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

A Laboratory Exercise for Genotyping Two Human Single Nucleotide Polymorphisms

ERIC Educational Resources Information Center

Fernando, James; Carlson, Bradley; LeBard, Timothy; McCarthy, Michael; Umali, Finianne; Ashton, Bryce; Rose, Ferrill F., Jr.

2016-01-01

The dramatic decrease in the cost of sequencing a human genome is leading to an era in which a wide range of students will benefit from having an understanding of human genetic variation. Since over 90% of sequence variation between humans is in the form of single nucleotide polymorphisms (SNPs), a laboratory exercise has been devised in order to…

Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications.

PubMed

Di Baldassarre, Angela; Cimetta, Elisa; Bollini, Sveva; Gaggi, Giulia; Ghinassi, Barbara

2018-05-25

Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

Detection of stain formation on teeth by oral antiseptic solution using fiber optic displacement sensor

NASA Astrophysics Data System (ADS)

Rahman, H. A.; Rahim, H. R. A.; Harun, S. W.; Yasin, M.; Apsari, R.; Ahmad, H.; Wan Abas, W. A. B.

2013-02-01

The application of a simple intensity modulated fiber optic displacement sensor for the detection of stain formation on human teeth is demonstrated. The proposed sensor uses a concentric type bundled plastic optical fiber (POF) as a probe in conjunction with the surfaces of five human teeth as the reflecting targets. Prior to the experiment, the stains were produced extrinsically by soaking the teeth in different concentrations of oral antiseptic solution containing hexetidine. The concentration of the oral antiseptic solution is measured in volume%. For a concentration change from 0% to 80%, the peak voltage decreases exponentially from 1.15 mV to 0.41 mV with a measured resolution of 0.48% and 1.75% for concentration ranges of 0-40% and 40-80%, respectively. The correlation between the detector output and variation in the color of human tooth surface has successfully been examined. Simple in design and low in cost, this sensor can detect color changes due to hexetidine-induced stain on a tooth surface in a fast and convenient way. Thus, this sensor will be very promising in esthetic dentistry, dental color matching techniques, chemical and biomedical applications.

Multiple-Locus Variable-Number Tandem-Repeat Analysis in Genotyping Yersinia enterocolitica Strains from Human and Porcine Origins

PubMed Central

Laukkanen-Ninios, R.; Ortiz Martínez, P.; Siitonen, A.; Fredriksson-Ahomaa, M.; Korkeala, H.

2013-01-01

Sporadic and epidemiologically linked Yersinia enterocolitica strains (n = 379) isolated from fecal samples from human patients, tonsil or fecal samples from pigs collected at slaughterhouses, and pork samples collected at meat stores were genotyped using multiple-locus variable-number tandem-repeat analysis (MLVA) with six loci, i.e., V2A, V4, V5, V6, V7, and V9. In total, 312 different MLVA types were found. Similar types were detected (i) in fecal samples collected from human patients over 2 to 3 consecutive years, (ii) in samples from humans and pigs, and (iii) in samples from pigs that originated from the same farms. Among porcine strains, we found farm-specific MLVA profiles. Variations in the numbers of tandem repeats from one to four for variable-number tandem-repeat (VNTR) loci V2A, V5, V6, and V7 were observed within a farm. MLVA was applicable for serotypes O:3, O:5,27, and O:9 and appeared to be a highly discriminating tool for distinguishing sporadic and outbreak-related strains. With long-term use, interpretation of the results became more challenging due to variations in more-discriminating loci, as was observed for strains originating from pig farms. Additionally, we encountered unexpectedly short V2A VNTR fragments and sequenced them. According to the sequencing results, updated guidelines for interpreting V2A VNTR results were prepared. PMID:23637293

INTERINDIVIDUAL VARIATION IN THE METABOLISM OF ARSENIC IN HUMAN HEPATOCYTES

EPA Science Inventory

The liver is the major site for the enzymatic methylation of inorganic arsenic (iAs) in humans. Primary cultures of normal human hepatocytes isolated from tissue obtained at surgery or from donor livers have been used to study interindividual variation in the capacity of live...

Sr - an element shows the way - Applications of Sr isotopes for provenance, tracing and migration (Invited)

NASA Astrophysics Data System (ADS)

Prohaska, T.; Irrgeher, J.; Zitek, A.; Teschler Nicola, M.

2010-12-01

Strontium - named after the small Scottish town Strontian - as such is an element with little popularity. Firstly described by Martin Heinrich Klaproth in 1798, the metal is used in metallurgy to some extent whereas its compounds are interesting in glass industries, electronics and pyrotechnics. The element has chemical similarity to Ca and makes up 1/60 of the earth’s amount of the latter. Nonetheless, it is its isotopic composition which makes Sr so interesting for a large number of scientists. The natural composition of the four naturally occurring isotopes (84Sr, 86Sr 87Sr and 88Sr) varies in nature due to the radioactive decay of 87Rb to 87Sr. Thus, it was early recognized as geochronometer especially in Ca rich matrices. With increasing precision of applied methodology, the natural variation of the 87Sr/86Sr isotope ratio (analyzed at first mainly by thermal ionization mass spectrometry (TIMS)) became more and more popular in provenance studies. The natural variation of the ratio is mainly determined by the geological age and the original composition of the rock and can be used therefore as fingerprint of the local geology. The ratio is transferred with no significant fractionation via the water into plants and finally via the food chain into animal and human tissues (especially bones and teeth). As the element is chemically similar to Ca, it appears in most matrices. The use for provenance studies is supported by the fact that the long half life (4.8 x 1010 years) does not lead to an alteration during the time scales which are investigated (from recent samples to human or animal skeletal remains which date back up to 30.000 BC). The uniqueness of the system besides the natural variation is defined by the ubiquity in nature and the relatively high (and thus measurable) elemental concentration in most tissues. It was finally the advent of multiple collector inductively coupled plasma mass spectrometry (MC-ICP-MS) which augmented the number of applications presented for Sr isotope ratios simply supported by the fact that a higher statistical number of samples could be analyzed. Further supported by direct introductions systems such as laser ablation, the popularity of Sr in science has increased steadily. A number of fields of applications make nowadays use of the system so far: anthropology and archaeology as well as food science, chemical technology, forensic science, medicine or biology. The Sr isotope system will be presented along with analytical techniques applied. Selected examples making use of the natural Sr isotopic variation will be reported: Proof of provenance of food, forensic applications and migration studies on prehistoric cultures or modern biological systems. In addition, the application of enriched Sr isotope spikes will be presented. The spikes are administered in order to investigate Sr turnovers (e.g. as proxy for Ca in biomedical studies), marking tissues for tracing and migration experiments and investigating environmental processes.

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases.

PubMed

Bueno, Anibal; Rodríguez-López, Rocío; Reyes-Palomares, Armando; Rojano, Elena; Corpas, Manuel; Nevado, Julián; Lapunzina, Pablo; Sánchez-Jiménez, Francisca; Ranea, Juan A G

2018-06-26

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8-9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype-phenotype relationships. We aimed to improve the identification of statistically consistent genotype-phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype-patient-genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes.

Analysis of Geomagnetic Disturbances and Cosmic Ray Intensity Variations in Relation to Medical Data from Rome

NASA Astrophysics Data System (ADS)

Giannaropoulou, E.; Papailiou, M.; Mavromichalaki, H.; Tsipis, A.

2010-07-01

Over the last few years many studies have been conducted concerning the possible influence of geomagnetic and solar activity and cosmic ray activity on human physiological state and in particular on human cardio - health state. As it is shown the human organism is sensitive to environmental changes and reacts to them through a series of variations of its physiological parameters such as heart rate, arterial systolic and diastolic blood pressure, etc. In this paper daily mean values of heart rate, as they were registered for a group of 2.028 volunteers during medical examinations in the Polyclinico Tor Vergata, Rome, Italy are analyzed in relation to daily cosmic ray intensity variations, as measured by the Neutron Monitor of the University of Athens and daily variations of the geomagnetic indices Dst, Ap and Kp. The results from this study show that geomagnetic activity changes and cosmic rays intensity variations may regulate the human homeostasis.

A study of voice production characteristics of astronuat speech during Apollo 11 for speaker modeling in space.

PubMed

Yu, Chengzhu; Hansen, John H L

2017-03-01

Human physiology has evolved to accommodate environmental conditions, including temperature, pressure, and air chemistry unique to Earth. However, the environment in space varies significantly compared to that on Earth and, therefore, variability is expected in astronauts' speech production mechanism. In this study, the variations of astronaut voice characteristics during the NASA Apollo 11 mission are analyzed. Specifically, acoustical features such as fundamental frequency and phoneme formant structure that are closely related to the speech production system are studied. For a further understanding of astronauts' vocal tract spectrum variation in space, a maximum likelihood frequency warping based analysis is proposed to detect the vocal tract spectrum displacement during space conditions. The results from fundamental frequency, formant structure, as well as vocal spectrum displacement indicate that astronauts change their speech production mechanism when in space. Moreover, the experimental results for astronaut voice identification tasks indicate that current speaker recognition solutions are highly vulnerable to astronaut voice production variations in space conditions. Future recommendations from this study suggest that successful applications of speaker recognition during extended space missions require robust speaker modeling techniques that could effectively adapt to voice production variation caused by diverse space conditions.

GALT protein database: querying structural and functional features of GALT enzyme.

PubMed

d'Acierno, Antonio; Facchiano, Angelo; Marabotti, Anna

2014-09-01

Knowledge of the impact of variations on protein structure can enhance the comprehension of the mechanisms of genetic diseases related to that protein. Here, we present a new version of GALT Protein Database, a Web-accessible data repository for the storage and interrogation of structural effects of variations of the enzyme galactose-1-phosphate uridylyltransferase (GALT), the impairment of which leads to classic Galactosemia, a rare genetic disease. This new version of this database now contains the models of 201 missense variants of GALT enzyme, including heterozygous variants, and it allows users not only to retrieve information about the missense variations affecting this protein, but also to investigate their impact on substrate binding, intersubunit interactions, stability, and other structural features. In addition, it allows the interactive visualization of the models of variants collected into the database. We have developed additional tools to improve the use of the database by nonspecialized users. This Web-accessible database (http://bioinformatica.isa.cnr.it/GALT/GALT2.0) represents a model of tools potentially suitable for application to other proteins that are involved in human pathologies and that are subjected to genetic variations. © 2014 WILEY PERIODICALS, INC.

Establishment of an international database for genetic variants in esophageal cancer.

PubMed

Vihinen, Mauno

2016-10-01

The establishment of a database has been suggested in order to collect, organize, and distribute genetic information about esophageal cancer. The World Organization for Specialized Studies on Diseases of the Esophagus and the Human Variome Project will be in charge of a central database of information about esophageal cancer-related variations from publications, databases, and laboratories; in addition to genetic details, clinical parameters will also be included. The aim will be to get all the central players in research, clinical, and commercial laboratories to contribute. The database will follow established recommendations and guidelines. The database will require a team of dedicated curators with different backgrounds. Numerous layers of systematics will be applied to facilitate computational analyses. The data items will be extensively integrated with other information sources. The database will be distributed as open access to ensure exchange of the data with other databases. Variations will be reported in relation to reference sequences on three levels--DNA, RNA, and protein-whenever applicable. In the first phase, the database will concentrate on genetic variations including both somatic and germline variations for susceptibility genes. Additional types of information can be integrated at a later stage. © 2016 New York Academy of Sciences.

Atlas warping for brain morphometry

NASA Astrophysics Data System (ADS)

Machado, Alexei M. C.; Gee, James C.

1998-06-01

In this work, we describe an automated approach to morphometry based on spatial normalizations of the data, and demonstrate its application to the analysis of gender differences in the human corpus callosum. The purpose is to describe a population by a reduced and representative set of variables, from which a prior model can be constructed. Our approach is rooted in the assumption that individual anatomies can be considered as quantitative variations on a common underlying qualitative plane. We can therefore imagine that a given individual's anatomy is a warped version of some referential anatomy, also known as an atlas. The spatial warps which transform a labeled atlas into anatomic alignment with a population yield immediate knowledge about organ size and shape in the group. Furthermore, variation within the set of spatial warps is directly related to the anatomic variation among the subjects. Specifically, the shape statistics--mean and variance of the mappings--for the population can be calculated in a special basis, and an eigendecomposition of the variance performed to identify the most significant modes of shape variation. The results obtained with the corpus callosum study confirm the existence of substantial anatomical differences between males and females, as reported in previous experimental work.

Variational Transition State Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Truhlar, Donald G.

2016-09-29

This is the final report on a project involving the development and applications of variational transition state theory. This project involved the development of variational transition state theory for gas-phase reactions, including optimized multidimensional tunneling contributions and the application of this theory to gas-phase reactions with a special emphasis on developing reaction rate theory in directions that are important for applications to combustion. The development of variational transition state theory with optimized multidimensional tunneling as a useful computational tool for combustion kinetics involved eight objectives.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

PubMed

Wojcik, Sylwia E; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z; Rai, Kanti R; Kipps, Thomas J; Keating, Michael J; Croce, Carlo M; Calin, George A

2010-02-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer

PubMed Central

Wojcik, Sylwia E.; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S.; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z.; Rai, Kanti R.; Kipps, Thomas J.; Keating, Michael J.

2010-01-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas. PMID:19926640

A customized vision system for tracking humans wearing reflective safety clothing from industrial vehicles and machinery.

PubMed

Mosberger, Rafael; Andreasson, Henrik; Lilienthal, Achim J

2014-09-26

This article presents a novel approach for vision-based detection and tracking of humans wearing high-visibility clothing with retro-reflective markers. Addressing industrial applications where heavy vehicles operate in the vicinity of humans, we deploy a customized stereo camera setup with active illumination that allows for efficient detection of the reflective patterns created by the worker's safety garments. After segmenting reflective objects from the image background, the interest regions are described with local image feature descriptors and classified in order to discriminate safety garments from other reflective objects in the scene. In a final step, the trajectories of the detected humans are estimated in 3D space relative to the camera. We evaluate our tracking system in two industrial real-world work environments on several challenging video sequences. The experimental results indicate accurate tracking performance and good robustness towards partial occlusions, body pose variation, and a wide range of different illumination conditions.

A Customized Vision System for Tracking Humans Wearing Reflective Safety Clothing from Industrial Vehicles and Machinery

PubMed Central

Mosberger, Rafael; Andreasson, Henrik; Lilienthal, Achim J.

2014-01-01

This article presents a novel approach for vision-based detection and tracking of humans wearing high-visibility clothing with retro-reflective markers. Addressing industrial applications where heavy vehicles operate in the vicinity of humans, we deploy a customized stereo camera setup with active illumination that allows for efficient detection of the reflective patterns created by the worker's safety garments. After segmenting reflective objects from the image background, the interest regions are described with local image feature descriptors and classified in order to discriminate safety garments from other reflective objects in the scene. In a final step, the trajectories of the detected humans are estimated in 3D space relative to the camera. We evaluate our tracking system in two industrial real-world work environments on several challenging video sequences. The experimental results indicate accurate tracking performance and good robustness towards partial occlusions, body pose variation, and a wide range of different illumination conditions. PMID:25264956

Investigating human geographic origins using dual-isotope (87Sr/86Sr, δ18O) assignment approaches.

PubMed

Laffoon, Jason E; Sonnemann, Till F; Shafie, Termeh; Hofman, Corinne L; Brandes, Ulrik; Davies, Gareth R

2017-01-01

Substantial progress in the application of multiple isotope analyses has greatly improved the ability to identify nonlocal individuals amongst archaeological populations over the past decades. More recently the development of large scale models of spatial isotopic variation (isoscapes) has contributed to improved geographic assignments of human and animal origins. Persistent challenges remain, however, in the accurate identification of individual geographic origins from skeletal isotope data in studies of human (and animal) migration and provenance. In an attempt to develop and test more standardized and quantitative approaches to geographic assignment of individual origins using isotopic data two methods, combining 87Sr/86Sr and δ18O isoscapes, are examined for the Circum-Caribbean region: 1) an Interval approach using a defined range of fixed isotopic variation per location; and 2) a Likelihood assignment approach using univariate and bivariate probability density functions. These two methods are tested with enamel isotope data from a modern sample of known origin from Caracas, Venezuela and further explored with two archaeological samples of unknown origin recovered from Cuba and Trinidad. The results emphasize both the potential and limitation of the different approaches. Validation tests on the known origin sample exclude most areas of the Circum-Caribbean region and correctly highlight Caracas as a possible place of origin with both approaches. The positive validation results clearly demonstrate the overall efficacy of a dual-isotope approach to geoprovenance. The accuracy and precision of geographic assignments may be further improved by better understanding of the relationships between environmental and biological isotope variation; continued development and refinement of relevant isoscapes; and the eventual incorporation of a broader array of isotope proxy data.

MR susceptibility imaging

NASA Astrophysics Data System (ADS)

Duyn, Jeff

2013-04-01

This work reviews recent developments in the use of magnetic susceptibility contrast for human MRI, with a focus on the study of brain anatomy. The increase in susceptibility contrast with modern high field scanners has led to novel applications and insights into the sources and mechanism contributing to this contrast in brain tissues. Dedicated experiments have demonstrated that in most of healthy brain, iron and myelin dominate tissue susceptibility variations, although their relative contribution varies substantially. Local variations in these compounds can affect both amplitude and frequency of the MRI signal. In white matter, the myelin sheath introduces an anisotropic susceptibility that has distinct effects on the water compartments inside the axons, between the myelin sheath, and the axonal space, and renders their signals dependent on the angle between the axon and the magnetic field. This offers opportunities to derive tissue properties specific to these cellular compartments.

Host Genetic Control of the Microbiome in Humans and Maise or Relating Host Genetic Variation to the Microbiome (2011 JGI User Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ley, Ruth

2011-03-23

The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Ruth Ley of Cornell University gives a presentation on "Relating Host Genetic Variation to themore » Microbiome" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011.« less

Chemical ecology of interactions between human skin microbiota and mosquitoes.

PubMed

Verhulst, Niels O; Takken, Willem; Dicke, Marcel; Schraa, Gosse; Smallegange, Renate C

2010-10-01

Microbiota on the human skin plays a major role in body odour production. The human microbial and chemical signature displays a qualitative and quantitative correlation. Genes may influence the chemical signature by shaping the composition of the microbiota. Recent studies on human skin microbiota, using 16S rRNA gene sequencing, found a high inter- and intrapersonal variation in bacterial species on the human skin, which is relatively stable over time. Human body odours mediate the attraction of mosquitoes to their blood hosts. Odours produced by skin microbiota are attractive to mosquitoes as shown by in vitro studies, and variation in bacterial species on the human skin may explain the variation in mosquito attraction between humans. Detailed knowledge of the ecology and genetics of human skin microbiota is needed in order to unravel the evolutionary mechanisms that underlie the interactions between mosquitoes and their hosts. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Identification of structural variation in mouse genomes.

PubMed

Keane, Thomas M; Wong, Kim; Adams, David J; Flint, Jonathan; Reymond, Alexandre; Yalcin, Binnaz

2014-01-01

Structural variation is variation in structure of DNA regions affecting DNA sequence length and/or orientation. It generally includes deletions, insertions, copy-number gains, inversions, and transposable elements. Traditionally, the identification of structural variation in genomes has been challenging. However, with the recent advances in high-throughput DNA sequencing and paired-end mapping (PEM) methods, the ability to identify structural variation and their respective association to human diseases has improved considerably. In this review, we describe our current knowledge of structural variation in the mouse, one of the prime model systems for studying human diseases and mammalian biology. We further present the evolutionary implications of structural variation on transposable elements. We conclude with future directions on the study of structural variation in mouse genomes that will increase our understanding of molecular architecture and functional consequences of structural variation.

Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario

PubMed Central

Gunz, Philipp; Bookstein, Fred L.; Mitteroecker, Philipp; Stadlmayr, Andrea; Seidler, Horst; Weber, Gerhard W.

2009-01-01

The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

Observing Consistency in Online Communication Patterns for User Re-Identification

PubMed Central

Venter, Hein S.

2016-01-01

Comprehension of the statistical and structural mechanisms governing human dynamics in online interaction plays a pivotal role in online user identification, online profile development, and recommender systems. However, building a characteristic model of human dynamics on the Internet involves a complete analysis of the variations in human activity patterns, which is a complex process. This complexity is inherent in human dynamics and has not been extensively studied to reveal the structural composition of human behavior. A typical method of anatomizing such a complex system is viewing all independent interconnectivity that constitutes the complexity. An examination of the various dimensions of human communication pattern in online interactions is presented in this paper. The study employed reliable server-side web data from 31 known users to explore characteristics of human-driven communications. Various machine-learning techniques were explored. The results revealed that each individual exhibited a relatively consistent, unique behavioral signature and that the logistic regression model and model tree can be used to accurately distinguish online users. These results are applicable to one-to-one online user identification processes, insider misuse investigation processes, and online profiling in various areas. PMID:27918593

Applications of the 1000 Genomes Project resources.

PubMed

Zheng-Bradley, Xiangqun; Flicek, Paul

2017-05-01

The 1000 Genomes Project created a valuable, worldwide reference for human genetic variation. Common uses of the 1000 Genomes dataset include genotype imputation supporting Genome-wide Association Studies, mapping expression Quantitative Trait Loci, filtering non-pathogenic variants from exome, whole genome and cancer genome sequencing projects, and genetic analysis of population structure and molecular evolution. In this article, we will highlight some of the multiple ways that the 1000 Genomes data can be and has been utilized for genetic studies. © The Author 2016. Published by Oxford University Press.

Morphological variation in Homo erectus and the origins of developmental plasticity

PubMed Central

Antón, Susan C.; Taboada, Hannah G.; Middleton, Emily R.; Rainwater, Christopher W.; Taylor, Andrea B.; Turner, Trudy R.; Turnquist, Jean E.; Weinstein, Karen J.; Williams, Scott A.

2016-01-01

Homo erectus was the first hominin to exhibit extensive range expansion. This extraordinary departure from Africa, especially into more temperate climates of Eurasia, has been variously related to technological, energetic and foraging shifts. The temporal and regional anatomical variation in H. erectus suggests that a high level of developmental plasticity, a key factor in the ability of H. sapiens to occupy a variety of habitats, may also have been present in H. erectus. Developmental plasticity, the ability to modify development in response to environmental conditions, results in differences in size, shape and dimorphism across populations that relate in part to levels of resource sufficiency and extrinsic mortality. These differences predict not only regional variations but also overall smaller adult sizes and lower levels of dimorphism in instances of resource scarcity and high predator load. We consider the metric variation in 35 human and non-human primate ‘populations’ from known environmental contexts and 14 time- and space-restricted paleodemes of H. erectus and other fossil Homo. Human and non-human primates exhibit more similar patterns of variation than expected, with plasticity evident, but in differing patterns by sex across populations. The fossil samples show less evidence of variation than expected, although H. erectus varies more than Neandertals. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298467

Feedforward object-vision models only tolerate small image variations compared to human

PubMed Central

Ghodrati, Masoud; Farzmahdi, Amirhossein; Rajaei, Karim; Ebrahimpour, Reza; Khaligh-Razavi, Seyed-Mahdi

2014-01-01

Invariant object recognition is a remarkable ability of primates' visual system that its underlying mechanism has constantly been under intense investigations. Computational modeling is a valuable tool toward understanding the processes involved in invariant object recognition. Although recent computational models have shown outstanding performances on challenging image databases, they fail to perform well in image categorization under more complex image variations. Studies have shown that making sparse representation of objects by extracting more informative visual features through a feedforward sweep can lead to higher recognition performances. Here, however, we show that when the complexity of image variations is high, even this approach results in poor performance compared to humans. To assess the performance of models and humans in invariant object recognition tasks, we built a parametrically controlled image database consisting of several object categories varied in different dimensions and levels, rendered from 3D planes. Comparing the performance of several object recognition models with human observers shows that only in low-level image variations the models perform similar to humans in categorization tasks. Furthermore, the results of our behavioral experiments demonstrate that, even under difficult experimental conditions (i.e., briefly presented masked stimuli with complex image variations), human observers performed outstandingly well, suggesting that the models are still far from resembling humans in invariant object recognition. Taken together, we suggest that learning sparse informative visual features, although desirable, is not a complete solution for future progresses in object-vision modeling. We show that this approach is not of significant help in solving the computational crux of object recognition (i.e., invariant object recognition) when the identity-preserving image variations become more complex. PMID:25100986

Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms

PubMed Central

Haraksingh, Rajini R.; Abyzov, Alexej; Gerstein, Mark; Urban, Alexander E.; Snyder, Michael

2011-01-01

Accurate and efficient genome-wide detection of copy number variants (CNVs) is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications. PMID:22140474

Asylum applications respond to temperature fluctuations.

PubMed

Missirian, Anouch; Schlenker, Wolfram

2017-12-22

International negotiations on climate change, along with recent upsurges in migration across the Mediterranean Sea, have highlighted the need to better understand the possible effects of climate change on human migration-in particular, across national borders. Here we examine how, in the recent past (2000-2014), weather variations in 103 source countries translated into asylum applications to the European Union, which averaged 351,000 per year in our sample. We find that temperatures that deviated from the moderate optimum (~20°C) increased asylum applications in a nonlinear fashion, which implies an accelerated increase under continued future warming. Holding everything else constant, asylum applications by the end of the century are predicted to increase, on average, by 28% (98,000 additional asylum applications per year) under representative concentration pathway (RCP) scenario 4.5 and by 188% (660,000 additional applications per year) under RCP 8.5 for the 21 climate models in the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP). Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The genomic landscape of human cellular circadian variation points to a novel role for the signalosome

PubMed Central

Gaspar, Ludmila; Howald, Cedric; Popadin, Konstantin; Maier, Bert; Mauvoisin, Daniel; Moriggi, Ermanno; Gutierrez-Arcelus, Maria; Falconnet, Emilie; Borel, Christelle; Kunz, Dieter; Kramer, Achim; Gachon, Frederic; Dermitzakis, Emmanouil T; Antonarakis, Stylianos E

2017-01-01

The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype. PMID:28869038

Genome Variation Map: a data repository of genome variations in BIG Data Center

PubMed Central

Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang

2018-01-01

Abstract The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. PMID:29069473

Genome-Wide Fine-Scale Recombination Rate Variation in Drosophila melanogaster

PubMed Central

Song, Yun S.

2012-01-01

Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and diversity. PMID:23284288

CNVcaller: highly efficient and widely applicable software for detecting copy number variations in large populations.

PubMed

Wang, Xihong; Zheng, Zhuqing; Cai, Yudong; Chen, Ting; Li, Chao; Fu, Weiwei; Jiang, Yu

2017-12-01

The increasing amount of sequencing data available for a wide variety of species can be theoretically used for detecting copy number variations (CNVs) at the population level. However, the growing sample sizes and the divergent complexity of nonhuman genomes challenge the efficiency and robustness of current human-oriented CNV detection methods. Here, we present CNVcaller, a read-depth method for discovering CNVs in population sequencing data. The computational speed of CNVcaller was 1-2 orders of magnitude faster than CNVnator and Genome STRiP for complex genomes with thousands of unmapped scaffolds. CNV detection of 232 goats required only 1.4 days on a single compute node. Additionally, the Mendelian consistency of sheep trios indicated that CNVcaller mitigated the influence of high proportions of gaps and misassembled duplications in the nonhuman reference genome assembly. Furthermore, multiple evaluations using real sheep and human data indicated that CNVcaller achieved the best accuracy and sensitivity for detecting duplications. The fast generalized detection algorithms included in CNVcaller overcome prior computational barriers for detecting CNVs in large-scale sequencing data with complex genomic structures. Therefore, CNVcaller promotes population genetic analyses of functional CNVs in more species. © The Authors 2017. Published by Oxford University Press.

CNVcaller: highly efficient and widely applicable software for detecting copy number variations in large populations

PubMed Central

Wang, Xihong; Zheng, Zhuqing; Cai, Yudong; Chen, Ting; Li, Chao; Fu, Weiwei

2017-01-01

Abstract Background The increasing amount of sequencing data available for a wide variety of species can be theoretically used for detecting copy number variations (CNVs) at the population level. However, the growing sample sizes and the divergent complexity of nonhuman genomes challenge the efficiency and robustness of current human-oriented CNV detection methods. Results Here, we present CNVcaller, a read-depth method for discovering CNVs in population sequencing data. The computational speed of CNVcaller was 1–2 orders of magnitude faster than CNVnator and Genome STRiP for complex genomes with thousands of unmapped scaffolds. CNV detection of 232 goats required only 1.4 days on a single compute node. Additionally, the Mendelian consistency of sheep trios indicated that CNVcaller mitigated the influence of high proportions of gaps and misassembled duplications in the nonhuman reference genome assembly. Furthermore, multiple evaluations using real sheep and human data indicated that CNVcaller achieved the best accuracy and sensitivity for detecting duplications. Conclusions The fast generalized detection algorithms included in CNVcaller overcome prior computational barriers for detecting CNVs in large-scale sequencing data with complex genomic structures. Therefore, CNVcaller promotes population genetic analyses of functional CNVs in more species. PMID:29220491

Looking back on a half century of repeat magnetic measurements in France

NASA Astrophysics Data System (ADS)

Alexandrescu, Mioara Mandea; Gilder, Stuart; Courtillot, Vincent; Le Mouël, Jean Louis; Gilbert, Daniel

Birds do it. Bees do it. And with the discovery of lodestone over 2200 years ago, humans too could incorporate the Earth's magnetic field into their daily lives. Some of the oldest applications for tracking the magnetic field were in land and sea navigation. Magnetic field measurements quickly became an important economic factor in world trade, with documented use dating from the 11th century in China.The measurements are important in other applications as well. For example, rapid field variations are generated by solar activity and its interaction with the terrestrial environment. Large magnetic storms can disrupt satellite operation, communication systems, power transmission networks, and so forth [Campbell, 1997].Geomagnetism also provides a unique opportunity to explore the Earth's outer core, which is mostly liquid (molten) iron, where the field is generated. Field measurements can also yield valuable insights into the location of mineral deposits and aid in applications in the petroleum industry.

Body size and allometric variation in facial shape in children.

PubMed

Larson, Jacinda R; Manyama, Mange F; Cole, Joanne B; Gonzalez, Paula N; Percival, Christopher J; Liberton, Denise K; Ferrara, Tracey M; Riccardi, Sheri L; Kimwaga, Emmanuel A; Mathayo, Joshua; Spitzmacher, Jared A; Rolian, Campbell; Jamniczky, Heather A; Weinberg, Seth M; Roseman, Charles C; Klein, Ophir; Lukowiak, Ken; Spritz, Richard A; Hallgrimsson, Benedikt

2018-02-01

Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape. Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures. The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures. Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally. © 2017 Wiley Periodicals, Inc.

Evaluating intra- and inter-individual variation in the human placental transcriptome.

PubMed

Hughes, David A; Kircher, Martin; He, Zhisong; Guo, Song; Fairbrother, Genevieve L; Moreno, Carlos S; Khaitovich, Philipp; Stoneking, Mark

2015-03-19

Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. We estimate that on average, 33.2%, 58.9%, and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals, and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they each account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling, and metabolism. Many biological traits demonstrate correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection, directional selection, or diversifying selection. We apportion placental gene expression variation into individual, population, and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

PubMed Central

Hecker, Laura A.; Edwards, Albert O.; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H.; Brown, William L.; Issa, Peter Charbel; Scholl, Hendrik P.; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E.; Bailey, Kent R.; Oppermann, Martin

2010-01-01

Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues. PMID:19825847

In vitro activation of the neuro-transduction mechanism in sensitive organotypic human skin model.

PubMed

Martorina, Francesca; Casale, Costantino; Urciuolo, Francesco; Netti, Paolo A; Imparato, Giorgia

2017-01-01

Recent advances in tissue engineering have encouraged researchers to endeavor the production of fully functional three-dimensional (3D) thick human tissues in vitro. Here, we report the fabrication of a fully innervated human skin tissue in vitro that recapitulates and replicates skin sensory function. Previous attempts to innervate in vitro 3D skin models did not demonstrate an effective functionality of the nerve network. In our approach, we initially engineer functional human skin tissue based on fibroblast-generated dermis and differentiated epidermis; then, we promote rat dorsal root ganglion (DRG) neurons axon ingrowth in the de-novo developed tissue. Neurofilaments network infiltrates the entire native dermis extracellular matrix (ECM), as demonstrated by immunofluorescence and second harmonic generation (SHG) imaging. To prove sensing functionality of the tissue, we use topical applications of capsaicin, an agonist of transient receptor protein-vanilloid 1 (TRPV1) channel, and quantify calcium currents resulting from variations of Ca ++ concentration in DRG neurons innervating our model. Calcium currents generation demonstrates functional cross-talking between dermis and epidermis compartments. Moreover, through a computational fluid dynamic (CFD) analysis, we set fluid dynamic conditions for a non-planar skin equivalent growth, as proof of potential application in creating skin grafts tailored on-demand for in vivo wound shape. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

PubMed

McNally, Elizabeth M; Puckelwartz, Megan J

2015-01-01

With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

Comparative Study of Seven Commercial Kits for Human DNA Extraction from Urine Samples Suitable for DNA Biomarker-Based Public Health Studies

PubMed Central

El Bali, Latifa; Diman, Aurélie; Bernard, Alfred; Roosens, Nancy H. C.; De Keersmaecker, Sigrid C. J.

2014-01-01

Human genomic DNA extracted from urine could be an interesting tool for large-scale public health studies involving characterization of genetic variations or DNA biomarkers as a result of the simple and noninvasive collection method. These studies, involving many samples, require a rapid, easy, and standardized extraction protocol. Moreover, for practicability, there is a necessity to collect urine at a moment different from the first void and to store it appropriately until analysis. The present study compared seven commercial kits to select the most appropriate urinary human DNA extraction procedure for epidemiological studies. DNA yield has been determined using different quantification methods: two classical, i.e., NanoDrop and PicoGreen, and two species-specific real-time quantitative (q)PCR assays, as DNA extracted from urine contains, besides human, microbial DNA also, which largely contributes to the total DNA yield. In addition, the kits giving a good yield were also tested for the presence of PCR inhibitors. Further comparisons were performed regarding the sampling time and the storage conditions. Finally, as a proof-of-concept, an important gene related to smoking has been genotyped using the developed tools. We could select one well-performing kit for the human DNA extraction from urine suitable for molecular diagnostic real-time qPCR-based assays targeting genetic variations, applicable to large-scale studies. In addition, successful genotyping was possible using DNA extracted from urine stored at −20°C for several months, and an acceptable yield could also be obtained from urine collected at different moments during the day, which is particularly important for public health studies. PMID:25365790

In-vitro characterization of stress corrosion cracking of aluminium-free magnesium alloys for temporary bio-implant applications.

PubMed

Choudhary, Lokesh; Singh Raman, R K; Hofstetter, Joelle; Uggowitzer, Peter J

2014-09-01

The complex interaction between physiological stresses and corrosive human body fluid may cause premature failure of metallic biomaterials due to the phenomenon of stress corrosion cracking. In this study, the susceptibility to stress corrosion cracking of biodegradable and aluminium-free magnesium alloys ZX50, WZ21 and WE43 was investigated by slow strain rate tensile testing in a simulated human body fluid. Slow strain rate tensile testing results indicated that each alloy was susceptible to stress corrosion cracking, and this was confirmed by fractographic features of transgranular and/or intergranular cracking. However, the variation in alloy susceptibility to stress corrosion cracking is explained on the basis of their electrochemical and microstructural characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Oximetry: a new non-invasive method to detect metabolic effects induced by a local application of mechanical vibration

NASA Astrophysics Data System (ADS)

Felici, A.; Trombetta, C.; Abundo, P.; Foti, C.; Rosato, N.

2012-10-01

Mechanical vibrations application is increasingly common in clinical practice due to the effectiveness induced by these stimuli on the human body. Local vibration (LV) application allows to apply and act only where needed, focusing the treatment on the selected body segment. An experimental device for LV application was used to generate the vibrations. The aim of this study was to detect and analyze the metabolic effects induced by LV on the brachial bicep muscle by means of an oximeter. This device monitors tissue and muscle oxygenation using NIRS (Near Infrared Spectroscopy) and is able to determine the concentration of haemoglobin and oxygen saturation in the tissue. In a preliminary stage we also investigated the effects induced by LV application, by measuring blood pressure, heart rate, oxygen saturation and temperature. These data confirmed that the effects induced by LV application are actually localized. The results of the measurements obtained using the oximeter during the vibration application, have shown a variation of the concentrations. In particular an increase of oxygenate haemoglobin was shown, probably caused by an increased muscle activity and/or a rise in local temperature detected during the application.

Colour in digital pathology: a review.

PubMed

Clarke, Emily L; Treanor, Darren

2017-01-01

Colour is central to the practice of pathology because of the use of coloured histochemical and immunohistochemical stains to visualize tissue features. Our reliance upon histochemical stains and light microscopy has evolved alongside a wide variation in slide colour, with little investigation into the implications of colour variation. However, the introduction of the digital microscope and whole-slide imaging has highlighted the need for further understanding and control of colour. This is because the digitization process itself introduces further colour variation which may affect diagnosis, and image analysis algorithms often use colour or intensity measures to detect or measure tissue features. The US Food and Drug Administration have released recent guidance stating the need to develop a method of controlling colour reproduction throughout the digitization process in whole-slide imaging for primary diagnostic use. This comprehensive review introduces applied basic colour physics and colour interpretation by the human visual system, before discussing the importance of colour in pathology. The process of colour calibration and its application to pathology are also included, as well as a summary of the current guidelines and recommendations regarding colour in digital pathology. © 2016 John Wiley & Sons Ltd.

Sexual dimorphism and population variation in the adult mandible : Forensic applications of geometric morphometrics.

