Recruitment and selection in violent extremist organizations: Exploring what industrial and organizational psychology might contribute.

PubMed

Hunter, Samuel T; Shortland, Neil D; Crayne, Matthew P; Ligon, Gina S

2017-04-01

For many terrorist organizations, also known as violent extremist organizations (VEOs), their ability to perpetuate violence is often contingent upon successful recruitment and selection of organizational members. Although academic work on terrorist recruitment and selection has improved in recent years, researchers have generally focused more heavily on aspects of radicalization rather than organization attraction and entry. Moreover, a number of terrorism scholars have lamented the lack of conceptual frameworks with which to interpret and extend findings linked to recruitment and selection, specifically. In light of these difficulties, we propose that considering literature bases outside of terrorism may be useful in extending lines of inquiry and offering alternative ways of thinking about how terrorist organizations operate. Specifically, we draw on Industrial and Organizational Psychology, Human Resource Management, and Organizational Behavior literature bases to offer alternative and extended modes of thought on terrorist recruitment and selection. In doing so, we believe both terrorism and more traditional organizational scholars can make substantive and novel contributions to future investigations of increasingly pressing issues surrounding violent extremism. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

76 FR 45582 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-29

... and effectiveness of human generic drug products for use in the treatment of a broad spectrum of human... concerning the safety and effectiveness of marketed and investigational human drug products for use in... and evaluates available data concerning the safety and effectiveness of marketed and investigational...

Technology Enabled Learning. Symposium.

ERIC Educational Resources Information Center

2002

This document contains three papers on technology-enabled learning and human resource development. Among results found in "Current State of Technology-enabled Learning Programs in Select Federal Government Organizations: a Case Study of Ten Organizations" (Letitia A. Combs) are the following: the dominant delivery method is traditional…

[Evolution of pathogenic micro-organisms as a challenge for medicine].

PubMed

Vaara, Martti

2009-01-01

Successful parasitic micro-organisms are able to adapt to the circumstances of the host's organ system, and it is usually not expedient for them to kill their host. Under selection pressure, the evolution of micro-organisms is vastly quicker that that of man. The selection pressure brought about by rapid ecological changes and alterations associated with human action provides for the development of new, dangerous pathogens and transformation of familiar pathogens to become more dangerous. Progress in molecular biology has thus far not yielded as many new tools for the treatment of infectious diseases as the hopes were in the early 2000's.

A role for relaxed selection in the evolution of the language capacity

PubMed Central

Deacon, Terrence W.

2010-01-01

Explaining the extravagant complexity of the human language and our competence to acquire it has long posed challenges for natural selection theory. To answer his critics, Darwin turned to sexual selection to account for the extreme development of language. Many contemporary evolutionary theorists have invoked incredibly lucky mutation or some variant of the assimilation of acquired behaviors to innate predispositions in an effort to explain it. Recent evodevo approaches have identified developmental processes that help to explain how complex functional synergies can evolve by Darwinian means. Interestingly, many of these developmental mechanisms bear a resemblance to aspects of Darwin's mechanism of natural selection, often differing only in one respect (e.g., form of duplication, kind of variation, competition/cooperation). A common feature is an interplay between processes of stabilizing selection and processes of relaxed selection at different levels of organism function. These may play important roles in the many levels of evolutionary process contributing to language. Surprisingly, the relaxation of selection at the organism level may have been a source of many complex synergistic features of the human language capacity, and may help explain why so much language information is “inherited” socially. PMID:20445088

Geometric Cues, Reference Frames, and the Equivalence of Experienced-Aligned and Novel-Aligned Views in Human Spatial Memory

ERIC Educational Resources Information Center

Kelly, Jonathan W.; Sjolund, Lori A.; Sturz, Bradley R.

2013-01-01

Spatial memories are often organized around reference frames, and environmental shape provides a salient cue to reference frame selection. To date, however, the environmental cues responsible for influencing reference frame selection remain relatively unknown. To connect research on reference frame selection with that on orientation via…

Preparation of human drug metabolites using fungal peroxygenases

Treesearch

Marzena Poraj-Kobielska; Matthias Kinne; René Ullrich; Katrin Scheibner; Gernot Kayser; Kenneth E. Hammel; Martin Hofrichter

2011-01-01

The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus...

Experimental selective posterior semicircular canal laser deafferentation.

PubMed

Naguib, Maged B

2005-05-01

In this experimental study, we attempted to perform selective deafferentation of the posterior semicircular canal ampulla of guinea pigs using carbon dioxide laser beam. The results of this study document the efficacy of this procedure in achieving deafferentation of the posterior semicircular canal safely with regards to the other semicircular canals, the otolithic organ and the organ of hearing. Moreover, the procedure is performed with relative ease compared with other procedures previously described for selective deafferentation of the posterior semicircular canal. The clinical application of such a procedure for the treatment of intractable benign paroxysmal positional vertigo in humans is suggested.

The cultural evolution of emergent group-level traits.

PubMed

Smaldino, Paul E

2014-06-01

Many of the most important properties of human groups - including properties that may give one group an evolutionary advantage over another - are properly defined only at the level of group organization. Yet at present, most work on the evolution of culture has focused solely on the transmission of individual-level traits. I propose a conceptual extension of the theory of cultural evolution, particularly related to the evolutionary competition between cultural groups. The key concept in this extension is the emergent group-level trait. This type of trait is characterized by the structured organization of differentiated individuals and constitutes a unit of selection that is qualitatively different from selection on groups as defined by traditional multilevel selection (MLS) theory. As a corollary, I argue that the traditional focus on cooperation as the defining feature of human societies has missed an essential feature of cooperative groups. Traditional models of cooperation assume that interacting with one cooperator is equivalent to interacting with any other. However, human groups involve differential roles, meaning that receiving aid from one individual is often preferred to receiving aid from another. In this target article, I discuss the emergence and evolution of group-level traits and the implications for the theory of cultural evolution, including ramifications for the evolution of human cooperation, technology, and cultural institutions, and for the equivalency of multilevel selection and inclusive fitness approaches.

Comparative Analysis of Human Communication Networks in Selected Formal Organizations.

ERIC Educational Resources Information Center

Farace, Richard V.; Johnson, Jerome David

This paper briefly describes the organization of a "data bank" containing research on communication networks, specifies the kinds of information compiled about various network properties, discusses some specific results of the work done to date, and presents some general conclusions about the overall project and its potential advantages to…

The impact of pesticides on oxidative stress level in human organism and their activity as an endocrine disruptor.

PubMed

Jabłońska-Trypuć, Agata; Wołejko, Elżbieta; Wydro, Urszula; Butarewicz, Andrzej

2017-07-03

Pesticides cause serious environmental and health problems both to humans and animals. The aim of this review is to discuss selected herbicides and fungicides regarding their mode of action and their influence on basic oxidative stress parameters and endocrine disruption properties tested in selected cell cultures in vitro. Because of numerous difficulties which animal studies are subject to, cell cultures are an excellent experimental model reflecting human exposure to different pesticides through all relevant routes. This experimental model can be used to monitor aggregate and cumulative pesticide exposures.

A Review of Circadian Effects on Selected Human Information Processing Tasks.

DTIC Science & Technology

1989-04-03

uling, and Diurnal Rhythms in Man," Acta Psychologies, Vol. 27, pp. 436-442, 1967. 32. Shephard, R.p "Sleep, Biorhythms and Human Performance ." Sports ...DISTRIBUTION/AVAILABILITY OF REPORT U=* assifted 2b. DECL0SSIFICATION/DOWNGRADING SCHEDULE0’ Approved for ý .c release; distribution It ted. 4. PERFORMING ...ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORG0.. .,N REPORT NUMBER(S) NAMRL Monograph 37 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOC. 7a. NAME

SHRM Work & Family Survey Report, 1992.

ERIC Educational Resources Information Center

Society for Human Resource Management, Alexandria, VA.

In March 1992, a random sample of 5,600 human resource professionals was selected from the membership of the Society for Human Resource Management (SHRM) and surveyed regarding family issues in the workplace. Respondents were asked to provide information on the size and other characteristics of their organization and workplace practices, and were…

Sustainability in Recruitment and Selection: Building a Framework of Practices

ERIC Educational Resources Information Center

Jepsen, Denise M.; Grob, Suzanne

2015-01-01

Much has been written about the role of human resources professionals in creating sustainable organizations. However, despite recognition that organizational human resources functions have an important role to play in sustainability, researchers tend to focus on strategic issues and sustainability. This higher-order focus has often meant that…

How to create a health care organization that can succeed in an unpredictable future.

PubMed

Olden, Peter C; Haynos, Jessika

2013-01-01

For those who manage organizations, it has been said that success does not come from predicting the future but instead comes from creating an organization that can succeed in an unpredictable future. Managers are responsible for creating such an organization. To do that, managers can apply management-related principles and methods. This article explains selected principles of organization structure, human resources, culture, decision making, and change management and how to apply them to health care organizations. If done well, that will help such organizations succeed in an unpredictable future.

76 FR 39403 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002... Representative on an FDA Advisory Committee AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting that any industry organizations interested in...

76 FR 19101 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002... Representative on an FDA Advisory Committee AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting that any industry organizations interested in...

Shifts in outcrossing rates and changes to floral traits are associated with the evolution of herbicide resistance in the common morning glory.

PubMed

Kuester, Adam; Fall, Eva; Chang, Shu-Mei; Baucom, Regina S

2017-01-01

Human-mediated selection can strongly influence the evolutionary response of natural organisms within ecological timescales. But what traits allow for, or even facilitate, adaptation to the strong selection humans impose on natural systems? Using a combination of laboratory and greenhouse studies of 32 natural populations of the common agricultural weed, Ipomoea purpurea, we show that herbicide-resistant populations self-fertilise more than susceptible populations. We likewise show that anther-stigma distance, a floral trait associated with self-fertilisation in this species, exhibits a nonlinear relationship with resistance such that the most and least resistant populations exhibit lower anther-stigma separation compared to populations with moderate levels of resistance. Overall, our results extend the general finding that plant mating can be impacted by human-mediated agents of selection to that of the extreme selection of the agricultural system. This work highlights the influence of human-mediated selection on rapid responses of natural populations that can lead to unexpected long-term evolutionary consequences. © 2016 John Wiley & Sons Ltd/CNRS.

Report on Nutrition and Special Groups. Part 1--Food Stamps.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Nutrition and Human Needs.

The contents of this report by the staff of the Senate Select Committee on Nutrition and Human Needs--based on information gathered at the National Nutrition Policy hearings, from testimony before the Select Committee and the Senate Agriculture Committee and through staff investigation--are organized in nine chapters, as follows: (1) Food Stamp…

Cultural group selection plays an essential role in explaining human cooperation: A sketch of the evidence.