PubMed

Franklin, Daniel; O'Higgins, Paul; Oxnard, Charles E; Dadour, Ian

2007-03-01

This article forms part of an ongoing series of investigations designed to apply three-dimensional (3D) technology to problems in forensic anthropology. We report here on new morphometric data examining sexual dimorphism and population variation in the adult human mandible. The material is sourced from dissection hall subjects of South African and American origin consequently the sex and a statement of age are known for each individual. Thirty-eight bilateral 3D landmarks were designed and acquired using a Microscribe G2X portable digitizer. The shape analysis software morphologika (www.york.ac.uk/res/fme) is used to analyze the 3D coordinates of the landmarks. A selection of multivariate statistics is applied to visualize the pattern, and assess the significance of, shape variation between the sexes and populations. The determination of sex and identification of population affinity are two important aspects of forensic investigation. Our results indicate that the adult mandible can be used to identify both sex and population affinity with increased sensitivity and objectivity compared to standard analytical techniques.

Displaying Sensed Tactile Cues with a Fingertip Haptic Device.

PubMed

Pacchierotti, Claudio; Prattichizzo, Domenico; Kuchenbecker, Katherine J

2015-01-01

Telerobotic systems enable humans to explore and manipulate remote environments for applications such as surgery and disaster response, but few such systems provide the operator with cutaneous feedback. This article presents a novel approach to remote cutaneous interaction; our method is compatible with any fingertip tactile sensor and any mechanical tactile display device, and it does not require a position/force or skin deformation model. Instead, it directly maps the sensed stimuli to the best possible input commands for the device's motors using a data set recorded with the tactile sensor inside the device. As a proof of concept, we considered a haptic system composed of a BioTac tactile sensor, in charge of measuring contact deformations, and a custom 3-DoF cutaneous device with a flat contact platform, in charge of applying deformations to the user's fingertip. To validate the proposed approach and discover its inherent tradeoffs, we carried out two remote tactile interaction experiments. The first one evaluated the error between the tactile sensations registered by the BioTac in a remote environment and the sensations created by the cutaneous device for six representative tactile interactions and 27 variations of the display algorithm. The normalized average errors in the best condition were 3.0 percent of the BioTac's full 12-bit scale. The second experiment evaluated human subjects' experiences for the same six remote interactions and eight algorithm variations. The average subjective rating for the best algorithm variation was 8.2 out of 10, where 10 is best.

Humans and Deep Networks Largely Agree on Which Kinds of Variation Make Object Recognition Harder.

PubMed

Kheradpisheh, Saeed R; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

2016-01-01

View-invariant object recognition is a challenging problem that has attracted much attention among the psychology, neuroscience, and computer vision communities. Humans are notoriously good at it, even if some variations are presumably more difficult to handle than others (e.g., 3D rotations). Humans are thought to solve the problem through hierarchical processing along the ventral stream, which progressively extracts more and more invariant visual features. This feed-forward architecture has inspired a new generation of bio-inspired computer vision systems called deep convolutional neural networks (DCNN), which are currently the best models for object recognition in natural images. Here, for the first time, we systematically compared human feed-forward vision and DCNNs at view-invariant object recognition task using the same set of images and controlling the kinds of transformation (position, scale, rotation in plane, and rotation in depth) as well as their magnitude, which we call "variation level." We used four object categories: car, ship, motorcycle, and animal. In total, 89 human subjects participated in 10 experiments in which they had to discriminate between two or four categories after rapid presentation with backward masking. We also tested two recent DCNNs (proposed respectively by Hinton's group and Zisserman's group) on the same tasks. We found that humans and DCNNs largely agreed on the relative difficulties of each kind of variation: rotation in depth is by far the hardest transformation to handle, followed by scale, then rotation in plane, and finally position (much easier). This suggests that DCNNs would be reasonable models of human feed-forward vision. In addition, our results show that the variation levels in rotation in depth and scale strongly modulate both humans' and DCNNs' recognition performances. We thus argue that these variations should be controlled in the image datasets used in vision research.

A test of genetic models for the evolutionary maintenance of same-sex sexual behaviour.

PubMed

Hoskins, Jessica L; Ritchie, Michael G; Bailey, Nathan W

2015-06-22

The evolutionary maintenance of same-sex sexual behaviour (SSB) has received increasing attention because it is perceived to be an evolutionary paradox. The genetic basis of SSB is almost wholly unknown in non-human animals, though this is key to understanding its persistence. Recent theoretical work has yielded broadly applicable predictions centred on two genetic models for SSB: overdominance and sexual antagonism. Using Drosophila melanogaster, we assayed natural genetic variation for male SSB and empirically tested predictions about the mode of inheritance and fitness consequences of alleles influencing its expression. We screened 50 inbred lines derived from a wild population for male-male courtship and copulation behaviour, and examined crosses between the lines for evidence of overdominance and antagonistic fecundity selection. Consistent variation among lines revealed heritable genetic variation for SSB, but the nature of the genetic variation was complex. Phenotypic and fitness variation was consistent with expectations under overdominance, although predictions of the sexual antagonism model were also supported. We found an unexpected and strong paternal effect on the expression of SSB, suggesting possible Y-linkage of the trait. Our results inform evolutionary genetic mechanisms that might maintain low but persistently observed levels of male SSB in D. melanogaster, but highlight a need for broader taxonomic representation in studies of its evolutionary causes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

PubMed

Wang, Linli; Chen, Yuehua; Guan, Chunyan; Zhao, Zhiju; Li, Qiang; Yang, Jianguo; Mo, Jian; Wang, Bin; Wu, Wei; Yang, Xiaohui; Song, Libing; Li, Jun

2017-11-02

Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important. To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses. We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system. The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

GF-1 and Landsat observed a 40-year wetland spatiotemporal variation and its coupled environmental factors in Yangtze River estuary

NASA Astrophysics Data System (ADS)

Sun, Nan; Zhu, Weining; Cheng, Qian

2018-07-01

Wetlands are health indicators of aquatic ecosystems and also vulnerable to regional environmental and socio-economic changes. For exploring wetland spatiotemporal variations in estuarine and coastal regions of the Yangtze River, we extracted wetland information from 40-year time-series images of Landsat, GF-1, and other satellites, using the classification method of decision tree. Potential environmental and socio-economic factors which may drive wetland variations were analyzed. Results show that the wetland area in Yangtze River estuary has increased 663 km2, but it was only contributed by the increasing of human-made wetlands (767 km2), which were mostly caused by economic growth and constructions of human-made hydro-projects in Yangtze Delta. In comparison, natural wetlands, such as tidal flats and marshes, have decreased 163 km2. Land reclamation has changed these natural wetlands into reservoirs, aquaculture ponds and paddy fields. Wetlands in Shanghai and Qidong urban regions were mainly affected by human activities, while wetland variations in Chongming Island were mainly controlled by natural factors such as the upstream discharge, precipitation, diurnal variation of tidal level and long-term sea level rising. The general trend is that the natural wetland was transformed into the human-made wetland, and the human-made wetland was transformed into construction land.

Rare variation facilitates inferences of fine-scale population structure in humans.

PubMed

O'Connor, Timothy D; Fu, Wenqing; Mychaleckyj, Josyf C; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S; Leal, Suzanne M; Smith, Joshua D; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Akey, Joshua M

2015-03-01

Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European-American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Parietal structure and function explain human variation in working memory biases of visual attention.

PubMed

Soto, David; Rotshtein, Pia; Kanai, Ryota

2014-04-01

Recent research indicates that human attention appears inadvertently biased by items that match the contents of working memory (WM). WM-biases can lead to attentional costs when the memory content matches goal-irrelevant items and to attentional benefits when it matches the sought target. Here we used functional and structural MRI data to determine the neural basis of human variation in WM biases. We asked whether human variation in WM-benefits and WM-costs merely reflects the process of attentional capture by the contents of WM or whether variation in WM biases may be associated with distinct forms of cognitive control over internal WM signals based on selection goals. Human ability to use WM contents to facilitate selection was positively correlated with gray matter volume in the left superior posterior parietal cortex (PPC), while the ability to overcome interference by WM-matching distracters was associated with the left inferior PPC in the anterior IPS. Functional activity in the left PPC, measured by functional MRI, also predicted the magnitude of WM-costs on selection. Both structure and function of left PPC mediate the expression of WM biases in human visual attention. Copyright © 2013 Elsevier Inc. All rights reserved.

Population structure and cultural geography of a folktale in Europe

PubMed Central

Ross, Robert M.; Greenhill, Simon J.; Atkinson, Quentin D.

2013-01-01

Despite a burgeoning science of cultural evolution, relatively little work has focused on the population structure of human cultural variation. By contrast, studies in human population genetics use a suite of tools to quantify and analyse spatial and temporal patterns of genetic variation within and between populations. Human genetic diversity can be explained largely as a result of migration and drift giving rise to gradual genetic clines, together with some discontinuities arising from geographical and cultural barriers to gene flow. Here, we adapt theory and methods from population genetics to quantify the influence of geography and ethnolinguistic boundaries on the distribution of 700 variants of a folktale in 31 European ethnolinguistic populations. We find that geographical distance and ethnolinguistic affiliation exert significant independent effects on folktale diversity and that variation between populations supports a clustering concordant with European geography. This pattern of geographical clines and clusters parallels the pattern of human genetic diversity in Europe, although the effects of geographical distance and ethnolinguistic boundaries are stronger for folktales than genes. Our findings highlight the importance of geography and population boundaries in models of human cultural variation and point to key similarities and differences between evolutionary processes operating on human genes and culture. PMID:23390109

Reproducibility of telomere length assessment: an international collaborative study.

PubMed

Martin-Ruiz, Carmen M; Baird, Duncan; Roger, Laureline; Boukamp, Petra; Krunic, Damir; Cawthon, Richard; Dokter, Martin M; van der Harst, Pim; Bekaert, Sofie; de Meyer, Tim; Roos, Goran; Svenson, Ulrika; Codd, Veryan; Samani, Nilesh J; McGlynn, Liane; Shiels, Paul G; Pooley, Karen A; Dunning, Alison M; Cooper, Rachel; Wong, Andrew; Kingston, Andrew; von Zglinicki, Thomas

2015-10-01

Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories. We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques. Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63-0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant (P = 0.06). Gel-based and PCR-based techniques were not different in accuracy. Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories. © The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization.

PubMed

Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Van Roy, Nadine; Vandesompele, Jo; Hooyberghs, Jef

2017-01-01

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine.

A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton.

PubMed

Vioarsdóttir, Una Strand; O'Higgins, Paul; Stringer, Chris

2002-09-01

This study examines interpopulation variations in the facial skeleton of 10 modern human populations and places these in an ontogenetic perspective. It aims to establish the extent to which the distinctive features of adult representatives of these populations are present in the early post natal period and to what extent population differences in ontogenetic scaling and allometric trajectories contribute to distinct facial forms. The analyses utilize configurations of facial landmarks and are carried out using geometric morphometric methods. The results of this study show that modern human populations can be distinguished based on facial shape alone, irrespective of age or sex, indicating the early presence of differences. Additionally, some populations have statistically distinct facial ontogenetic trajectories that lead to the development of further differences later in ontogeny. We conclude that population-specific facial morphologies develop principally through distinctions in facial shape probably already present at birth and further accentuated and modified to variable degrees during growth. These findings raise interesting questions regarding the plasticity of facial growth patterns in modern humans. Further, they have important implications in relation to the study of growth in the face of fossil hominins and in relation to the possibility of developing effective discriminant functions for the identification of population affinities of immature facial skeletal material. Such tools would be of value in archaeological, forensic and anthropological applications. The findings of this study underline the need to examine more deeply, and in more detail, the ontogenetic basis of other causes of craniometric variation, such as sexual dimorphism and hominin species differentiation.

Understanding human DNA sequence variation.

PubMed

Kidd, K K; Pakstis, A J; Speed, W C; Kidd, J R

2004-01-01

Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an "out of Africa" hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics.

Planning the Human Variome Project: The Spain Report†

PubMed Central

Kaput, Jim; Cotton, Richard G. H.; Hardman, Lauren; Al Aqeel, Aida I.; Al-Aama, Jumana Y.; Al-Mulla, Fahd; Aretz, Stefan; Auerbach, Arleen D.; Axton, Myles; Bapat, Bharati; Bernstein, Inge T.; Bhak, Jong; Bleoo, Stacey L.; Blöcker, Helmut; Brenner, Steven E.; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T.; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M. Rosário N.; Ekong, Rosemary; Flanagan, Simon B.; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V.; Greenblatt, Marc S.; Hamosh, Ada; Hancock, John M.; Hardison, Ross; Harrison, Terence M.; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J.; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L.; Macrae, Finlay A.; Maglott, Donna; Marafie, Makia J.; Marsh, Steven G.E.; Matsubara, Yoichi; Messiaen, Ludwine M.; Möslein, Gabriela; Netea, Mihai G.; Norton, Melissa L.; Oefner, Peter J.; Oetting, William S.; O’Leary, James C.; de Ramirez, Ana Maria Oller; Paalman, Mark H.; Parboosingh, Jillian; Patrinos, George P.; Perozzi, Giuditta; Phillips, Ian R.; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J.; Ramesar, Rajkumar S.; Richards, C. Sue; Savige, Judith; Scheible, Dagmar G.; Scott, Rodney J.; Seminara, Daniela; Shephard, Elizabeth A.; Sijmons, Rolf H.; Smith, Timothy D.; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V.; Taylor, Graham R.; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J.; Vihinen, Mauno; Watson, Michael; Webb, Elizabeth; Weber, Thomas K.; Yeager, Meredith; Yeom, Young I.; Yim, Seon-Hee; Yoo, Hyang-Sook

2018-01-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Since variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. PMID:19306394

Planning the human variome project: the Spain report.

PubMed

Kaput, Jim; Cotton, Richard G H; Hardman, Lauren; Watson, Michael; Al Aqeel, Aida I; Al-Aama, Jumana Y; Al-Mulla, Fahd; Alonso, Santos; Aretz, Stefan; Auerbach, Arleen D; Bapat, Bharati; Bernstein, Inge T; Bhak, Jong; Bleoo, Stacey L; Blöcker, Helmut; Brenner, Steven E; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M Rosário N; Ekong, Rosemary; Flanagan, Simon B; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V; Greenblatt, Marc S; Hamosh, Ada; Hancock, John M; Hardison, Ross; Harrison, Terence M; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L; Macrae, Finlay A; Maglott, Donna; Marafie, Makia J; Marsh, Steven G E; Matsubara, Yoichi; Messiaen, Ludwine M; Möslein, Gabriela; Netea, Mihai G; Norton, Melissa L; Oefner, Peter J; Oetting, William S; O'Leary, James C; de Ramirez, Ana Maria Oller; Paalman, Mark H; Parboosingh, Jillian; Patrinos, George P; Perozzi, Giuditta; Phillips, Ian R; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J; Ramesar, Rajkumar S; Richards, C Sue; Savige, Judith; Scheible, Dagmar G; Scott, Rodney J; Seminara, Daniela; Shephard, Elizabeth A; Sijmons, Rolf H; Smith, Timothy D; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V; Taylor, Graham R; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J; Vihinen, Mauno; Webb, Elizabeth; Weber, Thomas K; Yeager, Meredith; Yeom, Young I; Yim, Seon-Hee; Yoo, Hyang-Sook

2009-04-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. (c) 2009 Wiley-Liss, Inc.

Metabolome-genome-wide association study dissects genetic architecture for generating natural variation in rice secondary metabolism

PubMed Central

Matsuda, Fumio; Nakabayashi, Ryo; Yang, Zhigang; Okazaki, Yozo; Yonemaru, Jun-ichi; Ebana, Kaworu; Yano, Masahiro; Saito, Kazuki

2015-01-01

Plants produce structurally diverse secondary (specialized) metabolites to increase their fitness for survival under adverse environments. Several bioactive compounds for new drugs have been identified through screening of plant extracts. In this study, genome-wide association studies (GWAS) were conducted to investigate the genetic architecture behind the natural variation of rice secondary metabolites. GWAS using the metabolome data of 175 rice accessions successfully identified 323 associations among 143 single nucleotide polymorphisms (SNPs) and 89 metabolites. The data analysis highlighted that levels of many metabolites are tightly associated with a small number of strong quantitative trait loci (QTLs). The tight association may be a mechanism generating strains with distinct metabolic composition through the crossing of two different strains. The results indicate that one plant species produces more diverse phytochemicals than previously expected, and plants still contain many useful compounds for human applications. PMID:25267402

41 CFR 50-204.35 - Application for variations from radiation levels.

Code of Federal Regulations, 2012 CFR

2012-07-01

... variations from radiation levels. 50-204.35 Section 50-204.35 Public Contracts and Property Management Other... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation levels. (a) In accordance with policy expressed in the Federal Radiation Council's memorandum concerning...

41 CFR 50-204.35 - Application for variations from radiation levels.

Code of Federal Regulations, 2011 CFR

2011-07-01

... variations from radiation levels. 50-204.35 Section 50-204.35 Public Contracts and Property Management Other... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation levels. (a) In accordance with policy expressed in the Federal Radiation Council's memorandum concerning...

41 CFR 50-204.35 - Application for variations from radiation levels.

Code of Federal Regulations, 2013 CFR

2013-07-01

... variations from radiation levels. 50-204.35 Section 50-204.35 Public Contracts and Property Management Other... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation levels. (a) In accordance with policy expressed in the Federal Radiation Council's memorandum concerning...

41 CFR 50-204.35 - Application for variations from radiation levels.

Code of Federal Regulations, 2014 CFR

2014-07-01

... variations from radiation levels. 50-204.35 Section 50-204.35 Public Contracts and Property Management Other... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation levels. (a) In accordance with policy expressed in the Federal Radiation Council's memorandum concerning...

Accelerated Simulation of Kinetic Transport Using Variational Principles and Sparsity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caflisch, Russel

This project is centered on the development and application of techniques of sparsity and compressed sensing for variational principles, PDEs and physics problems, in particular for kinetic transport. This included derivation of sparse modes for elliptic and parabolic problems coming from variational principles. The research results of this project are on methods for sparsity in differential equations and their applications and on application of sparsity ideas to kinetic transport of plasmas.

The evolution of personality variation in humans and other animals.

PubMed

Nettle, Daniel

2006-09-01

A comprehensive evolutionary framework for understanding the maintenance of heritable behavioral variation in humans is yet to be developed. Some evolutionary psychologists have argued that heritable variation will not be found in important, fitness-relevant characteristics because of the winnowing effect of natural selection. This article propounds the opposite view. Heritable variation is ubiquitous in all species, and there are a number of frameworks for understanding its persistence. The author argues that each of the Big Five dimensions of human personality can be seen as the result of a trade-off between different fitness costs and benefits. As there is no unconditionally optimal value of these trade-offs, it is to be expected that genetic diversity will be retained in the population. ((c) 2006 APA, all rights reserved).

Relating Human Genetic Variation to Variation in Drug Responses

PubMed Central

Madian, Ashraf G.; Wheeler, Heather E.; Jones, Richard Baker; Dolan, M. Eileen

2012-01-01

Although sequencing a single human genome was a monumental effort a decade ago, more than one thousand genomes have now been sequenced. The task ahead lies in transforming this information into personalized treatment strategies that are tailored to the unique genetics of each individual. One important aspect of personalized medicine is patient-to-patient variation in drug response. Pharmacogenomics addresses this issue by seeking to identify genetic contributors to human variation in drug efficacy and toxicity. Here, we present a summary of the current status of this field, which has evolved from studies of single candidate genes to comprehensive genome-wide analyses. Additionally, we discuss the major challenges in translating this knowledge into a systems-level understanding of drug physiology with the ultimate goal of developing more effective personalized clinical treatment strategies. PMID:22840197

The roles of the outdoors and occupants in contributing to a potential pan-microbiome of the built environment: a review.

PubMed

Leung, Marcus H Y; Lee, Patrick K H

2016-05-24

Recent high-throughput sequencing technology has led to an expansion of knowledge regarding the microbial communities (microbiome) across various built environments (BEs). The microbiome of the BE is dependent upon building factors and conditions that govern how outdoor microbes enter and persist in the BE. Additionally, occupants are crucial in shaping the microbiome of the BE by releasing human-associated microorganisms and resuspending microbes on floors and surfaces. Therefore, both the outdoors and occupants act as major sources of microorganisms found in the BE. However, most characterizations of the microbiome of the BE have been conducted in the Western world. Notably, outdoor locations and population groups present geographical variations in outdoor and human microbiomes, respectively. Given the influences of the outdoor and human microbiomes on BE microbiology, and the geographical variations in outdoor and human microbiomes, it is likely that the microbiomes of BEs also vary by location. The summation of microbiomes between BEs contribute to a potential BE pan-microbiome, which will both consist of microbes that are ubiquitous in indoor environments around the world, and microbes that appear to be endemic to particular geographical locations. Importantly, the BE pan-microbiome can potentially question the global application of our current views on indoor microbiology. In this review, we first provide an assessment on the roles of building and occupant properties on shaping the microbiome of the BE. This is then followed by a description of geographical variations in the microbiomes of the outdoors and humans, the two main sources of microbes in BEs. We present evidence of differences in microbiomes of BEs around the world, demonstrating the existence of a global pan-microbiome of the BE that is larger than the microbiome of any single indoor environment. Finally, we discuss the significance of understanding the BE pan-microbiome and identifying universal and location-specific relationships between building and occupant characteristics and indoor microbiology. This review highlights the much needed efforts towards determining the pan-microbiome of the BE, thereby identifying general and location-specific links between the microbial communities of the outdoors, human, and BE ecosystems, ultimately improving the health, comfort, and productivity of occupants around the world.

Random genetic drift, natural selection, and noise in human cranial evolution.

PubMed

Roseman, Charles C

2016-08-01

This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest.

PubMed

Pappas, D J; Lizee, A; Paunic, V; Beutner, K R; Motyer, A; Vukcevic, D; Leslie, S; Biesiada, J; Meller, J; Taylor, K D; Zheng, X; Zhao, L P; Gourraud, P-A; Hollenbach, J A; Mack, S J; Maiers, M

2018-05-22

Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall, <27.8% of subjects were correctly imputed for all HLA loci by any method. Concordance across all loci was not enhanced via the application of confidence thresholds; reliance on confidence scores across methods only led to noticeable improvement (+3.2%) for HLA-DRB1. As the HLA complex is highly relevant to the study of human health and disease, a standardized assessment of SNP-based HLA imputation methods is crucial for advancing genomic research. Considerable room remains for the improvement of HLA-B and especially HLA-DRB1 imputation methods, and no imputation method is as accurate as molecular genotyping. The application of large, ancestrally diverse HLA and SNP reference data sets and multiple imputation methods has the potential to make SNP-based HLA imputation methods a tractable option for determining HLA genotypes.

Human genetics as a model for target validation: finding new therapies for diabetes.

PubMed

Thomsen, Soren K; Gloyn, Anna L

2017-06-01

Type 2 diabetes is a global epidemic with major effects on healthcare expenditure and quality of life. Currently available treatments are inadequate for the prevention of comorbidities, yet progress towards new therapies remains slow. A major barrier is the insufficiency of traditional preclinical models for predicting drug efficacy and safety. Human genetics offers a complementary model to assess causal mechanisms for target validation. Genetic perturbations are 'experiments of nature' that provide a uniquely relevant window into the long-term effects of modulating specific targets. Here, we show that genetic discoveries over the past decades have accurately predicted (now known) therapeutic mechanisms for type 2 diabetes. These findings highlight the potential for use of human genetic variation for prospective target validation, and establish a framework for future applications. Studies into rare, monogenic forms of diabetes have also provided proof-of-principle for precision medicine, and the applicability of this paradigm to complex disease is discussed. Finally, we highlight some of the limitations that are relevant to the use of genome-wide association studies (GWAS) in the search for new therapies for diabetes. A key outstanding challenge is the translation of GWAS signals into disease biology and we outline possible solutions for tackling this experimental bottleneck.

Parallel Analysis of 124 Universal SNPs for Human Identification by Targeted Semiconductor Sequencing

PubMed Central

Zhang, Suhua; Bian, Yingnan; Zhang, Zheren; Zheng, Hancheng; Wang, Zheng; Zha, Lagabaiyila; Cai, Jifeng; Gao, Yuzhen; Ji, Chaoneng; Hou, Yiping; Li, Chengtao

2015-01-01

SNPs, abundant in human genome with lower mutation rate, are attractive to genetic application like forensic, anthropological and evolutionary studies. Universal SNPs showing little allelic frequency variation among populations while remaining highly informative for human identification were obtained from previous studies. However, genotyping tools target only dozens of markers simultaneously, limiting their applications. Here, 124 SNPs were simultaneous tested using Ampliseq technology with Ion Torrent PGM platform. Concordance study was performed with 2 reference samples of 9947A and 9948 between NGS and Sanger sequencing. Full concordance were obtained except genotype of rs576261 with 9947A. Parameter of FMAR (%) was introduced for NGS data analysis for the first time, evaluating allelic performance, sensitivity testing and mixture testing. FMAR values for accurate heterozygotes should be range from 50% to 60%, for homozygotes or Y-SNP should be above 90%. SNPs of rs7520386, rs4530059, rs214955, rs1523537, rs2342747, rs576261 and rs12997453 were recognized as poorly performing loci, either with allelic imbalance or with lower coverage. Sensitivity testing demonstrated that with DNA range from 10 ng-0.5 ng, all correct genotypes were obtained. For mixture testing, a clear linear correlation (R2 = 0.9429) between the excepted FMAR and observed FMAR values of mixtures was observed. PMID:26691610

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

DOE PAGES

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; ...

2016-12-29

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here in this article, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with highmore » reproducibility (CV ≤ 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. Lastly, this SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.« less

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids.

PubMed

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M; Kim, Young-Mo; Burnum-Johnson, Kristin E; Orton, Daniel J; Apffel, Alex; Ibrahim, Yehia M; Monroe, Matthew E; Moore, Ronald J; Smith, Jordan N; Ma, Jian; Renslow, Ryan S; Thomas, Dennis G; Blackwell, Anne E; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O; Teeguarden, Justin G; Smith, Richard D; Baker, Erin S

2016-12-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

PubMed Central

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M.; Kim, Young-Mo; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Apffel, Alex; Ibrahim, Yehia M.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Jordan N.; Ma, Jian; Renslow, Ryan S.; Thomas, Dennis G.; Blackwell, Anne E.; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T.; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O.; Teeguarden, Justin G.; Smith, Richard D.; Baker, Erin S.

2017-01-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure. PMID:29276770

[Intradiscal temperature variation resulting from radiofrequency thermal therapy. Cadaver study].

PubMed

Ramírez-León, J F; Rugeles-Ortiz, J G; Barreto-perea, J A; Alonso-cuéllar, G O

2014-01-01

Disc disease is one of the most common causes of lumbar pain. The new era of treatments for degenerative disc disease involves the use of minimally-invasive thermal technologies allowing for collagen remodeling and destruction of nociceptors in the annulus. However, a better understanding of the treatment pathophysiology is needed. The purpose of this study was to measure intradiscal temperature variation after thermodiscoplasty. A human cadaver spine specimen was obtained and divided into blocks, each composed of two intervertebral plates and an intact disc. Radio frequency was applied at five spots with three different time intervals. Temperature was measured in each of the combinations. Units were weighed before and after treatment. Finally, the disc was exposed and the tightening achieved with each radio frequency application was measured. Data were analyzed with the SPSS software. The mean weight reduction obtained was 1.4 g on average (SD 0.599), with values between 0.5 and 2.6 grams. Mean temperature in the posterior rim of the annulus was 37.6 degrees C and mean temperature variation was 3.0 degrees C (SD 6.407). Mean tightening achieved in all blocks overall was 1.4 mm. The results obtained show the effectiveness of radio frequency thermodiscoplasty when performed within the safety parameters. Temperature values with radio frequency were lower than those found in comparable studies. The weight and the tightening show the effect of disc shrinking and dehydration. This report is an effective tool to define time parameters for the application of this technology.

Genome Variation Map: a data repository of genome variations in BIG Data Center.

PubMed

Song, Shuhui; Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang; Zhang, Zhang

2018-01-04

The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mechanistic understanding of human-wildlife conflict through a novel application of dynamic occupancy models.

PubMed

Goswami, Varun R; Medhi, Kamal; Nichols, James D; Oli, Madan K

2015-08-01

Crop and livestock depredation by wildlife is a primary driver of human-wildlife conflict, a problem that threatens the coexistence of people and wildlife globally. Understanding mechanisms that underlie depredation patterns holds the key to mitigating conflicts across time and space. However, most studies do not consider imperfect detection and reporting of conflicts, which may lead to incorrect inference regarding its spatiotemporal drivers. We applied dynamic occupancy models to elephant crop depredation data from India between 2005 and 2011 to estimate crop depredation occurrence and model its underlying dynamics as a function of spatiotemporal covariates while accounting for imperfect detection of conflicts. The probability of detecting conflicts was consistently <1.0 and was negatively influenced by distance to roads and elevation gradient, averaging 0.08-0.56 across primary periods (distinct agricultural seasons within each year). The probability of crop depredation occurrence ranged from 0.29 (SE 0.09) to 0.96 (SE 0.04). The probability that sites raided by elephants in primary period t would not be raided in primary period t + 1 varied with elevation gradient in different seasons and was influenced negatively by mean rainfall and village density and positively by distance to forests. Negative effects of rainfall variation and distance to forests best explained variation in the probability that sites not raided by elephants in primary period t would be raided in primary period t + 1. With our novel application of occupancy models, we teased apart the spatiotemporal drivers of conflicts from factors that influence how they are observed, thereby allowing more reliable inference on mechanisms underlying observed conflict patterns. We found that factors associated with increased crop accessibility and availability (e.g., distance to forests and rainfall patterns) were key drivers of elephant crop depredation dynamics. Such an understanding is essential for rigorous prediction of future conflicts, a critical requirement for effective conflict management in the context of increasing human-wildlife interactions. © 2015 Society for Conservation Biology.

Evaluation of a disintegrin-like and metalloprotease with thrombospondin type 1 repeat motifs 13 (ADAMTS13) activity enzyme-linked immunosorbent assay for measuring plasma ADAMTS13 activity in dogs.

PubMed

Maruyama, Haruhiko; Kaneko, Michiko; Otake, Taiga; Kano, Rui; Yamaya, Yoshiki; Watari, Toshihiro; Hasegawa, Atsuhiko; Kamata, Hiroshi

2014-03-01

A disintegrin-like and metalloprotease with thrombospondin type 1 repeat motifs 13 (ADAMTS13) is a von Willebrand factor (vWF)-cleaving protease. Deficiencies in ADAMTS13 activity are known to cause thrombotic diseases in human beings. The present study evaluated whether the human ADAMTS13 activity enzyme-linked immunosorbent assay (ELISA) kit containing human vWF73 (a minimal substrate) and anti-N10 antibody (which specifically recognizes the decapeptide of the C-terminal edge of cleaved vWF by human ADAMTS13) is applicable to the measurement of canine plasma ADAMTS13 activity. Human vWF73 fused with a GST-tag and a His-tag (GST-hvWF73-His) was reacted with recombinant canine (rc)ADAMTS13, canine plasma, and human plasma, and then used in Western blotting using anti-N10 antibody. Linearity and intra- and interassay reproducibility of the human ADAMTS13 activity ELISA kit in canine plasma were further evaluated. Finally, plasma ADAMTS13 activity was measured in 13 healthy dogs and 6 dogs with bacteremia using the human ADAMTS13 activity ELISA kit. Cleaved products with a 28-kDa GST-hvWF73-His were detected specifically in rcADAMTS13 as well as in human ADAMTS13, and also in canine plasma by anti-N10 antibody, showing excellent linearity. Intra-assay coefficient of variation (CV) was 3.0-12.4%, and interassay CV was 11.5-12.5%. The ADAMTS13 activity was significantly lower in dogs with bacteremia than in healthy dogs (P = 0.0025). The current study revealed that the human ADAMTS13 activity ELISA kit is applicable for measurement of canine plasma ADAMTS13 activity to elucidate the pathology of thrombotic diseases in dogs.

Possible psycho-physiological consequences of human long-term space missions

NASA Astrophysics Data System (ADS)

Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.

Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an

Meiotic gene-conversion rate and tract length variation in the human genome.

PubMed

Padhukasahasram, Badri; Rannala, Bruce

2013-02-27

Meiotic recombination occurs in the form of two different mechanisms called crossing-over and gene-conversion and both processes have an important role in shaping genetic variation in populations. Although variation in crossing-over rates has been studied extensively using sperm-typing experiments, pedigree studies and population genetic approaches, our knowledge of variation in gene-conversion parameters (ie, rates and mean tract lengths) remains far from complete. To explore variability in population gene-conversion rates and its relationship to crossing-over rate variation patterns, we have developed and validated using coalescent simulations a comprehensive Bayesian full-likelihood method that can jointly infer crossing-over and gene-conversion rates as well as tract lengths from population genomic data under general variable rate models with recombination hotspots. Here, we apply this new method to SNP data from multiple human populations and attempt to characterize for the first time the fine-scale variation in gene-conversion parameters along the human genome. We find that the estimated ratio of gene-conversion to crossing-over rates varies considerably across genomic regions as well as between populations. However, there is a great degree of uncertainty associated with such estimates. We also find substantial evidence for variation in the mean conversion tract length. The estimated tract lengths did not show any negative relationship with the local heterozygosity levels in our analysis.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.30.

Use of high-radiant flux, high-resolution DMD light engines in industrial applications

NASA Astrophysics Data System (ADS)

Müller, Alexandra; Ram, Surinder

2014-03-01

The field of application of industrial projectors is growing day by day. New Digital Micromirror Device (DMD) - based applications like 3D printing, 3D scanning, Printed Circuit Board (PCB) board printing and others are getting more and more sophisticated. The technical demands for the projection system are rising as new and more stringent requirements appear. The specification for industrial projection systems differ substantially from the ones of business and home beamers. Beamers are designed to please the human eye. Bright colors and image enhancement are far more important than uniformity of the illumination or image distortion. The human eye, followed by the processing of the brain can live with quite high intensity variations on the screen and image distortion. On the other hand, a projector designed for use in a specialized field has to be tailored regarding its unique requirements in order to make no quality compromises. For instance, when the image is projected onto a light sensitive resin, a good uniformity of the illumination is crucial for good material hardening (curing) results. The demands on the hardware and software are often very challenging. In the following we will review some parameters that have to be considered carefully for the design of industrial projectors in order to get the optimum result without compromises.

The UF family of hybrid phantoms of the developing human fetus for computational radiation dosimetry

NASA Astrophysics Data System (ADS)

Maynard, Matthew R.; Geyer, John W.; Aris, John P.; Shifrin, Roger Y.; Bolch, Wesley

2011-08-01

Historically, the development of computational phantoms for radiation dosimetry has primarily been directed at capturing and representing adult and pediatric anatomy, with less emphasis devoted to models of the human fetus. As concern grows over possible radiation-induced cancers from medical and non-medical exposures of the pregnant female, the need to better quantify fetal radiation doses, particularly at the organ-level, also increases. Studies such as the European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) hope to improve our understanding of cancer risks following chronic in utero radiation exposure. For projects such as SOLO, currently available fetal anatomic models do not provide sufficient anatomical detail for organ-level dose assessment. To address this need, two fetal hybrid computational phantoms were constructed using high-quality magnetic resonance imaging and computed tomography image sets obtained for two well-preserved fetal specimens aged 11.5 and 21 weeks post-conception. Individual soft tissue organs, bone sites and outer body contours were segmented from these images using 3D-DOCTOR™ and then imported to the 3D modeling software package Rhinoceros™ for further modeling and conversion of soft tissue organs, certain bone sites and outer body contours to deformable non-uniform rational B-spline surfaces. The two specimen-specific phantoms, along with a modified version of the 38 week UF hybrid newborn phantom, comprised a set of base phantoms from which a series of hybrid computational phantoms was derived for fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. The methodology used to construct the series of phantoms accounted for the following age-dependent parameters: (1) variations in skeletal size and proportion, (2) bone-dependent variations in relative levels of bone growth, (3) variations in individual organ masses and total fetal masses and (4) statistical percentile variations in skeletal size, individual organ masses and total fetal masses. The resulting series of fetal hybrid computational phantoms is applicable to organ-level and bone-level internal and external radiation dosimetry for human fetuses of various ages and weight percentiles

Application of Method of Variation to Analyze and Predict Human Induced Modifications of Water Resource Systems

NASA Astrophysics Data System (ADS)

Dessu, S. B.; Melesse, A. M.; Mahadev, B.; McClain, M.

2010-12-01

Water resource systems have often used gravitational surface and subsurface flows because of their practicality in hydrological modeling and prediction. Activities such as inter/intra-basin water transfer, the use of small pumps and the construction of micro-ponds challenge the tradition of natural rivers as water resource management unit. On the contrary, precipitation is barely affected by topography and plot harvesting in wet regions can be more manageable than diverting from rivers. Therefore, it is indicative to attend to systems where precipitation drives the dynamics while the internal mechanics constitutes spectrum of human activity and decision in a network of plots. The trade-in volume and path of harvested precipitation depends on water balance, energy balance and the kinematics of supply and demand. Method of variation can be used to understand and predict the implication of local excess precipitation harvest and exchange on the natural water system. A system model was developed using the variational form of Euler-Bernoulli’s equation for the Kenyan Mara River basin. Satellite derived digital elevation models, precipitation estimates, and surface properties such as fractional impervious surface area, are used to estimate the available water resource. Four management conditions are imposed in the model: gravitational flow, open water extraction and high water use investment at upstream and downstream respectively. According to the model, the first management maintains the basin status quo while the open source management could induce externality. The high water market at the upstream in the third management offers more than 50% of the basin-wide total revenue to the upper third section of the basin thus may promote more harvesting. The open source and upstream exploitation suggest potential drop of water availability to downstream. The model exposed the latent potential of economic gradient to reconfigure the flow network along the direction where the marginal benefit is maximized. Therefore, the variation model can help to predict the possible human induced modification of natural water system in order to gain the maximum productivity and benefit.

The Geographic Distribution of Human Y Chromosome Variation

PubMed Central

Hammer, M. F.; Spurdle, A. B.; Karafet, T.; Bonner, M. R.; Wood, E. T.; Novelletto, A.; Malaspina, P.; Mitchell, R. J.; Horai, S.; Jenkins, T.; Zegura, S. L.