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

Human cooperation is highly unusual. We live in large groups composed mostly of non-relatives. Evolutionists have proposed a number of explanations for this pattern, including cultural group selection and extensions of more general processes such as reciprocity, kin selection, and multi-level selection acting on genes. Evolutionary processes are consilient; they affect several different empirical domains, such as patterns of behavior and the proximal drivers of that behavior. In this target article, we sketch the evidence from five domains that bear on the explanatory adequacy of cultural group selection and competing hypotheses to explain human cooperation. Does cultural transmission constitute an inheritance system that can evolve in a Darwinian fashion? Are the norms that underpin institutions among the cultural traits so transmitted? Do we observe sufficient variation at the level of groups of considerable size for group selection to be a plausible process? Do human groups compete, and do success and failure in competition depend upon cultural variation? Do we observe adaptations for cooperation in humans that most plausibly arose by cultural group selection? If the answer to one of these questions is "no," then we must look to other hypotheses. We present evidence, including quantitative evidence, that the answer to all of the questions is "yes" and argue that we must take the cultural group selection hypothesis seriously. If culturally transmitted systems of rules (institutions) that limit individual deviance organize cooperation in human societies, then it is not clear that any extant alternative to cultural group selection can be a complete explanation.

Data on occurrence of selected trace metals, organochlorines, and semivolatile organic compounds in edible fish tissues from Lake Worth, Fort Worth, Texas, 1999

USGS Publications Warehouse

Moring, J. Bruce

2002-01-01

A public-health assessment conducted for the Texas Department of Health and the Agency for Toxic Substances and Disease Registry concluded that exposure to contaminants through the aquatic food chain is an indeterminate human-health hazard in Lake Worth, Fort Worth, Texas. In 1999, the U.S. Geological Survey, in cooperation with the U.S. Air Force and in collaboration with the Texas Department of Health, collected samples of edible fish tissues from Lake Worth for analysis of selected trace metals, organochlorines, and semivolatile organic compounds to support a human-health risk assessment. Left-side, skin-off fillet samples were collected from 10 individuals each of channel catfish, common carp, freshwater drum (gaspergou), largemouth bass, and white crappie but only from five smallmouth buffalo. The U.S. Geological Survey National Water Quality Laboratory analyzed the samples for 22 trace metals, 40 organochlorine pesticides and polychlorinated biphenyls, and 75 semivolatile organic compounds.

Crossing borders to bind proteins--a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set.

PubMed

Baltzer, Lars

2011-06-01

A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation.

Identification of non-streptococcal organisms from human dental plaque grown on the Streptococcus-selective medium mitis-salivarius agar.

PubMed

Kim, Yeon-Hee; Lee, Si Young

2015-02-01

Mitis-salivarius (MS) agar has been used widely in microbial epidemiological studies because oral viridans streptococci can be selectively grown on this medium. Even though the previous findings reported the limited selecting power of MS agar for streptococcus strains, the identities of non-streptococcal strains from human oral samples which can grow on this medium are not clear yet. In this study, we identified non-streptococcal organisms grown on MS agar plates by polymerase chain reaction (PCR) amplification and sequencing of the 16S ribosomal RNA (rRNA) gene. Eighty bacterial colonies on MS plates were isolated from plaque samples, and bacterial identification was achieved with the rapid ID 32 Strep system and mini API reader. The bacterial colonies identified as non-streptococci by the API system were selected for further identification. The 16S rRNA gene was amplified by PCR and verified using DNA sequencing analysis for identification. Sequences were compared with those of reference organisms in the genome database of the National Center for Biotechnology Information using the Basic Local Alignment Search Tool (BLAST). Among the 11 isolated non-streptococcal strains on MS plates, 3 strains were identified as Actinomyces naeslundii, 7 strains were identified as Actinomyces oris and 1 strain were identified as Actinomyces sp. using Blastn. In this study, we showed that some oral Actinomyces species can grow on Streptococcus-selective MS agar plates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of a new measurement system to detect selectively volatile organic compounds derived from the human body.

PubMed

Kanou, S; Nagaoka, T; Kobayashi, N; Kurahashi, M; Takeda, S; Aoki, T; Tsuji, T; Urano, T; Abe, T; Magatani, K

2013-01-01

A new concept expired gas measurement system used double cold-trap method was developed. The system could detect selectively volatile organic compound (VOC) derived from the human body. The gas chromatography (GC) profiles of healthy volunteer's expired gas collected by our system were analyzed. As a result, 60 VOCs were detected from the healthy volunteer's expired gas. We examined 14 VOCs among them further, which could be converted to the concentration from the GC profiles. The concentration of almost VOCs decreased when the subjects inspired purified air compared with the atmosphere. On the other hand, isoprene was almost the same. It was strongly suggested that these VOCs were derived from the human body because the concentration of these VOCs in the atmosphere were nearly zero. Expired gas of two sleep apnea syndrome (SAS) patients were analyzed as preliminary study. As a result of the study, the concentration of some VOCs contained in the expired gas of the SAS patients showed higher value than a healthy controls.

Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

PubMed

Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine

2009-05-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.

Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study

PubMed Central

Pinsk, Mark A.; Arcaro, Michael; Weiner, Kevin S.; Kalkus, Jan F.; Inati, Souheil J.; Gross, Charles G.; Kastner, Sabine

2009-01-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169

Antibiotic prescribing for upper respiratory-tract infections in primary care.

PubMed

Patterson, Craig A; Mackson, Judith M; Weekes, Lynn M

2003-01-01

The use and overuse of antibiotics in humans is a major contributor to the selection of antibiotic resistance organisms. Recent evidence has shown that primary care prescribing selects for resistances of clinical importance. The National Prescribing Service runs both educational and audit activities. The latter provide some insight into general practice attitudes toward antibiotic prescribing.

The study and application of four kinds of organic ion-selective microsensors

NASA Astrophysics Data System (ADS)

Yu, Bi; Zheng, Xiao; Feng, Chu; Hong, Wen-Bing; Liu, Jun-Tao; Wang, Ru-Jiang

1991-09-01

Four kinds of organic ion-selective microelectrodes (two barrels, tip diameter 0.1-0.5 micron) have been developed for the measurement of acetylcholine, histamine, serotonin, and bile acid. Physiological and pathological models on the cellular or sub-cellular level have been established for the purpose of basic and clinical pharmacological research, treatment or diagnosis of certain diseases. The acetylcholine sensitive microelectrode has been applied to the study of acetylcholine activity in single erythrocytes of normal human subjects and patients suffering from manic depressive disorders. The bile acid selective microelectrode has been used for the direct measurement of intracellular bile acid activities both in colorectal cancer and colorectal mucosa in living condition.

Reducing health risk assigned to organic emissions from a chemical weapons incinerator.

PubMed

Laman, David M; Weiler, B Douglas; Skeen, Rodney S

2013-03-01

Organic emissions from a chemical weapons incinerator have been characterized with an improved set of analytical methods to reduce the human health risk assigned to operations of the facility. A gas chromatography/mass selective detection method with substantially reduced detection limits has been used in conjunction with scanning electron microscopy/energy dispersive X-ray spectrometry and Fourier transform infrared microscopy to improve the speciation of semi-volatile and non-volatile organics emitted from the incinerator. The reduced detection limits have allowed a significant reduction in the assumed polycyclic aromatic hydrocarbon (PAH) and aminobiphenyl (ABP) emission rates used as inputs to the human health risk assessment for the incinerator. A mean factor of 17 decrease in assigned human health risk is realized for six common local exposure scenarios as a result of the reduced PAH and ABP detection limits.

77 FR 47853 - Request for Notification From Industry Organizations Interested in Participating in Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... pediatric labeling dispute involving FDA-regulated products, (9) pediatric ethical issues including research... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0781...

A Selected Bibliography of Readings in Management Theory and Practice. Exchange Bibliography No. 637.

ERIC Educational Resources Information Center

Pressley, Milton M., Ed.

Given that management can be defined as the activity that allocates and utilizes resources to achieve group or organizational goals, anyone who is in a position to assign and use a group's or organization's human or nonhuman resuources may benefit by making use of selected readings from this bibliography. The editor has divided the bibliography…

Impact of human activities on the ecology of nontuberculous mycobacteria.

PubMed

Falkinham, Joseph O

2010-06-01

Nontuberculous mycobacteria (NTM) are environmental opportunistic pathogens of humans and animals. They are found in a wide variety of habitats to which humans are exposed, including drinking water distribution systems and household water and plumbing. In that regard, they are distinct from their obligate pathogenic relatives, the members of the Mycobacterium tuberculosis complex. Owing to the presence of NTM in the human environment, human activities have had direct impacts on their ecology and thereby their epidemiology. NTM are oligotrophic, able to grow at low organic matter concentrations and over a wide range of temperatures, and even at low oxygen concentrations. Thus, NTM are normal inhabitants of natural waters and drinking waters. Discovery of the presence of NTM-polluted soils is not surprising in light of the ability of NTM to degrade a variety of hydrocarbon pollutants. A major human activity selecting for the growth and predominance of mycobacteria in habitats is disinfection. In comparison to other bacteria, NTM are disinfectant, heavy metal and antibiotic resistant. Therefore, the use of any antimicrobial agent selects for mycobacteria. Use of disinfectant in drinking water treatment selects for mycobacteria that can grow and come to proliferate in drinking water distribution systems in the absence of disinfectant-sensitive competing microorganisms. NTM selection may also occur as a consequence of antibiotics in drinking water sources.

Synthetic biology: a challenge to mechanical explanations in biology?

PubMed

Morange, Michel

2012-01-01

In their plans to modify organisms, synthetic biologists have contrasted engineering and tinkering. By drawing this contrast between their endeavors and what has happened during the evolution of organisms by natural selection, they underline the novelty of their projects and justify their ambitions. Synthetic biologists are at odds with a long tradition that has considered organisms as "perfect machines." This tradition had already been questioned by Stephen Jay Gould in the 1970s and received a major blow with the comparison made by François Jacob between organisms and the results of "bricolage" (tinkering). These contrasts between engineering and tinkering, synthetic biology and evolution, have no raison d'être. Machines built by humans are increasingly inspired by observations made on organisms. This is not a simple reversal of the previous trend-the mechanical conception of organisms-in which the characteristics of the latter were explained by comparison with human-built machines. Relations between organisms and machines have always been complex and ambiguous.

Pathophysiological Progression Model for Selected Toxicological Endpoints

EPA Science Inventory

The existing continuum paradigms are effective models to organize toxicological data associated with endpoints used in human health assessments. A compendium of endpoints characterized along a pathophysiological continuum would serve to: weigh the relative importance of effects o...

Hearings Before the Select Committee on Nutrition and Human Needs of the United States Senate, Ninety-Third Congress, First Session. Nutrition Education--1973. Parts 3, 4, and 5--TV Advertising of Food to Children. Washington, D.C., March 5, 6, and 12, 1973.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Nutrition and Human Needs.

These hearings before the Senate Select Committee on Nutrition and Human Needs are organized in several parts (See UD 013 650 for Parts 1, 2, and 2A). The purpose of these hearings is to review the quality of advertising now being directed at children, and the health implications of that advertising; as well as what steps can be taken to use…

Retrospective and prospective perspectives on zoonotic brucellosis

PubMed Central

Moreno, Edgardo

2014-01-01

Members of the genus Brucella are pathogenic bacteria exceedingly well adapted to their hosts. The bacterium is transmitted by direct contact within the same host species or accidentally to secondary hosts, such as humans. Human brucellosis is strongly linked to the management of domesticated animals and ingestion of their products. Since the domestication of ungulates and dogs in the Fertile Crescent and Asia in 12000 and 33000 ya, respectively, a steady supply of well adapted emergent Brucella pathogens causing zoonotic disease has been provided. Likewise, anthropogenic modification of wild life may have also impacted host susceptibility and Brucella selection. Domestication and human influence on wild life animals are not neutral phenomena. Consequently, Brucella organisms have followed their hosts’ fate and have been selected under conditions that favor high transmission rate. The “arm race” between Brucella and their preferred hosts has been driven by genetic adaptation of the bacterium confronted with the evolving immune defenses of the host. Management conditions, such as clustering, selection, culling, and vaccination of Brucella preferred hosts have profound influences in the outcome of brucellosis and in the selection of Brucella organisms. Countries that have controlled brucellosis systematically used reliable smooth live vaccines, consistent immunization protocols, adequate diagnostic tests, broad vaccination coverage and sustained removal of the infected animals. To ignore and misuse tools and strategies already available for the control of brucellosis may promote the emergence of new Brucella variants. The unrestricted use of low-efficacy vaccines may promote a “false sense of security” and works towards selection of Brucella with higher virulence and transmission potential. PMID:24860561

Organic solvent and temperature-enhanced ion chromatography-high resolution mass spectrometry for the determination of low molecular weight organic and inorganic anions.

PubMed

Gilchrist, Elizabeth S; Nesterenko, Pavel N; Smith, Norman W; Barron, Leon P

2015-03-20

There has recently been increased interest in coupling ion chromatography (IC) to high resolution mass spectrometry (HRMS) to enable highly sensitive and selective analysis. Herein, the first comprehensive study focusing on the direct coupling of suppressed IC to HRMS without the need for post-suppressor organic solvent modification is presented. Chromatographic selectivity and added HRMS sensitivity offered by organic solvent-modified IC eluents on a modern hyper-crosslinked polymeric anion-exchange resin (IonPac AS18) are shown using isocratic eluents containing 5-50 mM hydroxide with 0-80% methanol or acetonitrile for a range of low molecular weight anions (<165 Da). Comprehensive experiments on IC thermodynamics over a temperature range between 20-45 °C with the eluent containing up to 60% of acetonitrile or methanol revealed markedly different retention behaviour and selectivity for the selected analytes on the same polymer based ion-exchange resin. Optimised sensitivity with HRMS was achieved with as low as 30-40% organic eluent content. Analytical performance characteristics are presented and compared with other IC-MS based works. This study also presents the first application of IC-HRMS to forensic detection of trace low-order anionic explosive residues in latent human fingermarks. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploring gene-culture interactions: insights from handedness, sexual selection and niche-construction case studies.

PubMed

Laland, Kevin N

2008-11-12

Genes and culture represent two streams of inheritance that for millions of years have flowed down the generations and interacted. Genetic propensities, expressed throughout development, influence what cultural organisms learn. Culturally transmitted information, expressed in behaviour and artefacts, spreads through populations, modifying selection acting back on populations. Drawing on three case studies, I will illustrate how this gene-culture coevolution has played a critical role in human evolution. These studies explore (i) the evolution of handedness, (ii) sexual selection with a culturally transmitted mating preference, and (iii) cultural niche construction and human evolution. These analyses shed light on how genes and culture shape each other, and on the significance of feedback mechanisms between biological and cultural processes.

Simultaneous determination of indoor ammonia pollution and its biological metabolite in the human body with a recyclable nanocrystalline lanthanide-functionalized MOF

NASA Astrophysics Data System (ADS)

Hao, Ji-Na; Yan, Bing

2016-01-01

A Eu3+ post-functionalized metal-organic framework of nanosized Ga(OH)bpydc(Eu3+@Ga(OH)bpydc, 1a) with intense luminescence is synthesized and characterized. Luminescence measurements reveal that 1a can detect ammonia gas selectively and sensitively among various indoor air pollutants. 1a can simultaneously determine a biological ammonia metabolite (urinary urea) in the human body, which is a rare example of a luminescent sensor that can monitor pollutants in the environment and also detect their biological markers. Furthermore, 1a exhibits appealing features including high selectivity and sensitivity, fast response, simple and quick regeneration, and excellent recyclability.A Eu3+ post-functionalized metal-organic framework of nanosized Ga(OH)bpydc(Eu3+@Ga(OH)bpydc, 1a) with intense luminescence is synthesized and characterized. Luminescence measurements reveal that 1a can detect ammonia gas selectively and sensitively among various indoor air pollutants. 1a can simultaneously determine a biological ammonia metabolite (urinary urea) in the human body, which is a rare example of a luminescent sensor that can monitor pollutants in the environment and also detect their biological markers. Furthermore, 1a exhibits appealing features including high selectivity and sensitivity, fast response, simple and quick regeneration, and excellent recyclability. Electronic supplementary information (ESI) available: Experimental section; XPS spectra; N2 adsorption-desorption isotherms; ICP data; SEM image; PXRD patterns and other luminescence data. See DOI: 10.1039/c5nr06066d

Managing effectively in the downsized organization.

PubMed

Arnold, Edwin; Pulich, Marcia

2003-01-01

Many health care institutions have downsized in recent years for a variety of reasons including cost savings and the need to be proactive in restructuring the organization for more effective performance. In a downsized organization, top management must develop new strategies to enable line managers at all levels to operate effectively. New policies for human resource strategic planning, selective hiring, employee empowerment, training and development, reduction of status distinctions, sharing of appropriate information with employees, and paying for performance must be implemented.

Alternate Models of Needs Assessment: Selecting the Right One for Your Organization.

ERIC Educational Resources Information Center

Leigh, Doug; Watkins, Ryan; Platt, William A.; Kaufman, Roger

2000-01-01

Defines needs assessment and compares different models in terms of levels (mega, macro, micro) and process and input. Recommends assessment of strengths and weakness of a model before using it in human resource development. (SK)

Proactive strategies to avoid infectious disease

PubMed Central

Stevenson, Richard J.; Case, Trevor I.; Oaten, Megan J.

2011-01-01

Infectious disease exerts a large selective pressure on all organisms. One response to this has been for animals to evolve energetically costly immune systems to counter infection, while another—the focus of this theme issue—has been the evolution of proactive strategies primarily to avoid infection. These strategies can be grouped into three types, all of which demonstrate varying levels of interaction with the immune system. The first concerns maternal strategies that function to promote the immunocompetence of their offspring. The second type of strategy influences mate selection, guiding the selection of a healthy mate and one who differs maximally from the self in their complement of antigen-coding genes. The third strategy involves two classes of behaviour. One relates to the capacity of the organisms to learn associations between cues indicative of pathogen threat and immune responses. The other relates to prevention and even treatment of infection through behaviours such as avoidance, grooming, quarantine, medicine and care of the sick. In humans, disease avoidance is based upon cognition and especially the emotion of disgust. Human disease avoidance is not without its costs. There is a propensity to reject healthy individuals who just appear sick—stigmatization—and the system may malfunction, resulting in various forms of psychopathology. Pathogen threat also appears to have been a highly significant and unrecognized force in shaping human culture so as to minimize infection threats. This cultural shaping process—moralization—can be co-opted to promote human health. PMID:22042913

Cultural evolution and emergent group-level traits through social heterosis.

PubMed

Nonacs, Peter; Kapheim, Karen M

2014-06-01

Smaldino proposes emergent properties of human groups, arising when individuals display both differentiation and organization, constitute a novel unit of cultural selection not addressed by current evolutionary theory. We propose existing theoretical frameworks for maintenance of genetic diversity - social heterosis and social genomes - can similarly explain the appearance and maintenance of human cultural diversity (i.e., group-level traits) and collaborative interdependence.

Human long intrinsically disordered protein regions are frequent targets of positive selection.

PubMed

Afanasyeva, Arina; Bockwoldt, Mathias; Cooney, Christopher R; Heiland, Ines; Gossmann, Toni I

2018-06-01

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species, it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here, we address this question by investigating the evolutionary pattern of more than 6600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a priori knowledge of disordered protein regions, and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs fourfold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts. © 2018 Afanasyeva et al.; Published by Cold Spring Harbor Laboratory Press.

Stress markers in relation to job strain in human service organizations.

PubMed

Ohlson, C G; Söderfeldt, M; Söderfeldt, B; Jones, I; Theorell, T

2001-01-01

Workers in human service organizations are often confronted with conflicting demands in providing care or education. The aim of this cross-sectional study was to relate levels of endocrine stress markers to perceived job strain in two human service organizations. Employees in two local units of the social insurance organization and two local units of the individual and family care sections of the social welfare in Sweden were selected and 103 employees participated (56% participation rate). The perceived job strain was assessed with a standardized questionnaire containing questions of the demand-control model. Questions specially designed to measure emotional demands were also included. The stress markers cortisol, prolactin, thyroid-stimulating hormone, testosterone and IgA and IgG were analysed in blood samples. The main finding was an association between high emotional strain and increased levels of prolactin. The levels of cortisol, but none of the other four stress markers, increased slightly with emotional strain. Emotional strain experienced in human service work may cause psychological stress. The increase in prolactin was modest but consistent with findings in other published studies on stress-related endocrine alterations. Copyright 2001 S. Karger AG, Basel.

Ethics review: Dark angels – the problem of death in intensive care

PubMed Central

2007-01-01

Critical care medicine has expanded the envelope of debilitating disease through the application of an aggressive and invasive care plan, part of which is designed to identify and reverse organ dysfunction before it proceeds to organ failure. For a select patient population, this care plan has been remarkably successful. But because patient selection is very broad, critical care sometimes yields amalgams of life in death: the state of being unable to participate in human life, unable to die, at least in the traditional sense. This work examines the emerging paradox of somatic versus brain death and why it matters to medical science. PMID:17254317

Biochemical, endocrine, and hematological factors in human oxygen tolerance extension: Predictive studies 6

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.; Clark, J. M.

1992-01-01

The Predictive Studies VI (Biochemical, endocrine, and hematological factors in human oxygen tolerance extension) Program consisted of two related areas of research activity, integrated in design and performance, that were each based on an ongoing analysis of human organ oxygen tolerance data obtained for the continuous oxygen exposures of the prior Predictive Studies V Program. The two research areas effectively blended broad investigation of systematically varied intermittent exposure patterns in animals with very selective evaluation of specific exposure patterns in man.

Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall

PubMed Central

Gelbard-Sagiv, Hagar; Mukamel, Roy; Harel, Michal; Malach, Rafael; Fried, Itzhak

2009-01-01

The emergence of memory, a trace of things past, into human consciousness is one of the greatest mysteries of the human mind. Whereas the neuronal basis of recognition memory can be probed experimentally in human and nonhuman primates, the study of free recall requires that the mind declare the occurrence of a recalled memory (an event intrinsic to the organism and invisible to an observer). Here, we report the activity of single neurons in the human hippocampus and surrounding areas when subjects first view cinematic episodes consisting of audiovisual sequences and again later when they freely recall these episodes. A subset of these neurons exhibited selective firing, which often persisted throughout and following specific episodes for as long as 12 seconds. Verbal reports of memories of these specific episodes at the time of free recall were preceded by selective reactivation of the same hippocampal and entorhinal cortex neurons. We suggest that this reactivation is an internally generated neuronal correlate for the subjective experience of spontaneous emergence of human recollection. PMID:18772395

Does natural selection organize ecosystems for the maintenance of high productivity and diversity?