1997-01-01

We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or ``YAP'' element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five ``YAP haplotypes'' in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 ``combination haplotypes''. All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions. PMID:9055088

Sequence polymorphism data of the hypervariable regions of mitochondrial DNA in the Yadav population of Haryana.

PubMed

Verma, Kapil; Sharma, Sapna; Sharma, Arun; Dalal, Jyoti; Bhardwaj, Tapeshwar

2018-06-01

Genetic variations among humans occur both within and among populations and range from single nucleotide changes to multiple-nucleotide variants. These multiple-nucleotide variants are useful for studying the relationships among individuals or various population groups. The study of human genetic variations can help scientists understand how different population groups are biologically related to one another. Sequence analysis of hypervariable regions of human mitochondrial DNA (mtDNA) has been successfully used for the genetic characterization of different population groups for forensic purposes. It is well established that different ethnic or population groups differ significantly in their mtDNA distributions. In the last decade, very little research has been conducted on mtDNA variations in the Indian population, although such data would be useful for elucidating the history of human population expansion across the world. Moreover, forensic studies on mtDNA variations in the Indian subcontinent are also scarce, particularly in the northern part of India. In this report, variations in the hypervariable regions of mtDNA were analyzed in the Yadav population of Haryana. Different molecular diversity indices were computed. Further, the obtained haplotypes were classified into different haplogroups and the phylogenetic relationship between different haplogroups was inferred.

Variation in umami perception and in candidate genes for the umami receptor in mice and humans1234

PubMed Central

Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, AA Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo

2009-01-01

The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5′-monophosphate and guanosine 5′-monophosphate. There is evidence that a heterodimeric G protein–coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR1 (glutamate receptor, metabotropic 1, Grm1) and mGluR4 (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species. PMID:19625681

Intra-individual metameric variation expressed at the enamel-dentine junction of lower post-canine dentition of South African fossil hominins and modern humans.

PubMed

Pan, Lei; Thackeray, John Francis; Dumoncel, Jean; Zanolli, Clément; Oettlé, Anna; de Beer, Frikkie; Hoffman, Jakobus; Duployer, Benjamin; Tenailleau, Christophe; Braga, José

2017-08-01

The aim of this study is to compare the degree and patterning of inter- and intra-individual metameric variation in South African australopiths, early Homo and modern humans. Metameric variation likely reflects developmental and taxonomical issues, and could also be used to infer ecological and functional adaptations. However, its patterning along the early hominin postcanine dentition, particularly among South African fossil hominins, remains unexplored. Using microfocus X-ray computed tomography (µXCT) and geometric morphometric tools, we studied the enamel-dentine junction (EDJ) morphology and we investigated the intra- and inter-individual EDJ metameric variation among eight australopiths and two early Homo specimens from South Africa, as well as 32 modern humans. Along post-canine dentition, shape changes between metameres represented by relative positions and height of dentine horns, outlines of the EDJ occlusal table are reported in modern and fossil taxa. Comparisons of EDJ mean shapes and multivariate analyses reveal substantial variation in the direction and magnitude of metameric shape changes among taxa, but some common trends can be found. In modern humans, both the direction and magnitude of metameric shape change show increased variability in M 2 -M 3 compared to M 1 -M 2 . Fossil specimens are clustered together showing similar magnitudes of shape change. Along M 2 -M 3 , the lengths of their metameric vectors are not as variable as those of modern humans, but they display considerable variability in the direction of shape change. The distalward increase of metameric variation along the modern human molar row is consistent with the odontogenetic models of molar row structure (inhibitory cascade model). Though much remains to be tested, the variable trends and magnitudes in metamerism in fossil hominins reported here, together with differences in the scale of shape change between modern humans and fossil hominins may provide valuable information regarding functional morphology and developmental processes in fossil species. © 2017 Wiley Periodicals, Inc.

Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

PubMed Central

Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

2014-01-01

Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death.

PubMed

Pettersson, Jenny; Mossberg, Ann-Kristin; Svanborg, Catharina

2006-06-23

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of apo alpha-lactalbumin and oleic acid, formed in casein after low pH treatment of human milk. This study examined if HAMLET-like complexes are present in casein from different species and if isolated alpha-lactalbumin from those species can form such complexes with oleic acid. Casein from human, bovine, equine, and porcine milk was separated by ion exchange chromatography and active complexes were only found in human casein. This was not explained by alpha-lactalbumin sequence variation, as purified bovine, equine, porcine, and caprine alpha-lactalbumins formed complexes with oleic acid with biological activity similar to HAMLET. We conclude that structural variation of alpha-lactalbumins does not preclude the formation of HAMLET-like complexes and that natural HAMLET formation in casein was unique to human milk, which also showed the highest oleic acid content.

From forensic epigenetics to forensic epigenomics: broadening DNA investigative intelligence.

PubMed

Vidaki, Athina; Kayser, Manfred

2017-12-21

Human genetic variation is a major resource in forensics, but does not allow all forensically relevant questions to be answered. Some questions may instead be addressable via epigenomics, as the epigenome acts as an interphase between the fixed genome and the dynamic environment. We envision future forensic applications of DNA methylation analysis that will broaden DNA-based forensic intelligence. Together with genetic prediction of appearance and biogeographic ancestry, epigenomic lifestyle prediction is expected to increase the ability of police to find unknown perpetrators of crime who are not identifiable using current forensic DNA profiling.

The study of human mutation rates. Progress report, 1989--1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neel, J.V.

1992-12-01

We will describe recent developments regarding the question of induced mutations in the survivors of the atomic bombings of Hiroshima and Nagasaki. As part of that work we, describe some developments with respect to the Amerindian blood samples collected under DoE sponsorship between 1964 and 1982. Then developments regarding the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to the study of genetic variation and mutation affecting protein characteristics. In particular, we will report on the identification and isolation of genes of especial interest as reflected in the behavior of the proteins which they encode.

The study of human mutation rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neel, J.V.

1992-01-01

We will describe recent developments regarding the question of induced mutations in the survivors of the atomic bombings of Hiroshima and Nagasaki. As part of that work we, describe some developments with respect to the Amerindian blood samples collected under DoE sponsorship between 1964 and 1982. Then developments regarding the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to the study of genetic variation and mutation affecting protein characteristics. In particular, we will report on the identification and isolation of genes of especial interest as reflected in the behavior of the proteins which they encode.

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

Solid Freeform Fabrication: An Enabling Technology for Future Space Missions

NASA Technical Reports Server (NTRS)

Taminger, Karen M. B.; Hafley, Robert A.; Dicus, Dennis L.

2002-01-01

The emerging class of direct manufacturing processes known as Solid Freeform Fabrication (SFF) employs a focused energy beam and metal feedstock to build structural parts directly from computer aided design (CAD) data. Some variations on existing SFF techniques have potential for application in space for a variety of different missions. This paper will focus on three different applications ranging from near to far term to demonstrate the widespread potential of this technology for space-based applications. One application is the on-orbit construction of large space structures, on the order of tens of meters to a kilometer in size. Such structures are too large to launch intact even in a deployable design; their extreme size necessitates assembly or erection of such structures in space. A low-earth orbiting satellite with a SFF system employing a high-energy beam for high deposition rates could be employed to construct large space structures using feedstock launched from Earth. A second potential application is a small, multifunctional system that could be used by astronauts on long-duration human exploration missions to manufacture spare parts. Supportability of human exploration missions is essential, and a SFF system would provide flexibility in the ability to repair or fabricate any part that may be damaged or broken during the mission. The system envisioned would also have machining and welding capabilities to increase its utility on a mission where mass and volume are extremely limited. A third example of an SFF application in space is a miniaturized automated system for structural health monitoring and repair. If damage is detected using a low power beam scan, the beam power can be increased to perform repairs within the spacecraft or satellite structure without the requirement of human interaction or commands. Due to low gravity environment for all of these applications, wire feedstock is preferred to powder from a containment, handling, and safety standpoint. The energy beams may be either electron beam or laser, and the developments required for either energy source to achieve success in these applications will be discussed.

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

DNA methylation-based variation between human populations.

PubMed

Kader, Farzeen; Ghai, Meenu

2017-02-01

Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

A combination of PhP typing and β-d-glucuronidase gene sequence variation analysis for differentiation of Escherichia coli from humans and animals.

PubMed

Masters, N; Christie, M; Katouli, M; Stratton, H

2015-06-01

We investigated the usefulness of the β-d-glucuronidase gene variance in Escherichia coli as a microbial source tracking tool using a novel algorithm for comparison of sequences from a prescreened set of host-specific isolates using a high-resolution PhP typing method. A total of 65 common biochemical phenotypes belonging to 318 E. coli strains isolated from humans and domestic and wild animals were analysed for nucleotide variations at 10 loci along a 518 bp fragment of the 1812 bp β-d-glucuronidase gene. Neighbour-joining analysis of loci variations revealed 86 (76.8%) human isolates and 91.2% of animal isolates were correctly identified. Pairwise hierarchical clustering improved assignment; where 92 (82.1%) human and 204 (99%) animal strains were assigned to their respective cluster. Our data show that initial typing of isolates and selection of common types from different hosts prior to analysis of the β-d-glucuronidase gene sequence improves source identification. We also concluded that numerical profiling of the nucleotide variations can be used as a valuable approach to differentiate human from animal E. coli. This study signifies the usefulness of the β-d-glucuronidase gene as a marker for differentiating human faecal pollution from animal sources.

Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle

PubMed Central

Pirinen, Eija; Canto, Carles; Jo, Young-Suk; Morato, Laia; Zhang, Hongbo; Menzies, Keir; Williams, Evan G.; Mouchiroud, Laurent; Moullan, Norman; Hagberg, Carolina; Li, Wei; Timmers, Silvie; Imhof, Ralph; Verbeek, Jef; Pujol, Aurora; van Loon, Barbara; Viscomi, Carlo; Zeviani, Massimo; Schrauwen, Patrick; Sauve, Anthony; Schoonjans, Kristina; Auwerx, Johan

2014-01-01

SUMMARY We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial function remains to be explored. Here, we show tight negative correlation between Parp-1 expression and energy expenditure in heterogeneous mouse populations, indicating that variations in PARP-1 activity have an impact on metabolic homeostasis. Notably, these genetic correlations can be translated into pharmacological applications. Long-term treatment with PARP inhibitors enhances fitness in mice by increasing the abundance of mitochondrial respiratory complexes and boosting mitochondrial respiratory capacity. Furthermore, PARP inhibitors reverse mitochondrial defects in primary myotubes of obese humans and attenuate genetic defects of mitochondrial metabolism in human fibroblasts and C. elegans. Overall, our work validates in worm, mouse and human models that PARP inhibition may be used to treat both genetic and acquired muscle dysfunction linked to defective mitochondrial function. PMID:24814482

Evaluation of Quality Assessment Protocols for High Throughput Genome Resequencing Data

PubMed Central

Chiara, Matteo; Pavesi, Giulio

2017-01-01

Large-scale initiatives aiming to recover the complete sequence of thousands of human genomes are currently being undertaken worldwide, concurring to the generation of a comprehensive catalog of human genetic variation. The ultimate and most ambitious goal of human population scale genomics is the characterization of the so-called human “variome,” through the identification of causal mutations or haplotypes. Several research institutions worldwide currently use genotyping assays based on Next-Generation Sequencing (NGS) for diagnostics and clinical screenings, and the widespread application of such technologies promises major revolutions in medical science. Bioinformatic analysis of human resequencing data is one of the main factors limiting the effectiveness and general applicability of NGS for clinical studies. The requirement for multiple tools, to be combined in dedicated protocols in order to accommodate different types of data (gene panels, exomes, or whole genomes) and the high variability of the data makes difficult the establishment of a ultimate strategy of general use. While there already exist several studies comparing sensitivity and accuracy of bioinformatic pipelines for the identification of single nucleotide variants from resequencing data, little is known about the impact of quality assessment and reads pre-processing strategies. In this work we discuss major strengths and limitations of the various genome resequencing protocols are currently used in molecular diagnostics and for the discovery of novel disease-causing mutations. By taking advantage of publicly available data we devise and suggest a series of best practices for the pre-processing of the data that consistently improve the outcome of genotyping with minimal impacts on computational costs. PMID:28736571

Evidence for large inversion polymorphisms in the human genome from HapMap data

PubMed Central

Bansal, Vikas; Bashir, Ali; Bafna, Vineet

2007-01-01

Knowledge about structural variation in the human genome has grown tremendously in the past few years. However, inversions represent a class of structural variation that remains difficult to detect. We present a statistical method to identify large inversion polymorphisms using unusual Linkage Disequilibrium (LD) patterns from high-density SNP data. The method is designed to detect chromosomal segments that are inverted (in a majority of the chromosomes) in a population with respect to the reference human genome sequence. We demonstrate the power of this method to detect such inversion polymorphisms through simulations done using the HapMap data. Application of this method to the data from the first phase of the International HapMap project resulted in 176 candidate inversions ranging from 200 kb to several megabases in length. Our predicted inversions include an 800-kb polymorphic inversion at 7p22, a 1.1-Mb inversion at 16p12, and a novel 1.2-Mb inversion on chromosome 10 that is supported by the presence of two discordant fosmids. Analysis of the genomic sequence around inversion breakpoints showed that 11 predicted inversions are flanked by pairs of highly homologous repeats in the inverted orientation. In addition, for three candidate inversions, the inverted orientation is represented in the Celera genome assembly. Although the power of our method to detect inversions is restricted because of inherently noisy LD patterns in population data, inversions predicted by our method represent strong candidates for experimental validation and analysis. PMID:17185644

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

PubMed Central

Minor, Robin K.; Allard, Joanne S.; Younts, Caitlin M.; Ward, Theresa M.

2010-01-01

The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance life span and health span. Using calorie restriction (CR)—which is well known to improve both health and longevity in controlled studies—as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation. PMID:20371545

ResistoMap-online visualization of human gut microbiota antibiotic resistome.

PubMed

Yarygin, Konstantin S; Kovarsky, Boris A; Bibikova, Tatyana S; Melnikov, Damir S; Tyakht, Alexander V; Alexeev, Dmitry G

2017-07-15

We created ResistoMap—a Web-based interactive visualization of the presence of genetic determinants conferring resistance to antibiotics, biocides and heavy metals in human gut microbiota. ResistoMap displays the data on more than 1500 published gut metagenomes of world populations including both healthy subjects and patients. Multiparameter display filters allow visual assessment of the associations between the meta-data and proportions of resistome. The geographic map navigation layer allows to state hypotheses regarding the global trends of antibiotic resistance and correlates the gut resistome variations with the national clinical guidelines on antibiotics application. ResistoMap was implemented using AngularJS, CoffeeScript, D3.js and TopoJSON. The tool is publicly available at http://resistomap.rcpcm.org. yarygin@phystech.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN..., home-based, combination programs, and family child care options defined in this part, the Director of the Office of Head Start retains the right to fund alternative program variations to meet the unique...

Local, Regional, and Global Albedo Variations on Mars From Recent Space-Based Observations: Implications for Future Human Explorers

NASA Astrophysics Data System (ADS)

Bell, J. F.; Wellington, D. F.

2017-06-01

We describe recent as well as historic albedo variations on Mars as observed by space-based telescopes, orbiters, and surface missions, and speculate that some regions might offer fewer dust-related problems for future human explorers than others.

PopHuman: the human population genomics browser

PubMed Central

Mulet, Roger; Villegas-Mirón, Pablo; Hervas, Sergi; Sanz, Esteve; Velasco, Daniel; Bertranpetit, Jaume; Laayouni, Hafid

2018-01-01

Abstract The 1000 Genomes Project (1000GP) represents the most comprehensive world-wide nucleotide variation data set so far in humans, providing the sequencing and analysis of 2504 genomes from 26 populations and reporting >84 million variants. The availability of this sequence data provides the human lineage with an invaluable resource for population genomics studies, allowing the testing of molecular population genetics hypotheses and eventually the understanding of the evolutionary dynamics of genetic variation in human populations. Here we present PopHuman, a new population genomics-oriented genome browser based on JBrowse that allows the interactive visualization and retrieval of an extensive inventory of population genetics metrics. Efficient and reliable parameter estimates have been computed using a novel pipeline that faces the unique features and limitations of the 1000GP data, and include a battery of nucleotide variation measures, divergence and linkage disequilibrium parameters, as well as different tests of neutrality, estimated in non-overlapping windows along the chromosomes and in annotated genes for all 26 populations of the 1000GP. PopHuman is open and freely available at http://pophuman.uab.cat. PMID:29059408

Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flow-mediated vasodilation: analysis of 672 individual repeated measurements.

PubMed

van Mil, Anke C C M; Greyling, Arno; Zock, Peter L; Geleijnse, Johanna M; Hopman, Maria T; Mensink, Ronald P; Reesink, Koen D; Green, Daniel J; Ghiadoni, Lorenzo; Thijssen, Dick H

2016-09-01

Brachial artery flow-mediated dilation (FMD) is a popular technique to examine endothelial function in humans. Identifying volunteer and methodological factors related to variation in FMD is important to improve measurement accuracy and applicability. Volunteer-related and methodology-related parameters were collected in 672 volunteers from eight affiliated centres worldwide who underwent repeated measures of FMD. All centres adopted contemporary expert-consensus guidelines for FMD assessment. After calculating the coefficient of variation (%) of the FMD for each individual, we constructed quartiles (n = 168 per quartile). Based on two regression models (volunteer-related factors and methodology-related factors), statistically significant components of these two models were added to a final regression model (calculated as β-coefficient and R). This allowed us to identify factors that independently contributed to the variation in FMD%. Median coefficient of variation was 17.5%, with healthy volunteers demonstrating a coefficient of variation 9.3%. Regression models revealed age (β = 0.248, P < 0.001), hypertension (β = 0.104, P < 0.001), dyslipidemia (β = 0.331, P < 0.001), time between measurements (β = 0.318, P < 0.001), lab experience (β = -0.133, P < 0.001) and baseline FMD% (β = 0.082, P < 0.05) as contributors to the coefficient of variation. After including all significant factors in the final model, we found that time between measurements, hypertension, baseline FMD% and lab experience with FMD independently predicted brachial artery variability (total R = 0.202). Although FMD% showed good reproducibility, larger variation was observed in conditions with longer time between measurements, hypertension, less experience and lower baseline FMD%. Accounting for these factors may improve FMD% variability.

United Network for Organ Sharing regional variations in appeal denial rates with non-standard Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exceptions: support for a national review board.

PubMed

Gish, Robert G; Wong, Robert J; Honerkamp-Smith, Gordon; Xu, Ronghui; Osorio, Robert W

2015-06-01

Although it has been generally recognized that there are inconsistencies among Regional Review Boards in the assignment of points for model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) exception patients with resulting considerable variation in appeal denial rates, data to actually prove this have been limited. We reviewed 6533 MELD/PELD exception applications submitted between 2005 and 2008, calculated the variation in approval/denial rates, and followed these cases through mid-2013 to assess the effects on patient outcomes. We found highly significant regional variations in denial rates for appeals by exception patients and in transplantation rates. The odds of transplant for patients whose appeals are approved is 2.45 times that of patients not approved; that this effect does not vary by region suggests that the variation in transplant rates is driven, at least in part, by the variation in appeal denial rates. Health deterioration or death accounts for more than two-thirds of wait list removals among patients removed for reasons other than transplant. Our findings add to the weight of evidence that a national review board that uses current clinical expertise, peer review literature, and data to consistently assign priority could reduce regional inequities and move toward equitable allocation of organs and compliance with the United States Department of Health & Human Services Final Rule. © 2015 The Authors. Clinical Transplantation. Published by John Wiley & Sons Ltd.

Medicinal Product Regulation: Portugal׳s Framework.

PubMed

Herdeiro, Maria Teresa; Bastos, Paulo D; Teixeira-Rodrigues, António; Roque, Fátima

2016-09-01

The pharmaceutical industry is one of the most tightly regulated sectors, and it is essential to know each country׳s legal framework to understand the regulation, approval, and marketing of medicinal products for human use. This article describes the main statutes and procedures governing medicinal products for human use in Portugal and the role of the country׳s National Medicines and Health Products Authority (Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.; INFARMED). From the most recently available data, an update of requests and approvals concerning marketing authorizations, variations, pricing, and reimbursements is provided. Data were sourced from the INFARMED website, Infomed (database of medicinal products for human use), and periodic reports issued by national authorities. Organic laws, acts, and law decrees published in the government gazette (Diário da República) are cited and reproduced as required. In 2015 Portugal ranked fifth in the European System of Medicines Evaluation in terms of the number of completed procedures as a reference member state. Approximately 80% of all approved drug applications in Portugal in 2015 were for generic drugs, mostly pertaining to the nervous system. In Portugal, INFARMED monitors drug quality, safety profile, and efficacy in all stages of the drug life cycle, ensuring patients' safety. The Portuguese market for medicinal products for human use has been appreciably changed by the advent of generic drugs. There is an increased trend for new request applications for biological and biotechnological substances. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

A reference human genome dataset of the BGISEQ-500 sequencer.

PubMed

Huang, Jie; Liang, Xinming; Xuan, Yuankai; Geng, Chunyu; Li, Yuxiang; Lu, Haorong; Qu, Shoufang; Mei, Xianglin; Chen, Hongbo; Yu, Ting; Sun, Nan; Rao, Junhua; Wang, Jiahao; Zhang, Wenwei; Chen, Ying; Liao, Sha; Jiang, Hui; Liu, Xin; Yang, Zhaopeng; Mu, Feng; Gao, Shangxian

2017-05-01

BGISEQ-500 is a new desktop sequencer developed by BGI. Using DNA nanoball and combinational probe anchor synthesis developed from Complete Genomics™ sequencing technologies, it generates short reads at a large scale. Here, we present the first human whole-genome sequencing dataset of BGISEQ-500. The dataset was generated by sequencing the widely used cell line HG001 (NA12878) in two sequencing runs of paired-end 50 bp (PE50) and two sequencing runs of paired-end 100 bp (PE100). We also include examples of the raw images from the sequencer for reference. Finally, we identified variations using this dataset, estimated the accuracy of the variations, and compared to that of the variations identified from similar amounts of publicly available HiSeq2500 data. We found similar single nucleotide polymorphism (SNP) detection accuracy for the BGISEQ-500 PE100 data (false positive rate [FPR] = 0.00020%, sensitivity = 96.20%) compared to the PE150 HiSeq2500 data (FPR = 0.00017%, sensitivity = 96.60%) better SNP detection accuracy than the PE50 data (FPR = 0.0006%, sensitivity = 94.15%). But for insertions and deletions (indels), we found lower accuracy for BGISEQ-500 data (FPR = 0.00069% and 0.00067% for PE100 and PE50 respectively, sensitivity = 88.52% and 70.93%) than the HiSeq2500 data (FPR = 0.00032%, sensitivity = 96.28%). Our dataset can serve as the reference dataset, providing basic information not just for future development, but also for all research and applications based on the new sequencing platform. © The Authors 2017. Published by Oxford University Press.

Statistical shape analysis of clavicular cortical bone with applications to the development of mean and boundary shape models.

PubMed

Lu, Yuan-Chiao; Untaroiu, Costin D

2013-09-01

During car collisions, the shoulder belt exposes the occupant's clavicle to large loading conditions which often leads to a bone fracture. To better understand the geometric variability of clavicular cortical bone which may influence its injury tolerance, twenty human clavicles were evaluated using statistical shape analysis. The interior and exterior clavicular cortical bone surfaces were reconstructed from CT-scan images. Registration between one selected template and the remaining 19 clavicle models was conducted to remove translation and rotation differences. The correspondences of landmarks between the models were then established using coordinates and surface normals. Three registration methods were compared: the LM-ICP method; the global method; and the SHREC method. The LM-ICP registration method showed better performance than the global and SHREC registration methods, in terms of compactness, generalization, and specificity. The first four principal components obtained by using the LM-ICP registration method account for 61% and 67% of the overall anatomical variation for the exterior and interior cortical bone shapes, respectively. The length was found to be the most significant variation mode of the human clavicle. The mean and two boundary shape models were created using the four most significant principal components to investigate the size and shape variation of clavicular cortical bone. In the future, boundary shape models could be used to develop probabilistic finite element models which may help to better understand the variability in biomechanical responses and injuries to the clavicle. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Functional and morphological correlates of mandibular symphyseal form in a living human sample.

PubMed

Holton, Nathan E; Franciscus, Robert G; Ravosa, Matthew J; Southard, Thomas E

2014-03-01

Variation in recent human mandibular form is often thought to reflect differences in masticatory behavior associated with variation in food preparation and subsistence strategies. Nevertheless, while mandibular variation in some human comparisons appear to reflect differences in functional loading, other comparisons indicate that this relationship is not universal. This suggests that morphological variation in the mandible is influenced by other factors that may obscure the effects of loading on mandibular form. It is likely that highly strained mandibular regions, including the corpus, are influenced by well-established patterns of lower facial skeletal integration. As such, it is unclear to what degree mandibular form reflects localized stresses incurred during mastication vs. a larger set of correlated features that may influence bone distribution patterns. In this study, we examine the relationship between mandibular symphyseal bone distribution (i.e., second moments of area, cortical bone area) and masticatory force production (i.e., in vivo maximal bite force magnitude and estimated symphyseal bending forces) along with lower facial shape variation in a sample of n = 20 living human male subjects. Our results indicate that while some aspects of symphyseal form (e.g., wishboning resistance) are significantly correlated with estimates of symphyseal bending force magnitude, others (i.e., vertical bending resistance) are more closely tied to variation in lower facial shape. This suggests that while the symphysis reflects variation in some variables related to functional loading, the complex and multifactorial influences on symphyseal form underscores the importance of exercising caution when inferring function from the mandible especially in narrow taxonomic comparisons. Copyright © 2013 Wiley Periodicals, Inc.

Self-Healable Sensors Based Nanoparticles for Detecting Physiological Markers via Skin and Breath: Toward Disease Prevention via Wearable Devices.

PubMed

Jin, Han; Huynh, Tan-Phat; Haick, Hossam

2016-07-13

Flexible and wearable electronic sensors are useful for the early diagnosis and monitoring of an individual's health state. Sampling of volatile organic compounds (VOCs) derived from human breath/skin or monitoring abrupt changes in heart-beat/breath rate should allow noninvasive monitoring of disease states at an early stage. Nevertheless, for many reported wearable sensing devices, interaction with the human body leads incidentally to unavoidable scratches and/or mechanical cuts and bring about malfunction of these devices. We now offer proof-of-concept of nanoparticle-based flexible sensor arrays with fascinating self-healing abilities. By integrating a self-healable polymer substrate with 5 kinds of functionalized gold nanoparticle films, a sensor array gives a fast self-healing (<3 h) and attractive healing efficiency in both the substrate and sensing films. The proposed platform was used in sensing pressure variation and 11 kinds of VOCs. The sensor array had satisfactory sensitivity, a low detection limit, and promising discrimination features in monitoring both of VOCs and pressure variation, even after full healing. These results presage a new type of smart sensing device, with a desirable performance in the possible detection and/or clinical application for a number of different purposes.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

PubMed

Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

2017-01-01

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

Genetics of sweet taste preferences†

PubMed Central

Bachmanov, Alexander A; Bosak, Natalia P; Floriano, Wely B; Inoue, Masashi; Li, Xia; Lin, Cailu; Murovets, Vladimir O; Reed, Danielle R; Zolotarev, Vasily A; Beauchamp, Gary K

2011-01-01

Sweet taste is a powerful factor influencing food acceptance. There is considerable variation in sweet taste perception and preferences within and among species. Although learning and homeostatic mechanisms contribute to this variation in sweet taste, much of it is genetically determined. Recent studies have shown that variation in the T1R genes contributes to within- and between-species differences in sweet taste. In addition, our ongoing studies using the mouse model demonstrate that a significant portion of variation in sweetener preferences depends on genes that are not involved in peripheral taste processing. These genes are likely involved in central mechanisms of sweet taste processing, reward and/or motivation. Genetic variation in sweet taste not only influences food choice and intake, but is also associated with proclivity to drink alcohol. Both peripheral and central mechanisms of sweet taste underlie correlation between sweet-liking and alcohol consumption in animal models and humans. All these data illustrate complex genetics of sweet taste preferences and its impact on human nutrition and health. Identification of genes responsible for within- and between-species variation in sweet taste can provide tools to better control food acceptance in humans and other animals. PMID:21743773

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

PubMed Central

Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W.; Grubert, Fabian; Candille, Sophie I.; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L.; Tang, Hua; Ricci, Emiliano; Snyder, Michael P.

2015-01-01

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. PMID:26297486

Modern applications of high energy ion beams: From "single-event burnout" to human eye cancer treatment

NASA Astrophysics Data System (ADS)

Homeyer, H.; Mahnke, H.-E.

1996-12-01

Energetic ion beams, originally the domain of nuclear physics, become increasingly important tools in many other fields of research and development. The choice of ion species and ion energy allows an enormously wide variation of the penetration depth and of the amount of the electronic stopping power. These features are utilized to modify or damage materials and living tissues in a specific way. Materials modification with energetic ion beams is one of the central aims of research and development at the ion beam laboratory, ISL-Berlin, a center for ion-beam applications at the Hahn-Meitner-Institut Berlin. In particular, energetic protons will be used for eye cancer treatment. Selected topics such as the "single-event burnout" of high power diodes and the eye cancer therapy setup will be presented in detail.

Determination of the 4-monohydroxy metabolites of perhexiline in human plasma, urine and liver microsomes by liquid chromatography.

PubMed

Davies, Benjamin J; Herbert, Megan K; Coller, Janet K; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

2006-11-07

The use of perhexiline (PHX) is limited by hepatic and neurological toxicity associated with elevated concentrations in plasma that are the result of polymorphism of the cytochrome P450 2D6 isoform (CYP2D6). PHX is cleared by hepatic oxidation that produces three 4-monohydroxy metabolites: cis-OH-PHX, trans1-OH-PHX and trans2-OH-PHX. The current study describes an HPLC-fluorescent method utilising pre-column derivatization with dansyl chloride. Following derivatization, the metabolites were resolved on a C18 column with a gradient elution using a mobile phase composed of methanol and water. The method described is suitable for the quantification of the metabolites in human plasma and urine following clinical doses and for kinetic studies using human liver microsomes. The method demonstrates sufficient sensitivity, accuracy and precision between 5.0 and 0.01, 50.0 and 0.2 and 1.0 and 0.005 mg/l in human plasma, urine and liver microsomes, respectively, with intra-assay coefficients of variation and bias <15%, except at the lowest limit of quantification (<20%). The inter-assay coefficients of variation and bias were <15%. The application of this method to plasma and urine samples of five CYP2D6 extensive metaboliser (EM) patients at steady state with respect to PHX dosing determined that the mean (+/-S.D.) renal clearances of trans1-OH-PHX and cis-OH-PHX were 1.58+/-0.35 and 0.16+/-0.06l/h, respectively. The mean (+/-S.D.) dose recovered in urine as free and glucuronidated 4-monohydroxy PHX metabolites was 20.6+/-11.6%.

Use of dietary indices to control for diet in human gut microbiota studies.

PubMed

Bowyer, Ruth C E; Jackson, Matthew A; Pallister, Tess; Skinner, Jane; Spector, Tim D; Welch, Ailsa A; Steves, Claire J

2018-04-25

Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.

41 CFR 50-204.35 - Application for variations from radiation levels.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Application for... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation... from time to time grant permission to employers to vary from the limitations contained in §§ 50-204.21...

Evaluation and recommendation of sensitivity analysis methods for application to Stochastic Human Exposure and Dose Simulation models.

PubMed

Mokhtari, Amirhossein; Christopher Frey, H; Zheng, Junyu

2006-11-01

Sensitivity analyses of exposure or risk models can help identify the most significant factors to aid in risk management or to prioritize additional research to reduce uncertainty in the estimates. However, sensitivity analysis is challenged by non-linearity, interactions between inputs, and multiple days or time scales. Selected sensitivity analysis methods are evaluated with respect to their applicability to human exposure models with such features using a testbed. The testbed is a simplified version of a US Environmental Protection Agency's Stochastic Human Exposure and Dose Simulation (SHEDS) model. The methods evaluated include the Pearson and Spearman correlation, sample and rank regression, analysis of variance, Fourier amplitude sensitivity test (FAST), and Sobol's method. The first five methods are known as "sampling-based" techniques, wheras the latter two methods are known as "variance-based" techniques. The main objective of the test cases was to identify the main and total contributions of individual inputs to the output variance. Sobol's method and FAST directly quantified these measures of sensitivity. Results show that sensitivity of an input typically changed when evaluated under different time scales (e.g., daily versus monthly). All methods provided similar insights regarding less important inputs; however, Sobol's method and FAST provided more robust insights with respect to sensitivity of important inputs compared to the sampling-based techniques. Thus, the sampling-based methods can be used in a screening step to identify unimportant inputs, followed by application of more computationally intensive refined methods to a smaller set of inputs. The implications of time variation in sensitivity results for risk management are briefly discussed.

A new metric of inclusive fitness predicts the human mortality profile.

PubMed

Newman, Saul J; Easteal, Simon

2015-01-01

Biological species have evolved characteristic patterns of age-specific mortality across their life spans. If these mortality profiles are shaped by natural selection they should reflect underlying variation in the fitness effect of mortality with age. Direct fitness models, however, do not accurately predict the mortality profiles of many species. For several species, including humans, mortality rates vary considerably before and after reproductive ages, during life-stages when no variation in direct fitness is possible. Variation in mortality rates at these ages may reflect indirect effects of natural selection acting through kin. To test this possibility we developed a new two-variable measure of inclusive fitness, which we term the extended genomic output or EGO. Using EGO, we estimate the inclusive fitness effect of mortality at different ages in a small hunter-gatherer population with a typical human mortality profile. EGO in this population predicts 90% of the variation in age-specific mortality. This result represents the first empirical measurement of inclusive fitness of a trait in any species. It shows that the pattern of human survival can largely be explained by variation in the inclusive fitness cost of mortality at different ages. More generally, our approach can be used to estimate the inclusive fitness of any trait or genotype from population data on birth dates and relatedness.

Food and fitness: associations between crop yields and life-history traits in a longitudinally monitored pre-industrial human population.

PubMed

Hayward, Adam D; Holopainen, Jari; Pettay, Jenni E; Lummaa, Virpi

2012-10-22

Severe food shortage is associated with increased mortality and reduced reproductive success in contemporary and historical human populations. Studies of wild animal populations have shown that subtle variation in environmental conditions can influence patterns of mortality, fecundity and natural selection, but the fitness implications of such subtle variation on human populations are unclear. Here, we use longitudinal data on local grain production, births, marriages and mortality so as to assess the impact of crop yield variation on individual age-specific mortality and fecundity in two pre-industrial Finnish populations. Although crop yields and fitness traits showed profound year-to-year variation across the 70-year study period, associations between crop yields and mortality or fecundity were generally weak. However, post-reproductive individuals of both sexes, and individuals of lower socio-economic status experienced higher mortality when crop yields were low. This is the first longitudinal, individual-based study of the associations between environmental variation and fitness traits in pre-industrial humans, which emphasizes the importance of a portfolio of mechanisms for coping with low food availability in such populations. The results are consistent with evolutionary ecological predictions that natural selection for resilience to food shortage is likely to weaken with age and be most severe on those with the fewest resources.

Temporal trend and source apportionment of water pollution in different functional zones of Qiantang River, China.

PubMed

Su, Shiliang; Li, Dan; Zhang, Qi; Xiao, Rui; Huang, Fang; Wu, Jiaping

2011-02-01

The increasingly serious river water pollution in developing countries poses great threat to environmental health and human welfare. The assignment of river function to specific uses, known as zoning, is a useful tool to reveal variations of water environmental adaptability to human impact. Therefore, characterizing the temporal trend and identifying responsible pollution sources in different functional zones could greatly improve our knowledge about human impacts on the river water environment. The aim of this study is to obtain a deeper understanding of temporal trends and sources of water pollution in different functional zones with a case study of the Qiantang River, China. Measurement data were obtained and pretreated for 13 variables from 41 monitoring sites in four categories of functional zones during the period 1996-2004. An exploratory approach, which combines smoothing and non-parametric statistical tests, was applied to characterize trends of four significant parameters (permanganate index, ammonia nitrogen, total cadmium and fluoride) accounting for differences among different functional zones identified by discriminant analysis. Aided by GIS, yearly pollution index (PI) for each monitoring site was further mapped to compare the within-group variations in temporal dynamics for different functional zones. Rotated principal component analysis and receptor model (absolute principle component score-multiple linear regression, APCS-MLR) revealed that potential pollution sources and their corresponding contributions varied among the four functional zones. Variations of APCS values for each site of one functional zone as well as their annual average values highlighted the uncertainties associated with cross space-time effects in source apportionment. All these results reinforce the notion that the concept of zoning should be taken seriously in water pollution control. Being applicable to other rivers, the framework of management-oriented source apportionment is thus believed to have potentials to offer new insights into water management and advance the source apportionment framework as an operational basis for national and local governments. © 2010 Elsevier Ltd. All rights reserved.

New Regions of the Human Genome Linked to Skin Color Variation in Some African Populations

Cancer.gov

In the first study of its kind, an international team of genomics researchers has identified new regions of the human genome that are associated with skin color variation in some African populations, opening new avenues for research on skin diseases and cancer in all populations.

Short-Term Variations in Response Distribution to Cortical Stimulation

ERIC Educational Resources Information Center

Lesser, Ronald P.; Lee, Hyang Woon; Webber, W. R. S.; Prince, Barry; Crone, Nathan E.; Miglioretti, Diana L.

2008-01-01

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change…

Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin.

PubMed

Kita, Ryosuke; Fraser, Hunter B

2016-10-01

Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual's gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation.

Buntaro Adachi (1865-1945): Japanese master of human anatomic variation.

PubMed

Watanabe, Koichi; Shoja, Mohammadali M; Loukas, Marios; Tubbs, R Shane

2012-11-01

Buntaro Adachi (1865-1945) was a Japanese physician, anatomist, and anthropologist and is most remembered for his study on human anatomic variation. At the end of 19th Century, one of the main focuses in anthropology was the comparison between the races. In Japan, anthropological studies of the origin of the modern Japanese race were carried out by Adachi and others. Adachi believed that differences went beyond the bones that were commonly studied in his day and, therefore, investigated soft tissues of the body. Two products of his intense study of variation of human anatomy were Das Arteriensystem der Japaner (The Arterial System of the Japanese) published in 1928 and Das Venensystem der Japaner (The Venous System of the Japanese) published in 1933 and 1940. These books received much attention and were praised by anatomists and anthropologists around the world. Even now, these books are invaluable as references for human anatomic variation. Herein, we provide an overview of the life and achievements of Buntaro Adachi and to our knowledge, this is the first such review in the English language. Copyright © 2012 Wiley Periodicals, Inc.

A Passive Learning Sensor Architecture for Multimodal Image Labeling: An Application for Social Robots.

PubMed

Gutiérrez, Marco A; Manso, Luis J; Pandya, Harit; Núñez, Pedro

2017-02-11

Object detection and classification have countless applications in human-robot interacting systems. It is a necessary skill for autonomous robots that perform tasks in household scenarios. Despite the great advances in deep learning and computer vision, social robots performing non-trivial tasks usually spend most of their time finding and modeling objects. Working in real scenarios means dealing with constant environment changes and relatively low-quality sensor data due to the distance at which objects are often found. Ambient intelligence systems equipped with different sensors can also benefit from the ability to find objects, enabling them to inform humans about their location. For these applications to succeed, systems need to detect the objects that may potentially contain other objects, working with relatively low-resolution sensor data. A passive learning architecture for sensors has been designed in order to take advantage of multimodal information, obtained using an RGB-D camera and trained semantic language models. The main contribution of the architecture lies in the improvement of the performance of the sensor under conditions of low resolution and high light variations using a combination of image labeling and word semantics. The tests performed on each of the stages of the architecture compare this solution with current research labeling techniques for the application of an autonomous social robot working in an apartment. The results obtained demonstrate that the proposed sensor architecture outperforms state-of-the-art approaches.

ZebraBeat: a flexible platform for the analysis of the cardiac rate in zebrafish embryos

NASA Astrophysics Data System (ADS)

de Luca, Elisa; Zaccaria, Gian Maria; Hadhoud, Marwa; Rizzo, Giovanna; Ponzini, Raffaele; Morbiducci, Umberto; Santoro, Massimo Mattia

2014-05-01

Heartbeat measurement is important in assesssing cardiac function because variations in heart rhythm can be the cause as well as an effect of hidden pathological heart conditions. Zebrafish (Danio rerio) has emerged as one of the most useful model organisms for cardiac research. Indeed, the zebrafish heart is easily accessible for optical analyses without conducting invasive procedures and shows anatomical similarity to the human heart. In this study, we present a non-invasive, simple, cost-effective process to quantify the heartbeat in embryonic zebrafish. To achieve reproducibility, high throughput and flexibility (i.e., adaptability to any existing confocal microscope system and with a user-friendly interface that can be easily used by researchers), we implemented this method within a software program. We show here that this platform, called ZebraBeat, can successfully detect heart rate variations in embryonic zebrafish at various developmental stages, and it can record cardiac rate fluctuations induced by factors such as temperature and genetic- and chemical-induced alterations. Applications of this methodology may include the screening of chemical libraries affecting heart rhythm and the identification of heart rhythm variations in mutants from large-scale forward genetic screens.

Image ratio features for facial expression recognition application.

PubMed

Song, Mingli; Tao, Dacheng; Liu, Zicheng; Li, Xuelong; Zhou, Mengchu

2010-06-01

Video-based facial expression recognition is a challenging problem in computer vision and human-computer interaction. To target this problem, texture features have been extracted and widely used, because they can capture image intensity changes raised by skin deformation. However, existing texture features encounter problems with albedo and lighting variations. To solve both problems, we propose a new texture feature called image ratio features. Compared with previously proposed texture features, e.g., high gradient component features, image ratio features are more robust to albedo and lighting variations. In addition, to further improve facial expression recognition accuracy based on image ratio features, we combine image ratio features with facial animation parameters (FAPs), which describe the geometric motions of facial feature points. The performance evaluation is based on the Carnegie Mellon University Cohn-Kanade database, our own database, and the Japanese Female Facial Expression database. Experimental results show that the proposed image ratio feature is more robust to albedo and lighting variations, and the combination of image ratio features and FAPs outperforms each feature alone. In addition, we study asymmetric facial expressions based on our own facial expression database and demonstrate the superior performance of our combined expression recognition system.

Path loss variation of on-body UWB channel in the frequency bands of IEEE 802.15.6 standard.

PubMed

Goswami, Dayananda; Sarma, Kanak C; Mahanta, Anil

2016-06-01

The wireless body area network (WBAN) has gaining tremendous attention among researchers and academicians for its envisioned applications in healthcare service. Ultra wideband (UWB) radio technology is considered as excellent air interface for communication among body area network devices. Characterisation and modelling of channel parameters are utmost prerequisite for the development of reliable communication system. The path loss of on-body UWB channel for each frequency band defined in IEEE 802.15.6 standard is experimentally determined. The parameters of path loss model are statistically determined by analysing measurement data. Both the line-of-sight and non-line-of-sight channel conditions are considered in the measurement. Variations of parameter values with the size of human body are analysed along with the variation of parameter values with the surrounding environments. It is observed that the parameters of the path loss model vary with the frequency band as well as with the body size and surrounding environment. The derived parameter values are specific to the particular frequency bands of IEEE 802.15.6 standard, which will be useful for the development of efficient UWB WBAN system.

Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project

PubMed Central

Horton, Roger; Gibson, Richard; Coggill, Penny; Miretti, Marcos; Allcock, Richard J.; Almeida, Jeff; Forbes, Simon; Gilbert, James G. R.; Halls, Karen; Harrow, Jennifer L.; Hart, Elizabeth; Howe, Kevin; Jackson, David K.; Palmer, Sophie; Roberts, Anne N.; Sims, Sarah; Stewart, C. Andrew; Traherne, James A.; Trevanion, Steve; Wilming, Laurens; Rogers, Jane; de Jong, Pieter J.; Elliott, John F.; Sawcer, Stephen; Todd, John A.; Trowsdale, John

2008-01-01

The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine. PMID:18193213

Advantages and pitfalls in the application of mixed-model association methods.

PubMed

Yang, Jian; Zaitlen, Noah A; Goddard, Michael E; Visscher, Peter M; Price, Alkes L

2014-02-01

Mixed linear models are emerging as a method of choice for conducting genetic association studies in humans and other organisms. The advantages of the mixed-linear-model association (MLMA) method include the prevention of false positive associations due to population or relatedness structure and an increase in power obtained through the application of a correction that is specific to this structure. An underappreciated point is that MLMA can also increase power in studies without sample structure by implicitly conditioning on associated loci other than the candidate locus. Numerous variations on the standard MLMA approach have recently been published, with a focus on reducing computational cost. These advances provide researchers applying MLMA methods with many options to choose from, but we caution that MLMA methods are still subject to potential pitfalls. Here we describe and quantify the advantages and pitfalls of MLMA methods as a function of study design and provide recommendations for the application of these methods in practical settings.

Physical and mechanical properties of PLA, and their functions in widespread applications - A comprehensive review.

PubMed

Farah, Shady; Anderson, Daniel G; Langer, Robert

2016-12-15

Poly(lactic acid) (PLA), so far, is the most extensively researched and utilized biodegradable aliphatic polyester in human history. Due to its merits, PLA is a leading biomaterial for numerous applications in medicine as well as in industry replacing conventional petrochemical-based polymers. The main purpose of this review is to elaborate the mechanical and physical properties that affect its stability, processability, degradation, PLA-other polymers immiscibility, aging and recyclability, and therefore its potential suitability to fulfill specific application requirements. This review also summarizes variations in these properties during PLA processing (i.e. thermal degradation and recyclability), biodegradation, packaging and sterilization, and aging (i.e. weathering and hygrothermal). In addition, we discuss up-to-date strategies for PLA properties improvements including components and plasticizer blending, nucleation agent addition, and PLA modifications and nanoformulations. Incorporating better understanding of the role of these properties with available improvement strategies is the key for successful utilization of PLA and its copolymers/composites/blends to maximize their fit with worldwide application needs. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatiotemporal Interpolation Methods for the Application of Estimating Population Exposure to Fine Particulate Matter in the Contiguous U.S. and a Real-Time Web Application.

PubMed

Li, Lixin; Zhou, Xiaolu; Kalo, Marc; Piltner, Reinhard

2016-07-25

Appropriate spatiotemporal interpolation is critical to the assessment of relationships between environmental exposures and health outcomes. A powerful assessment of human exposure to environmental agents would incorporate spatial and temporal dimensions simultaneously. This paper compares shape function (SF)-based and inverse distance weighting (IDW)-based spatiotemporal interpolation methods on a data set of PM2.5 data in the contiguous U.S. Particle pollution, also known as particulate matter (PM), is composed of microscopic solids or liquid droplets that are so small that they can get deep into the lungs and cause serious health problems. PM2.5 refers to particles with a mean aerodynamic diameter less than or equal to 2.5 micrometers. Based on the error statistics results of k-fold cross validation, the SF-based method performed better overall than the IDW-based method. The interpolation results generated by the SF-based method are combined with population data to estimate the population exposure to PM2.5 in the contiguous U.S. We investigated the seasonal variations, identified areas where annual and daily PM2.5 were above the standards, and calculated the population size in these areas. Finally, a web application is developed to interpolate and visualize in real time the spatiotemporal variation of ambient air pollution across the contiguous U.S. using air pollution data from the U.S. Environmental Protection Agency (EPA)'s AirNow program.

Spatiotemporal Interpolation Methods for the Application of Estimating Population Exposure to Fine Particulate Matter in the Contiguous U.S. and a Real-Time Web Application

PubMed Central

Li, Lixin; Zhou, Xiaolu; Kalo, Marc; Piltner, Reinhard

2016-01-01

Appropriate spatiotemporal interpolation is critical to the assessment of relationships between environmental exposures and health outcomes. A powerful assessment of human exposure to environmental agents would incorporate spatial and temporal dimensions simultaneously. This paper compares shape function (SF)-based and inverse distance weighting (IDW)-based spatiotemporal interpolation methods on a data set of PM2.5 data in the contiguous U.S. Particle pollution, also known as particulate matter (PM), is composed of microscopic solids or liquid droplets that are so small that they can get deep into the lungs and cause serious health problems. PM2.5 refers to particles with a mean aerodynamic diameter less than or equal to 2.5 micrometers. Based on the error statistics results of k-fold cross validation, the SF-based method performed better overall than the IDW-based method. The interpolation results generated by the SF-based method are combined with population data to estimate the population exposure to PM2.5 in the contiguous U.S. We investigated the seasonal variations, identified areas where annual and daily PM2.5 were above the standards, and calculated the population size in these areas. Finally, a web application is developed to interpolate and visualize in real time the spatiotemporal variation of ambient air pollution across the contiguous U.S. using air pollution data from the U.S. Environmental Protection Agency (EPA)’s AirNow program. PMID:27463722

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

PubMed Central

Xue, Cheng; Raveendran, Muthuswamy; Harris, R. Alan; Fawcett, Gloria L.; Liu, Xiaoming; White, Simon; Dahdouli, Mahmoud; Rio Deiros, David; Below, Jennifer E.; Salerno, William; Cox, Laura; Fan, Guoping; Ferguson, Betsy; Horvath, Julie; Johnson, Zach; Kanthaswamy, Sree; Kubisch, H. Michael; Liu, Dahai; Platt, Michael; Smith, David G.; Sun, Binghua; Vallender, Eric J.; Wang, Feng; Wiseman, Roger W.; Chen, Rui; Muzny, Donna M.; Gibbs, Richard A.; Yu, Fuli; Rogers, Jeffrey

2016-01-01

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease. PMID:27934697

Settlement-Size Scaling among Prehistoric Hunter-Gatherer Settlement Systems in the New World

PubMed Central

Haas, W. Randall; Klink, Cynthia J.; Maggard, Greg J.; Aldenderfer, Mark S.

2015-01-01

Settlement size predicts extreme variation in the rates and magnitudes of many social and ecological processes in human societies. Yet, the factors that drive human settlement-size variation remain poorly understood. Size variation among economically integrated settlements tends to be heavy tailed such that the smallest settlements are extremely common and the largest settlements extremely large and rare. The upper tail of this size distribution is often formalized mathematically as a power-law function. Explanations for this scaling structure in human settlement systems tend to emphasize complex socioeconomic processes including agriculture, manufacturing, and warfare—behaviors that tend to differentially nucleate and disperse populations hierarchically among settlements. But, the degree to which heavy-tailed settlement-size variation requires such complex behaviors remains unclear. By examining the settlement patterns of eight prehistoric New World hunter-gatherer settlement systems spanning three distinct environmental contexts, this analysis explores the degree to which heavy-tailed settlement-size scaling depends on the aforementioned socioeconomic complexities. Surprisingly, the analysis finds that power-law models offer plausible and parsimonious statistical descriptions of prehistoric hunter-gatherer settlement-size variation. This finding reveals that incipient forms of hierarchical settlement structure may have preceded socioeconomic complexity in human societies and points to a need for additional research to explicate how mobile foragers came to exhibit settlement patterns that are more commonly associated with hierarchical organization. We propose that hunter-gatherer mobility with preferential attachment to previously occupied locations may account for the observed structure in site-size variation. PMID:26536241

Global and disease-associated genetic variation in the human Fanconi anemia gene family

PubMed Central

Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

2014-01-01

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57 240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. PMID:25104853

Identification of species and genetic variation in Taenia isolates from human and swine of North India.

PubMed

Singh, Satyendra K; Prasad, Kashi N; Singh, Aloukick K; Gupta, Kamlesh K; Chauhan, Ranjeet S; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Pati, Binod K

2016-10-01

Taenia solium is the major cause of taeniasis and cysticercosis/neurocysticercosis (NCC) in the developing countries including India, but the existence of other Taenia species and genetic variation have not been studied in India. So, we studied the existence of different Taenia species, and sequence variation in Taenia isolates from human (proglottids and cysticerci) and swine (cysticerci) in North India. Amplification of cytochrome c oxidase subunit 1 gene (cox1) was done by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. We identified two species of Taenia i.e. T. solium and Taenia asiatica in our isolates. T. solium isolates showed similarity with Asian genotype and nucleotide variations from 0.25 to 1.01 %, whereas T. asiatica displayed nucleotide variations ranged from 0.25 to 0.5 %. These findings displayed the minimal genetic variations in North Indian isolates of T. solium and T. asiatica.

Population-genetic nature of copy number variations in the human genome.

PubMed

Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

2010-03-01

Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

The Limits of Human Stereopsis in Space and Time

PubMed Central

Kane, David; Guan, Phillip

2014-01-01

To encode binocular disparity, the visual system determines the image patches in one eye that yield the highest correlation with patches in the other eye. The computation of interocular correlation occurs after spatiotemporal filtering of monocular signals, which leads to restrictions on disparity variations that can support depth perception. We quantified those restrictions by measuring humans' ability to see disparity variation at a wide range of spatial and temporal frequencies. Lower-disparity thresholds cut off at very low spatiotemporal frequencies, which is consistent with the behavior of V1 neurons. Those thresholds are space–time separable, suggesting that the underlying neural mechanisms are separable. We also found that upper-disparity limits were characterized by a spatiotemporal, disparity-gradient limit; to be visible, disparity variation cannot exceed a fixed amount for a given interval in space–time. Our results illustrate that the disparity variations that humans can see are very restricted compared with the corresponding luminance variations. The results also provide insight into the neural mechanisms underlying depth from disparity, such as why stimuli with long interocular delays can still yield clear depth percepts. PMID:24453329

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

PubMed

Hassan, Nik Norliza Nik; Plazzer, John-Paul; Smith, Timothy D; Halim-Fikri, Hashim; Macrae, Finlay; Zubaidi, A A L; Zilfalil, Bin Alwi

2016-02-26

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world.

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

PubMed

Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

2010-10-01

PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans

PubMed Central

Berg, Ingrid L.; Neumann, Rita; Lam, Kwan-Wood G.; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A.; Jeffreys, Alec J.

2011-01-01

PRDM9 has recently been identified as a likely trans-regulator of meiotic recombination hot spots in humans and mice1-3. The protein contains a zinc finger array that in humans can recognise a short sequence motif associated with hot spots4, with binding to this motif possibly triggering hot-spot activity via chromatin remodelling5. We now show that variation in the zinc finger array in humans has a profound effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Very subtle changes within the array can create hot-spot non-activating and enhancing alleles, and even trigger the appearance of a new hot spot. PRDM9 thus appears to be the preeminent global regulator of hot spots in humans. Variation at this locus also influences aspects of genome instability, specifically a megabase-scale rearrangement underlying two genomic disorders6 as well as minisatellite instability7, implicating PRDM9 as a risk factor for some pathological genome rearrangements. PMID:20818382

Common genetic variation drives molecular heterogeneity in human iPSCs

PubMed Central

Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

2017-01-01

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

A variational theorem for creep with applications to plates and columns

NASA Technical Reports Server (NTRS)

Sanders, J Lyell, Jr; Mccomb, Harvey G , Jr; Schlechte, Floyd R

1958-01-01

A variational theorem is presented for a body undergoing creep. Solutions to problems of the creep behavior of plates, columns, beams, and shells can be obtained by means of the direct methods of the calculus of variations in conjunction with the stated theorem. The application of the theorem is illustrated for plates and columns by the solution of two sample problems.

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization

PubMed Central

Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Van Roy, Nadine; Vandesompele, Jo; Hooyberghs, Jef

2017-01-01

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine. PMID:28542229

Technologies in the Whole-Genome Age: MALDI-TOF-Based Genotyping.

PubMed

Vogel, Nicolas; Schiebel, Katrin; Humeny, Andreas

2009-01-01

With the decipherment of the human genome, new questions have moved into the focus of today's research. One key aspect represents the discovery of DNA variations capable to influence gene transcription, RNA splicing, or regulating processes, and their link to pathology. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) is a powerful tool for the qualitative investigation and relative quantification of variations like single nucleotide polymorphisms, DNA methylation, microsatellite instability, or loss of heterozygosity. After its introduction into proteomics, efforts were made to adopt this technique to DNA analysis. Initially intended for peptide/protein analysis, it held several difficulties for application to nucleic acids. Today, MALDI-TOF-MS has reached worldwide acceptance and application in nucleic acid research, with a wide spectrum of methods being available. One of the most versatile approaches relies on primer extension to genotype single alleles, microsatellite repeat lengths or the methylation status of a given cytosine. Optimized methods comprising intelligent primer design and proper nucleotide selection for primer extension enabled multiplexing of reactions, rendering the analysis more economic due to parallel genotyping of several alleles in a single experiment. Laboratories equipped with MALDI-TOF-MS possess a universal technical platform for the analysis of a large variety of different molecules.

The synthesis and characterization of hydrogel chitosan-alginate with the addition of plasticizer lauric acid for wound dressing application

NASA Astrophysics Data System (ADS)

Izak Rudyardjo, Djony; Wijayanto, Setiawan

2017-05-01

The writers conducted a study about the synthesis and characterization of hydrogel chitosan-alginate by addition plasticizer lauric acid for wound dressing application. The purpose was to find out the impact of lauric acid concentration variation on hydrogel chitosan-alginate to get the best mechanical and physical properties to be applied as wound dressing in accordance with existing standards. This study used commercially chitosan from extract of shells crab, commercially-available alginate from the extract of sargassum sp, and commercial lauric acid from palm starch. The addition of lauric acid was aimed to repair mechanical properties of hydrogel. The composition of chitosan-alginate is 4:1 (v/v), while the lauric acid concentration variations are 0%, 1%, 2%, 3%, 4%, and 5% w/v. The characterization of mechanical properties test (Tensile strength and Elongation at break) at hydrogel showed the hydrogel chitosan-alginate-lauric acid have the characteristic which meets the standard of mechanical properties for human skin. The best performance of hydrogel chitosan-alginate-lauric acid was obtained by increasing luric acid concentration by 4%, which has a thickness value of 125.46±0.63 µm, elongation 28.89±1.01 %, tensile strength (9.01±0.65) MPa, and ability to absorb liquids (601.45 ±1.24) %.

The Diversity Present in 5140 Human Mitochondrial Genomes

PubMed Central

Pereira, Luísa; Freitas, Fernando; Fernandes, Verónica; Pereira, Joana B.; Costa, Marta D.; Costa, Stephanie; Máximo, Valdemar; Macaulay, Vincent; Rocha, Ricardo; Samuels, David C.

2009-01-01

We analyzed the current status (as of the end of August 2008) of human mitochondrial genomes deposited in GenBank, amounting to 5140 complete or coding-region sequences, in order to present an overall picture of the diversity present in the mitochondrial DNA of the global human population. To perform this task, we developed mtDNA-GeneSyn, a computer tool that identifies and exhaustedly classifies the diversity present in large genetic data sets. The diversity observed in the 5140 human mitochondrial genomes was compared with all possible transitions and transversions from the standard human mitochondrial reference genome. This comparison showed that tRNA and rRNA secondary structures have a large effect in limiting the diversity of the human mitochondrial sequences, whereas for the protein-coding genes there is a bias toward less variation at the second codon positions. The analysis of the observed amino acid variations showed a tolerance of variations that convert between the amino acids V, I, A, M, and T. This defines a group of amino acids with similar chemical properties that can interconvert by a single transition. PMID:19426953

A portable fiber-optic raman spectrometer concept for evaluation of mineral content within enamel tissue.

PubMed

Akkus, Anna; Yang, Shan; Roperto, Renato; Mustafa, Hathem; Teich, Sorin; Akkus, Ozan

2017-02-01

Measurement of tooth enamel mineralization using a clinically viable method is essential since variation of mineralization may be used to monitor caries risk or in assessing the effectiveness of remineralization therapy. Fiber optic Raman systems are becoming more affordable and popular in context of biomedical applications. However, the applicability of fiber optic Raman systems for measurement of mineral content within enamel tissue has not been elucidated significantly in the prior literature. Human teeth with varying degrees of enamel mineralization were selected. In addition alligator, boar and buffalo teeth which have increasing amount of mineral content, respectively, were also included as another set of samples. Reference Raman measurements of mineralization were performed using a high-fidelity confocal Raman microscope. Analysis of human teeth by research grade Raman system indicated a 2-fold difference in the Raman intensities of v1 symmetric-stretch bands of mineral-related phosphate bonds and 7-fold increase in mineral related Raman intensities of animal teeth. However, fiber optic system failed to resolve the differences in the mineralization of human teeth. These results indicate that the sampling volume of fiber optic systems extends to the underlying dentin and that confocal aperture modification is essential to limit the sampling volume to within the enamel. Further research efforts will focus on putting together portable Raman systems integrated with confocal fiber probe. Key words: Enamel, mineral content, raman spectroscopy.

A novel approach for copy number variation analysis by combining multiplex PCR with matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Gao, Yonghui; Chen, Xiaoli; Wang, Jianhua; Shangguan, Shaofang; Dai, Yaohua; Zhang, Ting; Liu, Junling

2013-06-20

With the increasing interest in copy number variation as it pertains to human genomic variation, common phenotypes, and disease susceptibility, there is a pressing need for methods to accurately identify copy number. In this study, we developed a simple approach that combines multiplex PCR with matrix-assisted laser desorption ionization time-of-flight mass spectrometry for submicroscopic copy number variation detection. Two pairs of primers were used to simultaneously amplify query and endogenous control regions in the same reaction. Using a base extension reaction, the two amplicons were then distinguished and quantified in a mass spectrometry map. The peak ratio between the test region and the endogenous control region was manually calculated. The relative copy number could be determined by comparing the peak ratio between the test and control samples. This method generated a copy number measurement comparable to those produced by two other commonly used methods - multiplex ligation-dependent probe amplification and quantitative real-time PCR. Furthermore, it can discriminate a wide range of copy numbers. With a typical 384-format SpectroCHIP, at least six loci on 384 samples can be analyzed simultaneously in a hexaplex assay, making this assay adaptable for high throughput, and potentially applicable for large-scale association studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes1234

PubMed Central

Chen, Qing-Ying; Alarcon, Suzanne; Tharp, Anilet; Ahmed, Osama M; Estrella, Nelsa L; Greene, Tiffani A; Rucker, Joseph; Breslin, Paul AS

2009-01-01

Background: The TAS1R1 and TAS1R3 G protein–coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans. Objective: We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste. Design: In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay. Results: A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5′-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells. Conclusions: There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception. PMID:19587085

Segmental Duplications and Copy-Number Variation in the Human Genome

PubMed Central

Sharp, Andrew J. ; Locke, Devin P. ; McGrath, Sean D. ; Cheng, Ze ; Bailey, Jeffrey A. ; Vallente, Rhea U. ; Pertz, Lisa M. ; Clark, Royden A. ; Schwartz, Stuart ; Segraves, Rick ; Oseroff, Vanessa V. ; Albertson, Donna G. ; Pinkel, Daniel ; Eichler, Evan E. 

2005-01-01

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders. PMID:15918152

Pitch (F0) and formant profiles of human vowels and vowel-like baboon grunts: The role of vocalizer body size and voice-acoustic allometry

NASA Astrophysics Data System (ADS)

Rendall, Drew; Kollias, Sophie; Ney, Christina; Lloyd, Peter

2005-02-01

Key voice features-fundamental frequency (F0) and formant frequencies-can vary extensively between individuals. Much of the variation can be traced to differences in the size of the larynx and vocal-tract cavities, but whether these differences in turn simply reflect differences in speaker body size (i.e., neutral vocal allometry) remains unclear. Quantitative analyses were therefore undertaken to test the relationship between speaker body size and voice F0 and formant frequencies for human vowels. To test the taxonomic generality of the relationships, the same analyses were conducted on the vowel-like grunts of baboons, whose phylogenetic proximity to humans and similar vocal production biology and voice acoustic patterns recommend them for such comparative research. For adults of both species, males were larger than females and had lower mean voice F0 and formant frequencies. However, beyond this, F0 variation did not track body-size variation between the sexes in either species, nor within sexes in humans. In humans, formant variation correlated significantly with speaker height but only in males and not in females. Implications for general vocal allometry are discussed as are implications for speech origins theories, and challenges to them, related to laryngeal position and vocal tract length. .

PopHuman: the human population genomics browser.

PubMed

Casillas, Sònia; Mulet, Roger; Villegas-Mirón, Pablo; Hervas, Sergi; Sanz, Esteve; Velasco, Daniel; Bertranpetit, Jaume; Laayouni, Hafid; Barbadilla, Antonio

2018-01-04

The 1000 Genomes Project (1000GP) represents the most comprehensive world-wide nucleotide variation data set so far in humans, providing the sequencing and analysis of 2504 genomes from 26 populations and reporting >84 million variants. The availability of this sequence data provides the human lineage with an invaluable resource for population genomics studies, allowing the testing of molecular population genetics hypotheses and eventually the understanding of the evolutionary dynamics of genetic variation in human populations. Here we present PopHuman, a new population genomics-oriented genome browser based on JBrowse that allows the interactive visualization and retrieval of an extensive inventory of population genetics metrics. Efficient and reliable parameter estimates have been computed using a novel pipeline that faces the unique features and limitations of the 1000GP data, and include a battery of nucleotide variation measures, divergence and linkage disequilibrium parameters, as well as different tests of neutrality, estimated in non-overlapping windows along the chromosomes and in annotated genes for all 26 populations of the 1000GP. PopHuman is open and freely available at http://pophuman.uab.cat. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

STOPGAP: a database for systematic target opportunity assessment by genetic association predictions.

PubMed

Shen, Judong; Song, Kijoung; Slater, Andrew J; Ferrero, Enrico; Nelson, Matthew R

2017-09-01

We developed the STOPGAP (Systematic Target OPportunity assessment by Genetic Association Predictions) database, an extensive catalog of human genetic associations mapped to effector gene candidates. STOPGAP draws on a variety of publicly available GWAS associations, linkage disequilibrium (LD) measures, functional genomic and variant annotation sources. Algorithms were developed to merge the association data, partition associations into non-overlapping LD clusters, map variants to genes and produce a variant-to-gene score used to rank the relative confidence among potential effector genes. This database can be used for a multitude of investigations into the genes and genetic mechanisms underlying inter-individual variation in human traits, as well as supporting drug discovery applications. Shell, R, Perl and Python scripts and STOPGAP R data files (version 2.5.1 at publication) are available at https://github.com/StatGenPRD/STOPGAP . Some of the most useful STOPGAP fields can be queried through an R Shiny web application at http://stopgapwebapp.com . matthew.r.nelson@gsk.com. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Understanding and monitoring the consequences of human impacts on intraspecific variation.

PubMed

Mimura, Makiko; Yahara, Tetsukazu; Faith, Daniel P; Vázquez-Domínguez, Ella; Colautti, Robert I; Araki, Hitoshi; Javadi, Firouzeh; Núñez-Farfán, Juan; Mori, Akira S; Zhou, Shiliang; Hollingsworth, Peter M; Neaves, Linda E; Fukano, Yuya; Smith, Gideon F; Sato, Yo-Ichiro; Tachida, Hidenori; Hendry, Andrew P

2017-02-01

Intraspecific variation is a major component of biodiversity, yet it has received relatively little attention from governmental and nongovernmental organizations, especially with regard to conservation plans and the management of wild species. This omission is ill-advised because phenotypic and genetic variations within and among populations can have dramatic effects on ecological and evolutionary processes, including responses to environmental change, the maintenance of species diversity, and ecological stability and resilience. At the same time, environmental changes associated with many human activities, such as land use and climate change, have dramatic and often negative impacts on intraspecific variation. We argue for the need for local, regional, and global programs to monitor intraspecific genetic variation. We suggest that such monitoring should include two main strategies: (i) intensive monitoring of multiple types of genetic variation in selected species and (ii) broad-brush modeling for representative species for predicting changes in variation as a function of changes in population size and range extent. Overall, we call for collaborative efforts to initiate the urgently needed monitoring of intraspecific variation.

Liquid chromatography determination of 10-hydroxycamptothecin in human serum by a column-switching system containing a pre-column with restricted access media and its application to a clinical pharmacokinetic study.

PubMed

Ma, Jun; Jia, Zheng-Ping; Zhang, Qiang; Fan, Jun-Jie; Jiang, Ning-Xi; Wang, Rong; Xie, Hua; Wang, Juan

2003-10-25

A simple, rapid, sensitive column-switching HPLC method is described for the analysis of the 10-hydroxycamptothecin (HCPT) in human serum. A pre-column containing restricted access media (RAM) is used for the sample clean-up and trace enrichment and is combined with a C18 column for the final separation. The analytical time is 8 min. The HCPT is monitored with fluorescence detector, excitation and emission wavelengths being 385 and 539 nm, respectively. There is a linear response range of 1-1000 ng/ml with correlation coefficient of 0.998 while the limit of quantification is 0.1 ng/ml. The intra-day and inter-day variations are less than 5%. This analytic procedure has been applied to a pharmacokinetic study of HCPT in clinical patients and the pharmacokinetic parameters of one-compartment model are calculated.

The thermoregulatory theory of yawning: what we know from over 5 years of research

PubMed Central

Gallup, Andrew C.; Eldakar, Omar T.

2012-01-01

Over the past 5 years numerous reports have confirmed and replicated the specific brain cooling and thermal window predictions derived from the thermoregulatory theory of yawning, and no study has found evidence contrary to these findings. Here we review the comparative research supporting this model of yawning among homeotherms, while highlighting a recent report showing how the expression of contagious yawning in humans is altered by seasonal climate variation. The fact that yawning is constrained to a thermal window of ambient temperature provides unique and compelling support in favor of this theory. Heretofore, no existing alternative hypothesis of yawning can explain these results, which have important implications for understanding the potential functional role of this behavior, both physiologically and socially, in humans and other animals. In discussion we stress the broader applications of this work in clinical settings, and counter the various criticisms of this theory. PMID:23293583

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model.

PubMed

Saccone, Scott F; Quan, Jiaxi; Jones, Peter L

2012-04-15

Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. BioQ is freely available to the public at http://bioq.saclab.net.

In Vivo Noninvasive Analysis of Human Forearm Muscle Function and Fatigue: Applications to EVA Operations and Training Maneuvers

NASA Technical Reports Server (NTRS)

Fotedar, L. K.; Marshburn, T.; Quast, M. J.; Feeback, D. L.

1999-01-01

Forearm muscle fatigue is one of the major limiting factors affecting endurance during performance of deep-space extravehicular activity (EVA) by crew members. Magnetic resonance (MR) provides in vivo noninvasive analysis of tissue level metabolism and fluid exchange dynamics in exercised forearm muscles through the monitoring of proton magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P-31-MRS) parameter variations. Using a space glove box and EVA simulation protocols, we conducted a preliminary MRS/MRI study in a small group of human test subjects during submaximal exercise and recovery and following exhaustive exercise. In assessing simulated EVA-related muscle fatigue and function, this pilot study revealed substantial changes in the MR image longitudinal relaxation times (T2) as an indicator of specific muscle activation and proton flux as well as changes in spectral phosphocreatine-to-phosphate (PCr/Pi) levels as a function of tissue bioenergetic potential.

High-pressure endurable flexible tactile actuator based on microstructured dielectric elastomer

NASA Astrophysics Data System (ADS)

Pyo, Dongbum; Ryu, Semin; Kyung, Ki-Uk; Yun, Sungryul; Kwon, Dong-Soo

2018-02-01

We demonstrate a robust flexible tactile actuator that is capable of working under high external pressures. The tactile actuator is based on a pyramidal microstructured dielectric elastomer layer inducing variation in both mechanical and dielectric properties. The vibrational performance of the actuator can be modulated by changing the geometric parameter of the microstructures. We evaluated the performance of the actuator under high-pressure loads up to 25 kPa, which is over the typical range of pressure applied when humans touch or manipulate objects. Due to the benefit of nonlinearity of the pyramidal structure, the actuator could maintain high mechanical output under various external pressures in the frequency range of 100-200 Hz, which is the most sensitive to vibration acceleration for human finger pads. The responses are not only fast, reversible, and highly durable under consecutive cyclic operations, but also large enough to impart perceivable vibrations for haptic feedback on practical wearable device applications.

Autonomous facial recognition system inspired by human visual system based logarithmical image visualization technique

NASA Astrophysics Data System (ADS)

Wan, Qianwen; Panetta, Karen; Agaian, Sos

2017-05-01

Autonomous facial recognition system is widely used in real-life applications, such as homeland border security, law enforcement identification and authentication, and video-based surveillance analysis. Issues like low image quality, non-uniform illumination as well as variations in poses and facial expressions can impair the performance of recognition systems. To address the non-uniform illumination challenge, we present a novel robust autonomous facial recognition system inspired by the human visual system based, so called, logarithmical image visualization technique. In this paper, the proposed method, for the first time, utilizes the logarithmical image visualization technique coupled with the local binary pattern to perform discriminative feature extraction for facial recognition system. The Yale database, the Yale-B database and the ATT database are used for computer simulation accuracy and efficiency testing. The extensive computer simulation demonstrates the method's efficiency, accuracy, and robustness of illumination invariance for facial recognition.

Cystic fibrosis genetics: from molecular understanding to clinical application.

PubMed

Cutting, Garry R

2015-01-01

The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethal autosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the discovery of the disease-causing gene.

Human Genetics and Islam: Scientific and Medical Aspects

PubMed Central

Ghareeb, Bilal A.A.

2011-01-01

Objective: To relate diverse aspects of genetics and its applications to concepts in the Glorious Qur’an and the ḥadīth. Study Design: The author compared passages from the Glorious Qur’an and ḥadīth with modern concepts in genetics, such as recessive inheritance, genetic counseling, genetic variation, cytoplasmic inheritance, sex chromosomes, genetics-environment interactions, gender determination, and the hypothesis of “pairing in the universe.” Conclusions: A fresh understanding of Islamic scripture reveals references to principles of genetics that predate contemporary discoveries. This highlights the need for further exploration of possible links between science and religion. PMID:23610491

Application of a coupled enzyme assay to characterize nicotinamide riboside kinases.

PubMed

Dölle, Christian; Ziegler, Mathias

2009-02-15

The recently identified nicotinamide riboside kinases (Nrks) constitute a distinct pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Here we present the combination of an established optical adenosine triphosphatase (ATPase) test, the pyruvate kinase/lactate dehydrogenase system, with the Nrk-catalyzed reaction to determine kinetic properties of these enzymes, in particular affinities for ATP. The assay allows variation of both nucleoside and phosphate donor substrates, thereby providing major advantages for the characterization of these enzymes. We confirm previously established kinetic parameters and identify differences in substrate selectivity between the two human Nrk isoforms. The proposed assay is inexpensive and may be applied for high-throughput screening.

Cystic fibrosis genetics: from molecular understanding to clinical application

PubMed Central

Cutting, Garry R.

2015-01-01

The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

PubMed

Barbero, Ana M; Frasch, H Frederick

2009-02-01

Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (P<0.0001), with an intra species average coefficient of variation of skin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (P<0.0001), with an average intra species coefficient of variation of 19% for guinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, P<0.0001, n=12). When permeability data was not reported a factor of difference (FOD) of animal to human skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3

Environmental metabolomics: a SWOT analysis (strengths, weaknesses, opportunities, and threats).

PubMed

Miller, Marion G

2007-02-01

Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively explored. This review will use a SWOT analysis model to discuss some of the strengths, weaknesses, opportunities, and threats that are apparent to an investigator venturing into this relatively new field. SWOT has been used extensively in business settings to uncover new outlooks and identify problems that would impede progress. The field of environmental metabolomics provides great opportunities for discovery, and this is recognized by a high level of interest in potential applications. However, understanding the biological consequence of environmental exposures can be confounded by inter- and intra-individual differences. Metabolomic profiles can yield a plethora of data, the interpretation of which is complex and still being evaluated and researched. The development of the field will depend on the availability of technologies for data handling and that permit ready access metabolomic databases. Understanding the relevance of metabolomic endpoints to organism health vs adaptation vs variation is an important step in understanding what constitutes a substantive environmental threat. Metabolomic applications in reproductive research are discussed. Overall, the development of a comprehensive mechanistic-based interpretation of metabolomic changes offers the possibility of providing information that will significantly contribute to the protection of human health and the environment.