PubMed Central

Leigh, Egbert Giles; Vermeij, Geerat Jacobus

2002-01-01

Three types of evidence suggest that natural ecosystems are organized for high productivity and diversity: (i) changes not previously experienced by a natural ecosystem, such as novel human disturbances, tend to diminish its productivity and/or diversity, just as 'random' changes in a machine designed for a function usually impair its execution of that function; (ii) humans strive to recreate properties of natural ecosystems to enhance productivity of artificial ones, as farmers try to recreate properties of natural soils in their fields; and (iii) productivity and diversity have increased during the Earth's history as a whole, and after every major biotic crisis. Natural selection results in ecosystems organized to maintain high productivity of organic matter and diversity of species, just as competition among individuals in Adam Smith's ideal economy favours high production of wealth and diversity of occupations. In nature, poorly exploited energy attracts more efficient users. This circumstance favours the opening of new ways of life and more efficient recycling of resources, and eliminates most productivity-reducing 'ecological monopolies'. Ecological dominants tend to be replaced by successors with higher metabolism, which respond to more stimuli and engage in more varied interactions. Finally, increasingly efficient predators and herbivores favour faster turnover of resources. PMID:12079531

Impact of HLA diversity on donor selection in organ and stem cell transplantation.

PubMed

Tiercy, Jean-Marie; Claas, Frans

2013-01-01

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

The Puzzle of HIV Neutral and Selective Evolution.

PubMed

Leitner, Thomas

2018-06-01

HIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that. HIV evolution is also a clear example of strong positive selection, that is, mutants have a survival advantage. How do these facts come together?

Exploring the multiplicity of soil-human interactions: organic carbon content, agro-forest landscapes and the Italian local communities.

PubMed

Salvati, Luca; Barone, Pier Matteo; Ferrara, Carlotta

2015-05-01

Topsoil organic carbon (TOC) and soil organic carbon (SOC) are fundamental in the carbon cycle influencing soil functions and attributes. Many factors have effects on soil carbon content such as climate, parent material, land topography and the human action including agriculture, which sometimes caused a severe loss in soil carbon content. This has resulted in a significant differentiation in TOC or SOC at the continental scale due to the different territorial and socioeconomic conditions. The present study proposes an exploratory data analysis assessing the relationship between the spatial distribution of soil organic carbon and selected socioeconomic attributes at the local scale in Italy with the aim to provide differentiated responses for a more sustainable use of land. A strengths, weaknesses, opportunities and threats (SWOT) analysis contributed to understand the effectiveness of local communities responses for an adequate comprehension of the role of soil as carbon sink.

The role of the hippocampus in navigation is memory

PubMed Central

2017-01-01

There is considerable research on the neurobiological mechanisms within the hippocampal system that support spatial navigation. In this article I review the literature on navigational strategies in humans and animals, observations on hippocampal function in navigation, and studies of hippocampal neural activity in animals and humans performing different navigational tasks and tests of memory. Whereas the hippocampus is essential to spatial navigation via a cognitive map, its role derives from the relational organization and flexibility of cognitive maps and not from a selective role in the spatial domain. Correspondingly, hippocampal networks map multiple navigational strategies, as well as other spatial and nonspatial memories and knowledge domains that share an emphasis on relational organization. These observations suggest that the hippocampal system is not dedicated to spatial cognition and navigation, but organizes experiences in memory, for which spatial mapping and navigation are both a metaphor for and a prominent application of relational memory organization. PMID:28148640

Development of urine standard reference materials for metabolites of organic chemicals including polycyclic aromatic hydrocarbons, phthalates, phenols, parabens, and volatile organic compounds.

PubMed

Schantz, Michele M; Benner, Bruce A; Heckert, N Alan; Sander, Lane C; Sharpless, Katherine E; Vander Pol, Stacy S; Vasquez, Y; Villegas, M; Wise, Stephen A; Alwis, K Udeni; Blount, Benjamin C; Calafat, Antonia M; Li, Zheng; Silva, Manori J; Ye, Xiaoyun; Gaudreau, Éric; Patterson, Donald G; Sjödin, Andreas

2015-04-01

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers' Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers' Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants.

Development of urine standard reference materials for metabolites of organic chemicals including polycyclic aromatic hydrocarbons, phthalates, phenols, parabens, and volatile organic compounds

PubMed Central

Schantz, Michele M.; Benner, Bruce A.; Heckert, N. Alan; Sander, Lane C.; Sharpless, Katherine E.; Vander Pol, Stacy S.; Vasquez, Y.; Villegas, M.; Wise, Stephen A.; Alwis, K. Udeni; Blount, Benjamin C.; Calafat, Antonia M.; Li, Zheng; Silva, Manori J.; Ye, Xiaoyun; Gaudreau, Éric; Patterson, Donald G.; Sjödin, Andreas

2016-01-01

Two new Standard Reference Materials (SRMs), SRM 3672 Organic Contaminants in Smokers’ Urine (Frozen) and SRM 3673 Organic Contaminants in Non-Smokers’ Urine (Frozen), have been developed in support of studies for assessment of human exposure to select organic environmental contaminants. Collaborations among three organizations resulted in certified values for 11 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and reference values for 11 phthalate metabolites, 8 environmental phenols and parabens, and 24 volatile organic compound (VOC) metabolites. Reference values are also available for creatinine and the free forms of caffeine, theobromine, ibuprofen, nicotine, cotinine, and 3-hydroxycotinine. These are the first urine Certified Reference Materials characterized for metabolites of organic environmental contaminants. Noteworthy, the mass fractions of the environmental organic contaminants in the two SRMs are within the ranges reported in population survey studies such as the National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS). These SRMs will be useful as quality control samples for ensuring compatibility of results among population survey studies and will fill a void to assess the accuracy of analytical methods used in studies monitoring human exposure to these organic environmental contaminants. PMID:25651899

Soldier Capability - Army Combat Effectiveness (SCACE). Volume 2. Selected Bibliography

DTIC Science & Technology

1981-02-01

Human Resources Research Office, June 1963. 388. McLachlan, Joseph C., et al. Navy-Wide Standardized Proficiency Testing Program for Fleet JEZEBEL...Directorate of Evaluation, August 1979. 428. Olmstead, Joseph A., et al. Research on Training for Brigade Com- mand Groups: Factors Contributing to Unit...orormance Human Rsurces Research Organization, August 1972. 686. Vitola, B. M., Guinn, N., and Wilbourn , J. N. acm o Various Enlistment Standards on

Developing Trust in Virtual Teams

ERIC Educational Resources Information Center

Germain, Marie-Line

2011-01-01

Rapid globalization, advances in technology, flatter organizational structures, synergistic cooperation among firms, and a shift to knowledge work environments have led to the increasing use of virtual teams in organizations. Selecting, training, and socializing employees in virtual teamwork has therefore become an important human resource…

Inferring the Mode of Selection from the Transient Response to Demographic Perturbations

NASA Astrophysics Data System (ADS)

Balick, Daniel; Do, Ron; Reich, David; Sunyaev, Shamil

2014-03-01

Despite substantial recent progress in theoretical population genetics, most models work under the assumption of a constant population size. Deviations from fixed population sizes are ubiquitous in natural populations, many of which experience population bottlenecks and re-expansions. The non-equilibrium dynamics introduced by a large perturbation in population size are generally viewed as a confounding factor. In the present work, we take advantage of the transient response to a population bottleneck to infer features of the mode of selection and the distribution of selective effects. We develop an analytic framework and a corresponding statistical test that qualitatively differentiates between alleles under additive and those under recessive or more general epistatic selection. This statistic can be used to bound the joint distribution of selective effects and dominance effects in any diploid sexual organism. We apply this technique to human population genetic data, and severely restrict the space of allowed selective coefficients in humans. Additionally, one can test a set of functionally or medically relevant alleles for the primary mode of selection, or determine the local regional variation in dominance coefficients along the genome.

Poverty of the stimulus revisited.

PubMed

Berwick, Robert C; Pietroski, Paul; Yankama, Beracah; Chomsky, Noam

2011-01-01

A central goal of modern generative grammar has been to discover invariant properties of human languages that reflect "the innate schematism of mind that is applied to the data of experience" and that "might reasonably be attributed to the organism itself as its contribution to the task of the acquisition of knowledge" (Chomsky, 1971). Candidates for such invariances include the structure dependence of grammatical rules, and in particular, certain constraints on question formation. Various "poverty of stimulus" (POS) arguments suggest that these invariances reflect an innate human endowment, as opposed to common experience: Such experience warrants selection of the grammars acquired only if humans assume, a priori, that selectable grammars respect substantive constraints. Recently, several researchers have tried to rebut these POS arguments. In response, we illustrate why POS arguments remain an important source of support for appeal to a priori structure-dependent constraints on the grammars that humans naturally acquire. Copyright © 2011 Cognitive Science Society, Inc.

It's not all about us: evolution and maintenance of Cryptococcus virulence requires selection outside the human host.

PubMed

Gerstein, Aleeza C; Nielsen, Kirsten

2017-04-01

Cryptococcus is predominantly an AIDS-related pathogen that causes significant morbidity and mortality in immunocompromised patients. Research studies have historically focused on understanding how the organism causes human disease through the use of in vivo and in vitro model systems to identify virulence factors. Cryptococcus is not an obligate pathogen, however, as human-human transmission is either absent or rare. Selection in the environment must thus be invoked to shape the evolution of this taxa, and directly influences genotypic and trait diversity. Importantly, the evolution and maintenance of pathogenicity must also stem directly from environmental selection. To that end, here we examine abiotic and biotic stresses in the environment, and discuss how they could shape the factors that are commonly identified as important virulence traits. We identify a number of important unanswered questions about Cryptococcus diversity and evolution that are critical for understanding this deadly pathogen, and discuss how implementation of modern sampling and genomic tools could be utilized to answer these questions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Biocatalytic synthesis of 4-pregnen-20,21-diol-3-one, a selective inhibitor of human 5alpha-reductase type II.

PubMed

Hannemann, Frank; Bernhardt, Rita; Jose, Joachim

2007-10-01

Biocatalysis, the conversion of substrates into valuable products by the use of enzymes, has some striking advantages in comparison to standard organic chemistry for drug synthesis. By biocatalysis, substrates that contain several identical reactive groups at different positions can be converted with high regio-selectivity and enantio-selectivity. In this study, an E. coli isolate (E132) was identified which was able to convert the steroid desoxycorticosterone into the product 4-pregnen-20,21-diol-3-one in real terms. The product was purified from the cell culture supernatant by HPLC and its structure was demonstrated by mass spectrometry and NMR spectroscopy. It was tested on inhibition of human 5alpha-reductases type I and type II. At a concentration of 10 microM, inhibition was 49.0% for type I and 81.8% for type II, whereas there was no inhibition of human aromatase (CYP19) at 20 microM and human 17alpha-hydroxylase-C17,20-lyase (CYP17) at 2.5 microM detectable. The IC50 value of 4-pregnen-20,21-diol-3-one for human 5alpha-reductase type II was determined to be 1.56 microM.