Seasonal variation in human reproduction: environmental factors.

PubMed

Bronson, F H

1995-06-01

Almost all human populations exhibit seasonal variation in births, owing mostly to seasonal variation in the frequency of conception. This review focuses on the degree to which environmental factors like nutrition, temperature and photoperiod contribute to these seasonal patterns by acting directly on the reproductive axis. The reproductive strategy of humans is basically that of the apes: Humans have the capacity to reproduce continuously, albeit slowly, unless inhibited by environmental influences. Two, and perhaps three, environmental factors probably act routinely as seasonal inhibitors in some human populations. First, it seems likely that ovulation is regulated seasonally in populations experiencing seasonal variation in food availability. More specifically, it seems likely that inadequate food intake or the increased energy expenditure required to obtain food, or both, can delay menarche, suppress the frequency of ovulation in the nonlactating adult, and prolong lactational amenorrhea in these populations on a seasonal basis. This action is most easily seen in tropical subsistence societies where food availability often varies greatly owing to seasonal variation in rainfall; hence births in these populations often correlate with rainfall. Second, it seems likely that seasonally high temperatures suppress spermatogenesis enough to influence the incidence of fertilization in hotter latitudes, but possibly only in males wearing clothing that diminishes scrotal cooling. Since most of our knowledge about this phenomenon comes from temperate latitudes, the sensitivity of spermatogenesis in both human and nonhuman primates to heat in the tropics needs further study. It is quite possible that high temperatures suppress ovulation and early embryo survival seasonally in some of these same populations. Since we know less than desired about the effect of heat stress on ovulation and early pregnancy in nonhuman mammals, and nothing at all about it in humans or any of the other primates, this is an important area for future research. Third, correlational data suggest that there may be some degree of regulation of reproduction by photoperiod in humans at middle to higher latitudes. Populations at these latitudes often show a peak in presumed conceptions associated with the vernal equinox. On the other hand, evidence gathered by neuroendocrinologists tends to argue against reproductive photoresponsiveness in humans.

The Human Semicircular Canals Orientation Is More Similar to the Bonobos than to the Chimpanzees

PubMed Central

El Khoury, Marwan; Braga, José; Dumoncel, Jean; Nancy, Javotte; Esclassan, Remi; Vaysse, Frederic

2014-01-01

For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens), bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee – bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a “random walk” (Brownian motion) evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology. PMID:24710502

Comparative genomic hybridization.

PubMed

Pinkel, Daniel; Albertson, Donna G

2005-01-01

Altering DNA copy number is one of the many ways that gene expression and function may be modified. Some variations are found among normal individuals ( 14, 35, 103 ), others occur in the course of normal processes in some species ( 33 ), and still others participate in causing various disease states. For example, many defects in human development are due to gains and losses of chromosomes and chromosomal segments that occur prior to or shortly after fertilization, whereas DNA dosage alterations that occur in somatic cells are frequent contributors to cancer. Detecting these aberrations, and interpreting them within the context of broader knowledge, facilitates identification of critical genes and pathways involved in biological processes and diseases, and provides clinically relevant information. Over the past several years array comparative genomic hybridization (array CGH) has demonstrated its value for analyzing DNA copy number variations. In this review we discuss the state of the art of array CGH and its applications in medical genetics and cancer, emphasizing general concepts rather than specific results.

Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.

PubMed

French, Anna; Bravery, Christopher; Smith, James; Chandra, Amit; Archibald, Peter; Gold, Joseph D; Artzi, Natalie; Kim, Hae-Won; Barker, Richard W; Meissner, Alexander; Wu, Joseph C; Knowles, Jonathan C; Williams, David; García-Cardeña, Guillermo; Sipp, Doug; Oh, Steve; Loring, Jeanne F; Rao, Mahendra S; Reeve, Brock; Wall, Ivan; Carr, Andrew J; Bure, Kim; Stacey, Glyn; Karp, Jeffrey M; Snyder, Evan Y; Brindley, David A

2015-03-01

There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes. ©AlphaMed Press.

Designing deep sequencing experiments: detecting structural variation and estimating transcript abundance.

PubMed

Bashir, Ali; Bansal, Vikas; Bafna, Vineet

2010-06-18

Massively parallel DNA sequencing technologies have enabled the sequencing of several individual human genomes. These technologies are also being used in novel ways for mRNA expression profiling, genome-wide discovery of transcription-factor binding sites, small RNA discovery, etc. The multitude of sequencing platforms, each with their unique characteristics, pose a number of design challenges, regarding the technology to be used and the depth of sequencing required for a particular sequencing application. Here we describe a number of analytical and empirical results to address design questions for two applications: detection of structural variations from paired-end sequencing and estimating mRNA transcript abundance. For structural variation, our results provide explicit trade-offs between the detection and resolution of rearrangement breakpoints, and the optimal mix of paired-read insert lengths. Specifically, we prove that optimal detection and resolution of breakpoints is achieved using a mix of exactly two insert library lengths. Furthermore, we derive explicit formulae to determine these insert length combinations, enabling a 15% improvement in breakpoint detection at the same experimental cost. On empirical short read data, these predictions show good concordance with Illumina 200 bp and 2 Kbp insert length libraries. For transcriptome sequencing, we determine the sequencing depth needed to detect rare transcripts from a small pilot study. With only 1 Million reads, we derive corrections that enable almost perfect prediction of the underlying expression probability distribution, and use this to predict the sequencing depth required to detect low expressed genes with greater than 95% probability. Together, our results form a generic framework for many design considerations related to high-throughput sequencing. We provide software tools http://bix.ucsd.edu/projects/NGS-DesignTools to derive platform independent guidelines for designing sequencing experiments (amount of sequencing, choice of insert length, mix of libraries) for novel applications of next generation sequencing.

Enabling Consistency in Pluripotent Stem Cell-Derived Products for Research and Development and Clinical Applications Through Material Standards

PubMed Central

Bravery, Christopher; Smith, James; Chandra, Amit; Archibald, Peter; Gold, Joseph D.; Artzi, Natalie; Kim, Hae-Won; Barker, Richard W.; Meissner, Alexander; Wu, Joseph C.; Knowles, Jonathan C.; Williams, David; García-Cardeña, Guillermo; Sipp, Doug; Oh, Steve; Loring, Jeanne F.; Rao, Mahendra S.; Reeve, Brock; Wall, Ivan; Carr, Andrew J.; Bure, Kim; Stacey, Glyn; Karp, Jeffrey M.

2015-01-01

Summary There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify “signatures” for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes. PMID:25650438

Genetics of Resistant Hypertension: the Missing Heritability and Opportunities.

PubMed

Teixeira, Samantha K; Pereira, Alexandre C; Krieger, Jose E

2018-05-19

Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use. Here, we propose the combined use of resistant hypertension as a trait for mapping genetic determinants in humans and the integration of new large-scale technologies to approach in model systems the multidimensional nature of the problem. New large-scale efforts in the genetic and genomic arenas are paving the way for an increased and granular understanding of genetic determinants of hypertension. New technologies for whole genome sequence and large-scale forward genetic screens can help prioritize gene and gene-pathways for downstream characterization and large-scale population studies, and guided pharmacological design can be used to drive discoveries to the translational application through better risk stratification and new therapeutic approaches. Although significant challenges remain in the mapping and identification of genetic determinants of hypertension, new large-scale technological approaches have been proposed to surpass some of the shortcomings that have limited progress in the area for the last three decades. The incorporation of these technologies to hypertension research may significantly help in the understanding of inter-individual blood pressure variation and the deployment of new phenotyping and treatment approaches for the condition.

Human-aided admixture may fuel ecosystem transformation during biological invasions: theoretical and experimental evidence.

PubMed

Molofsky, Jane; Keller, Stephen R; Lavergne, Sébastien; Kaproth, Matthew A; Eppinga, Maarten B

2014-04-01

Biological invasions can transform our understanding of how the interplay of historical isolation and contemporary (human-aided) dispersal affects the structure of intraspecific diversity in functional traits, and in turn, how changes in functional traits affect other scales of biological organization such as communities and ecosystems. Because biological invasions frequently involve the admixture of previously isolated lineages as a result of human-aided dispersal, studies of invasive populations can reveal how admixture results in novel genotypes and shifts in functional trait variation within populations. Further, because invasive species can be ecosystem engineers within invaded ecosystems, admixture-induced shifts in the functional traits of invaders can affect the composition of native biodiversity and alter the flow of resources through the system. Thus, invasions represent promising yet under-investigated examples of how the effects of short-term evolutionary changes can cascade across biological scales of diversity. Here, we propose a conceptual framework that admixture between divergent source populations during biological invasions can reorganize the genetic variation underlying key functional traits, leading to shifts in the mean and variance of functional traits within invasive populations. Changes in the mean or variance of key traits can initiate new ecological feedback mechanisms that result in a critical transition from a native ecosystem to a novel invasive ecosystem. We illustrate the application of this framework with reference to a well-studied plant model system in invasion biology and show how a combination of quantitative genetic experiments, functional trait studies, whole ecosystem field studies and modeling can be used to explore the dynamics predicted to trigger these critical transitions.

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

PubMed Central

Huang, Liang; Nho, Kwangsik; Deng, Min; Chen, Qiang; Weinberger, Daniel R.; Vasquez, Alejandro Arias; Rijpkema, Mark; Mattay, Venkata S.; Saykin, Andrew J.; Shen, Li; Fernández, Guillén; Franke, Barbara; Chen, Jing-chun; Chen, Xiang-ning; Wang, Jin-kai; Xiao, Xiao; Qi, Xue-bin; Xiang, Kun; Peng, Ying-Mei; Cao, Xiang-yu; Li, Yi; Shi, Xiao-dong; Gan, Lin; Su, Bing

2012-01-01

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development. PMID:23226269

Global and disease-associated genetic variation in the human Fanconi anemia gene family.

PubMed

Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

2014-12-20

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Culture rather than genes provides greater scope for the evolution of large-scale human prosociality

PubMed Central

Bell, Adrian V.; Richerson, Peter J.; McElreath, Richard

2009-01-01

Whether competition among large groups played an important role in human social evolution is dependent on how variation, whether cultural or genetic, is maintained between groups. Comparisons between genetic and cultural differentiation between neighboring groups show how natural selection on large groups is more plausible on cultural rather than genetic variation. PMID:19822753

Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

ERIC Educational Resources Information Center

Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

2004-01-01

This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

Recommendations of the 2006 Human Variome Project meeting.

PubMed

Cotton, Richard G H; Appelbe, William; Auerbach, Arleen D; Becker, Kevin; Bodmer, Walter; Boone, D Joe; Boulyjenkov, Victor; Brahmachari, Samir; Brody, Lawrence; Brookes, Anthony; Brown, Alastair F; Byers, Peter; Cantu, Jose Maria; Cassiman, Jean-Jacques; Claustres, Mireille; Concannon, Patrick; Cotton, Richard G H; den Dunnen, Johan T; Flicek, Paul; Gibbs, Richard; Hall, Judith; Hasler, Julia; Katz, Michael; Kwok, Pui-Yan; Laradi, Sandrine; Lindblom, Annika; Maglott, Donna; Marsh, Steven; Masimirembwa, Collen Muto; Minoshima, Shinsei; de Ramirez, Ana Maria Oller; Pagon, Roberta; Ramesar, Raj; Ravine, David; Richards, Sue; Rimoin, David; Ring, Huijun Z; Scriver, Charles R; Sherry, Stephen; Shimizu, Nobuyoshi; Stein, Lincoln; Tadmouri, Ghazi Omar; Taylor, Graham; Watson, Michael

2007-04-01

Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations.

Characterising the variations in ethnic skin colours: a new calibrated data base for human skin.

PubMed

Xiao, K; Yates, J M; Zardawi, F; Sueeprasan, S; Liao, N; Gill, L; Li, C; Wuerger, S

2017-02-01

Accurate skin colour measurements are important for numerous medical applications including the diagnosis and treatment of cutaneous disorders and the provision of maxillofacial soft tissue prostheses. In this study, we obtained accurate skin colour measurements from four different ethnic groups (Caucasian, Chinese, Kurdish, Thai) and at four different body locations (Forehead, cheek, inner arm, back of hand) with a view of establishing a new skin colour database for medical and cosmetic applications. Skin colours are measured using a spectrophotometer and converted to a device-independent standard colour appearance space (CIELAB) where skin colour is expressed as values along the three dimensions: Lightness L*, Redness a* and Yellowness b*. Skin colour differences and variation are then evaluated as a function of ethnicity and body location. We report three main results: (1) When plotted in a standard colour appearance space (CIELAB), skin colour distributions for the four ethnic groups overlap significantly, although there are systematic mean differences. Between ethnicities, the most significant skin colour differences occur along the yellowness dimension, with Thai skin exhibiting the highest yellowness (b*) value and Caucasian skin the lowest value. Facial redness (a*) is invariant across the four ethnic groups. (2) Between different body locations, there are significant variations in redness (a*), with the forehead showing the highest redness value and the inner arm the lowest. (3) The colour gamut is smallest in the Chinese sample and largest in the Caucasian sample, with the Chinese gamut lying entirely the Caucasian gamut. Similarly, the largest variability in skin tones is found in the Caucasian group, and the smallest in the Chinese group. Broadly speaking, skin colour variation can be explained by two main factors: individual differences in lightness and yellowness are mostly due to ethnicity, whereas differences in redness are primarily due to different body locations. Variations in lightness are more idiosyncratic probably reflecting the large influence of environmental factors such as exposure to sun. © 2016 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd.

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

PubMed

Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

2015-11-01

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

Recent Progress in Electronic Skin

PubMed Central

Wang, Xiandi; Dong, Lin; Zhang, Hanlu; Yu, Ruomeng; Wang, Zhong Lin

2015-01-01

The skin is the largest organ of the human body and can sense pressure, temperature, and other complex environmental stimuli or conditions. The mimicry of human skin's sensory ability via electronics is a topic of innovative research that could find broad applications in robotics, artificial intelligence, and human–machine interfaces, all of which promote the development of electronic skin (e‐skin). To imitate tactile sensing via e‐skins, flexible and stretchable pressure sensor arrays are constructed based on different transduction mechanisms and structural designs. These arrays can map pressure with high resolution and rapid response beyond that of human perception. Multi‐modal force sensing, temperature, and humidity detection, as well as self‐healing abilities are also exploited for multi‐functional e‐skins. Other recent progress in this field includes the integration with high‐density flexible circuits for signal processing, the combination with wireless technology for convenient sensing and energy/data transfer, and the development of self‐powered e‐skins. Future opportunities lie in the fabrication of highly intelligent e‐skins that can sense and respond to variations in the external environment. The rapidly increasing innovations in this area will be important to the scientific community and to the future of human life. PMID:27980911

Statistical total correlation spectroscopy scaling for enhancement of metabolic information recovery in biological NMR spectra.

PubMed

Maher, Anthony D; Fonville, Judith M; Coen, Muireann; Lindon, John C; Rae, Caroline D; Nicholson, Jeremy K

2012-01-17

The high level of complexity in nuclear magnetic resonance (NMR) metabolic spectroscopic data sets has fueled the development of experimental and mathematical techniques that enhance latent biomarker recovery and improve model interpretability. We previously showed that statistical total correlation spectroscopy (STOCSY) can be used to edit NMR spectra to remove drug metabolite signatures that obscure metabolic variation of diagnostic interest. Here, we extend this "STOCSY editing" concept to a generalized scaling procedure for NMR data that enhances recovery of latent biochemical information and improves biological classification and interpretation. We call this new procedure STOCSY-scaling (STOCSY(S)). STOCSY(S) exploits the fixed proportionality in a set of NMR spectra between resonances from the same molecule to suppress or enhance features correlated with a resonance of interest. We demonstrate this new approach using two exemplar data sets: (a) a streptozotocin rat model (n = 30) of type 1 diabetes and (b) a human epidemiological study utilizing plasma NMR spectra of patients with metabolic syndrome (n = 67). In both cases significant biomarker discovery improvement was observed by using STOCSY(S): the approach successfully suppressed interfering NMR signals from glucose and lactate that otherwise dominate the variation in the streptozotocin study, which then allowed recovery of biomarkers such as glycine, which were otherwise obscured. In the metabolic syndrome study, we used STOCSY(S) to enhance variation from the high-density lipoprotein cholesterol peak, improving the prediction of individuals with metabolic syndrome from controls in orthogonal projections to latent structures discriminant analysis models and facilitating the biological interpretation of the results. Thus, STOCSY(S) is a versatile technique that is applicable in any situation in which variation, either biological or otherwise, dominates a data set at the expense of more interesting or important features. This approach is generally appropriate for many types of NMR-based complex mixture analyses and hence for wider applications in bioanalytical science.

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

PubMed

Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

2018-06-19

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

DNA microarrays: a powerful genomic tool for biomedical and clinical research

PubMed Central

Trevino, Victor; Falciani, Francesco; Barrera-Saldaña, Hugo A.

2007-01-01

Among the many benefits of the Human Genome Project are new and powerful tools such as the genome-wide hybridization devices referred as microarrays. Initially designed to measure gene transcriptional levels, microarray technologies are now used for comparing other genome features among individuals and their tissues and cells. Results provide valuable information on disease subcategories, disease prognosis, and treatment outcome. Likewise, reveal differences in genetic makeup, regulatory mechanisms and subtle variations are approaching the era of personalized medicine. To understand this powerful tool, its versatility and how it is dramatically changing the molecular approach to biomedical and clinical research, this review describes the technology, its applications, a didactic step-by-step review of a typical microarray protocol, and a real experiment. Finally, it calls the attention of the medical community to integrate multidisciplinary teams, to take advantage of this technology and its expanding applications that in a slide reveals our genetic inheritance and destiny. PMID:17660860

A Facile Method to Establish Human Induced Pluripotent Stem Cells From Adult Blood Cells Under Feeder-Free and Xeno-Free Culture Conditions: A Clinically Compliant Approach

PubMed Central

Chou, Bin-Kuan; Gu, Haihui; Gao, Yongxing; Dowey, Sarah N.; Wang, Ying; Shi, Jun; Li, Yanxin; Ye, Zhaohui; Cheng, Tao

2015-01-01

Reprogramming human adult blood mononuclear cells (MNCs) cells by transient plasmid expression is becoming increasingly popular as an attractive method for generating induced pluripotent stem (iPS) cells without the genomic alteration caused by genome-inserting vectors. However, its efficiency is relatively low with adult MNCs compared with cord blood MNCs and other fetal cells and is highly variable among different adult individuals. We report highly efficient iPS cell derivation under clinically compliant conditions via three major improvements. First, we revised a combination of three EBNA1/OriP episomal vectors expressing five transgenes, which increased reprogramming efficiency by ≥10–50-fold from our previous vectors. Second, human recombinant vitronectin proteins were used as cell culture substrates, alleviating the need for feeder cells or animal-sourced proteins. Finally, we eliminated the previously critical step of manually picking individual iPS cell clones by pooling newly emerged iPS cell colonies. Pooled cultures were then purified based on the presence of the TRA-1-60 pluripotency surface antigen, resulting in the ability to rapidly expand iPS cells for subsequent applications. These new improvements permit a consistent and reliable method to generate human iPS cells with minimal clonal variations from blood MNCs, including previously difficult samples such as those from patients with paroxysmal nocturnal hemoglobinuria. In addition, this method of efficiently generating iPS cells under feeder-free and xeno-free conditions allows for the establishment of clinically compliant iPS cell lines for future therapeutic applications. PMID:25742692

Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

PubMed

Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

2018-06-01

Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster.

PubMed

Zhou, Shanshan; Morozova, Tatiana V; Hussain, Yasmeen N; Luoma, Sarah E; McCoy, Lenovia; Yamamoto, Akihiko; Mackay, Trudy F C; Anholt, Robert R H

2016-07-01

Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations. Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure. To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs. We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system. Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations. Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124:1062-1070; http://dx.doi.org/10.1289/ehp.1510513.

Facial Cosmetics and Attractiveness: Comparing the Effect Sizes of Professionally-Applied Cosmetics and Identity.

PubMed

Jones, Alex L; Kramer, Robin S S

2016-01-01

Forms of body decoration exist in all human cultures. However, in Western societies, women are more likely to engage in appearance modification, especially through the use of facial cosmetics. How effective are cosmetics at altering attractiveness? Previous research has hinted that the effect is not large, especially when compared to the variation in attractiveness observed between individuals due to differences in identity. In order to build a fuller understanding of how cosmetics and identity affect attractiveness, here we examine how professionally-applied cosmetics alter attractiveness and compare this effect with the variation in attractiveness observed between individuals. In Study 1, 33 YouTube models were rated for attractiveness before and after the application of professionally-applied cosmetics. Cosmetics explained a larger proportion of the variation in attractiveness compared with previous studies, but this effect remained smaller than variation caused by differences in attractiveness between individuals. Study 2 replicated the results of the first study with a sample of 45 supermodels, with the aim of examining the effect of cosmetics in a sample of faces with low variation in attractiveness between individuals. While the effect size of cosmetics was generally large, between-person variability due to identity remained larger. Both studies also found interactions between cosmetics and identity-more attractive models received smaller increases when cosmetics were worn. Overall, we show that professionally-applied cosmetics produce a larger effect than self-applied cosmetics, an important theoretical consideration for the field. However, the effect of individual differences in facial appearance is ultimately more important in perceptions of attractiveness.

Facial Cosmetics and Attractiveness: Comparing the Effect Sizes of Professionally-Applied Cosmetics and Identity

PubMed Central

Kramer, Robin S. S.

2016-01-01

Forms of body decoration exist in all human cultures. However, in Western societies, women are more likely to engage in appearance modification, especially through the use of facial cosmetics. How effective are cosmetics at altering attractiveness? Previous research has hinted that the effect is not large, especially when compared to the variation in attractiveness observed between individuals due to differences in identity. In order to build a fuller understanding of how cosmetics and identity affect attractiveness, here we examine how professionally-applied cosmetics alter attractiveness and compare this effect with the variation in attractiveness observed between individuals. In Study 1, 33 YouTube models were rated for attractiveness before and after the application of professionally-applied cosmetics. Cosmetics explained a larger proportion of the variation in attractiveness compared with previous studies, but this effect remained smaller than variation caused by differences in attractiveness between individuals. Study 2 replicated the results of the first study with a sample of 45 supermodels, with the aim of examining the effect of cosmetics in a sample of faces with low variation in attractiveness between individuals. While the effect size of cosmetics was generally large, between-person variability due to identity remained larger. Both studies also found interactions between cosmetics and identity–more attractive models received smaller increases when cosmetics were worn. Overall, we show that professionally-applied cosmetics produce a larger effect than self-applied cosmetics, an important theoretical consideration for the field. However, the effect of individual differences in facial appearance is ultimately more important in perceptions of attractiveness. PMID:27727311

Gold nanoparticles for high-throughput genotyping of long-range haplotypes

NASA Astrophysics Data System (ADS)

Chen, Peng; Pan, Dun; Fan, Chunhai; Chen, Jianhua; Huang, Ke; Wang, Dongfang; Zhang, Honglu; Li, You; Feng, Guoyin; Liang, Peiji; He, Lin; Shi, Yongyong

2011-10-01

Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance.

Three-dimensional scaffolding to investigate neuronal derivatives of human embryonic stem cells.

PubMed

Soman, Pranav; Tobe, Brian T D; Lee, Jin Woo; Winquist, Alicia M; Singec, Ilyas; Vecchio, Kenneth S; Snyder, Evan Y; Chen, Shaochen

2012-10-01

Access to unlimited numbers of live human neurons derived from stem cells offers unique opportunities for in vitro modeling of neural development, disease-related cellular phenotypes, and drug testing and discovery. However, to develop informative cellular in vitro assays, it is important to consider the relevant in vivo environment of neural tissues. Biomimetic 3D scaffolds are tools to culture human neurons under defined mechanical and physico-chemical properties providing an interconnected porous structure that may potentially enable a higher or more complex organization than traditional two-dimensional monolayer conditions. It is known that even minor variations in the internal geometry and mechanical properties of 3D scaffolds can impact cell behavior including survival, growth, and cell fate choice. In this report, we describe the design and engineering of 3D synthetic polyethylene glycol (PEG)-based and biodegradable gelatin-based scaffolds generated by a free form fabrication technique with precise internal geometry and elastic stiffnesses. We show that human neurons, derived from human embryonic stem (hESC) cells, are able to adhere to these scaffolds and form organoid structures that extend in three dimensions as demonstrated by confocal and electron microscopy. Future refinements of scaffold structure, size and surface chemistries may facilitate long term experiments and designing clinically applicable bioassays.

Construction and application of 3D model sequence to illustrate the development of the human embryo

NASA Astrophysics Data System (ADS)

Mizuta, Shinobu; Kakusho, Koh; Minekura, Yutaka; Minoh, Michihiko; Nakatsu, Tomoko; Shiota, Kohei

2002-05-01

Embryology is one of the basic subjects in medical education, to learn the process of human development especially from fertilization to birth. The shape deformation in the development of human embryo is one of the most important points to be comprehended, but it is difficult to illustrate the deformation by texts, 2D drawings, photographs and so on, because it is extremely complicated. The purpose of our research is to construct a 3D model sequence to illustrate the deformation of human embryo, and to make the model sequence into the teaching materials for medical education. Firstly, 3D images of the specimens of human embryo were acquired using MR microscopy. Next, an initial 3D model sequence was manually modified by comparing with the features of the acquired images under the supervision of medical doctors, because the images were influenced not only by the noise or limitation of resolution in MR image acquisition, but also by the variation of shape depending on the difference of subject. Using the constructed 3D model sequence, CG animations and an interactive VRML system were composed as the teaching materials for embryology. These materials were quite helpful to understand the shape deformation compared with the conventional materials.

Primer Vector Optimization: Survey of Theory, New Analysis and Applications

NASA Technical Reports Server (NTRS)

Guzman, J. J.; Mailhe, L. M.; Schiff, C.; Hughes, S. P.; Folta, D. C.

2002-01-01

In this paper, a summary of primer vector theory is presented. The applicability of primer vector theory is examined in an effort to understand when and why the theory can fail. For example, since the Calculus of Variations is based on "small" variations, singularities in the linearized (variational) equations of motion along the arcs must be taken into account. These singularities are a recurring problem in analyse that employ small variations. Two examples, the initialization of an orbit and a line of apsides rotation, are presented. Recommendations, future work, and the possible addition of other optimization techniques are also discussed.

Human Footprint Variation while Performing Load Bearing Tasks

PubMed Central

Wall-Scheffler, Cara M.; Wagnild, Janelle; Wagler, Emily

2015-01-01

Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition. Generally such estimates are made by comparing footprint evidence with modern controls; however, previous studies have not accounted for the variation in footprint dimensions coming from load bearing activities. It is likely that a portion of the hominins who created these fossil footprints were carrying a significant load, such as offspring or foraging loads, which caused variation in the footprint which could extend to variation in any estimations concerning the footprint’s maker. To identify significant variation in footprints due to load-bearing tasks, we had participants (N = 30, 15 males and 15 females) walk at a series of speeds carrying a 20kg pack on their back, side and front. Paint was applied to the bare feet of each participant to create footprints that were compared in terms of foot length, foot width and foot area. Female foot length and width increased during multiple loaded conditions. An appreciation of footprint variability associated with carrying loads adds an additional layer to our understanding of the behavior and morphology of extinct hominin populations. PMID:25738496

GEMINI: Integrative Exploration of Genetic Variation and Genome Annotations

PubMed Central

Paila, Umadevi; Chapman, Brad A.; Kirchner, Rory; Quinlan, Aaron R.

2013-01-01

Modern DNA sequencing technologies enable geneticists to rapidly identify genetic variation among many human genomes. However, isolating the minority of variants underlying disease remains an important, yet formidable challenge for medical genetics. We have developed GEMINI (GEnome MINIng), a flexible software package for exploring all forms of human genetic variation. Unlike existing tools, GEMINI integrates genetic variation with a diverse and adaptable set of genome annotations (e.g., dbSNP, ENCODE, UCSC, ClinVar, KEGG) into a unified database to facilitate interpretation and data exploration. Whereas other methods provide an inflexible set of variant filters or prioritization methods, GEMINI allows researchers to compose complex queries based on sample genotypes, inheritance patterns, and both pre-installed and custom genome annotations. GEMINI also provides methods for ad hoc queries and data exploration, a simple programming interface for custom analyses that leverage the underlying database, and both command line and graphical tools for common analyses. We demonstrate GEMINI's utility for exploring variation in personal genomes and family based genetic studies, and illustrate its ability to scale to studies involving thousands of human samples. GEMINI is designed for reproducibility and flexibility and our goal is to provide researchers with a standard framework for medical genomics. PMID:23874191

Regional Variation in the Structural Response and Geometrical Properties of Human Ribs

PubMed Central

Cormier, Joseph M.; Stitzel, Joel D.; Duma, Stefan M.; Matsuoka, Fumio

2005-01-01

By incorporating material and geometrical properties into a model of the human thorax one can develop an injury criterion that is a function of stress and strain of the material and not a function of the global response of the thorax. Previous research on the mechanical properties of ribs has focused on a limited set of specific ribs. For this study a total of 52 rib specimens were removed from four cadaver subjects. Variation in peak moment by thoracic region was significant (p < 0.01) with average values of 2, 2.9 and 3.9 N-m for the anterior, lateral and posterior regions respectively. Two geometrical properties, radius of gyration and distance from the neutral axis, showed significant variation by region (p < 0.0001) as well as by rib level (p = < 0.01, 0.05). The results of this study can be used to update current models of the human thorax to account for the variation in strength and geometrical properties throughout the rib cage. Accounting for the variation in rib properties by region will improve injury predictive measures and, therefore, the ability to design systems to prevent thoracic injury. PMID:16179146

P450 GENETIC VARIATION: IMPLICATIONS FOR ENVIRONMENTAL AND WORKPLACE EXPOSURE

EPA Science Inventory

The Cytochrome P450 array detoxifies many chemicals by catalyzing the conversion of mostly hydrophobic chemicals into more hydrophilic forms that can subsequently be excreted by the body. Human genetic variation in the genes for these enzymes produces wide variations in the abili...

Fear of humans and its relationships with productivity in laying hens at commercial farms.

PubMed

Barnett, J L; Hemsworth, P H; Newman, E A

1992-09-01

1. The relationship between the behavioural responses of laying hens to humans and productivity was determined at 16 commercial sheds from 14 farms. 2. A number of behaviour variables were moderately to highly correlated with production variables; for example, the proportion of birds that moved away from an approaching experimenter in an unfamiliar environment ('shute test') was negatively correlated with peak hen day production, (PKHDP). 3. Behavioural responses to humans accounted for between 23 and 63% of the variation in a number of production variables, including PKHDP and the duration of a high level of production. 4. Inclusion of farm factor variables increased the amount of variation accounted for by the behaviour variables. For example, adding the variable 'time/day spent in the shed by stockpeople' to the behaviour variables 'the proportion of birds that moved away from an approaching human' in the shute test and 'the number of times birds in cages adopted an erect posture' in response to an approaching human increased the variation accounted for in PKHDP from 53 to 61%. 5. The results suggest that fear of humans may be a factor that limits the productivity of commercial laying hens.

Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry.

PubMed

Tadayon, Sayed H; Vaziri-Pashkam, Maryam; Kahali, Pegah; Ansari Dezfouli, Mitra; Abbassian, Abdolhossein

2016-01-01

Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with this subset of brain asymmetry variation we performed a genome-wide association study followed by replication in an independent cohort. We identified one SNP (rs11691187) that had genome-wide significant association (P Combined = 2.40e-08). The rs11691187 is in the first intron of VIT. In a follow-up analysis, we found that VIT gene expression is associated with brain asymmetry in six donors of the Allen Human Brain Atlas. Based on these findings we suggest that VIT contributes to normal brain asymmetry variation. Our results can shed light on disorders associated with altered brain asymmetry.

Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

PubMed Central

DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-01-01

ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

Practical guidelines addressing ethical issues pertaining to the curation of human locus-specific variation databases (LSDBs)

PubMed Central

Povey, Sue; Al Aqeel, Aida I; Cambon-Thomsen, Anne; Dalgleish, Raymond; den Dunnen, Johan T; Firth, Helen V; Greenblatt, Marc S; Barash, Carol Isaacson; Parker, Michael; Patrinos, George P; Savige, Judith; Sobrido, Maria-Jesus; Winship, Ingrid; Cotton, Richard GH

2010-01-01

More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO). Hum Mutat 31:–6, 2010. © 2010 Wiley-Liss, Inc. PMID:20683926

Read clouds uncover variation in complex regions of the human genome

PubMed Central

Bishara, Alex; Liu, Yuling; Weng, Ziming; Kashef-Haghighi, Dorna; Newburger, Daniel E.; West, Robert; Sidow, Arend; Batzoglou, Serafim

2015-01-01

Although an increasing amount of human genetic variation is being identified and recorded, determining variants within repeated sequences of the human genome remains a challenge. Most population and genome-wide association studies have therefore been unable to consider variation in these regions. Core to the problem is the lack of a sequencing technology that produces reads with sufficient length and accuracy to enable unique mapping. Here, we present a novel methodology of using read clouds, obtained by accurate short-read sequencing of DNA derived from long fragment libraries, to confidently align short reads within repeat regions and enable accurate variant discovery. Our novel algorithm, Random Field Aligner (RFA), captures the relationships among the short reads governed by the long read process via a Markov Random Field. We utilized a modified version of the Illumina TruSeq synthetic long-read protocol, which yielded shallow-sequenced read clouds. We test RFA through extensive simulations and apply it to discover variants on the NA12878 human sample, for which shallow TruSeq read cloud sequencing data are available, and on an invasive breast carcinoma genome that we sequenced using the same method. We demonstrate that RFA facilitates accurate recovery of variation in 155 Mb of the human genome, including 94% of 67 Mb of segmental duplication sequence and 96% of 11 Mb of transcribed sequence, that are currently hidden from short-read technologies. PMID:26286554

NDVI-Based analysis on the influence of human activities on vegetation variation on Hainan Island

NASA Astrophysics Data System (ADS)

Luo, Hongxia; Dai, Shengpei; Xie, Zhenghui; Fang, Jihua

2018-02-01

Using the Moderate Resolution Imaging Spectroradiometer-normalized difference vegetation index (NDVI) dataset, we analyzed the predicted NDVI values variation and the influence of human activities on vegetation on Hainan Island during 2001-2015. We investigated the roles of human activities in vegetation variation, particularly from 2002 when implemented the Grain-for-Greenprogram on Hainan Island. The trend analysis, linear regression model and residual analysis were used to analyze the data. The results of the study showed that (1) The predicted vegetation on Hainan Island showed an general upward trend with a linear growth rate of 0.0025/10y (p<0.05) over the past 15 years. The areas where vegetation increasedaccounted for 52.28%, while the areas where vegetation decreased accounted for 47.72%. (2) The residual NDVI values across the region significantly increased, with a growth rate of 0.023/10y.The vegetation increased across 35.95% of Hainan Island, while it decreased in 20.2% of the area as a result of human activities. (3) In general, human activities had played a positive role in the vegetation increase on Hainan Island, and the residual NDVI trend of this region showed positive outcomes for vegetation variation after implementing ecological engineering projects. However, it indicated a growing risk of vegetation degradation in the coastal region of Hainan Island as a result of rapid urbanization, land reclamation.

[Quantitative measures for assessing the functional state of the human body during diagnostic procedure].

PubMed

Artemenko, M V

2008-01-01

Two approaches to calculation of the qualitative measures for assessing the functional state level of human body are considered. These approaches are based on image and fuzzy set recognition theories and are used to construct diagnostic decision rules. The first approach uses the data on deviation of detected parameters from those for healthy persons; the second approach analyzes the degree of deviation of detected parameters from the approximants characterizing the correlation differences between the parameters. A method for synthesis of decision rules and the results of blood count-based research for a number of diseases (hemophilia, thrombocytopathy, hypertension, arrhythmia, hepatic cirrhosis, trichophytia) are considered. An effect of a change in the functional link between the cholesterol content in blood and the relative rate of variation of AST and ALT enzymes in blood from direct proportional (healthy state) to inverse proportional (hepatic cirrhosis) is discussed. It is shown that analysis of correlation changes in detected parameters of the human body state during diagnostic process is more effective for application in decision support systems than the state space analysis.

The Role of Constitutional Copy Number Variants in Breast Cancer

PubMed Central

Walker, Logan C.; Wiggins, George A.R.; Pearson, John F.

2015-01-01

Constitutional copy number variants (CNVs) include inherited and de novo deviations from a diploid state at a defined genomic region. These variants contribute significantly to genetic variation and disease in humans, including breast cancer susceptibility. Identification of genetic risk factors for breast cancer in recent years has been dominated by the use of genome-wide technologies, such as single nucleotide polymorphism (SNP)-arrays, with a significant focus on single nucleotide variants. To date, these large datasets have been underutilised for generating genome-wide CNV profiles despite offering a massive resource for assessing the contribution of these structural variants to breast cancer risk. Technical challenges remain in determining the location and distribution of CNVs across the human genome due to the accuracy of computational prediction algorithms and resolution of the array data. Moreover, better methods are required for interpreting the functional effect of newly discovered CNVs. In this review, we explore current and future application of SNP array technology to assess rare and common CNVs in association with breast cancer risk in humans. PMID:27600231

Monte Carlo simulation of reflection spectra of random multilayer media strongly scattering and absorbing light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meglinskii, I V

2001-12-31

The reflection spectra of a multilayer random medium - the human skin - strongly scattering and absorbing light are numerically simulated. The propagation of light in the medium and the absorption spectra are simulated by the stochastic Monte Carlo method, which combines schemes for calculations of real photon trajectories and the statistical weight method. The model takes into account the inhomogeneous spatial distribution of blood vessels, water, and melanin, the degree of blood oxygenation, and the hematocrit index. The attenuation of the incident radiation caused by reflection and refraction at Fresnel boundaries of layers inside the medium is also considered.more » The simulated reflection spectra are compared with the experimental reflection spectra of the human skin. It is shown that a set of parameters that was used to describe the optical properties of skin layers and their possible variations, despite being far from complete, is nevertheless sufficient for the simulation of the reflection spectra of the human skin and their quantitative analysis. (laser applications and other topics in quantum electronics)« less

Direct noninvasive observation of near infrared photobleaching of autofluorescence in human volar side fingertips in vivo

NASA Astrophysics Data System (ADS)

Deng, Bin; Wright, Colin; Lewis-Clark, Eric; Shaheen, G.; Geier, Roman; Chaiken, J.

2010-02-01

Human transdermal in vivo spectroscopic applications for tissue analysis involving near infrared (NIR) light often must contend with broadband NIR fluorescence that, depending on what kind of spectroscopy is being employed, can degrade signal to noise ratios and dynamic range. Such NIR fluorescence, i.e. "autofluorescence" is well known to originate in blood tissues and various other endogenous materials associated with the static tissues. Results of recent experiments on human volar side fingertips in vivo are beginning to provide a relative ordering of the contributions from various sources. Preliminary results involving the variation in the bleaching effect across different individuals suggest that for 830 nm excitation well over half of the total fluorescence comes from the static tissues and remainder originates with the blood tissues, i.e. the plasma and the hematocrit. Of the NIR fluorescence associated with the static tissue, over half originates with products of well-known post-enzymatic glycation reactions, i.e. Maillard chemistry, in the skin involving glucose and other carbohydrates and skin proteins like collagen and cytosol proteins.

Biotechnological synthesis of drug metabolites using human cytochrome P450 isozymes heterologously expressed in fission yeast.

PubMed

Peters, Frank T; Bureik, Matthias; Maurer, Hans H

2009-07-01

Cytochrome P450 mono-oxygenases (CYPs) are the major enzymes involved in the metabolism of drugs and poisons in humans. The variation of their activity - due to genetic polymorphisms or enzyme inhibition/induction - potentially increases the risk of side effects or toxicity. Studies on CYP-dependent metabolism are important in drug-development or toxicity studies. Reference standards of drug metabolites required for such studies, especially in the context of metabolites in safety testing (MIST), are often not commercially available and their classical chemical synthesis can be cumbersome. Recently, a biotechnological approach using human CYP isozymes heterologously expressed in fission yeast was developed for the synthesis of drug metabolites. Among other aspects, this approach has the distinct advantages that the reactions run under mild conditions and that only the final product must be isolated and characterized. This review overviews the first practical applications of this new approach and discusses the selection of substrates, metabolites and fission yeast strains as well as important aspects of incubation, product isolation and clean-up.

Genetics of the dentofacial variation in human malocclusion

PubMed Central

Moreno Uribe, L. M.; Miller, S. F.

2015-01-01

Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes. PMID:25865537

Seasonal variation in the free-running period in two Talitrus saltator populations from Italian beaches differing in morphodynamics and human disturbance

NASA Astrophysics Data System (ADS)

Nardi, M.; Morgan, E.; Scapini, F.

2003-10-01

The sandhopper Talitrus saltator Montagu (Amphipoda) is a widespread species adapted to different changing environmental conditions and which typically shows a clear circadian rhythm of locomotor activity. The populations from two beaches on the western Italian coast differing in coastline dynamics (eroded versus dynamically stable) and human disturbance (inside a natural park versus freely used and cleaned for leisure) were studied to highlight intrapopulation variation in the endogenous locomotor rhythm. The activity of adult sandhoppers was studied under constant laboratory conditions within individual recording chambers. Variation of the free-running period was analysed at individual level within each population. Greater variability was found than previously reported for the circadian rhythm period of T. saltator, and seasonal variation was shown for the first time. Differences in the level of variation were correlated with coastline dynamics.

Application of Variational Methods to the Thermal Entrance Region of Ducts

NASA Technical Reports Server (NTRS)

Sparrow, E. M.; Siegel. R.

1960-01-01

A variational method is presented for solving eigenvalue problems which arise in connection with the analysis of convective heat transfer in the thermal entrance region of ducts. Consideration is given, to both situations where the temperature profile depends upon one cross-sectional coordinate (e.g. circular tube) or upon two cross-sectional coordinates (e.g. rectangular duct). The variational method is illustrated and verified by application to laminar heat transfer in a circular tube and a parallel-plate channel, and good agreement with existing numerical solutions is attained. Then, application is made to laminar heat transfer in a square duct as a check, an alternate computation for the square duct is made using a method indicated by Misaps and Pohihausen. The variational method can, in principle, also be applied to problems in turbulent heat transfer.

Screening the low molecular weight fraction of human serum using ATR-IR spectroscopy.

PubMed

Bonnier, Franck; Brachet, Guillaume; Duong, Romain; Sojinrin, Tobiloba; Respaud, Renaud; Aubrey, Nicolas; Baker, Matthew J; Byrne, Hugh J; Chourpa, Igor

2016-10-01

Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. Spectroscopic detection of potential serum biomarkers present at relatively low concentrations can be improved using pre-analytical depletion of the HMWF. In the present study, human serum fractionation by centrifugal filtration was used prior to analysis by Attenuated Total Reflection infrared spectroscopy. Using a model sample based on glycine spiked serum, it is demonstrated that the screening of the LMWF can be applied to quantify blinded concentrations up to 50 times lower. Moreover, the approach is easily transferable to different bodily fluids which would support the development of more efficient and suitable clinical protocols exploring vibrational spectroscopy based ex-vivo diagnostic tools. Revealing serum LMWF for spectral serological diagnostic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal comfort modelling of body temperature and psychological variations of a human exercising in an outdoor environment

NASA Astrophysics Data System (ADS)

Vanos, Jennifer K.; Warland, Jon S.; Gillespie, Terry J.; Kenny, Natasha A.

2012-01-01

Human thermal comfort assessments pertaining to exercise while in outdoor environments can improve urban and recreational planning. The current study applied a simple four-segment skin temperature approach to the COMFA (COMfort FormulA) outdoor energy balance model. Comparative results of measured mean skin temperature ( {{bar{T}}}nolimits_{{Msk}} ) with predicted {{bar{T}}}nolimits_{{sk}} indicate that the model accurately predicted {{bar{T}}}nolimits_{{sk}} , showing significantly strong agreement ( r = 0.859, P < 0.01) during outdoor exercise (cycling and running). The combined 5-min mean variation of the {{bar{T}}}nolimits_{{sk}} RMSE was 1.5°C, with separate cycling and running giving RMSE of 1.4°C and 1.6°C, respectively, and no significant difference in residuals. Subjects' actual thermal sensation (ATS) votes displayed significant strong rank correlation with budget scores calculated using both measured and predicted {{bar{T}}}nolimits_{{sk}} ( r s = 0.507 and 0.517, respectively, P < 0.01). These results show improved predictive strength of ATS of subjects as compared to the original and updated COMFA models. This psychological improvement, plus {{bar{T}}}nolimits_{{sk}} and T c validations, enables better application to a variety of outdoor spaces. This model can be used in future research studying linkages between thermal discomfort, subsequent decreases in physical activity, and negative health trends.

Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon.

PubMed

Akuffo, Afua A; Alontaga, Aileen Y; Metcalf, Rainer; Beatty, Matthew S; Becker, Andreas; McDaniel, Jessica M; Hesterberg, Rebecca S; Goodheart, William E; Gunawan, Steven; Ayaz, Muhammad; Yang, Yan; Karim, Md Rezaul; Orobello, Morgan E; Daniel, Kenyon; Guida, Wayne; Yoder, Jeffrey A; Rajadhyaksha, Anjali M; Schönbrunn, Ernst; Lawrence, Harshani R; Lawrence, Nicholas J; Epling-Burnette, Pearlie K

2018-04-20

Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging the DDB1-CUL4A-Roc1-RBX1 E3 ubiquitin ligase in human cells but not in mouse cells, suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBN's activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBN's nonprimate sequence variations. With a series of recombinant thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants retain their drug-binding properties to both classical immunomodulatory drugs and dBET1, a chemical compound and targeting ligand designed to degrade bromodomain-containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1 stimulates CRBN's E3 ubiquitin-conjugating function and degrades BRD4 in both mouse and human cells. This insight paves the way for studies of CRBN-dependent proteasome-targeting molecules in nonprimate models and provides a new understanding of CRBN's substrate-recruiting function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

A Quantitative Analysis of the Effects of Human Activities and Climate Change on Rainfall-Runoff in Xiaoqing River Basin

NASA Astrophysics Data System (ADS)

Yang, Y.; Cao, S.; Liu, C.; Liu, Y.

2017-12-01

It is a hot topic to study the effects of human activities on the rainfall-runoff relationship and quantitatively analyze the influencing factors. According to the flexibility of Copula function to capture multivariate interdependent structure, the Copula structure between rainfall and runoff was analyzed by using the rainfall-runoff variation test method based on Archimedean Copula function to diagnose the variation of rainfall-runoff relationship. The correlation of rainfall-runoff relationship could be directly analyzed by Copula function, which could intuitively display the change of runoff in the same rainfall before and after the mutation period. The statistical method was used to simulate the underlying surface conditions before the abrupt point, and the effects of climate change and human activities on runoff changes were calculated. It can finally figure out the effects of human activities on the rainfall-runoff relationship. Taking xiaoqing river for example, the results showed that the rainfall-runoff relationship in the Xiaoqing River Basin variated in 1996 mainly due to the continuous increase of water consumption in the watershed and the change of the runoff attenuation caused by the large-scale water conservancy projects. And interannual or annual change of rainfall was not obvious; compared with the year before the variation , the runoff capacity of the basin was weakened under the same rainfall conditions after the variation ; Rainfall and runoff distribution were significantly changed and the same magnitude of rainfall and probability of runoff change were significantly different in different periods; The statistical method was used to simulate the runoff from 1996 to 2016. Compared with that from 1960 to 1995, the result showed that the contribution rate of human activities to runoff reduction was 46.8% and that of climate change was 53.2%. By relevant reference, rainfall-runoff correlation and analysis of human activities, the result was verified to be reasonable. The study can be applied to other watersheds, or used to diagnose the variation of the relationship between meteorological elements and hydrological elements so as to provide scientific basis for rational exploitation and utilization of river water resources, as well as soil and water conservation.

A high-resolution cattle CNV map by population-scale genome sequencing

USDA-ARS?s Scientific Manuscript database

Copy Number Variations (CNVs) are common genomic structural variations that have been linked to human diseases and phenotypic traits. CNVs represent an important type of genetic variation among cattle breeds and even individual animals; however, only low-resolution maps of cattle CNVs currently exis...

The science behind One Health: at the interface of humans, animals, and the environment.

PubMed

Murtaugh, Michael P; Steer, Clifford J; Sreevatsan, Srinand; Patterson, Ned; Kennedy, Shaun; Sriramarao, P

2017-05-01

Humans face a grand quality-of-life challenge as growing demands for resources for an ever-expanding population threaten the existence of wildlife populations, degrade land, and pollute air and water. Public investment and policy decisions that will shape future interactions of humans, animals, and the environment need scientific input to help find common ground for durable and sustainable success. The Second International Conference on One Medicine One Science brought together a broad range of scientists, trainees, regulatory authorities, and health experts from 34 countries to inform and discuss the human impacts of air quality; the complexities of water quality, access, and conflicts; the opportunities and uncertainties in precision medicine; and the role of science communication in health policy formulation. Workshops focused on the roles and development of physician-scientists and multidisciplinary teams in complex problem solving, Big Data tools for analysis and visualization, international policy development processes, and health models that benefit animals and humans. Key realizations were that local and regional health challenges at the interface of humans, animals, and the environment are variations of the same overarching conflicts and that international gatherings provide new opportunities for investigation and policy development that are broadly applicable. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Closed ecological life-support systems and their applications

NASA Astrophysics Data System (ADS)

Gitelson, Josef I.

The advent of man-made closed ecosystems (CES) is a solution of the fundamental problem-egress of humans beyond the Earth's biosphere, providing biological basis for exploitation of Space and celestial bodies. Yet, before proceeding to these ambitious project elements of closed life-support biotechnologies, there can be found diverse applications on Earth in human settlements providing for high quality of life under extreme environment conditions: high latitudes, deserts, mountains and industrially polluted areas. This presentation considers these variations of terrestrial applications of CELSS technologies. The version of CES under development is based on making direct use of the light energy in plant photosynthesis. In this case life support of one man on the Earth orbit requires solar light collected from 5-10m2. Among terrestrial applications of prime importance is the development of an ecohome designed to provide people with a high quality of life in Arctic and Antarctic territories. The developed technology of cascade employment of energy makes possible (expending 10-15 kw of installed power per a house-3-5 member family) to provide for: permanent supply of fresh vitamin-full vegetables, absorption and processing oaf excreta, purification of water and air in the living quarters, habitual colour and light conditions in the premises in winter making up to sensorial deprivation and, finally, psychological comfort of close contact with the plants during the long polar night. Ecohabitat based on the technology described in realistic today and depends only on the energy available and the resolution and readiness (sagacity) of the decision-makers to be committed with ecohome assigning. The ecological and economical significance of construction of ecohabitats for the northern territories of Canada, Alaska and Russia is apparent. This principle can be used (with considerable economy of energy and construction costs) to maintain normal partial pressure of oxygen inside the house for human life in alpine conditions.

Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

PubMed Central

Schwen, Lars Ole; Schenk, Arne; Kreutz, Clemens; Timmer, Jens; Bartolomé Rodríguez, María Matilde; Kuepfer, Lars; Preusser, Tobias

2015-01-01

The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale. PMID:26222615

Nutrigenomics in the modern era.

PubMed

Mathers, John C

2017-08-01

The concept that interactions between nutrition and genetics determine phenotype was established by Garrod at the beginning of the 20th century through his ground-breaking work on inborn errors of metabolism. A century later, the science and technologies involved in sequencing of the human genome stimulated development of the scientific discipline which we now recognise as nutritional genomics (nutrigenomics). Much of the early hype around possible applications of this new science was unhelpful and raised expectations, which have not been realised as quickly as some would have hoped. However, major advances have been made in quantifying the contribution of genetic variation to a wide range of phenotypes and it is now clear that for nutrition-related phenotypes, such as obesity and common complex diseases, the genetic contribution made by SNP alone is often modest. There is much scope for innovative research to understand the roles of less well explored types of genomic structural variation, e.g. copy number variants, and of interactions between genotype and dietary factors, in phenotype determination. New tools and models, including stem cell-based approaches and genome editing, have huge potential to transform mechanistic nutrition research. Finally, the application of nutrigenomics research offers substantial potential to improve public health e.g. through the use of metabolomics approaches to identify novel biomarkers of food intake, which will lead to more objective and robust measures of dietary exposure. In addition, nutrigenomics may have applications in the development of personalised nutrition interventions, which may facilitate larger, more appropriate and sustained changes in eating (and other lifestyle) behaviours and help to reduce health inequalities.

Dilution space ratio of 2H and 18O of doubly labeled water method in humans.

PubMed

Sagayama, Hiroyuki; Yamada, Yosuke; Racine, Natalie M; Shriver, Timothy C; Schoeller, Dale A

2016-06-01

Variation of the dilution space ratio (Nd/No) between deuterium ((2)H) and oxygen-18 ((18)O) impacts the calculation of total energy expenditure (TEE) by doubly labeled water (DLW). Our aim was to examine the physiological and methodological sources of variation of Nd/No in humans. We analyzed data from 2,297 humans (0.25-89 yr old). This included the variables Nd/No, total body water, TEE, body mass index (BMI), and percent body fat (%fat). To differentiate between physiologic and methodologic sources of variation, the urine samples from 54 subjects were divided and blinded and analyzed separately, and repeated DLW dosing was performed in an additional 55 participants after 6 mo. Sex, BMI, and %fat did not significantly affect Nd/No, for which the interindividual SD was 0.017. The measurement error from the duplicate urine sample sets was 0.010, and intraindividual SD of Nd/No in repeats experiments was 0.013. An additional SD of 0.008 was contributed by calibration of the DLW dose water. The variation of measured Nd/No in humans was distributed within a small range and measurement error accounted for 68% of this variation. There was no evidence that Nd/No differed with respect to sex, BMI, and age between 1 and 80 yr, and thus use of a constant value is suggested to minimize the effect of stable isotope analysis error on calculation of TEE in the DLW studies in humans. Based on a review of 103 publications, the average dilution space ratio is 1.036 for individuals between 1 and 80 yr of age. Copyright © 2016 the American Physiological Society.

Lack of Sexual Minorities' Rights as a Barrier to HIV Prevention Among Men Who Have Sex with Men and Transgender Women in Asia: A Systematic Review.

PubMed

Anderson, James E; Kanters, Steve

2015-03-01

This study set out to assess the relationship between variation in human rights for sexual minorities in Asian countries and indicators of HIV prevention among men who have sex with men (MSM) and transgender women. To quantitatively measure the relationship between variation in HIV prevention and variation in human rights for sexual minorities, this study developed the Sexual Orientation and Gender Identity (SOGI) Human Rights Index (an original index with scores ranging from 0.0 to 1.0). Subsequently, this study collected 237 epidemiological and behavioral studies from 22 Asian countries and performed a series of meta-analyses in order to calculate national averages for five indicators of HIV prevention: HIV prevalence, inconsistent condom use, recent HIV testing, adequate HIV knowledge, and exposure to HIV prevention services. A change of human rights for sexual minorities from a score of 0.0 to 1.0 as measured by the SOGI Human Rights Index was correlated with a decrease in unprotected anal intercourse by 25.5% (p=0.075), and increases in recent HIV testing by 42.9% (p=0.011), HIV knowledge by 29.5% (p=0.032), and exposure to HIV prevention services by 37.9% (p=0.119). The relationship between HIV prevalence and variation in human rights for sexual minorities was not statistically significant. Our study found correlations between human rights and indicators of HIV prevention, further supporting the need for increased rights among marginalized populations. The paucity of studies from many Asian countries as well as the disparity in how indicators of HIV prevention are measured reveals a need for increased coverage and standardization of MSM serological and behavioral data in order to better inform evidence-based policymaking.

A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus.

PubMed

Golden, Allison; Stevens, Eric J; Yokobe, Lindsay; Faulx, Dunia; Kalnoky, Michael; Peck, Roger; Valdez, Melissa; Steel, Cathy; Karabou, Potochoziou; Banla, Méba; Soboslay, Peter T; Adade, Kangi; Tekle, Afework H; Cama, Vitaliano A; Fischer, Peter U; Nutman, Thomas B; Unnasch, Thomas R; de los Santos, Tala; Domingo, Gonzalo J

2016-01-01

Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests. A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 2011-2014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions. The recombinant human anti-Ov16 IgG4 antibody-based positive control will benefit inter-laboratory validation of ELISA assays and serve as quality control (QC) reagents for Ov16 RDTs at different points of the supply chain from manufacturer to field use.

SNPnexus: assessing the functional relevance of genetic variation to facilitate the promise of precision medicine.

PubMed

Dayem Ullah, Abu Z; Oscanoa, Jorge; Wang, Jun; Nagano, Ai; Lemoine, Nicholas R; Chelala, Claude

2018-05-11

Broader functional annotation of genetic variation is a valuable means for prioritising phenotypically-important variants in further disease studies and large-scale genotyping projects. We developed SNPnexus to meet this need by assessing the potential significance of known and novel SNPs on the major transcriptome, proteome, regulatory and structural variation models. Since its previous release in 2012, we have made significant improvements to the annotation categories and updated the query and data viewing systems. The most notable changes include broader functional annotation of noncoding variants and expanding annotations to the most recent human genome assembly GRCh38/hg38. SNPnexus has now integrated rich resources from ENCODE and Roadmap Epigenomics Consortium to map and annotate the noncoding variants onto different classes of regulatory regions and noncoding RNAs as well as providing their predicted functional impact from eight popular non-coding variant scoring algorithms and computational methods. A novel functionality offered now is the support for neo-epitope predictions from leading tools to facilitate its use in immunotherapeutic applications. These updates to SNPnexus are in preparation for its future expansion towards a fully comprehensive computational workflow for disease-associated variant prioritization from sequencing data, placing its users at the forefront of translational research. SNPnexus is freely available at http://www.snp-nexus.org.

Implementation of a new fuzzy vector control of induction motor.

PubMed

Rafa, Souad; Larabi, Abdelkader; Barazane, Linda; Manceur, Malik; Essounbouli, Najib; Hamzaoui, Abdelaziz

2014-05-01

The aim of this paper is to present a new approach to control an induction motor using type-1 fuzzy logic. The induction motor has a nonlinear model, uncertain and strongly coupled. The vector control technique, which is based on the inverse model of the induction motors, solves the coupling problem. Unfortunately, in practice this is not checked because of model uncertainties. Indeed, the presence of the uncertainties led us to use human expertise such as the fuzzy logic techniques. In order to maintain the decoupling and to overcome the problem of the sensitivity to the parametric variations, the field-oriented control is replaced by a new block control. The simulation results show that the both control schemes provide in their basic configuration, comparable performances regarding the decoupling. However, the fuzzy vector control provides the insensitivity to the parametric variations compared to the classical one. The fuzzy vector control scheme is successfully implemented in real-time using a digital signal processor board dSPACE 1104. The efficiency of this technique is verified as well as experimentally at different dynamic operating conditions such as sudden loads change, parameter variations, speed changes, etc. The fuzzy vector control is found to be a best control for application in an induction motor. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats

PubMed Central

Armour, John A. L.; Palla, Raquel; Zeeuwen, Patrick L. J. M.; den Heijer, Martin; Schalkwijk, Joost; Hollox, Edward J.

2007-01-01

Recent work has demonstrated an unexpected prevalence of copy number variation in the human genome, and has highlighted the part this variation may play in predisposition to common phenotypes. Some important genes vary in number over a high range (e.g. DEFB4, which commonly varies between two and seven copies), and have posed formidable technical challenges for accurate copy number typing, so that there are no simple, cheap, high-throughput approaches suitable for large-scale screening. We have developed a simple comparative PCR method based on dispersed repeat sequences, using a single pair of precisely designed primers to amplify products simultaneously from both test and reference loci, which are subsequently distinguished and quantified via internal sequence differences. We have validated the method for the measurement of copy number at DEFB4 by comparison of results from >800 DNA samples with copy number measurements by MAPH/REDVR, MLPA and array-CGH. The new Paralogue Ratio Test (PRT) method can require as little as 10 ng genomic DNA, appears to be comparable in accuracy to the other methods, and for the first time provides a rapid, simple and inexpensive method for copy number analysis, suitable for application to typing thousands of samples in large case-control association studies. PMID:17175532

The Human Pelvis: Variation in structure and function during gait

PubMed Central

Lewis, Cara L.; Laudicina, Natalie M.; Khuu, Anne; Loverro, Kari L.

2017-01-01

The shift to habitual bipedalism 4–6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. PMID:28297184

Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.

PubMed

Greenblum, Sharon; Turnbaugh, Peter J; Borenstein, Elhanan

2012-01-10

The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.

Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

PubMed

Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

2012-10-05

Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Dental size variation in the Atapuerca-SH Middle Pleistocene hominids.

PubMed

Bermúdez de Castro, J M; Sarmiento, S; Cunha, E; Rosas, A; Bastir, M

2001-09-01

The Middle Pleistocene Atapuerca-Sima de los Huesos (SH) site in Spain has yielded the largest sample of fossil hominids so far found from a single site and belonging to the same biological population. The SH dental sample includes a total of 452 permanent and deciduous teeth, representing a minimum of 27 individuals. We present a study of the dental size variation in these hominids, based on the analysis of the mandibular permanent dentition: lateral incisors, n=29; canines, n=27; third premolars, n=30; fourth premolars, n=34; first molars, n=38; second molars, n=38. We have obtained the buccolingual diameter and the crown area (measured on occlusal photographs) of these teeth, and used the bootstrap method to assess the amount of variation in the SH sample compared with the variation of a modern human sample from the Museu Antropologico of the Universidade of Coimbra (Portugal). The SH hominids have, in general terms, a dental size variation higher than that of the modern human sample. The analysis is especially conclusive for the canines. Furthermore, we have estimated the degree of sexual dimorphism of the SH sample by obtaining male and female dental subsamples by means of sexing the large sample of SH mandibular specimens. We obtained the index of sexual dimorphism (ISD=male mean/female mean) and the values were compared with those obtained from the sexed modern human sample from Coimbra, and with data found in the literature concerning several recent human populations. In all tooth classes the ISD of the SH hominids was higher than that of modern humans, but the differences were generally modest, except for the canines, thus suggesting that canine size sexual dimorphism in Homo heidelbergensis was probably greater than that of modern humans. Since the approach of sexing fossil specimens has some obvious limitations, these results should be assessed with caution. Additional data from SH and other European Middle Pleistocene sites would be necessary to test this hypothesis. Copyright 2001 Academic Press.

The interaction of neutral evolutionary processes with climatically-driven adaptive changes in the 3D shape of the human os coxae.

PubMed

Betti, Lia; von Cramon-Taubadel, Noreen; Manica, Andrea; Lycett, Stephen J

2014-08-01

Differences in the breadth of the pelvis among modern human populations and among extinct hominin species have often been interpreted in the light of thermoregulatory adaptation, whereby a larger pelvic girdle would help preserve body temperature in cold environments while a narrower pelvis would help dissipate heat in tropical climates. There is, however, a theoretical problem in interpreting a pattern of variation as evidence of selection without first accounting for the effects of neutral evolutionary processes (i.e., mutation, genetic drift and migration). Here, we analyse 3D configurations of 27 landmarks on the os coxae of 1494 modern human individuals representing 30 male and 23 female populations from five continents and a range of climatic conditions. We test for the effects of climate on the size and shape of the pelvic bone, while explicitly accounting for population history (i.e., geographically-mediated gene flow and genetic drift). We find that neutral processes account for a substantial proportion of shape variance in the human os coxae in both sexes. Beyond the neutral pattern due to population history, temperature is a significant predictor of shape and size variation in the os coxae, at least in males. The effect of climate on the shape of the pelvic bone, however, is comparatively limited, explaining only a small percentage of shape variation in males and females. In accordance with previous hypotheses, the size of the os coxae tends to increase with decreasing temperature, although the significance of the association is reduced when population history is taken into account. In conclusion, the shape and size of the human os coxae reflect both neutral evolutionary processes and climatically-driven adaptive changes. Neutral processes have a substantial effect on pelvic variation, suggesting such factors will need to be taken into account in future studies of human and fossil hominin coxal variation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of variational and Galerkin equations to linear and nonlinear finite element analysis

NASA Technical Reports Server (NTRS)

Yu, Y.-Y.

1974-01-01

The paper discusses the application of the variational equation to nonlinear finite element analysis. The problem of beam vibration with large deflection is considered. The variational equation is shown to be flexible in both the solution of a general problem and in the finite element formulation. Difficulties are shown to arise when Galerkin's equations are used in the consideration of the finite element formulation of two-dimensional linear elasticity and of the linear classical beam.

Heterospecific SNP diversity in humans and rhesus macaque (Macaca mulatta)

PubMed Central

Ng, Jillian; Trask, Jessica Satkoski; Smith, David Glenn; Kanthaswamy, Sree

2018-01-01

Background Conservation of single nucleotide polymorphisms (SNPs) between human and other primates (i.e., heterospecific SNPs) in candidate genes can be used to assess the utility of those organisms as models for human biomedical research. Methods 59,691 heterospecific SNPs in 22 rhesus macaques and 20 humans were analyzed for human trait associations and 4,207 heterospecific SNPs biallelic in both taxa were compared for genetic variation. Results Variation comparisons at the 4,207 SNPs showed that humans were more genetically diverse than rhesus macaques with observed and expected heterozygosities of 0.337 and 0.323 versus 0.119 and 0.102, and minor allele frequencies of 0.239 and 0.063, respectively. 431 of the 59,691 heterospecific SNPs are reportedly associated with human-specific traits. Conclusion While comparisons between human and rhesus macaque genomes are plausible, functional studies of heterospecific SNPs are necessary to determine whether rhesus macaque alleles are associated with the same phenotypes as their corresponding human alleles. PMID:25963897

Runoff response to climate change and human activities in a typical karst watershed, SW China.

PubMed

Xu, Yan; Wang, Shijie; Bai, Xiaoyong; Shu, Dongcai; Tian, Yichao

2018-01-01

This study aims to reveal the runoff variation characteristics of long time series in a karst region, analyse comprehensively its different driving factors, and estimate quantitatively the contribution rates of climate change and human activities to net runoff variation. Liudong river basin, a typical karst watershed in southwest China, is the study site. Statistical methods, such as linear fitting, the Morlet wavelet analysis, normalized curve and double mass curve, are applied to analyse the runoff of the watershed. Results show that the runoff in the karst watershed during the research period exhibits a three-stage change and the abrupt change points are the years 1981 and 2007: (1) 1968-1980, the runoff initially exhibited a trend of sustained decreasing and then an abrupt fluctuation. The runoff was obviously destroyed through precipitation-producing processes. Improper land utilisation and serious forest and grass destruction intensified the fluctuation variation amplitude of the runoff. (2) 1981-2006, the changing processes of runoff and precipitation exhibited good synchronism. Precipitation significantly affected runoff variation and human activities had a slight interference degree. (3) 2007-2013, the fluctuation range of runoff was considerably smaller than that of precipitation. The significant growth of forest and grassland areas and the increase in water consumption mitigated runoff fluctuation and greatly diminished runoff variation amplitude. According to calculation, the relative contribution rates of precipitation and human activities to net runoff variation with 1981-2007 as the reference period were -81% and 181% in average, respectively, during 1968-1980, and -117% and 217% in average, respectively, during 2007-2013. In general, the analysis of runoff variation trend and of the contribution rate of its main influencing factors in the typical karst watershed for nearly half a century may be significant to solve the drought problem in the karst region and for the sustainable development of the drainage basin.

Runoff response to climate change and human activities in a typical karst watershed, SW China

PubMed Central

Xu, Yan; Wang, Shijie; Shu, Dongcai; Tian, Yichao

2018-01-01

This study aims to reveal the runoff variation characteristics of long time series in a karst region, analyse comprehensively its different driving factors, and estimate quantitatively the contribution rates of climate change and human activities to net runoff variation. Liudong river basin, a typical karst watershed in southwest China, is the study site. Statistical methods, such as linear fitting, the Morlet wavelet analysis, normalized curve and double mass curve, are applied to analyse the runoff of the watershed. Results show that the runoff in the karst watershed during the research period exhibits a three-stage change and the abrupt change points are the years 1981 and 2007: (1) 1968–1980, the runoff initially exhibited a trend of sustained decreasing and then an abrupt fluctuation. The runoff was obviously destroyed through precipitation-producing processes. Improper land utilisation and serious forest and grass destruction intensified the fluctuation variation amplitude of the runoff. (2) 1981–2006, the changing processes of runoff and precipitation exhibited good synchronism. Precipitation significantly affected runoff variation and human activities had a slight interference degree. (3) 2007–2013, the fluctuation range of runoff was considerably smaller than that of precipitation. The significant growth of forest and grassland areas and the increase in water consumption mitigated runoff fluctuation and greatly diminished runoff variation amplitude. According to calculation, the relative contribution rates of precipitation and human activities to net runoff variation with 1981–2007 as the reference period were −81% and 181% in average, respectively, during 1968–1980, and −117% and 217% in average, respectively, during 2007–2013. In general, the analysis of runoff variation trend and of the contribution rate of its main influencing factors in the typical karst watershed for nearly half a century may be significant to solve the drought problem in the karst region and for the sustainable development of the drainage basin. PMID:29494602

Preliminary study on the time-related changes of the infrared thermal images of the human body

NASA Astrophysics Data System (ADS)

Li, Ziru; Zhang, Xusheng; Lin, Gang; Chen, Zhigang

2009-08-01

It is of great importance to study the manifestations and the influencing factors of the time-related changes of infrared thermal images (ITI) of human body since the variable body surface temperature distribution seriously affected the application of ITI in medicine. In this paper, manifestations of time-related changes of the ITI of human body from three double-blind randomized trials and their correlation with meteorological factors (e.g. temperature, pressure, humidity, cold front passage and tropical cyclone landing) were studied. The trials were placebo or drug controlled studying the influences of Chinese medicine health food (including Shengsheng capsule with immunity adjustment function, Shengan capsule with sleep improvement function and Shengyi capsule with the function of helping to decrease serum lipid) on the ITI of human body. In the first thirty-six days of the trials images were scanned every six days and image data in the seven observation time spots (including the 0, 6, 12, 18, 24, 30, 36 day of the trial) were used for the time-related study. For every subject the scanned time was fixed in the day within two hours. The ITI features which could reflect the functions of the health foods were studied. The indexes of the features were relative magnitude (temperature difference between the viewing area and the reference area). Results showed that the variation tendencies of the trial group and control group were basically the same in placebo controlled trials and some of the long-term effects of Chinese medicine health food could be reflected significantly in certain time spots in the first thirty-six days. Time-related changes of the ITI of human body were closely related with meteorological factors but there were other influencing factors still need to be studied. As the ITI of human body could reflect the influences of Chinese medicine health foods and are closely related with meteorology, there are bright prospects for the application of ITI in health monitor.

Mutation detection using ENDO1: application to disease diagnostics in humans and TILLING and Eco-TILLING in plants.

PubMed

Triques, Karine; Piednoir, Elodie; Dalmais, Marion; Schmidt, Julien; Le Signor, Christine; Sharkey, Mark; Caboche, Michel; Sturbois, Bénédicte; Bendahmane, Abdelhafid

2008-04-23

Most enzymatic mutation detection methods are based on the cleavage of heteroduplex DNA by a mismatch-specific endonuclease at mismatch sites and the analysis of the digestion product on a DNA sequencer. Important limitations of these methods are the availability of a mismatch-specific endonuclease, their sensitivity in detecting one allele in pool of DNA, the cost of the analysis and the ease by which the technique could be implemented in a standard molecular biology laboratory. The co-agroinfiltration of ENDO1 and p19 constructs into N. benthamiana leaves allowed high level of transient expression of a mismatch-specific and sensitive endonuclease, ENDO1 from Arabidopsis thaliana. We demonstrate the broad range of uses of the produced enzyme in detection of mutations. In human, we report the diagnosis of the G1691A mutation in Leiden factor-V gene associated with venous thrombosis and the fingerprinting of HIV-1 quasispecies in patients subjected to antiretroviral treatments. In plants, we report the use of ENDO1 system for detection of mutant alleles of Retinoblastoma-related gene by TILLING in Pisum sativum and discovery of natural sequence variations by Eco-TILLING in Arabidopsis thaliana. We introduce a cost-effective tool based on a simplified purification protocol of a mismatch-specific and sensitive endonuclease, ENDO1. Especially, we report the successful applications of ENDO1 in mutation diagnostics in humans, fingerprinting of complex population of viruses, and in TILLING and Eco-TILLING in plants.

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells.

PubMed

Tsai, Yihuan; Cutts, Josh; Kimura, Azuma; Varun, Divya; Brafman, David A

2015-07-01

Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery. Copyright © 2015. Published by Elsevier B.V.

Heterogeneity of Human Research Ethics Committees and Research Governance Offices across Australia: An observational study.

PubMed

De Smit, Elisabeth; Kearns, Lisa S; Clarke, Linda; Dick, Jonathan; Hill, Catherine L; Hewitt, Alex W

2016-01-01

Conducting ethically grounded research is a fundamental facet of all investigations. Nevertheless, the administrative burdens of current ethics review are substantial, and calls have been made for a reduction in research waste. To describe the heterogeneity in administration and documentation required by Human Research Ethics Committees (HRECs) and Research Governance Offices (RGOs) across Australia. In establishing a nationwide study to investigate the molecular aetiology of Giant Cell Arteritis (GCA), for which archived pathological specimens from around Australia are being recruited, we identified variation across separate HREC and RGO requirements. Submission paperwork and correspondence from each collaborating site and its representative office for research were reviewed. This data was interrogated to evaluate differences in current guidelines. Twenty-five pathology departments across seven Australian States collaborated in this study. All states, except Victoria, employed a single ethics review model. There was discrepancy amongst HRECs as to which application process applied to our study: seven requested completion of a "National Ethics Application Form" and three a "Low Negligible Risk" form. Noticeable differences in guidelines included whether electronic submission was sufficient. There was variability in the total number of documents submitted (range five to 22) and panel review turnaround time (range nine to 136 days). We demonstrate the challenges and illustrate the heavy workload involved in receiving widespread ethics and governance approval across Australia. We highlight the need to simplify, homogenise, and nationalise human ethics for non-clinical trial studies. Reducing unnecessary administration will enable investigators to achieve research aims more efficiently.

Sugar-coated: exopolysaccharide producing lactic acid bacteria for food and human health applications.

PubMed

Ryan, P M; Ross, R P; Fitzgerald, G F; Caplice, N M; Stanton, C

2015-03-01

The human enteric microbiome represents a veritable organ relied upon by the host for a range of metabolic and homeostatic functions. Through the production of metabolites such as short chain fatty acids (SCFA), folate, vitamins B and K, lactic acid, bacteriocins, peroxides and exopolysaccharides, the bacteria of the gut microbiome provide nutritional components for colonocytes, liver and muscle cells, competitively exclude potential pathogenic organisms and modulate the hosts immune system. Due to the extensive variation in structure, size and composition, microbial exopolysaccharides represent a useful set of versatile natural ingredients for the food industrial sector, both in terms of their rheological properties and in many cases, their associated health benefits. The exopolysaccharide-producing bacteria that fall within the 35 Lactobacillus and five Bifidobacterium species which have achieved qualified presumption of safety (QPS) and generally recognised as safe (GRAS) status are of particular interest, as their inclusion in food products can avoid considerable scrutiny. In addition, additives commonly utilised by the food industry are becoming unattractive to the consumer, due to the demand for a more 'natural' and 'clean labelled' diet. In situ production of exopolysaccharides by food-grade cultures in many cases confers similar rheological and sensory properties in fermented dairy products, as traditional additives, such as hydrocolloids, collagen and alginate. This review will focus on microbial synthesis of exopolysaccharides, the human health benefits of dietary exopolysaccharides and the technofunctional applications of exopolysaccharide-synthesising microbes in the food industry.