Changing organisms in rapidly changing anthropogenic landscapes: the significance of the ‘Umwelt’-concept and functional habitat for animal conservation

PubMed Central

Van Dyck, Hans

2012-01-01

There is a growing recognition for the significance of evolutionary thinking in ecology and conservation biology. However, ecology and conservation studies often work with species-specific, fixed traits that ignore intraspecific variation. The way the habitat of a species is considered is an example of typological thinking biased by human perception. Structural habitat units (e.g., land cover types) as perceived by humans may not represent functional habitat units for other organisms. Human activity may also interfere with the environmental information used by organisms. Therefore, the Umwelt-concept from ethology needs to be integrated in the way we think about habitat and habitat selection. It states that different organisms live in different perceptual worlds dealing with specific subsamples of the environment as a result of their evolutionary and developmental history. The resource-based habitat concept is a functional habitat model based on resource distributions (consumables and conditions) and individual movements. This behavioural approach takes into account aspects that relate to the perceptual world of organisms. This approach may offer new opportunities for conservation and may help avoid failures with habitat restoration. Perceptual ability may be subject to adaptive change, but it may also constrain organisms from showing adaptive behaviours in rapidly changing environments. PMID:25568037

Changing organisms in rapidly changing anthropogenic landscapes: the significance of the 'Umwelt'-concept and functional habitat for animal conservation.

PubMed

Van Dyck, Hans

2012-02-01

There is a growing recognition for the significance of evolutionary thinking in ecology and conservation biology. However, ecology and conservation studies often work with species-specific, fixed traits that ignore intraspecific variation. The way the habitat of a species is considered is an example of typological thinking biased by human perception. Structural habitat units (e.g., land cover types) as perceived by humans may not represent functional habitat units for other organisms. Human activity may also interfere with the environmental information used by organisms. Therefore, the Umwelt-concept from ethology needs to be integrated in the way we think about habitat and habitat selection. It states that different organisms live in different perceptual worlds dealing with specific subsamples of the environment as a result of their evolutionary and developmental history. The resource-based habitat concept is a functional habitat model based on resource distributions (consumables and conditions) and individual movements. This behavioural approach takes into account aspects that relate to the perceptual world of organisms. This approach may offer new opportunities for conservation and may help avoid failures with habitat restoration. Perceptual ability may be subject to adaptive change, but it may also constrain organisms from showing adaptive behaviours in rapidly changing environments.

Recombination walking: genetic selection of clones from pooled libraries of yeast artificial chromosomes by homologous recombination.

PubMed Central

Miller, A M; Savinelli, E A; Couture, S M; Hannigan, G M; Han, Z; Selden, R F; Treco, D A

1993-01-01

Recombination walking is based on the genetic selection of specific human clones from a yeast artificial chromosome (YAC) library by homologous recombination. The desired clone is selected from a pooled (unordered) YAC library, eliminating labor-intensive steps typically used in organizing and maintaining ordered YAC libraries. Recombination walking represents an efficient approach to library screening and is well suited for chromosome-walking approaches to the isolation of genes associated with common diseases. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8367472

Cyclodextrin-Based Metal-Organic Nanotube as Fluorescent Probe for Selective Turn-On Detection of Hydrogen Sulfide in Living Cells Based on H2S-Involved Coordination Mechanism

NASA Astrophysics Data System (ADS)

Xin, Xuelian; Wang, Jingxin; Gong, Chuanfang; Xu, Hai; Wang, Rongming; Ji, Shijie; Dong, Hanxiao; Meng, Qingguo; Zhang, Liangliang; Dai, Fangna; Sun, Daofeng

2016-02-01

Hydrogen sulfide (H2S) has been considered as the third biologically gaseous messenger (gasotransmitter) after nitric oxide (NO) and carbon monoxide (CO). Fluorescent detection of H2S in living cells is very important to human health because it has been found that the abnormal levels of H2S in human body can cause Alzheimer’s disease, cancers and diabetes. Herein, we develop a cyclodextrin-based metal-organic nanotube, CD-MONT-2, possessing a {Pb14} metallamacrocycle for efficient detection of H2S. CD-MONT-2‧ (the guest-free form of CD-MONT-2) exhibits turn-on detection of H2S with high selectivity and moderate sensitivity when the material was dissolved in DMSO solution. Significantly, CD-MONT-2‧ can act as a fluorescent turn-on probe for highly selective detection of H2S in living cells. The sensing mechanism in the present work is based on the coordination of H2S as the auxochromic group to the central Pb(II) ion to enhance the fluorescence intensity, which is studied for the first time.

Architecture of human translation initiation factor 3

PubMed Central

Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

2013-01-01

SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

Directed Selection of Biochars for Amending Metal Contaminated Mine Soils

EPA Science Inventory

Approximately 500,000 abandoned mines across the U.S. pose a considerable, pervasive risk to human health and the environment. World-wide the problem is even larger. Lime, organic matter, biosolids and other amendments have been used to decrease metal bioavailability in contami...

Aptamer-functionalized Magnetic Conjugated Organic Frameworks for Selective Extraction of Trace Hydroxylated Polychlorinated Biphenyls in Human Serum.

PubMed

Jiang, Dandan; Hu, Tingting; Zheng, Haijiao; Xu, Guoxing; Jia, Qiong

2018-05-02

Herein, a novel solid phase extraction adsorbent based on aptamer-functionalized magnetic conjugated organic frameworks (COFs) was developed for selective extraction of trace hydroxylated polychlorinated biphenyls (OH-PCBs). The material possessed advantages of superparamagnetism of magnetic core, high surface area and porous structure of COFs, and high specific affinity of aptamer. In combination with high-performance liquid chromatography/mass spectrometry, the aptamer-functionalized magnetic COFs was used for the capture of hydroxy-2',3',4',5,5'-pentachlorobiphenyl (2-OH-CB 124) in human serum. The method provided a linear range of 0.01-40 ng mL-1 with a good correlation coefficient (R2= 0.9973). The limit of detection was found to be as low as 2.1 pg mL-1. Furthermore, the material possessed good reusability and could be applied in replicate at least for 10 extraction cycles with recoveries over 90%. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibitory effect of selective cyclooxygenase-2 inhibitor etoricoxib on human organic anion transporter 3 (hOAT3).

PubMed

Honjo, Hiroaki; Uwai, Yuichi; Iwamoto, Kikuo

2011-04-01

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) delay the elimination of methotrexate. One of the mechanisms is thought to be inhibition of methotrexate uptake via human organic anion transporter 3 (hOAT3, SLC22A8) in the renal proximal tubule by NSAIDs. In this study, we evaluated the inhibitory effects of selective cyclooxygenase-2 inhibitor etoricoxib on hOAT3 by uptake experiments using Xenopus laevis oocytes. The injection of hOAT3 cRNA stimulated the uptake of methotrexate into the oocytes, and its transport was inhibited by etoricoxib. Etoricoxib inhibited estrone sulfate uptake by hOAT3 dose dependently, and the 50% inhibitory concentration was estimated to be 9.8 µM. Eadie-Hofstee plot analysis showed that etoricoxib inhibited hOAT3 in a competitive manner. These findings show that etoricoxib has inhibitory effect on hOAT3, and that the potential is comparable to that of traditional NSAIDs. ©2011 Bentham Science Publishers Ltd.

Cloning humans? Biological, ethical, and social considerations.

PubMed

Ayala, Francisco J

2015-07-21

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits.

Cloning humans? Biological, ethical, and social considerations

PubMed Central

Ayala, Francisco J.

2015-01-01

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits. PMID:26195738

Serial grouping of 2D-image regions with object-based attention in humans.

PubMed

Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R

2016-06-13

After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas.

2009 Epigenetics Gordon Research Conference (August 9 - 14, 2009)

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

Jeanie Lee

Epigenetics refers to the study of heritable changes in genome function that occur without a change in primary DNA sequence. The 2009 Gordon Conference in Epigenetics will feature discussion of various epigenetic phenomena, emerging understanding of their underlying mechanisms, and the growing appreciation that human, animal, and plant health all depend on proper epigenetic control. Special emphasis will be placed on genome-environment interactions particularly as they relate to human disease. Towards improving knowledge of molecular mechanisms, the conference will feature international leaders studying the roles of higher order chromatin structure, noncoding RNA, repeat elements, nuclear organization, and morphogenic evolution. Traditionalmore » and new model organisms are selected from plants, fungi, and metazoans.« less

Simultaneous determination of indoor ammonia pollution and its biological metabolite in the human body with a recyclable nanocrystalline lanthanide-functionalized MOF.

PubMed

Hao, Ji-Na; Yan, Bing

2016-02-07

A Eu(3+) post-functionalized metal-organic framework of nanosized Ga(OH)bpydc(Eu(3+)@Ga(OH)bpydc, 1a) with intense luminescence is synthesized and characterized. Luminescence measurements reveal that 1a can detect ammonia gas selectively and sensitively among various indoor air pollutants. 1a can simultaneously determine a biological ammonia metabolite (urinary urea) in the human body, which is a rare example of a luminescent sensor that can monitor pollutants in the environment and also detect their biological markers. Furthermore, 1a exhibits appealing features including high selectivity and sensitivity, fast response, simple and quick regeneration, and excellent recyclability.

Genomics of Preterm Birth

PubMed Central

Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

2015-01-01

The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

Darwinian medicine and psoriasis.

PubMed

Romaní de Gabriel, J

2015-04-01

Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Validation of the analytical method for the simultaneous determination of selected polybrominated diphenyl ethers, polychlorinated biphenyls and organochlorine pesticides in human blood serum by gas chromatography with microelectron capture detector.

PubMed

Matuszak, Małgorzata; Minorczyk, Maria; Góralczyk, Katarzyna; Hernik, Agnieszka; Struciński, Paweł; Liszewska, Monika; Czaja, Katarzyna; Korcz, Wojciech; Łyczewska, Monika; Ludwicki, Jan K

2016-01-01

Polybrominated diphenyl ethers (PBDEs) as other persistent organic pollutants like polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) pose a significant hazard to human health, mainly due to interference with the endocrine system and carcinogenetic effects. Humans are exposed to these substances mainly through a food of animal origin. These pollutants are globally detected in human matrices which requires to dispose reliable and simple analytical method that would enable further studies to assess the exposure of specific human populations to these compounds. The purpose of this study was to modify and validate of the analytical procedure for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum samples. The analytical measurement was performed by GC-µECD following preparation of serum samples (denaturation, multiple extraction, lipid removal). Identity of the compounds was confirmed by GC-MS. The method was characterised by the appropriate linearity, good repeatability (CV below 20%). The recoveries ranged from 52.9 to 125.0% depending on compound and level of fortification. The limit of quantification was set at 0.03 ng mL(-1) of serum. The modified analytical method proved to be suitable for the simultaneous determination of selected PBDEs, PCBs and OCPs in human blood serum by GC-µECD with good precision.

The challenges of organizing an international course in Latin America.

PubMed

Vairo, Filippo; López, Mónica Luján; Cruz, Carolina Uribe; Corrêa, Priscila Gomes; Baldo, Guilherme

2014-03-01

The Latin American School of Human and Medical Genetics (ELAG) is the main course of its kind in the genetics field in Latin America. Here we describe the main challenges regarding the organization of such event, including how we obtain funding and how we proceed with student selection. Thus, we aim to share our experience with other groups that intend to follow this format to create similar events in other areas in this region of the world.