Development of Osseointegrated Implants for Soldier Amputees Following Orthopaedic Extremity Trauma

DTIC Science & Technology

2007-08-01

bone fracture. The first year of research focused on determining morphometric variations in the internal structure of the human femur as a function...hypotheses the research will determine morphometric variations in the internal structure of the human femur as a function of gender, age, and ethnic...QUARTER 1): To perform the sizing studies for the sheep implants an IACUC exempt morphometric study was conducted using cadaveric sheep

Development of Osseointegrated Implants for Soldier Amputees Following Orthopaedic Extremity Trauma

DTIC Science & Technology

2008-08-01

specimens, histology and mechanical testing of implants. The second focus of Year 2 was human morphometric studies on variations due to ethnicity, gender...custom implants in above-knee patients with amputations would require expensive custom type implants, a morphometric study was conducted on human...male and female cadaveric femurs. Morphometric variations of the periosteal surface of long bones have been identified with changing age, gender and

Understanding variation in human fertility: what can we learn from evolutionary demography?

PubMed

Sear, Rebecca; Lawson, David W; Kaplan, Hillard; Shenk, Mary K

2016-04-19

Decades of research on human fertility has presented a clear picture of how fertility varies, including its dramatic decline over the last two centuries in most parts of the world. Why fertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions. © 2016 The Author(s).

Understanding variation in human fertility: what can we learn from evolutionary demography?

PubMed Central

Sear, Rebecca; Lawson, David W.; Kaplan, Hillard

2016-01-01

Decades of research on human fertility has presented a clear picture of how fertility varies, including its dramatic decline over the last two centuries in most parts of the world. Why fertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions. PMID:27022071

Tree community variation in a tropical continental island according to slope aspect and human interference.

PubMed

Gonçalves, Nathan B; Nettesheim, Felipe C; Conde, Marilena M S

2018-01-01

Associating description of unrecorded tropical tree community structure to sampling approaches that can help determine mechanisms behind floristic variation is important to further the comprehension of how plant species coexist at tropical forests. Thus, this study had the goals of (i) evaluating tree community structure on the continental island of Marambaia (23°4'37.09"S; 43°59'2.15"W) and (ii) testing the prediction that there are local scale changes in a tropical tree community structure between slopes facing different geographic orientation and with distinct human interference history. We established 60 (0.6 ha) sampling units in three different slope sites with distinct predominant geographic orientation and human interference. We sampled all woody trees with diameter at breast height (dbh) ≥ 5 cm. We found a total of 1.170 individuals representing 220 species, 120 genera and 50 families. The overall tree community structure and structural descriptors (abundance of individuals, basal area, species richness and diversity) varied extensively between the sites. The evidence presented here supports that local scale topography variations and human interference history can be important factors contributing to the known floristic heterogeneity of the Atlantic Rainforest. Future work on the study area should focus on disentangling effects from distinct causal factors over tree community variation and species occurrence.

The Convergent Evolution of Blue Iris Pigmentation in Primates Took Distinct Molecular Paths

PubMed Central

Meyer, Wynn K; Zhang, Sidi; Hayakawa, Sachiko; Imai, Hiroo; Przeworski, Molly

2013-01-01

How many distinct molecular paths lead to the same phenotype? One approach to this question has been to examine the genetic basis of convergent traits, which likely evolved repeatedly under a shared selective pressure. We investigated the convergent phenotype of blue iris pigmentation, which has arisen independently in four primate lineages: humans, blue-eyed black lemurs, Japanese macaques, and spider monkeys. Characterizing the phenotype across these species, we found that the variation within the blue-eyed subsets of each species occupies strongly overlapping regions of CIE L*a*b* color space. Yet whereas Japanese macaques and humans display continuous variation, the phenotypes of blue-eyed black lemurs and their sister species (whose irises are brown) occupy more clustered subspaces. Variation in an enhancer of OCA2 is primarily responsible for the phenotypic difference between humans with blue and brown irises. In the orthologous region, we found no variant that distinguishes the two lemur species or associates with quantitative phenotypic variation in Japanese macaques. Given the high similarity between the blue iris phenotypes in these species and that in humans, this finding implies that evolution has used different molecular paths to reach the same end. Am J Phys Anthropol 151:398–407, 2013.© 2013 Wiley Periodicals, Inc. PMID:23640739

An experimental loop design for the detection of constitutional chromosomal aberrations by array CGH

PubMed Central

2009-01-01

Background Comparative genomic hybridization microarrays for the detection of constitutional chromosomal aberrations is the application of microarray technology coming fastest into routine clinical application. Through genotype-phenotype association, it is also an important technique towards the discovery of disease causing genes and genomewide functional annotation in human. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient against a normal reference sample. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the "normal" reference instead of a patient aberration. Instead, we apply an experimental loop design that compares three patients in three hybridizations. Results We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of 27 patients seen at our genetics center, we observed that the linear models of the log ratios are advantageous over the mixed models of the absolute intensities. Conclusion The loop design and the performance of the statistical analysis contribute to the quick adoption of array CGH as a routine diagnostic tool. They lower the detection limit of mosaicisms and improve the assignment of copy number variation for genetic association studies. PMID:19925645

An experimental loop design for the detection of constitutional chromosomal aberrations by array CGH.

PubMed

Allemeersch, Joke; Van Vooren, Steven; Hannes, Femke; De Moor, Bart; Vermeesch, Joris Robert; Moreau, Yves

2009-11-19

Comparative genomic hybridization microarrays for the detection of constitutional chromosomal aberrations is the application of microarray technology coming fastest into routine clinical application. Through genotype-phenotype association, it is also an important technique towards the discovery of disease causing genes and genomewide functional annotation in human. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient against a normal reference sample. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the "normal" reference instead of a patient aberration. Instead, we apply an experimental loop design that compares three patients in three hybridizations. We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of 27 patients seen at our genetics center, we observed that the linear models of the log ratios are advantageous over the mixed models of the absolute intensities. The loop design and the performance of the statistical analysis contribute to the quick adoption of array CGH as a routine diagnostic tool. They lower the detection limit of mosaicisms and improve the assignment of copy number variation for genetic association studies.

Catheter Insertion Reference Trajectory Construction Method Using Photoelastic Stress Analysis for Quantification of Respect for Tissue During Endovascular Surgery Simulation

NASA Astrophysics Data System (ADS)

Tercero, Carlos; Ikeda, Seiichi; Fukuda, Toshio; Arai, Fumihito; Negoro, Makoto; Takahashi, Ikuo

2011-10-01

There is a need to develop quantitative evaluation for simulator based training in medicine. Photoelastic stress analysis can be used in human tissue modeling materials; this enables the development of simulators that measure respect for tissue. For applying this to endovascular surgery, first we present a model of saccular aneurism where stress variation during micro-coils deployment is measured, and then relying on a bi-planar vision system we measure a catheter trajectory and compare it to a reference trajectory considering respect for tissue. New photoelastic tissue modeling materials will expand the applications of this technology to other medical training domains.

The Effective Mutation Rate at Y Chromosome Short Tandem Repeats, with Application to Human Population-Divergence Time

PubMed Central

Zhivotovsky, Lev A.; Underhill, Peter A.; Cinnioğlu, Cengiz; Kayser, Manfred; Morar, Bharti; Kivisild, Toomas; Scozzari, Rosaria; Cruciani, Fulvio; Destro-Bisol, Giovanni; Spedini, Gabriella; Chambers, Geoffrey K.; Herrera, Rene J.; Yong, Kiau Kiun; Gresham, David; Tournev, Ivailo; Feldman, Marcus W.; Kalaydjieva, Luba

2004-01-01

We estimate an effective mutation rate at an average Y chromosome short-tandem repeat locus as 6.9×10-4 per 25 years, with a standard deviation across loci of 5.7×10-4, using data on microsatellite variation within Y chromosome haplogroups defined by unique-event polymorphisms in populations with documented short-term histories, as well as comparative data on worldwide populations at both the Y chromosome and various autosomal loci. This value is used to estimate the times of the African Bantu expansion, the divergence of Polynesian populations (the Maoris, Cook Islanders, and Samoans), and the origin of Gypsy populations from Bulgaria. PMID:14691732

Insights into esophagus tissue architecture using two-photon confocal microscopy

NASA Astrophysics Data System (ADS)

Liu, Nenrong; Wang, Yue; Feng, Shangyuan; Chen, Rong

2013-08-01

In this paper, microstructures of human esophageal mucosa were evaluated using the two-photon laser scanning confocal microscopy (TPLSCM), based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). The distribution of epithelial cells, muscle fibers of muscularis mucosae has been distinctly obtained. Furthermore, esophageal submucosa characteristics with cancer cells invading into were detected. The variation of collagen, elastin and cancer cells is very relevant to the pathology in esophagus, especially early esophageal cancer. Our experimental results indicate that the MPM technique has the much more advantages for label-free imaging, and has the potential application in vivo in the clinical diagnosis and monitoring of early esophageal cancer.

Face recognition based on matching of local features on 3D dynamic range sequences

NASA Astrophysics Data System (ADS)

Echeagaray-Patrón, B. A.; Kober, Vitaly

2016-09-01

3D face recognition has attracted attention in the last decade due to improvement of technology of 3D image acquisition and its wide range of applications such as access control, surveillance, human-computer interaction and biometric identification systems. Most research on 3D face recognition has focused on analysis of 3D still data. In this work, a new method for face recognition using dynamic 3D range sequences is proposed. Experimental results are presented and discussed using 3D sequences in the presence of pose variation. The performance of the proposed method is compared with that of conventional face recognition algorithms based on descriptors.

A survey of parametrized variational principles and applications to computational mechanics

NASA Technical Reports Server (NTRS)

Felippa, Carlos A.

1993-01-01

This survey paper describes recent developments in the area of parametrized variational principles (PVP's) and selected applications to finite-element computational mechanics. A PVP is a variational principle containing free parameters that have no effect on the Euler-Lagrange equations. The theory of single-field PVP's based on gauge functions (also known as null Lagrangians) is a subset of the inverse problem of variational calculus that has limited value. On the other hand, multifield PVP's are more interesting from theoretical and practical standpoints. Following a tutorial introduction, the paper describes the recent construction of multifield PVP's in several areas of elasticity and electromagnetics. It then discusses three applications to finite-element computational mechanics: the derivation of high-performance finite elements, the development of element-level error indicators, and the constructions of finite element templates. The paper concludes with an overview of open research areas.

Plant extracts as potential mosquito larvicides

PubMed Central

Ghosh, Anupam; Chowdhury, Nandita; Chandra, Goutam

2012-01-01

Mosquitoes act as a vector for most of the life threatening diseases like malaria, yellow fever, dengue fever, chikungunya ferver, filariasis, encephalitis, West Nile Virus infection, etc. Under the Integrated Mosquito Management (IMM), emphasis was given on the application of alternative strategies in mosquito control. The continuous application of synthetic insecticides causes development of resistance in vector species, biological magnification of toxic substances through the food chain and adverse effects on environmental quality and non target organisms including human health. Application of active toxic agents from plant extracts as an alternative mosquito control strategy was available from ancient times. These are non-toxic, easily available at affordable prices, biodegradable and show broad-spectrum target-specific activities against different species of vector mosquitoes. In this article, the current state of knowledge on phytochemical sources and mosquitocidal activity, their mechanism of action on target population, variation of their larvicidal activity according to mosquito species, instar specificity, polarity of solvents used during extraction, nature of active ingredient and promising advances made in biological control of mosquitoes by plant derived secondary metabolites have been reviewed. PMID:22771587

Plant extracts as potential mosquito larvicides.

PubMed

Ghosh, Anupam; Chowdhury, Nandita; Chandra, Goutam

2012-05-01

Mosquitoes act as a vector for most of the life threatening diseases like malaria, yellow fever, dengue fever, chikungunya ferver, filariasis, encephalitis, West Nile Virus infection, etc. Under the Integrated Mosquito Management (IMM), emphasis was given on the application of alternative strategies in mosquito control. The continuous application of synthetic insecticides causes development of resistance in vector species, biological magnification of toxic substances through the food chain and adverse effects on environmental quality and non target organisms including human health. Application of active toxic agents from plant extracts as an alternative mosquito control strategy was available from ancient times. These are non-toxic, easily available at affordable prices, biodegradable and show broad-spectrum target-specific activities against different species of vector mosquitoes. In this article, the current state of knowledge on phytochemical sources and mosquitocidal activity, their mechanism of action on target population, variation of their larvicidal activity according to mosquito species, instar specificity, polarity of solvents used during extraction, nature of active ingredient and promising advances made in biological control of mosquitoes by plant derived secondary metabolites have been reviewed.

An Application of System Dynamics Analysis to Ecosystem Management at the Poinsett Weapons Range, Shaw AFB SC

DTIC Science & Technology

1997-12-01

younger trees with thinner sapwood and greater heartwood diameter than other trees in the area . The RCW requires approximately 6 inches in diameter...and management areas and have explored applications of system dynamics modeling at the graduate level. The attached application addresses specific...Population Sensitivity to Birth Rate 62 10. RCW Population with Variation of Relatedness Entity 64 11. RCW Population with Variation of Foraging Area

Oxytocin, vasopressin, and the neurogenetics of sociality.

PubMed

Donaldson, Zoe R; Young, Larry J

2008-11-07

There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.

Environmental and spatial drivers of taxonomic, functional, and phylogenetic characteristics of bat communities in human-modified landscapes.

PubMed

Cisneros, Laura M; Fagan, Matthew E; Willig, Michael R

2016-01-01

Assembly of species into communities following human disturbance (e.g., deforestation, fragmentation) may be governed by spatial (e.g., dispersal) or environmental (e.g., niche partitioning) mechanisms. Variation partitioning has been used to broadly disentangle spatial and environmental mechanisms, and approaches utilizing functional and phylogenetic characteristics of communities have been implemented to determine the relative importance of particular environmental (or niche-based) mechanisms. Nonetheless, few studies have integrated these quantitative approaches to comprehensively assess the relative importance of particular structuring processes. We employed a novel variation partitioning approach to evaluate the relative importance of particular spatial and environmental drivers of taxonomic, functional, and phylogenetic aspects of bat communities in a human-modified landscape in Costa Rica. Specifically, we estimated the amount of variation in species composition (taxonomic structure) and in two aspects of functional and phylogenetic structure (i.e., composition and dispersion) along a forest loss and fragmentation gradient that are uniquely explained by landscape characteristics (i.e., environment) or space to assess the importance of competing mechanisms. The unique effects of space on taxonomic, functional and phylogenetic structure were consistently small. In contrast, landscape characteristics (i.e., environment) played an appreciable role in structuring bat communities. Spatially-structured landscape characteristics explained 84% of the variation in functional or phylogenetic dispersion, and the unique effects of landscape characteristics significantly explained 14% of the variation in species composition. Furthermore, variation in bat community structure was primarily due to differences in dispersion of species within functional or phylogenetic space along the gradient, rather than due to differences in functional or phylogenetic composition. Variation among bat communities was related to environmental mechanisms, especially niche-based (i.e., environmental) processes, rather than spatial mechanisms. High variation in functional or phylogenetic dispersion, as opposed to functional or phylogenetic composition, suggests that loss or gain of niche space is driving the progressive loss or gain of species with particular traits from communities along the human-modified gradient. Thus, environmental characteristics associated with landscape structure influence functional or phylogenetic aspects of bat communities by effectively altering the ways in which species partition niche space.

Environmental and spatial drivers of taxonomic, functional, and phylogenetic characteristics of bat communities in human-modified landscapes

PubMed Central

Fagan, Matthew E.; Willig, Michael R.

2016-01-01

Background Assembly of species into communities following human disturbance (e.g., deforestation, fragmentation) may be governed by spatial (e.g., dispersal) or environmental (e.g., niche partitioning) mechanisms. Variation partitioning has been used to broadly disentangle spatial and environmental mechanisms, and approaches utilizing functional and phylogenetic characteristics of communities have been implemented to determine the relative importance of particular environmental (or niche-based) mechanisms. Nonetheless, few studies have integrated these quantitative approaches to comprehensively assess the relative importance of particular structuring processes. Methods We employed a novel variation partitioning approach to evaluate the relative importance of particular spatial and environmental drivers of taxonomic, functional, and phylogenetic aspects of bat communities in a human-modified landscape in Costa Rica. Specifically, we estimated the amount of variation in species composition (taxonomic structure) and in two aspects of functional and phylogenetic structure (i.e., composition and dispersion) along a forest loss and fragmentation gradient that are uniquely explained by landscape characteristics (i.e., environment) or space to assess the importance of competing mechanisms. Results The unique effects of space on taxonomic, functional and phylogenetic structure were consistently small. In contrast, landscape characteristics (i.e., environment) played an appreciable role in structuring bat communities. Spatially-structured landscape characteristics explained 84% of the variation in functional or phylogenetic dispersion, and the unique effects of landscape characteristics significantly explained 14% of the variation in species composition. Furthermore, variation in bat community structure was primarily due to differences in dispersion of species within functional or phylogenetic space along the gradient, rather than due to differences in functional or phylogenetic composition. Discussion Variation among bat communities was related to environmental mechanisms, especially niche-based (i.e., environmental) processes, rather than spatial mechanisms. High variation in functional or phylogenetic dispersion, as opposed to functional or phylogenetic composition, suggests that loss or gain of niche space is driving the progressive loss or gain of species with particular traits from communities along the human-modified gradient. Thus, environmental characteristics associated with landscape structure influence functional or phylogenetic aspects of bat communities by effectively altering the ways in which species partition niche space. PMID:27761338

Variational principles for dissipative (sub)systems, with applications to the theory of linear dispersion and geometrical optics

DOE PAGES

Dodin, I. Y.; Zhmoginov, A. I.; Ruiz, D. E.

2017-02-24

Applications of variational methods are typically restricted to conservative systems. Some extensions to dissipative systems have been reported too but require ad hoc techniques such as the artificial doubling of the dynamical variables. We propose a different approach. Here, we show that for a broad class of dissipative systems of practical interest, variational principles can be formulated using constant Lagrange multipliers and Lagrangians nonlocal in time, which allow treating reversible and irreversible dynamics on the same footing. A general variational theory of linear dispersion is formulated as an example. Particularly, we present a variational formulation for linear geometrical optics inmore » a general dissipative medium, which is allowed to be nonstationary, inhomogeneous, anisotropic, and exhibit both temporal and spatial dispersion simultaneously.« less

The Prediction of Length-of-day Variations Based on Gaussian Processes

NASA Astrophysics Data System (ADS)

Lei, Y.; Zhao, D. N.; Gao, Y. P.; Cai, H. B.

2015-01-01

Due to the complicated time-varying characteristics of the length-of-day (LOD) variations, the accuracies of traditional strategies for the prediction of the LOD variations such as the least squares extrapolation model, the time-series analysis model, and so on, have not met the requirements for real-time and high-precision applications. In this paper, a new machine learning algorithm --- the Gaussian process (GP) model is employed to forecast the LOD variations. Its prediction precisions are analyzed and compared with those of the back propagation neural networks (BPNN), general regression neural networks (GRNN) models, and the Earth Orientation Parameters Prediction Comparison Campaign (EOP PCC). The results demonstrate that the application of the GP model to the prediction of the LOD variations is efficient and feasible.

Applicability of drinking water treatment residue for lake restoration in relation to metal/metalloid risk assessment

PubMed Central

Yuan, Nannan; Wang, Changhui; Pei, Yuansheng; Jiang, Helong

2016-01-01

Drinking water treatment residue (DWTR), a byproduct generated during potable water production, exhibits a high potential for recycling to control eutrophication. However, this beneficial recycling is hampered by unclear metal/metalloid pollution risks related to DWTR. In this study, the pollution risks of Al, As, Ba, Be, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, and Zn due to DWTR application were first evaluated for lake water based on human health risk assessment models and comparison of regulatory standards. The risks of DWTR were also evaluated for sediments on the basis of toxicity characteristics leaching procedure and fractionation in relation to risk assessment code. Variations in the biological behaviors of metal/metalloid in sediments caused by DWTR were assessed using Chironomus plumosus larvae and Hydrilla verticillata. Kinetic luminescent bacteria test (using Aliivibrio fischeri) was conducted to analyze the possibility of acute and chronic detrimental effects of sediment with DWTR application. According to the obtained results, we identify a potential undesirable effect of DWTR related to Fe and Mn (typically under anaerobic conditions); roughly present a dosage threshold calculation model; and recommend a procedure for DWTR prescreening to ensure safe application. Overall, managed DWTR application is necessary for successful eutrophication control. PMID:27929083

Applicability of drinking water treatment residue for lake restoration in relation to metal/metalloid risk assessment

NASA Astrophysics Data System (ADS)

Yuan, Nannan; Wang, Changhui; Pei, Yuansheng; Jiang, Helong

2016-12-01

Drinking water treatment residue (DWTR), a byproduct generated during potable water production, exhibits a high potential for recycling to control eutrophication. However, this beneficial recycling is hampered by unclear metal/metalloid pollution risks related to DWTR. In this study, the pollution risks of Al, As, Ba, Be, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, and Zn due to DWTR application were first evaluated for lake water based on human health risk assessment models and comparison of regulatory standards. The risks of DWTR were also evaluated for sediments on the basis of toxicity characteristics leaching procedure and fractionation in relation to risk assessment code. Variations in the biological behaviors of metal/metalloid in sediments caused by DWTR were assessed using Chironomus plumosus larvae and Hydrilla verticillata. Kinetic luminescent bacteria test (using Aliivibrio fischeri) was conducted to analyze the possibility of acute and chronic detrimental effects of sediment with DWTR application. According to the obtained results, we identify a potential undesirable effect of DWTR related to Fe and Mn (typically under anaerobic conditions); roughly present a dosage threshold calculation model; and recommend a procedure for DWTR prescreening to ensure safe application. Overall, managed DWTR application is necessary for successful eutrophication control.

Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes

PubMed Central

Gibbons, John G.; Branco, Alan T.; Godinho, Susana A.; Yu, Shoukai; Lemos, Bernardo

2015-01-01

Tandemly repeated ribosomal DNA (rDNA) arrays are among the most evolutionary dynamic loci of eukaryotic genomes. The loci code for essential cellular components, yet exhibit extensive copy number (CN) variation within and between species. CN might be partly determined by the requirement of dosage balance between the 5S and 45S rDNA arrays. The arrays are nonhomologous, physically unlinked in mammals, and encode functionally interdependent RNA components of the ribosome. Here we show that the 5S and 45S rDNA arrays exhibit concerted CN variation (cCNV). Despite 5S and 45S rDNA elements residing on different chromosomes and lacking sequence similarity, cCNV between these loci is strong, evolutionarily conserved in humans and mice, and manifested across individual genotypes in natural populations and pedigrees. Finally, we observe that bisphenol A induces rapid and parallel modulation of 5S and 45S rDNA CN. Our observations reveal a novel mode of genome variation, indicate that natural selection contributed to the evolution and conservation of cCNV, and support the hypothesis that 5S CN is partly determined by the requirement of dosage balance with the 45S rDNA array. We suggest that human disease variation might be traced to disrupted rDNA dosage balance in the genome. PMID:25583482

Read clouds uncover variation in complex regions of the human genome.

PubMed

Bishara, Alex; Liu, Yuling; Weng, Ziming; Kashef-Haghighi, Dorna; Newburger, Daniel E; West, Robert; Sidow, Arend; Batzoglou, Serafim

2015-10-01

Although an increasing amount of human genetic variation is being identified and recorded, determining variants within repeated sequences of the human genome remains a challenge. Most population and genome-wide association studies have therefore been unable to consider variation in these regions. Core to the problem is the lack of a sequencing technology that produces reads with sufficient length and accuracy to enable unique mapping. Here, we present a novel methodology of using read clouds, obtained by accurate short-read sequencing of DNA derived from long fragment libraries, to confidently align short reads within repeat regions and enable accurate variant discovery. Our novel algorithm, Random Field Aligner (RFA), captures the relationships among the short reads governed by the long read process via a Markov Random Field. We utilized a modified version of the Illumina TruSeq synthetic long-read protocol, which yielded shallow-sequenced read clouds. We test RFA through extensive simulations and apply it to discover variants on the NA12878 human sample, for which shallow TruSeq read cloud sequencing data are available, and on an invasive breast carcinoma genome that we sequenced using the same method. We demonstrate that RFA facilitates accurate recovery of variation in 155 Mb of the human genome, including 94% of 67 Mb of segmental duplication sequence and 96% of 11 Mb of transcribed sequence, that are currently hidden from short-read technologies. © 2015 Bishara et al.; Published by Cold Spring Harbor Laboratory Press.

Disrupting evolutionary processes: the effect of habitat fragmentation on collared lizards in the Missouri Ozarks.

PubMed

Templeton, A R; Robertson, R J; Brisson, J; Strasburg, J

2001-05-08

Humans affect biodiversity at the genetic, species, community, and ecosystem levels. This impact on genetic diversity is critical, because genetic diversity is the raw material of evolutionary change, including adaptation and speciation. Two forces affecting genetic variation are genetic drift (which decreases genetic variation within but increases genetic differentiation among local populations) and gene flow (which increases variation within but decreases differentiation among local populations). Humans activities often augment drift and diminish gene flow for many species, which reduces genetic variation in local populations and prevents the spread of adaptive complexes outside their population of origin, thereby disrupting adaptive processes both locally and globally within a species. These impacts are illustrated with collared lizards (Crotaphytus collaris) in the Missouri Ozarks. Forest fire suppression has reduced habitat and disrupted gene flow in this lizard, thereby altering the balance toward drift and away from gene flow. This balance can be restored by managed landscape burns. Some have argued that, although human-induced fragmentation disrupts adaptation, it will also ultimately produce new species through founder effects. However, population genetic theory and experiments predict that most fragmentation events caused by human activities will facilitate not speciation, but local extinction. Founder events have played an important role in the macroevolution of certain groups, but only when ecological opportunities are expanding rather than contracting. The general impact of human activities on genetic diversity disrupts or diminishes the capacity for adaptation, speciation, and macroevolutionary change. This impact will ultimately diminish biodiversity at all levels.

DNA capture and next-generation sequencing can recover whole mitochondrial genomes from highly degraded samples for human identification

PubMed Central

2013-01-01

Background Mitochondrial DNA (mtDNA) typing can be a useful aid for identifying people from compromised samples when nuclear DNA is too damaged, degraded or below detection thresholds for routine short tandem repeat (STR)-based analysis. Standard mtDNA typing, focused on PCR amplicon sequencing of the control region (HVS I and HVS II), is limited by the resolving power of this short sequence, which misses up to 70% of the variation present in the mtDNA genome. Methods We used in-solution hybridisation-based DNA capture (using DNA capture probes prepared from modern human mtDNA) to recover mtDNA from post-mortem human remains in which the majority of DNA is both highly fragmented (<100 base pairs in length) and chemically damaged. The method ‘immortalises’ the finite quantities of DNA in valuable extracts as DNA libraries, which is followed by the targeted enrichment of endogenous mtDNA sequences and characterisation by next-generation sequencing (NGS). Results We sequenced whole mitochondrial genomes for human identification from samples where standard nuclear STR typing produced only partial profiles or demonstrably failed and/or where standard mtDNA hypervariable region sequences lacked resolving power. Multiple rounds of enrichment can substantially improve coverage and sequencing depth of mtDNA genomes from highly degraded samples. The application of this method has led to the reliable mitochondrial sequencing of human skeletal remains from unidentified World War Two (WWII) casualties approximately 70 years old and from archaeological remains (up to 2,500 years old). Conclusions This approach has potential applications in forensic science, historical human identification cases, archived medical samples, kinship analysis and population studies. In particular the methodology can be applied to any case, involving human or non-human species, where whole mitochondrial genome sequences are required to provide the highest level of maternal lineage discrimination. Multiple rounds of in-solution hybridisation-based DNA capture can retrieve whole mitochondrial genome sequences from even the most challenging samples. PMID:24289217

A review of the established and suspected causes of variations in human sex ratio at birth.

PubMed

James, William H; Grech, Victor

2017-06-01

The human sex ratio (proportion male) at birth (SRB) varies with many variables. Some of this variation has an established proximate cause. For instance, low SRB (more females) at birth are associated with various forms of stressful events or circumstances during or prior to pregnancy. These low SRB are almost certainly mainly caused by maternal-stress-induced male foetal loss. Other types of SRB variation are thought to be caused by hormonal variation in either or both parents around the time of conception. One or other of these two types of proximate cause seems to be responsible for most of the established variation of SRB. This will be illustrated here in respect of some selected forms of SRB variation. It seems likely that a clarification of the hormonal causes of SRB variation will also help explain the striking (apparent) inconsistencies in the results of reported tests of the influential Trivers-Willard hypothesis. It is further proposed that an appreciation of the evidence that parental hormones influence SRB may enhance understanding of several important pathologies (hepatitis B, toxoplasmosis, testicular cancer, prostate cancer and autism). Copyright © 2017 Elsevier B.V. All rights reserved.

Extrahepatic arteries of the human liver - anatomical variants and surgical relevancies.

PubMed

Németh, Károly; Deshpande, Rahul; Máthé, Zoltán; Szuák, András; Kiss, Mátyás; Korom, Csaba; Nemeskéri, Ágnes; Kóbori, László

2015-10-01

The purpose of our study was to investigate the anatomical variations of the extrahepatic arterial structures of the liver with particular attention to rare variations and their potential impact on liver surgery. A total of 50 human abdominal organ complexes were used to prepare corrosion casts. A multicomponent resin mixture was injected into the abdominal aorta. The portal vein was injected with a different colored resin in 16 cases. Digestion of soft tissues was achieved using cc. KOH solution at 60-65 °C. Extrahepatic arterial variations were classified according to Michels. All specimens underwent 3D volumetric CT reconstruction. Normal anatomy was seen in 42% of cases, and variants were seen in the other 58%. No Michels type VI or X variations were present; however, in 18% of cases the extrahepatic arterial anatomy did not fit into Michels' classification. We report four new extrahepatic arterial variations. In contrast to the available data, normal anatomy was found much less frequently, whereas the prevalence of unclassified arterial variations was higher. We detected four previously unknown variations. Our data may contribute to the reduction of complications during surgical and radiological interventions in the upper abdomen. © 2015 Steunstichting ESOT.

LOVD: easy creation of a locus-specific sequence variation database using an "LSDB-in-a-box" approach.

PubMed

Fokkema, Ivo F A C; den Dunnen, Johan T; Taschner, Peter E M

2005-08-01

The completion of the human genome project has initiated, as well as provided the basis for, the collection and study of all sequence variation between individuals. Direct access to up-to-date information on sequence variation is currently provided most efficiently through web-based, gene-centered, locus-specific databases (LSDBs). We have developed the Leiden Open (source) Variation Database (LOVD) software approaching the "LSDB-in-a-Box" idea for the easy creation and maintenance of a fully web-based gene sequence variation database. LOVD is platform-independent and uses PHP and MySQL open source software only. The basic gene-centered and modular design of the database follows the recommendations of the Human Genome Variation Society (HGVS) and focuses on the collection and display of DNA sequence variations. With minimal effort, the LOVD platform is extendable with clinical data. The open set-up should both facilitate and promote functional extension with scripts written by the community. The LOVD software is freely available from the Leiden Muscular Dystrophy pages (www.DMD.nl/LOVD/). To promote the use of LOVD, we currently offer curators the possibility to set up an LSDB on our Leiden server. (c) 2005 Wiley-Liss, Inc.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis

PubMed Central

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L.; Chen, Lin S.

2017-01-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes (cis-eQTLs). More research is needed to identify effects of genetic variation on distant genes (trans-eQTLs) and understand their biological mechanisms. One common trans-eQTLs mechanism is “mediation” by a local (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are “cis-mediators” of trans-eQTLs, including those “cis-hubs” involved in regulation of many trans-genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans-eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis-mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis-hubs and trans-eQTL regulation across tissue types. PMID:29021290

Monitoring the wild black bear's reaction to human and environmental stressors

PubMed Central

2011-01-01

Background Bears are among the most physiologically remarkable mammals. They spend half their life in an active state and the other half in a state of dormancy without food or water, and without urinating, defecating, or physical activity, yet can rouse and defend themselves when disturbed. Although important data have been obtained in both captive and wild bears, long-term physiological monitoring of bears has not been possible until the recent advancement of implantable devices. Results Insertable cardiac monitors that were developed for use in human heart patients (Reveal® XT, Medtronic, Inc) were implanted in 15 hibernating bears. Data were recovered from 8, including 2 that were legally shot by hunters. Devices recorded low heart rates (pauses of over 14 seconds) and low respiration rates (1.5 breaths/min) during hibernation, dramatic respiratory sinus arrhythmias in the fall and winter months, and elevated heart rates in summer (up to 214 beats/min (bpm)) and during interactions with hunters (exceeding 250 bpm). The devices documented the first and last day of denning, a period of quiescence in two parturient females after birthing, and extraordinary variation in the amount of activity/day, ranging from 0 (winter) to 1084 minutes (summer). Data showed a transition toward greater nocturnal activity in the fall, preceding hibernation. The data-loggers also provided evidence of the physiological and behavioral responses of bears to our den visits to retrieve the data. Conclusions Annual variations in heart rate and activity have been documented for the first time in wild black bears. This technique has broad applications to wildlife management and physiological research, enabling the impact of environmental stressors from humans, changing seasons, climate change, social interactions and predation to be directly monitored over multiple years. PMID:21849079

Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

PubMed

Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert

2011-12-10

Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

PubMed

Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

High-Throughput Analysis of Global DNA Methylation Using Methyl-Sensitive Digestion.

PubMed

Shiratori, Hiromi; Feinweber, Carmen; Knothe, Claudia; Lötsch, Jörn; Thomas, Dominique; Geisslinger, Gerd; Parnham, Michael J; Resch, Eduard

2016-01-01

DNA methylation is a major regulatory process of gene transcription, and aberrant DNA methylation is associated with various diseases including cancer. Many compounds have been reported to modify DNA methylation states. Despite increasing interest in the clinical application of drugs with epigenetic effects, and the use of diagnostic markers for genome-wide hypomethylation in cancer, large-scale screening systems to measure the effects of drugs on DNA methylation are limited. In this study, we improved the previously established fluorescence polarization-based global DNA methylation assay so that it is more suitable for application to human genomic DNA. Our methyl-sensitive fluorescence polarization (MSFP) assay was highly repeatable (inter-assay coefficient of variation = 1.5%) and accurate (r2 = 0.99). According to signal linearity, only 50-80 ng human genomic DNA per reaction was necessary for the 384-well format. MSFP is a simple, rapid approach as all biochemical reactions and final detection can be performed in one well in a 384-well plate without purification steps in less than 3.5 hours. Furthermore, we demonstrated a significant correlation between MSFP and the LINE-1 pyrosequencing assay, a widely used global DNA methylation assay. MSFP can be applied for the pre-screening of compounds that influence global DNA methylation states and also for the diagnosis of certain types of cancer.

Subtelomeric Rearrangements and Copy Number Variations in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Christofolini, D. M.; De Paula Ramos, M. A.; Kulikowski, L. D.; Da Silva Bellucco, F. T.; Belangero, S. I. N.; Brunoni, D.; Melaragno, M. I.

2010-01-01

Background: The most prevalent type of structural variation in the human genome is represented by copy number variations that can affect transcription levels, sequence, structure and function of genes. Method: In the present study, we used the multiplex ligation-dependent probe amplification (MLPA) technique and quantitative PCR for the detection…

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.

PubMed

Sirugo, Giorgio; Hennig, Branwen J; Adeyemo, Adebowale A; Matimba, Alice; Newport, Melanie J; Ibrahim, Muntaser E; Ryckman, Kelli K; Tacconelli, Alessandra; Mariani-Costantini, Renato; Novelli, Giuseppe; Soodyall, Himla; Rotimi, Charles N; Ramesar, Raj S; Tishkoff, Sarah A; Williams, Scott M

2008-07-01

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

Why genes don't count (for racial differences in health).

PubMed Central

Goodman, A H

2000-01-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin." PMID:11076233

Why genes don't count (for racial differences in health).

PubMed

Goodman, A H

2000-11-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin."

GIS-supported investigation of human EHEC and cattle VTEC O157 infections in Sweden: geographical distribution, spatial variation and possible risk factors.

PubMed Central

Kistemann, Thomas; Zimmer, Sonja; Vågsholm, Ivar; Andersson, Yvonne

2004-01-01

This article describes the spatial and temporal distribution of verotoxin-producing Escherichia coli among humans (EHEC) and cattle (VTEC) in Sweden, in order to evaluate relationships between the incidence of EHEC in humans, prevalence of VTEC O157 in livestock and agricultural structure by an ecological study. The spatial patterns of the distribution of human infections were described and compared with spatial patterns of occurrence in cattle, using a Geographic Information System (GIS). The findings implicate a concentration of human infection and cattle prevalence in the southwest of Sweden. The use of probability mapping confirmed unusual patterns of infection rates. The comparison of human and cattle infection indicated a spatial and statistical association. The correlation between variables of the agricultural structure and human EHEC incidence was high, indicating a significant statistical association of cattle and farm density with human infection. The explained variation of a multiple linear regression model was 0.56. PMID:15188718

Using the Screened Coulomb Potential to Illustrate the Variational Method

ERIC Educational Resources Information Center

Zuniga, Jose; Bastida, Adolfo; Requena, Alberto

2012-01-01

The screened Coulomb potential, or Yukawa potential, is used to illustrate the application of the single and linear variational methods. The trial variational functions are expressed in terms of Slater-type functions, for which the integrals needed to carry out the variational calculations are easily evaluated in closed form. The variational…

Adaptation of human skin color in various populations.

PubMed

Deng, Lian; Xu, Shuhua

2018-01-01

Skin color is a well-recognized adaptive trait and has been studied extensively in humans. Understanding the genetic basis of adaptation of skin color in various populations has many implications in human evolution and medicine. Impressive progress has been made recently to identify genes associated with skin color variation in a wide range of geographical and temporal populations. In this review, we discuss what is currently known about the genetics of skin color variation. We enumerated several cases of skin color adaptation in global modern humans and archaic hominins, and illustrated why, when, and how skin color adaptation occurred in different populations. Finally, we provided a summary of the candidate loci associated with pigmentation, which could be a valuable reference for further evolutionary and medical studies. Previous studies generally indicated a complex genetic mechanism underlying the skin color variation, expanding our understanding of the role of population demographic history and natural selection in shaping genetic and phenotypic diversity in humans. Future work is needed to dissect the genetic architecture of skin color adaptation in numerous ethnic minority groups around the world, which remains relatively obscure compared with that of major continental groups, and to unravel the exact genetic basis of skin color adaptation.

Genetic alterations affecting cholesterol metabolism and human fertility.

PubMed

DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-11-01

Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

Human Variation in Short Regions Predisposed to Deep Evolutionary Conservation

PubMed Central

Loots, Gabriela G.; Ovcharenko, Ivan

2010-01-01

The landscape of the human genome consists of millions of short islands of conservation that are 100% conserved across multiple vertebrate genomes (termed “bricks”), the majority of which are located in noncoding regions. Several hundred thousand bricks are deeply conserved reaching the genomes of amphibians and fish. Deep phylogenetic conservation of noncoding DNA has been reported to be strongly associated with the presence of gene regulatory elements, introducing bricks as a proxy to the functional noncoding landscape of the human genome. Here, we report a significant overrepresentation of bricks in the promoters of transcription factors and developmental genes, where the high level of phylogenetic conservation correlates with an increase in brick overrepresentation. We also found that the presence of a brick dictates a predisposition to evolutionary constraint, with only 0.7% of the amniota brick central nucleotides being diverged within the primate lineage—an 11-fold reduction in the divergence rate compared with random expectation. Human single-nucleotide polymorphism (SNP) data explains only 3% of primate-specific variation in amniota bricks, thus arguing for a widespread fixation of brick mutations within the primate lineage and prior to human radiation. This variation, in turn, might have been utilized as a driving force for primate- and hominoid-specific adaptation. We also discovered a pronounced deviation from the evolutionary predisposition in the human lineage, with over 20-fold increase in the substitution rate at brick SNP sites over expected values. In addition, contrary to typical brick mutations, brick variation commonly encountered in the human population displays limited, if any, signatures of negative selection as measured by the minor allele frequency and population differentiation (F-statistical measure) measures. These observations argue for the plasticity of gene regulatory mechanisms in vertebrates—with evidence of strong purifying selection acting on the gene regulatory landscape of the human genome, where widespread advantageous mutations in putative regulatory elements are likely utilized in functional diversification and adaptation of species. PMID:20093432

Directional genomic hybridization for chromosomal inversion discovery and detection.

PubMed

Ray, F Andrew; Zimmerman, Erin; Robinson, Bruce; Cornforth, Michael N; Bedford, Joel S; Goodwin, Edwin H; Bailey, Susan M

2013-04-01

Chromosomal rearrangements are a source of structural variation within the genome that figure prominently in human disease, where the importance of translocations and deletions is well recognized. In principle, inversions-reversals in the orientation of DNA sequences within a chromosome-should have similar detrimental potential. However, the study of inversions has been hampered by traditional approaches used for their detection, which are not particularly robust. Even with significant advances in whole genome approaches, changes in the absolute orientation of DNA remain difficult to detect routinely. Consequently, our understanding of inversions is still surprisingly limited, as is our appreciation for their frequency and involvement in human disease. Here, we introduce the directional genomic hybridization methodology of chromatid painting-a whole new way of looking at structural features of the genome-that can be employed with high resolution on a cell-by-cell basis, and demonstrate its basic capabilities for genome-wide discovery and targeted detection of inversions. Bioinformatics enabled development of sequence- and strand-specific directional probe sets, which when coupled with single-stranded hybridization, greatly improved the resolution and ease of inversion detection. We highlight examples of the far-ranging applicability of this cytogenomics-based approach, which include confirmation of the alignment of the human genome database and evidence that individuals themselves share similar sequence directionality, as well as use in comparative and evolutionary studies for any species whose genome has been sequenced. In addition to applications related to basic mechanistic studies, the information obtainable with strand-specific hybridization strategies may ultimately enable novel gene discovery, thereby benefitting the diagnosis and treatment of a variety of human disease states and disorders including cancer, autism, and idiopathic infertility.

Defining Exercise Performance Metrics for Flight Hardware Development

NASA Technical Reports Server (NTRS)

Beyene, Nahon M.

2004-01-01

The space industry has prevailed over numerous design challenges in the spirit of exploration. Manned space flight entails creating products for use by humans and the Johnson Space Center has pioneered this effort as NASA's center for manned space flight. NASA Astronauts use a suite of flight exercise hardware to maintain strength for extravehicular activities and to minimize losses in muscle mass and bone mineral density. With a cycle ergometer, treadmill, and the Resistive Exercise Device available on the International Space Station (ISS), the Space Medicine community aspires to reproduce physical loading schemes that match exercise performance in Earth s gravity. The resistive exercise device presents the greatest challenge with the duty of accommodating 20 different exercises and many variations on the core set of exercises. This paper presents a methodology for capturing engineering parameters that can quantify proper resistive exercise performance techniques. For each specified exercise, the method provides engineering parameters on hand spacing, foot spacing, and positions of the point of load application at the starting point, midpoint, and end point of the exercise. As humans vary in height and fitness levels, the methodology presents values as ranges. In addition, this method shows engineers the proper load application regions on the human body. The methodology applies to resistive exercise in general and is in use for the current development of a Resistive Exercise Device. Exercise hardware systems must remain available for use and conducive to proper exercise performance as a contributor to mission success. The astronauts depend on exercise hardware to support extended stays aboard the ISS. Future plans towards exploration of Mars and beyond acknowledge the necessity of exercise. Continuous improvement in technology and our understanding of human health maintenance in space will allow us to support the exploration of Mars and the future of space exploration.

Human structural variation: mechanisms of chromosome rearrangements

PubMed Central

Weckselblatt, Brooke; Rudd, M. Katharine

2015-01-01

Chromosome structural variation (SV) is a normal part of variation in the human genome, but some classes of SV can cause neurodevelopmental disorders. Analysis of the DNA sequence at SV breakpoints can reveal mutational mechanisms and risk factors for chromosome rearrangement. Large-scale SV breakpoint studies have become possible recently owing to advances in next-generation sequencing (NGS) including whole-genome sequencing (WGS). These findings have shed light on complex forms of SV such as triplications, inverted duplications, insertional translocations, and chromothripsis. Sequence-level breakpoint data resolve SV structure and determine how genes are disrupted, fused, and/or misregulated by breakpoints. Recent improvements in breakpoint sequencing have also revealed non-allelic homologous recombination (NAHR) between paralogous long interspersed nuclear element (LINE) or human endogenous retrovirus (HERV) repeats as a cause of deletions, duplications, and translocations. This review covers the genomic organization of simple and complex constitutional SVs, as well as the molecular mechanisms of their formation. PMID:26209074

Variation in recombination rate may bias human genetic disease mapping studies.

PubMed

Boyle, A Susannah; Noor, Mohamed A F

2004-11-01

The availability of the human genome sequence and variability information (as from the International HapMap project) will enhance our ability to map genetic disorders and choose targets for therapeutic intervention. However, several factors, such as regional variation in recombination rate, can bias conclusions from genetic mapping studies. Here, we examine the impact of regional variation in recombination rate across the human genome. Through computer simulations and literature surveys, we conclude that genetic disorders have been mapped to regions of low recombination more often than expected if such diseases were randomly distributed across the genome. This concentration in low recombination regions may be an artifact, and disorders appearing to be caused by a few genes of large effect may be polygenic. Future genetic mapping studies should be conscious of this potential complication by noting the regional recombination rate of regions implicated in diseases.

The Human Pelvis: Variation in Structure and Function During Gait.

PubMed

Lewis, Cara L; Laudicina, Natalie M; Khuu, Anne; Loverro, Kari L

2017-04-01

The shift to habitual bipedalism 4-6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. Anat Rec, 300:633-642, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The utility of copy number variation (CNV) in studies of hypertension-related left ventricular hypertrophy (LVH): rationale, potential and challenges.

PubMed

Boonpeng, Hoh; Yusoff, Khalid

2013-03-01

The ultimate goal of human genetics is to understand the role of genome variation in elucidating human traits and diseases. Besides single nucleotide polymorphism (SNP), copy number variation (CNV), defined as gains or losses of a DNA segment larger than 1 kb, has recently emerged as an important tool in understanding heritable source of human genomic differences. It has been shown to contribute to genetic susceptibility of various common and complex diseases. Despite a handful of publications, its role in cardiovascular diseases remains largely unknown. Here, we deliberate on the currently available technologies for CNV detection. The possible utility and the potential roles of CNV in exploring the mechanisms of cardiac remodeling in hypertension will also be addressed. Finally, we discuss the challenges for investigations of CNV in cardiovascular diseases and its possible implications in diagnosis of hypertension-related left ventricular hypertrophy (LVH).

Sex bias in copy number variation of olfactory receptor gene family depends on ethnicity.

PubMed

Shadravan, Farideh

2013-01-01

Gender plays a pivotal role in the human genetic identity and is also manifested in many genetic disorders particularly mental retardation. In this study its effect on copy number variation (CNV), known to cause genetic disorders was explored. As the olfactory receptor (OR) repertoire comprises the largest human gene family, it was selected for this study, which was carried out within and between three populations, derived from 150 individuals from the 1000 Genome Project. Analysis of 3872 CNVs detected among 791 OR loci, in which 307 loci showed CNV, revealed the following novel findings: Sex bias in CNV was significantly more prevalent in uncommon than common CNV variants of OR pseudogenes, in which the male genome showed more CNVs; and in one-copy number loss compared to complete deletion of OR pseudogenes; both findings implying a more recent evolutionary role for gender. Sex bias in copy number gain was also detected. Another novel finding was that the observed sex bias was largely dependent on ethnicity and was in general absent in East Asians. Using a CNV public database for sick children (International Standard Cytogenomic Array Consortium) the application of these findings for improving clinical molecular diagnostics is discussed by showing an example of sex bias in CNV among kids with autism. Additional clinical relevance is discussed, as the most polymorphic CNV-enriched OR cluster in the human genome, located on chr 15q11.2, is found near the Prader-Willi syndrome/Angelman syndrome bi-directionally imprinted region associated with two well-known mental retardation syndromes. As olfaction represents the primitive cognition in most mammals, arguably in competition with the development of a larger brain, the extensive retention of OR pseudogenes in females of this study, might point to a parent-of-origin indirect regulatory role for OR pseudogenes in the embryonic development of human brain. Thus any perturbation in the temporal regulation of olfactory system could lead to developmental delay disorders including mental retardation.

Strange Beta: Chaotic Variations for Indoor Rock Climbing Route Setting

NASA Astrophysics Data System (ADS)

Phillips, Caleb; Bradley, Elizabeth

2011-04-01

In this paper we apply chaotic systems to the task of sequence variation for the purpose of aiding humans in setting indoor rock climbing routes. This work expands on prior work where similar variations were used to assist in dance choreography and music composition. We present a formalization for transcription of rock climbing problems and a variation generator that is tuned for this domain and addresses some confounding problems, including a new approach to automatic selection of initial conditions. We analyze our system with a large blinded study in a commercial climbing gym in cooperation with experienced climbers and expert route setters. Our results show that our system is capable of assisting a human setter in producing routes that are at least as good as, and in some cases better than, those produced traditionally.

A global reference for human genetic variation

PubMed Central

2016-01-01

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. PMID:26432245

Dissection of complex adult traits in a mouse synthetic population.

PubMed

Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

2012-08-01

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.

The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster

PubMed Central

Zhou, Shanshan; Morozova, Tatiana V.; Hussain, Yasmeen N.; Luoma, Sarah E.; McCoy, Lenovia; Yamamoto, Akihiko; Mackay, Trudy F.C.; Anholt, Robert R.H.

2016-01-01

Background: Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations. Objectives: Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure. Methods: To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs. Results: We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system. Conclusions: Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations. Citation: Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124:1062–1070; http://dx.doi.org/10.1289/ehp.1510513 PMID:26859824

Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model

PubMed Central

Kim, Joo-Sung; Artymovich, Katherine A.; Hall, David F.; Smith, Eric J.; Fulton, Richard; Bell, Julia; Dybas, Leslie; Mansfield, Linda S.; Tempelman, Robert; Wilson, David L.

2012-01-01

Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene Cj1139 (wlaN) during passage of C. jejuni NCTC11168 populations through Ross 308 broiler chickens. We hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. To test this hypothesis, we passaged C. jejuni strains NCTC11168, 33292, 81-176, KanR4 and CamR2 through broiler chickens and analysed the ability of passaged and non-passaged populations to colonize C57BL6 IL-10-deficient mice, our model for human colonization and disease. We utilized fragment analysis and nucleotide sequence analysis to measure phase variation in contingency genes. Passage through the chicken reservoir promoted phase variation in five specific contingency genes, and these ‘successful’ populations colonized mice. When phase variation did not occur in these same five contingency genes during chicken passage, these ‘unsuccessful’ populations failed to colonize mice. Phase variation during chicken passage generated small insertions or deletions (indels) in the homopolymeric tract (HT) in contingency genes. Single-colony isolates of C. jejuni strain KanR4 carrying an allele of contingency gene Cj0170 with a10G HT colonized mice at high frequency and caused disease symptoms, whereas single-colony isolates carrying the 9G allele failed to colonize mice. Supporting results were observed for the successful 9G allele of Cj0045 in strain 33292. These data suggest that phase variation in Cj0170 and Cj0045 is strongly associated with mouse colonization and disease, and that the chicken reservoir can play an active role in natural selection, phase variation and disease. PMID:22343355

Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model.

PubMed

Kim, Joo-Sung; Artymovich, Katherine A; Hall, David F; Smith, Eric J; Fulton, Richard; Bell, Julia; Dybas, Leslie; Mansfield, Linda S; Tempelman, Robert; Wilson, David L; Linz, John E

2012-05-01

Human illness due to Camplyobacter jejuni infection is closely associated with consumption of poultry products. We previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene Cj1139 (wlaN) during passage of C. jejuni NCTC11168 populations through Ross 308 broiler chickens. We hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. To test this hypothesis, we passaged C. jejuni strains NCTC11168, 33292, 81-176, KanR4 and CamR2 through broiler chickens and analysed the ability of passaged and non-passaged populations to colonize C57BL6 IL-10-deficient mice, our model for human colonization and disease. We utilized fragment analysis and nucleotide sequence analysis to measure phase variation in contingency genes. Passage through the chicken reservoir promoted phase variation in five specific contingency genes, and these 'successful' populations colonized mice. When phase variation did not occur in these same five contingency genes during chicken passage, these 'unsuccessful' populations failed to colonize mice. Phase variation during chicken passage generated small insertions or deletions (indels) in the homopolymeric tract (HT) in contingency genes. Single-colony isolates of C. jejuni strain KanR4 carrying an allele of contingency gene Cj0170 with a10G HT colonized mice at high frequency and caused disease symptoms, whereas single-colony isolates carrying the 9G allele failed to colonize mice. Supporting results were observed for the successful 9G allele of Cj0045 in strain 33292. These data suggest that phase variation in Cj0170 and Cj0045 is strongly associated with mouse colonization and disease, and that the chicken reservoir can play an active role in natural selection, phase variation and disease.

A Quantitative Comparison of the Similarity between Genes and Geography in Worldwide Human Populations

PubMed Central

Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A.

2012-01-01

Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure. PMID:22927824

A quantitative comparison of the similarity between genes and geography in worldwide human populations.

PubMed

Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A

2012-08-01

Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure.

Cultural group selection follows Darwin's classic syllogism for the operation of selection.

PubMed

Richerson, Peter; Baldini, Ryan; Bell, Adrian V; Demps, Kathryn; Frost, Karl; Hillis, Vicken; Mathew, Sarah; Newton, Emily K; Naar, Nicole; Newson, Lesley; Ross, Cody; Smaldino, Paul E; Waring, Timothy M; Zefferman, Matthew

2016-01-01

The main objective of our target article was to sketch the empirical case for the importance of selection at the level of groups on cultural variation. Such variation is massive in humans, but modest or absent in other species. Group selection processes acting on this variation is a framework for developing explanations of the unusual level of cooperation between non-relatives found in our species. Our case for cultural group selection (CGS) followed Darwin's classic syllogism regarding natural selection: If variation exists at the level of groups, if this variation is heritable, and if it plays a role in the success or failure of competing groups, then selection will operate at the level of groups. We outlined the relevant domains where such evidence can be sought and characterized the main conclusions of work in those domains. Most commentators agree that CGS plays some role in human evolution, although some were considerably more skeptical. Some contributed additional empirical cases. Some raised issues of the scope of CGS explanations versus competing ones.

Thickness and resistivity variations over the upper surface of the human skull.

PubMed

Law, S K

1993-01-01

A study of skull thickness and resistivity variations over the upper surface was made for an adult human skull. Physical measurements of thickness and qualitative analysis of photographs and CT scans of the skull were performed to determine internal and external features of the skull. Resistivity measurements were made using the four-electrode method and ranged from 1360 to 21400 Ohm-cm with an overall mean of 7560 +/- 4130 Ohm-cm. The presence of sutures was found to decrease resistivity substantially. The absence of cancellous bone was found to increase resistivity, particularly for samples from the temporal bone. An inverse relationship between skull thickness and resistivity was determined for trilayer bone (n = 12, p < 0.001). The results suggest that the skull cannot be considered a uniform layer and that local resistivity variations should be incorporated into realistic geometric and resistive head models to improve resolution in EEG. Influences of these variations on head models, methods for determining these variations, and incorporation into realistic head models, are discussed.

Protein degradation rate is the dominant mechanism accounting for the differences in protein abundance of basal p53 in a human breast and colorectal cancer cell line.

PubMed

Lakatos, Eszter; Salehi-Reyhani, Ali; Barclay, Michael; Stumpf, Michael P H; Klug, David R

2017-01-01

We determine p53 protein abundances and cell to cell variation in two human cancer cell lines with single cell resolution, and show that the fractional width of the distributions is the same in both cases despite a large difference in average protein copy number. We developed a computational framework to identify dominant mechanisms controlling the variation of protein abundance in a simple model of gene expression from the summary statistics of single cell steady state protein expression distributions. Our results, based on single cell data analysed in a Bayesian framework, lends strong support to a model in which variation in the basal p53 protein abundance may be best explained by variations in the rate of p53 protein degradation. This is supported by measurements of the relative average levels of mRNA which are very similar despite large variation in the level of protein.

High-performance metabolic profiling of plasma from seven mammalian species for simultaneous environmental chemical surveillance and bioeffect monitoring.

PubMed

Park, Youngja H; Lee, Kichun; Soltow, Quinlyn A; Strobel, Frederick H; Brigham, Kenneth L; Parker, Richard E; Wilson, Mark E; Sutliff, Roy L; Mansfield, Keith G; Wachtman, Lynn M; Ziegler, Thomas R; Jones, Dean P

2012-05-16

High-performance metabolic profiling (HPMP) by Fourier-transform mass spectrometry coupled to liquid chromatography gives relative quantification of thousands of chemicals in biologic samples but has had little development for use in toxicology research. In principle, the approach could be useful to detect complex metabolic response patterns to toxicologic exposures and to detect unusual abundances or patterns of potentially toxic chemicals. As an initial study to develop these possible uses, we applied HPMP and bioinformatics analysis to plasma of humans, rhesus macaques, marmosets, pigs, sheep, rats and mice to determine: (1) whether more chemicals are detected in humans living in a less controlled environment than captive species and (2) whether a subset of plasma chemicals with similar inter-species and intra-species variation could be identified for use in comparative toxicology. Results show that the number of chemicals detected was similar in humans (3221) and other species (range 2537-3373). Metabolite patterns were most similar within species and separated samples according to family and order. A total of 1485 chemicals were common to all species; 37% of these matched chemicals in human metabolomic databases and included chemicals in 137 out of 146 human metabolic pathways. Probability-based modularity clustering separated 644 chemicals, including many endogenous metabolites, with inter-species variation similar to intra-species variation. The remaining chemicals had greater inter-species variation and included environmental chemicals as well as GSH and methionine. Together, the data suggest that HPMP provides a platform that can be useful within human populations and controlled animal studies to simultaneously evaluate environmental exposures and biological responses to such exposures. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hybridization-based detection of Helicobacter pylori at human body temperature using advanced locked nucleic acid (LNA) probes.

PubMed

Fontenete, Sílvia; Guimarães, Nuno; Leite, Marina; Figueiredo, Céu; Wengel, Jesper; Filipe Azevedo, Nuno

2013-01-01

The understanding of the human microbiome and its influence upon human life has long been a subject of study. Hence, methods that allow the direct detection and visualization of microorganisms and microbial consortia (e.g. biofilms) within the human body would be invaluable. In here, we assessed the possibility of developing a variant of fluorescence in situ hybridization (FISH), named fluorescence in vivo hybridization (FIVH), for the detection of Helicobacter pylori. Using oligonucleotide variations comprising locked nucleic acids (LNA) and 2'-O-methyl RNAs (2'OMe) with two types of backbone linkages (phosphate or phosphorothioate), we were able to successfully identify two probes that hybridize at 37 °C with high specificity and sensitivity for H. pylori, both in pure cultures and in gastric biopsies. Furthermore, the use of this type of probes implied that toxic compounds typically used in FISH were either found to be unnecessary or could be replaced by a non-toxic substitute. We show here for the first time that the use of advanced LNA probes in FIVH conditions provides an accurate, simple and fast method for H. pylori detection and location, which could be used in the future for potential in vivo applications either for this microorganism or for others.

Hybridization-Based Detection of Helicobacter pylori at Human Body Temperature Using Advanced Locked Nucleic Acid (LNA) Probes

PubMed Central

Fontenete, Sílvia; Guimarães, Nuno; Leite, Marina; Figueiredo, Céu; Wengel, Jesper; Filipe Azevedo, Nuno

2013-01-01

The understanding of the human microbiome and its influence upon human life has long been a subject of study. Hence, methods that allow the direct detection and visualization of microorganisms and microbial consortia (e.g. biofilms) within the human body would be invaluable. In here, we assessed the possibility of developing a variant of fluorescence in situ hybridization (FISH), named fluorescence in vivo hybridization (FIVH), for the detection of Helicobacter pylori. Using oligonucleotide variations comprising locked nucleic acids (LNA) and 2’-O-methyl RNAs (2’OMe) with two types of backbone linkages (phosphate or phosphorothioate), we were able to successfully identify two probes that hybridize at 37 °C with high specificity and sensitivity for H. pylori, both in pure cultures and in gastric biopsies. Furthermore, the use of this type of probes implied that toxic compounds typically used in FISH were either found to be unnecessary or could be replaced by a non-toxic substitute. We show here for the first time that the use of advanced LNA probes in FIVH conditions provides an accurate, simple and fast method for H. pylori detection and location, which could be used in the future for potential in vivo applications either for this microorganism or for others. PMID:24278398

Comparative study between reconstructed and native human epidermis using nuclear microscopy

NASA Astrophysics Data System (ADS)

Ynsa, M. D.; Gontier, E.; Mavon, A.; Moretto, P.; Rosdy, M.

2006-08-01

The physiological status of native skin is suffering from large inter-individual variations, especially in terms of inorganic ions content. For this reason, together with the advent of ethic laws on animal experimentation, reconstructed skin or epidermis models are extensively employed nowadays in penetration studies for cosmetic or pharmacological applications. It has been already verified that reconstructed human epidermis (RHE) has similar physiological mechanisms to native human skin, but until now, there are few studies where the elemental concentrations of both skins, reconstructed and native, are compared. In this work, freeze-dried thin sections of human native skin obtained from surgery have been characterized using PIXE, RBS and STIM at the CENBG nuclear microprobe. RHE samples were treated and analyzed in the same conditions for comparison. The combination of the different imaging and analysis techniques made possible a clear delimitation and identification of skin ultrastructure. The elemental concentrations of P, S, Cl, K and Ca were measured in the different strata. For both skins, concentrations have been compared and significant differences in terms of elemental concentrations have been determined using statistical approaches. Similar physiological characteristics were pointed out in both skin models, in particular the Ca gradient presumably involved in the regulation of the barrier effect.

Exploring the Gaps in Practical Ethical Guidance for Animal Welfare Considerations of Field Interventions and Innovations Targeting Dogs and Cats.

PubMed

Tasker, Louisa; Getty, Susan F; Briggs, Joyce R; Benka, Valerie A W

2018-01-27

Domestic dogs ( Canis lupus familiaris ) and cats ( Felis silvestris catus ) are common species targeted by nongovernmental or intergovernmental organizations, veterinarians and government agencies worldwide, for field interventions (e.g., population management, rabies vaccination programs) or innovations (e.g., development of technologies or pharmaceuticals to improve animal welfare). We have a moral responsibility to ensure that the conduct of this work is humane for dogs or cats, and to consider the human communities in which the animals live. Ethical review is widely accepted as being integral to responsible practice, and it is fundamental to good science that underpins innovation. Despite the necessity of field interventions or innovations to advance the welfare of individuals or populations of animals, we found a lack of specific guidance and review processes to help navigate ethical dilemmas surrounding the conduct of such work. This can be detrimental to the wellbeing of animals and their human communities. Here we identify the gaps in existing ethical frameworks (specifically application of Reduction and Refinement principles, challenges of obtaining meaningful informed consent with variations in the quality of human-animal relationships, and limited resources regarding considerations of local stakeholders), and outline the need for additional tools to promote ethical conduct in the field.

Windowless ultrasound photoacoustic cell for in vivo mid-IR spectroscopy of human epidermis: Low interference by changes of air pressure, temperature, and humidity caused by skin contact opens the possibility for a non-invasive monitoring of glucose in the interstitial fluid

NASA Astrophysics Data System (ADS)

Pleitez, Miguel A.; Lieblein, Tobias; Bauer, Alexander; Hertzberg, Otto; von Lilienfeld-Toal, Hermann; Mäntele, Werner

2013-08-01

The application of a novel open, windowless cell for the photoacoustic infrared spectroscopy of human skin is described. This windowless cavity is tuned for optimum performance in the ultrasound range between 50 and 60 kHz. In combination with an external cavity tunable quantum cascade laser emitting in the range from ˜1000 cm-1 to 1245 cm-1, this approach leads to high signal-to-noise-ratio (SNR) for mid-infrared spectra of human skin. This opens the possibility to measure in situ the absorption spectrum of human epidermis in the mid-infrared region at high SNR in a few (˜5) seconds. Rapid measurement of skin spectra greatly reduces artifacts arising from movements. As compared to closed resonance cells, the windowless cell exhibits the advantage that the influence of air pressure variations, temperature changes, and air humidity buildup that are caused by the contact of the cell to the skin surface can be minimized. We demonstrate here that this approach can be used for continuous and non-invasive monitoring of the glucose level in human epidermis, and thus may form the basis for a non-invasive monitoring of the glucose level for diabetes patients.

Human genetics and sleep behavior.

PubMed

Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

2017-06-01

Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applications of low lift to drag ratio aerobrakes using angle of attack variation for control

NASA Technical Reports Server (NTRS)

Mulqueen, J. A.

1991-01-01

Several applications of low lift to drag ratio aerobrakes are investigated which use angle of attack variation for control. The applications are: return from geosynchronous or lunar orbit to low Earth orbit; and planetary aerocapture at Earth and Mars. A number of aerobrake design considerations are reviewed. It was found that the flow impingement behind the aerobrake and the aerodynamic heating loads are the primary factors that control the sizing of an aerobrake. The heating loads and other loads, such as maximum acceleration, are determined by the vehicle ballistic coefficient, the atmosphere entry conditions, and the trajectory design. Several formulations for defining an optimum trajectory are reviewed, and the various performance indices that can be used are evaluated. The 'nearly grazing' optimal trajectory was found to provide the best compromise between the often conflicting goals of minimizing the vehicle propulsive requirements and minimizing vehicle loads. The relationship between vehicle and trajectory design is investigated further using the results of numerical simulations of trajectories for each aerobrake application. The data show the sensitivity of the trajectories to several vehicle parameters and atmospheric density variations. The results of the trajectory analysis show that low lift to drag ratio aerobrakes, which use angle of attack variation for control, can potentially be used for a wide range of aerobrake applications.

Modular optical topometric sensor for 3D acquisition of human body surfaces and long-term monitoring of variations.

PubMed

Bischoff, Guido; Böröcz, Zoltan; Proll, Christian; Kleinheinz, Johannes; von Bally, Gert; Dirksen, Dieter

2007-08-01

Optical topometric 3D sensors such as laser scanners and fringe projection systems allow detailed digital acquisition of human body surfaces. For many medical applications, however, not only the current shape is important, but also its changes, e.g., in the course of surgical treatment. In such cases, time delays of several months between subsequent measurements frequently occur. A modular 3D coordinate measuring system based on the fringe projection technique is presented that allows 3D coordinate acquisition including calibrated color information, as well as the detection and visualization of deviations between subsequent measurements. In addition, parameters describing the symmetry of body structures are determined. The quantitative results of the analysis may be used as a basis for objective documentation of surgical therapy. The system is designed in a modular way, and thus, depending on the object of investigation, two or three cameras with different capabilities in terms of resolution and color reproduction can be utilized to optimize the set-up.

Adjusting Beliefs via Transformed Fuzzy Priors

NASA Astrophysics Data System (ADS)

Rattanadamrongaksorn, T.; Sirikanchanarak, D.; Sirisrisakulchai, J.; Sriboonchitta, S.

2018-02-01

Instead of leaving a decision to a pure data-driven system, intervention and collaboration by human would be preferred to fill the gap that machine cannot perform well. In financial applications, for instance, the inference and prediction during structural changes by critical factors; such as market conditions, administrative styles, political policies, etc.; have significant influences to investment strategies. With the conditions differing from the past, we believe that the decision should not be made by only the historical data but also with human estimation. In this study, the updating process by data fusion between expert opinions and statistical observations is thus proposed. The expert’s linguistic terms can be translated into mathematical expressions by the predefined fuzzy numbers and utilized as the initial knowledge for Bayesian statistical framework via the possibility-to-probability transformation. The artificial samples on five scenarios were tested in the univariate problem to demonstrate the methodology. The results showed the shifts and variations appeared on the parameters of the distributions and, as a consequence, adjust the degrees of belief accordingly.

Genetics of Bladder-Exstrophy-Epispadias Complex (BEEC): Systematic Elucidation of Mendelian and Multifactorial Phenotypes

PubMed Central

Reutter, Heiko; Keppler-Noreuil, Kim; E. Keegan, Catherine; Thiele, Holger; Yamada, Gen; Ludwig, Michael

2016-01-01

The Bladder-Exstrophy-Epispadias Complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and has a profound impact on continence, and on sexual and renal function. While previous reports of familial occurrence, in-creased recurrence among first-degree relatives, high concordance rates among monozygotic twins, and chromosomal aberra-tions were suggestive of causative genetic factors, the recent identification of copy number variations (CNVs), susceptibility regions and genes through the systematic application of array based analysis, candidate gene and genome-wide association studies (GWAS) provide strong evidence. These findings in human BEEC cohorts are underscored by the recent description of BEEC(-like) murine knock-out models. Here, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal uro-rectal development leading to the BEEC, demonstrating the importance of ISL1-pathway in human and mouse and propose SLC20A1 and CELSR3 as the first BEEC candidate genes, identified through systematic whole-exome sequencing (WES) in BEEC patients. PMID:27013921

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model

PubMed Central

Saccone, Scott F.; Quan, Jiaxi; Jones, Peter L.

2012-01-01

Motivation: Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. Results: We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. Availability and implementation: BioQ is freely available to the public at http://bioq.saclab.net Contact: ssaccone@wustl.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22426342

Oral Storytelling as Evidence of Pedagogy in Forager Societies.

PubMed

Scalise Sugiyama, Michelle

2017-01-01

Teaching is reportedly rare in hunter-gatherer societies, raising the question of whether it is a species-typical trait in humans. A problem with past studies is that they tend to conceptualize teaching in terms of Western pedagogical practices. In contrast, this study proceeds from the premise that teaching requires the ostensive manifestation of generalizable knowledge: the teacher must signal intent to share information, indicate the intended recipient, and transmit knowledge that is applicable beyond the present context. Certain features of human communication appear to be ostensive in function (e.g., eye contact, pointing, contingency, prosodic variation), and collectively serve as "natural pedagogy." Tellingly, oral storytelling in forager societies typically employs these and other ostensive behaviors, and is widely reported to be an important source of generalizable ecological and social knowledge. Despite this, oral storytelling has been conspicuously overlooked in studies of teaching in preliterate societies. Accordingly, this study presents evidence that oral storytelling involves the use of ostension and the transmission of generic knowledge, thereby meeting the criteria of pedagogy.

The integration of quantitative genetics, paleontology, and neontology reveals genetic underpinnings of primate dental evolution.

PubMed

Hlusko, Leslea J; Schmitt, Christopher A; Monson, Tesla A; Brasil, Marianne F; Mahaney, Michael C

2016-08-16

Developmental genetics research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative genetic analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying genetic mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental genetic patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two genetic outputs. Our results build on the mouse model by combining quantitative genetics and paleontology, and thereby elucidate how genetic mechanisms likely underlie major events in primate evolution.

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

DOE PAGES

Hu, Liya; Ramani, Sasirekha; Czako, Rita; ...

2015-09-30

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Liya; Ramani, Sasirekha; Czako, Rita

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Integrating common and rare genetic variation in diverse human populations.

PubMed

Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

2010-09-02

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of

Autozygome Sequencing Expands the Horizon of Human Knockout Research and Provides Novel Insights into Human Phenotypic Variation

PubMed Central

Anazi, Shamsa; Alshamekh, Shomoukh; Alkuraya, Fowzan S.

2013-01-01

The use of autozygosity as a mapping tool in the search for autosomal recessive disease genes is well established. We hypothesized that autozygosity not only unmasks the recessiveness of disease causing variants, but can also reveal natural knockouts of genes with less obvious phenotypic consequences. To test this hypothesis, we exome sequenced 77 well phenotyped individuals born to first cousin parents in search of genes that are biallelically inactivated. Using a very conservative estimate, we show that each of these individuals carries biallelic inactivation of 22.8 genes on average. For many of the 169 genes that appear to be biallelically inactivated, available data support involvement in modulating metabolism, immunity, perception, external appearance and other phenotypic aspects, and appear therefore to contribute to human phenotypic variation. Other genes with biallelic inactivation may contribute in yet unknown mechanisms or may be on their way to conversion into pseudogenes due to true recent dispensability. We conclude that sequencing the autozygome is an efficient way to map the contribution of genes to human phenotypic variation that goes beyond the classical definition of disease. PMID:24367280

Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

PubMed

Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

2014-04-01

Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. © 2014 Anatomical Society.

High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing

PubMed Central

Yun, S.H.; Vakoc, B.J.; Shishkov, M.; Desjardins, A.E.; Park, B.H.; de Boer, J.F.; Tearney, G.J.; Bouma, B.E.

2009-01-01

Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm. PMID:18542183

Calculating stage duration statistics in multistage diseases.

PubMed

Komarova, Natalia L; Thalhauser, Craig J

2011-01-01

Many human diseases are characterized by multiple stages of progression. While the typical sequence of disease progression can be identified, there may be large individual variations among patients. Identifying mean stage durations and their variations is critical for statistical hypothesis testing needed to determine if treatment is having a significant effect on the progression, or if a new therapy is showing a delay of progression through a multistage disease. In this paper we focus on two methods for extracting stage duration statistics from longitudinal datasets: an extension of the linear regression technique, and a counting algorithm. Both are non-iterative, non-parametric and computationally cheap methods, which makes them invaluable tools for studying the epidemiology of diseases, with a goal of identifying different patterns of progression by using bioinformatics methodologies. Here we show that the regression method performs well for calculating the mean stage durations under a wide variety of assumptions, however, its generalization to variance calculations fails under realistic assumptions about the data collection procedure. On the other hand, the counting method yields reliable estimations for both means and variances of stage durations. Applications to Alzheimer disease progression are discussed.

Cosmic ray interactions in the ground: Temporal variations in cosmic ray intensities and geophysical studies

NASA Technical Reports Server (NTRS)

Lal, D.

1986-01-01

Temporal variations in cosmic ray intensity have been deduced from observations of products of interactions of cosmic ray particles in the Moon, meteorites, and the Earth. Of particular interest is a comparison between the information based on Earth and that based on other samples. Differences are expected at least due to: (1) differences in the extent of cosmic ray modulation, and (2) changes in the geomagnetic dipole field. Any information on the global changes in the terrestrial cosmic ray intensity is therefore of importance. In this paper a possible technique for detecting changes in cosmic ray intensity is presented. The method involves human intervention and is applicable for the past 10,000 yrs. Studies of changes over longer periods of time are possible if supplementary data on age and history of the sample are available using other methods. Also discussed are the possibilities of studying certain geophysical processes, e.g., erosion, weathering, tectonic events based on studies of certain cosmic ray-produced isotopes for the past several million years.

Biochemical genetic variation in the Family Simuliidae: electrophoretic identification of the human biter in the isomorphic Simulium jenningsi group

Treesearch

Bernie May; Leah S. Bauer; Robert L. Vadas; Jeffrey Granett

1977-01-01

This paper describes inter- and intraspecific protein variation in the 3 closely related species of the Simulium jenningsi black fly group, S. jenningsi Malloch, S. Nyssa Stone and Snoddy, and S. n. sp. P. Snoddy and Bauer. Variation is described at single loci coding for the enzymes,...

Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

PubMed Central

Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

2017-01-01

One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering. PMID:28690602