Improving the Selection, Classification, and Utilization of Army Enlisted Personnel. Annual Report, 1985 Fiscal Year. Supplement

DTIC Science & Technology

1987-10-01

PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK Human Resources Research Organization 2 P 3 QA2 79 9"INiTNUMBERS 1100...classification tests which will validly predict carefully developed measures of job performance . The project addresses the 675,000-person enlisted personnel...are to include both Army-wide job performance measures based on newly developed rating scales, and direct hands-on measures of MOS-specific task

Develop Recovery Systems for Separations of Salts from Process Streams for use in Advanced Life Support System

NASA Technical Reports Server (NTRS)

Colon, Guillermo

1998-01-01

The main objectives of this project were the development of a four-compartment electrolytic cell using high selective membranes to remove nitrate from crop residue leachate and convert it to nitric acid, and the development of an six compartment electrodialysis cell to remove selectively sodium from urine wastes. The recovery of both plant inedible biomass and human wastes nutrients to sustain a biomass production system are important aspects in the development of a controlled ecological life support system (CELSS) to provide the basic human needs required for life support during long term space missions. A four-compartment electrolytic cell has been proposed to remove selectively nitrate from crop residue and to convert it to nitric acid, which is actually used in the NASA-KSC Controlled Ecological Life Support System to control the pH of the aerobic bioreactors and biomass production chamber. Human activities in a closed system require large amount of air, water and minerals to sustain life and also generate wastes. Before using human wastes as nutrients, these must be treated to reduce organic content and to remove some minerals which have adverse effects on plant growth. Of all the minerals present in human urine, sodium chloride (NACl) is the only one that can not be used as nutrient for most plants. Human activities also requires sodium chloride as part of the diet. Therefore, technology to remove and recover sodium chloride from wastes is highly desirable. A six-compartment electrodialysis cell using high selective membranes has been proposed to remove and recover NaCl from human urine.

Small-world human brain networks: Perspectives and challenges.

PubMed

Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

2017-06-01

Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human exposure, biomarkers, and fate of organotins in the environment.

PubMed

Okoro, Hussein K; Fatoki, Olalekan S; Adekola, Folahan A; Ximba, Bhekumusa J; Snyman, Reinette G; Opeolu, Beatrice

2011-01-01

Organotin compounds result from the addition of organic moieties to inorganic tin.Thus, one or more tin-carbon bonds exist in each organotin molecule. The organo-tin compounds are ubiquitous in the environment. Organotin compounds have many uses, including those as fungicides and stabilizers in plastics, among others in industry. The widespread use of organotins as antifouling agents in boat paints has resulted in pollution of freshwater and marine ecosystems. The presence of organotin compounds in freshwater and marine ecosystems is now understood to be a threat, because of the amounts found in water and the toxicity of some organotin compounds to aquatic organisms, and perhaps to humans as well. Organotin com-pounds are regarded by many to be global pollutants of a stature similar to biphenyl,mercury, and the polychlorinated dibenzodioxins. This stature results from the high toxicity, persistence, bioaccumulation, and endocrine disruptive features of even very low levels of selected organotin compounds.Efforts by selected governmental agencies and others have been undertaken to find a global solution to organotin pollution. France was the first country to ban the use of the organotins in 1980. This occurred before the international maritime organization (IMO) called for a global treaty to ban the application of tributyltin (TBT)-based paints. In this chapter, we review the organotin compounds with emphasis on the human exposure, fate, and distribution of them in the environment. The widespread use of the organotins and their high stability have led to contamination of some aquatic ecosystems. As a result, residues of the organotins may reach humans via food consumption. Notwithstanding the risk of human exposure, only limited data are available on the levels at which the organotins exist in foodstuffs consumed by humans. Moreover, the response of marine species to the organotins, such as TBT, has not been thoroughly investigated. Therefore, more data on the organotins and the consequences of exposure to them are needed. In particular, we believe the following areas need attention: expanded toxicity testing in aquatic species, human exposure, human body burdens, and the research to identify biomarkers for testing the toxicity of the organotins to marine invertebrates.

Quantification of selected volatile organic compounds in human urine by gas chromatography selective reagent ionization time of flight mass spectrometry (GC-SRI-TOF-MS) coupled with head-space solid-phase microextraction (HS-SPME).

PubMed

Mochalski, Paweł; Unterkofler, Karl

2016-08-07

Selective reagent ionization time of flight mass spectrometry with NO(+) as the reagent ion (SRI-TOF-MS(NO(+))) in conjunction with gas chromatography (GC) and head-space solid-phase microextraction (HS-SPME) was used to determine selected volatile organic compounds in human urine. A total of 16 volatiles exhibiting high incidence rates were quantified in the urine of 19 healthy volunteers. Amongst them there were ten ketones (acetone, 2-butanone, 3-methyl-2-butanone, 2-pentanone, 3-methyl-2-pentanone, 4-methyl-2-pentanone, 2-hexanone, 3-hexanone, 2-heptanone, and 4-heptanone), three volatile sulphur compounds (dimethyl sulfide, allyl methyl sulfide, and methyl propyl sulfide), and three heterocyclic compounds (furan, 2-methylfuran, 3-methylfuran). The concentrations of the species under study varied between 0.55 nmol L(-1) (0.05 nmol mmol(-1)creatinine) for allyl methyl sulfide and 11.6 μmol L(-1) (1.54 μmol mmol(-1)creatinine) for acetone considering medians. Limits of detection (LODs) ranged from 0.08 nmol L(-1) for allyl methyl sulfide to 1.0 nmol L(-1) for acetone and furan (with RSDs ranging from 5 to 9%). The presented experimental setup assists both real-time and GC analyses of volatile organic compounds, which can be performed consecutively using the same analytical system. Such an approach supports the novel concept of hybrid volatolomics, an approach which combines VOC profiles obtained from two or more body fluids to improve and complement the chemical information on the physiological status of an individual.

Examining the Premises Supporting the Empirically Supported Intervention Approach to Social Work Practice

ERIC Educational Resources Information Center

McBeath, Bowen; Briggs, Harold E.; Aisenberg, Eugene

2010-01-01

Federal, state, and local policymakers and funders have increasingly organized human service delivery functions around the selection and implementation of empirically supported interventions (ESIs), under the expectation that service delivery through such intervention frameworks results in improvements in cost-effectiveness and system performance.…

Non-targeted screening of house dust samples using accurate mass TOFMS

EPA Science Inventory

House dust exists as an environmental repository of chemicals to which we are exposed in our homes. A growing number of studies have targeted select persistent organic and inorganic pollutants found in house dust. Many have concluded that dust exists as an important human expos...

Influence of Land use on Phosphorus Concentrations in Southeastern US Piedmont Headwater

EPA Science Inventory

The South Fork Broad River (SFBR) watershed on the Georgia piedmont is impacted by extensive poultry and cattle production and rapid human population growth. Organic wastes produced by poultry and beef production are generally applied to pastures for disposal at a rate selected t...

A Fault Tree Approach to Analysis of Organizational Communication Systems.

ERIC Educational Resources Information Center

Witkin, Belle Ruth; Stephens, Kent G.

Fault Tree Analysis (FTA) is a method of examing communication in an organization by focusing on: (1) the complex interrelationships in human systems, particularly in communication systems; (2) interactions across subsystems and system boundaries; and (3) the need to select and "prioritize" channels which will eliminate noise in the…

Human Resource Policies for Women--A Study in Singapore.

ERIC Educational Resources Information Center

Lee, Jean S. K.; Pow, Jasmine C. L.

1999-01-01

Survey data from 100 Singapore organizations revealed the following: they tend to recruit women more for operations than supervisory/management jobs; 44% consider gender a selection criterion; recruitment ads often specify gender; and women's opportunities for promotion and training are limited as is their access to flexible work arrangements and…

Kohonen Self-Organizing Maps in Validity Maintenance for Automated Scoring of Constructed Response.

ERIC Educational Resources Information Center

Williamson, David M.; Bejar, Isaac I.

As the automated scoring of constructed responses reaches operational status, monitoring the scoring process becomes a primary concern, particularly if automated scoring is intended to operate completely unassisted by humans. Using actual candidate selections from the Architectural Registration Examination (n=326), this study uses Kohonen…

Comparison of selective staining of fungi in paraffin sections by light microscopy, SEM and BEI

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

Berman, E.L.; Laudate, A.; Carter, H.W.

Paraffin-embedded sections from human tissues with fungi or organisms classified with fungi were studied by light microscopy (LM), scanning electron microscopy (SEM), and the backscatter electron imaging (BEI) mode of the SEM. The fungal organisms selected for study were those familiar to the pathologist on the basis of their appearance in paraffin-embedded material stained with the Gomori-Grocott Chromic Acid Methenamine Silver Stain (GMS). The organisms were Actinomyces, Rhizopus, Cryptococcus, Histoplasma capsulatum, and Coccidia imitis. Sections were stained with the GMS Stain and/or the Becker modification of the GMS Stain (BGMS) and examined in the secondary electron imaging mode (SEI) andmore » BEI mode with an annular backscatter electron detector. This silver staining technique accentuated the wall of fungal organisms, in the backscatter mode. Depending on the fungal organism and type of silver stain employed, the GMS seemed the preferable stain. The advantages of SEM over LM were greater depth of focus and potential range of magnifications. BEI may also be used in conjunction with LM stain for microorganisms to establish their presence.« less

SU-E-T-399: Evaluation of Selection Criteria for Computational Human Phantoms for Use in Out-Of-Field Organ Dosimetry for Radiotherapy Patients

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

Pelletier, C; Jung, J; Lee, C

2015-06-15

Purpose: To quantify the dosimetric uncertainty due to organ position errors when using height and weight as phantom selection criteria in the UF/NCI Hybrid Phantom Library for the purpose of out-of-field organ dose reconstruction. Methods: Four diagnostic patient CT images were used to create 7-field IMRT plans. For each patient, dose to the liver, right lung, and left lung were calculated using the XVMC Monte Carlo code. These doses were taken to be the ground truth. For each patient, the phantom with the most closely matching height and weight was selected from the body size dependent phantom library. The patientmore » plans were then transferred to the computational phantoms and organ doses were recalculated. Each plan was also run on 4 additional phantoms with reference heights and or weights. Maximum and mean doses for the three organs were computed, and the DVHs were extracted and compared. One sample t-tests were performed to compare the accuracy of the height and weight matched phantoms against the additional phantoms in regards to both maximum and mean dose. Results: For one of the patients, the height and weight matched phantom yielded the most accurate results across all three organs for both maximum and mean doses. For two additional patients, the matched phantom yielded the best match for one organ only. In 13 of the 24 cases, the matched phantom yielded better results than the average of the other four phantoms, though the results were only statistically significant at the .05 level for three cases. Conclusion: Using height and weight matched phantoms does yield better results in regards to out-of-field dosimetry than using average phantoms. Height and weight appear to be moderately good selection criteria, though this selection criteria failed to yield any better results for one patient.« less

An ex vivo human skin model for studying skin barrier repair.

PubMed

Danso, Mogbekeloluwa O; Berkers, Tineke; Mieremet, Arnout; Hausil, Farzia; Bouwstra, Joke A

2015-01-01

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique. After stripping the explants, they were cultured in vitro to allow the regeneration of the SC. We selected two culture temperatures 32 °C and 37 °C and a period of either 4 or 8 days. After 8 days of culture, the explant generated SC at a similar thickness compared to native human SC. At 37 °C, the early and late epidermal differentiation programmes were executed comparably to native human skin with the exception of the barrier protein involucrin. At 32 °C, early differentiation was delayed, but the terminal differentiation proteins were expressed as in stripped explants cultured at 37 °C. Regarding the barrier properties, the SC lateral lipid organization was mainly hexagonal in the regenerated SC, whereas the lipids in native human SC adopt a more dense orthorhombic organization. In addition, the ceramide levels were higher in the cultured explants at 32 °C and 37 °C than in native human SC. In conclusion, we selected the stripped ex vivo skin model cultured at 37 °C as a candidate model to study skin barrier repair because epidermal and SC characteristics mimic more closely the native human skin than the ex vivo skin model cultured at 32 °C. Potentially, this model can be used for testing formulations for skin barrier repair. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Public health response to an imported case of canine melioidosis.

PubMed

Ryan, C W; Bishop, K; Blaney, D D; Britton, S J; Cantone, F; Egan, C; Elrod, M G; Frye, C W; Maxted, A M; Perkins, G

2018-06-01

Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin infection and solid organ abscesses. It is caused by Burkholderia pseudomallei, which in the United States is classified as a select agent, with "potential to pose a severe threat to both human and animal health, to plant health or to animal and plant products" (Federal Select Agent Program, http://www.selectagents.gov/, accessed 22 September 2016). Burkholderia pseudomallei is found in soil and surface water in the tropics, especially South-East Asia and northern Australia, where melioidosis is endemic. Human cases are rare in the United States and are usually associated with travel to endemic areas. Burkholderia pseudomallei can also infect animals. We describe a multijurisdictional public health response to a case of subclinical urinary B. pseudomallei infection in a dog that had been adopted into upstate New York from a shelter in Thailand. Investigation disclosed three human contacts with single, low-risk exposures to the dog's urine at his residence, and 16 human contacts with possible exposure to his urine or culture isolates at a veterinary hospital. Contacts were offered various combinations of symptom/fever monitoring, baseline and repeat B. pseudomallei serologic testing, and antibiotic post-exposure prophylaxis, depending on the nature of their exposure and their personal medical histories. The dog's owner accepted recommendations from public health authorities and veterinary clinicians for humane euthanasia. A number of animal rescue organizations actively facilitate adoptions into the United States of shelter dogs from South-East Asia. This may result in importation of B. pseudomallei into almost any community, with implications for human and animal health. © 2018 Blackwell Verlag GmbH.

Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations.

PubMed

Ajore, Ram; Raiser, David; McConkey, Marie; Jöud, Magnus; Boidol, Bernd; Mar, Brenton; Saksena, Gordon; Weinstock, David M; Armstrong, Scott; Ellis, Steven R; Ebert, Benjamin L; Nilsson, Björn

2017-04-01

Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53 -intact tumors ( P  ≪ 10 -10 ), and shRNA-mediated knockdown of RPGs activated p53 in TP53 -wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53 -mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Attaining human dignity for people with birth defects: a historical perspective.

PubMed

Christianson, Arnold L

2013-10-11

People with birth defects have been stigmatised, marginalised and discriminated against for millennia, diminishing their human dignity and abrogating their human rights. Beginning with the United Nations Universal Declaration of Human Rights, promulgated in 1947, the circumstances in which human dignity in healthcare for people with birth defects could be achieved arose, and this was accomplished over the next 65 years through the insight, hard work and dedication of a select group of people and organisations. In 2010 the World Health Organization prioritised services for the care and prevention of birth defects, particularly in middle- and low-income countries. Translating what has been achieved into human rights in healthcare for people with birth defects is the next objective. 

Facile preparation of core-shell magnetic metal-organic framework nanospheres for the selective enrichment of endogenous peptides.

PubMed

Xiong, Zhichao; Ji, Yongsheng; Fang, Chunli; Zhang, Quanqing; Zhang, Lingyi; Ye, Mingliang; Zhang, Weibing; Zou, Hanfa

2014-06-10

Facile preparation of core-shell magnetic metal-organic framework nanospheres by a layer-by-layer approach is presented. The nanospheres have high surface area (285.89 cm(2)  g(-1)), large pore volume (0.18 cm(3)  g(-1)), two kinds of mesopores (2.50 and 4.72 nm), excellent magnetic responsivity (55.65 emu g(-1)), structural stability, and good dispersibility. The combination of porosity, hydrophobicity, and uniform magnetism was exploited for effective enrichment of peptides with simultaneous exclusion of high molecular weight proteins. The nanospheres were successfully applied in the selective enrichment of endogenous peptides in human serum. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Policies and procedures in the workplace: how health care organizations compare.

PubMed

Loo, R

1993-01-01

Many organizations are implementing programs and services to manage the human and economic costs of stress. A mail survey was conducted of 500 randomly selected Canadian organizations having at least 500 employees. The survey tapped four major areas: organizational policies and procedures for managing stress; programs and services offered; perceived benefits and constraints for the organization; and projected future directions in this area. Analyses of returns from 210 organizations-43 health and 167 non-health-revealed various findings. For example, over half of health care organizations have policies and procedures as opposed to less than half of non-health care organizations. Also, health care organizations place greater emphasis on smoking cessation, weight control programs and on stress management training. Although some Canadian organizations are addressing stress, much more could and should be done, especially by organizations that do not yet recognize the impact of stress on employees and their work performance.

Effects of selective attention on the electrophysiological representation of concurrent sounds in the human auditory cortex.

PubMed

Bidet-Caulet, Aurélie; Fischer, Catherine; Besle, Julien; Aguera, Pierre-Emmanuel; Giard, Marie-Helene; Bertrand, Olivier

2007-08-29

In noisy environments, we use auditory selective attention to actively ignore distracting sounds and select relevant information, as during a cocktail party to follow one particular conversation. The present electrophysiological study aims at deciphering the spatiotemporal organization of the effect of selective attention on the representation of concurrent sounds in the human auditory cortex. Sound onset asynchrony was manipulated to induce the segregation of two concurrent auditory streams. Each stream consisted of amplitude modulated tones at different carrier and modulation frequencies. Electrophysiological recordings were performed in epileptic patients with pharmacologically resistant partial epilepsy, implanted with depth electrodes in the temporal cortex. Patients were presented with the stimuli while they either performed an auditory distracting task or actively selected one of the two concurrent streams. Selective attention was found to affect steady-state responses in the primary auditory cortex, and transient and sustained evoked responses in secondary auditory areas. The results provide new insights on the neural mechanisms of auditory selective attention: stream selection during sound rivalry would be facilitated not only by enhancing the neural representation of relevant sounds, but also by reducing the representation of irrelevant information in the auditory cortex. Finally, they suggest a specialization of the left hemisphere in the attentional selection of fine-grained acoustic information.

The challenges of organizing an international course in Latin America

PubMed Central

Vairo, Filippo; López, Mónica Luján; Cruz, Carolina Uribe; Corrêa, Priscila Gomes; Baldo, Guilherme

2014-01-01

The Latin American School of Human and Medical Genetics (ELAG) is the main course of its kind in the genetics field in Latin America. Here we describe the main challenges regarding the organization of such event, including how we obtain funding and how we proceed with student selection. Thus, we aim to share our experience with other groups that intend to follow this format to create similar events in other areas in this region of the world. PMID:24764750

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

PubMed

Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

2017-12-15

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

NASA Technical Reports Server (NTRS)

Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

2003-01-01

We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.

Proton-coupled organic cation antiporter-mediated uptake of apomorphine enantiomers in human brain capillary endothelial cell line hCMEC/D3.

PubMed

Okura, Takashi; Higuchi, Kei; Kitamura, Atsushi; Deguchi, Yoshiharu

2014-01-01

R(-)-Apomorphine is a dopamine agonist used for rescue management of motor function impairment associated with levodopa therapy in Parkinson's disease patients. The aim of this study was to examine the role of proton-coupled organic cation antiporter in uptake of R(-)-apomorphine and its S-enantiomer in human brain, using human endothelial cell line hCMEC/D3 as a model. Uptake of R(-)- or S(+)-apomorphine into hCMEC/D3 cells was measured under various conditions to evaluate its time-, concentration-, energy- and ion-dependency. Inhibition by selected organic cations was also examined. Uptakes of both R(-)- and S(+)-apomorphine increased with time. The initial uptake velocities of R(-)- and S(+)-apomorphine were concentration-dependent, with similar Km and Vmax values. The cell-to-medium (C/M) ratio of R(-)-apomorphine was significantly reduced by pretreatment with sodium azide, but was not affected by replacement of extracellular sodium ion with N-methylglucamine or potassium. Intracellular alkalization markedly reduced the uptake, while intracellular acidification increased it, suggesting that the uptake is driven by an oppositely directed proton gradient. The C/M ratio was significantly decreased by amantadine, verapamil, pyrilamine and diphenhydramine (substrates or inhibitors of proton-coupled organic cation antiporter), while tetraethylammonium (substrate of organic cation transporters (OCTs)) and carnitine (substrate of carnitine/organic cation transporter 2; (OCTN2)) had no effect. R(-)-Apomorphine uptake was competitively inhibited by diphenhydramine. Our results indicate that R(-)-apomorphine transport in human blood-brain barrier (BBB) model cells is similar to S(+)-apomorphine uptake. The transport was dependent on an oppositely directed proton gradient, but was sodium- or membrane potential-independent. The transport characteristics were consistent with involvement of the previously reported proton-coupled organic cation antiporter.

Geographically selective assortment of cycles in pandemics: meta-analysis of data collected by Chizhevsky.

PubMed

Gumarova, L; Cornélissen, G; Hillman, D; Halberg, F

2013-10-01

In the incidence patterns of cholera, diphtheria and croup during the past when they were of epidemic proportions, we document a set of cycles (periods), one of which was reported and discussed by A. L. Chizhevsky in the same data with emphasis on the mirroring in human disease of the ~11-year sunspot cycle. The data in this study are based on Chizhevsky’s book The Terrestrial Echo of Solar Storms and on records from the World Health Organization. For meta-analysis, we used the extended linear and nonlinear cosinor. We found a geographically selective assortment of various cycles characterizing the epidemiology of infections, which is the documented novel topic of this paper, complementing the earlier finding in the 21st century or shortly before, of a geographically selective assortment of cycles characterizing human sudden cardiac death. Solar effects, if any, interact with geophysical processes in contributing to this assortment.

Mupirocin-mucin agar for selective enumeration of Bifidobacterium bifidum.

PubMed

Pechar, Radko; Rada, Vojtech; Parafati, Lucia; Musilova, Sarka; Bunesova, Vera; Vlkova, Eva; Killer, Jiri; Mrazek, Jakub; Kmet, Vladimir; Svejstil, Roman

2014-11-17

Bifidobacterium bifidum is a bacterial species exclusively found in the human intestinal tract. This species is becoming increasingly popular as a probiotic organism added to lyophilized products. In this study, porcine mucin was used as the sole carbon source for the selective enumeration of B. bifidum in probiotic food additives. Thirty-six bifidobacterial strains were cultivated in broth with mucin. Only 13 strains of B. bifidum utilized the mucin to produce acids. B. bifidum was selectively enumerated in eight probiotic food supplements using agar (MM agar) containing mupirocin (100 mg/L) and mucin (20 g/L) as the sole carbon source. MM agar was fully selective if the B. bifidum species was presented together with Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and Bifidobacterium longum subsp. longum species and with lactic acid bacteria (lactobacilli, streptococci). Isolated strains of B. bifidum were identified using biochemical, PCR, MALDI-TOF procedures and 16S rRNA gene sequencing. The novel selective medium was also suitable for the isolation of B. bifidum strains from human fecal samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Shared Genetic Signals of Hypoxia Adaptation in Drosophila and in High-Altitude Human Populations

PubMed Central

Jha, Aashish R.; Zhou, Dan; Brown, Christopher D.; Kreitman, Martin; Haddad, Gabriel G.; White, Kevin P.

2016-01-01

The ability to withstand low oxygen (hypoxia tolerance) is a polygenic and mechanistically conserved trait that has important implications for both human health and evolution. However, little is known about the diversity of genetic mechanisms involved in hypoxia adaptation in evolving populations. We used experimental evolution and whole-genome sequencing in Drosophila melanogaster to investigate the role of natural variation in adaptation to hypoxia. Using a generalized linear mixed model we identified significant allele frequency differences between three independently evolved hypoxia-tolerant populations and normoxic control populations for approximately 3,800 single nucleotide polymorphisms. Around 50% of these variants are clustered in 66 distinct genomic regions. These regions contain genes that are differentially expressed between hypoxia-tolerant and normoxic populations and several of the differentially expressed genes are associated with metabolic processes. Additional genes associated with respiratory and open tracheal system development also show evidence of directional selection. RNAi-mediated knockdown of several candidate genes’ expression significantly enhanced survival in severe hypoxia. Using genomewide single nucleotide polymorphism data from four high-altitude human populations—Sherpas, Tibetans, Ethiopians, and Andeans, we found that several human orthologs of the genes under selection in flies are also likely under positive selection in all four high-altitude human populations. Thus, our results indicate that selection for hypoxia tolerance can act on standing genetic variation in similar genes and pathways present in organisms diverged by hundreds of millions of years. PMID:26576852

Global patterns of diversity and selection in human tyrosinase gene.

PubMed

Hudjashov, Georgi; Villems, Richard; Kivisild, Toomas

2013-01-01

Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.

Matrix effect on the determination of synthetic corticosteroids and diuretics by liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Dikunets, M. A.; Appolonova, S. A.; Rodchenkov, G. M.

2009-04-01

This work presents a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) procedure for selective and reliable screening of corticosteroids and diuretics in human urine. Sample preparation included the extraction, evaporation of the organic extract under nitrogen, and solution of the dry residue. The extract was analyzed by HPLC combined with tandem mass spectrometry using electro-spraying ionization at atmospheric pressure with negative ion recording. The mass spectra of all compounds were recorded, and the characteristic ions, retention times, and detection limits were determined. The procedure was validated by evaluating the degree of the matrix suppression of ionization, extraction of analytes from human biological liquid, and the selectivity and specificity of determination.

A facile and selective approach for enrichment of l-cysteine in human plasma sample based on zinc organic polymer: Optimization by response surface methodology.

PubMed

Bahrani, Sonia; Ghaedi, Mehrorang; Ostovan, Abbas; Javadian, Hamedreza; Mansoorkhani, Mohammad Javad Khoshnood; Taghipour, Tahere

2018-02-05

In this research, a facile and selective method was described to extract l-cysteine (l-Cys), an essential α-amino acid for anti-ageing playing an important role in human health, from human blood plasma sample. The importance of this research was the mild and time-consuming synthesis of zinc organic polymer (Zn-MOP) as an adsorbent and evaluation of its ability for efficient enrichment of l-Cys by ultrasound-assisted dispersive micro solid-phase extraction (UA-DMSPE) method. The structure of Zn-MOP was investigated by FT-IR, XRD and SEM. Analysis of variance (ANOVA) was applied for the experimental data to reach the best optimum conditions. The quantification of l-Cys was carried out by high performance liquid chromatography with UV detection set at λ=230nm. The calibration graph showed reasonable linear responses towards l-Cys concentrations in the range of 4.0-1000μg/L (r 2 =0.999) with low limit of detection (0.76μg/L, S/N=3) and RSD≤2.18 (n=3). The results revealed the applicability and high performance of this novel strategy in detecting trace l-Cys by Zn-MOP in complicated matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

Automated Selection of Regions of Interest for Intensity-based FRET Analysis of Transferrin Endocytic Trafficking in Normal vs. Cancer Cells

PubMed Central

Talati, Ronak; Vanderpoel, Andrew; Eladdadi, Amina; Anderson, Kate; Abe, Ken; Barroso, Margarida

2013-01-01

The overexpression of certain membrane-bound receptors is a hallmark of cancer progression and it has been suggested to affect the organization, activation, recycling and down-regulation of receptor-ligand complexes in human cancer cells. Thus, comparing receptor trafficking pathways in normal vs. cancer cells requires the ability to image cells expressing dramatically different receptor expression levels. Here, we have presented a significant technical advance to the analysis and processing of images collected using intensity based Förster resonance energy transfer (FRET) confocal microscopy. An automated Image J macro was developed to select region of interests (ROI) based on intensity and statistical-based thresholds within cellular images with reduced FRET signal. Furthermore, SSMD (strictly standardized mean differences), a statistical signal-to-noise ratio (SNR) evaluation parameter, was used to validate the quality of FRET analysis, in particular of ROI database selection. The Image J ROI selection macro together with SSMD as an evaluation parameter of SNR levels, were used to investigate the endocytic recycling of Tfn-TFR complexes at nanometer range resolution in human normal vs. breast cancer cells expressing significantly different levels of endogenous TFR. Here, the FRET-based assay demonstrates that Tfn-TFR complexes in normal epithelial vs. breast cancer cells show a significantly different E% behavior during their endocytic recycling pathway. Since E% is a relative measure of distance, we propose that these changes in E% levels represent conformational changes in Tfn-TFR complexes during endocytic pathway. Thus, our results indicate that Tfn-TFR complexes undergo different conformational changes in normal vs. cancer cells, indicating that the organization of Tfn-TFR complexes at the nanometer range is significantly altered during the endocytic recycling pathway in cancer cells. In summary, improvements in the automated selection of FRET ROI datasets allowed us to detect significant changes in E% with potential biological significance in human normal vs. cancer cells. PMID:23994873

Serial grouping of 2D-image regions with object-based attention in humans

PubMed Central

Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R

2016-01-01

After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas. DOI: http://dx.doi.org/10.7554/eLife.14320.001 PMID:27291188

Sources and functions of extracellular small RNAs in human circulation

PubMed Central

Fritz, Joëlle V.; Heintz-Buschart, Anna; Ghosal, Anubrata; Wampach, Linda; Etheridge, Alton; Galas, David; Wilmes, Paul

2017-01-01

Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation including microRNAs, tRNA, rRNA and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease contexts and have therefore been proposed as well-suited biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in receiving cells. Albeit controversial, exogenous ex-sRNAs derived from plants and microorganisms have also been described in human blood. Essential questions which remain to be conclusively addressed in the field concern the (i) presence and mechanistic sources of exogenous ex-sRNA in human bodily fluids, (ii) detection and measurement of ex-sRNA in human circulation, (iii) selectivity of ex-sRNA export and import, (iv) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (v) cell-, tissue-, organ- and organism-wide impacts of ex-sRNAs. We will survey the present state of knowledge of most of these questions in this review. PMID:27215587

Science in the Publicity Laboratory: The Case of Eugenics.

ERIC Educational Resources Information Center

Caudill, Edward

The eugenicists of the 1920s and 1930s aggressively pursued media attention and sought policy change for their cause of improving the human race by selective breeding. Eugenics gained momentum in the United States when the American Eugenics Society (AES) was organized in 1921. Policy formation and information dissemination were central to the…

Structures and Dynamics of Social Networks: Selection, Influence, and Self-Organization

ERIC Educational Resources Information Center

Go, Myong-Hyun

2010-01-01

This dissertation studies the social structures and dynamics of human networks: how peers at the micro level and physical environments at the macro level interact with the individual preferences and attributes and shape social dynamics. It is composed of three parts. The first essay, "Friendship Choices and Group Effects in Adolescent…

Graphics in Text: A Bibliography. Monograph No. 6.

ERIC Educational Resources Information Center

Macdonald-Ross, Michael; Smith, Eleanor

This bibliography lists books and articles discussing graphic aspects of human communication. References have been selected for their relevance to the design of self-instructional texts for the adult learner; for the most part, research on younger children, on non-text media, and on non-educational texts is not included. Items are organized into…

Integrated profiling of Furanocoumarins (FC) in Grapefruit hybrids toward selection of low FC varieties

USDA-ARS?s Scientific Manuscript database

Furanocoumarins (FC) are a class of organic chemical components in grapefruits and other diet plants. Some of them in grapefruit juice can induce potentially adverse interactions with human drugs and in that patients may be advised to avoid the fruit and juice. To develop low FC grapefruit cultivars...

Cognitive Modeling of Learning Abilities: A Status Report of LAMP.

ERIC Educational Resources Information Center

Kyllonen, Patrick C.; Christal, Raymond E.

Research activities underway as part of the Air Force's Learning Abilities Measurement Program (LAMP) are described. A major objective of the program is to devise new models of the nature and organization of human abilities, that could be applied to improve personnel selection and classification systems. The activities of the project have been…

78 FR 66653 - Patient Protection and Affordable Care Act; HHS Notice of Benefit and Payment Parameters for 2014...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... procedure, Adverse selection, Health care, Health insurance, Health records, Organization and functions... practice and procedure, Claims, Health care, Health insurance, Health plans, penalties, Reporting and... DEPARTMENT OF HEALTH AND HUMAN SERVICES 45 CFR Parts 153, 155, 156, 157, and 158 [CMS-9964-F3] RIN...

Education and Training. Annotated Bibliography. Author and Subject Index.

ERIC Educational Resources Information Center

United Nations Food and Agriculture Organization, Rome (Italy).

Food and Agriculture Organization (FAO) publications and documents issued by the Human Resources and Institutions division and by other technical divisions in the technical, economic, and social fields are selected, annotated and indexed in this bibliography. Documents issued prior to 1967 are not included but can be found in the Rural…

Representational Similarity of Body Parts in Human Occipitotemporal Cortex.

PubMed

Bracci, Stefania; Caramazza, Alfonso; Peelen, Marius V

2015-09-23

Regions in human lateral and ventral occipitotemporal cortices (OTC) respond selectively to pictures of the human body and its parts. What are the organizational principles underlying body part responses in these regions? Here we used representational similarity analysis (RSA) of fMRI data to test multiple possible organizational principles: shape similarity, physical proximity, cortical homunculus proximity, and semantic similarity. Participants viewed pictures of whole persons, chairs, and eight body parts (hands, arms, legs, feet, chests, waists, upper faces, and lower faces). The similarity of multivoxel activity patterns for all body part pairs was established in whole person-selective OTC regions. The resulting neural similarity matrices were then compared with similarity matrices capturing the hypothesized organizational principles. Results showed that the semantic similarity model best captured the neural similarity of body parts in lateral and ventral OTC, which followed an organization in three clusters: (1) body parts used as action effectors (hands, feet, arms, and legs), (2) noneffector body parts (chests and waists), and (3) face parts (upper and lower faces). Whole-brain RSA revealed, in addition to OTC, regions in parietal and frontal cortex in which neural similarity was related to semantic similarity. In contrast, neural similarity in occipital cortex was best predicted by shape similarity models. We suggest that the semantic organization of body parts in high-level visual cortex relates to the different functions associated with the three body part clusters, reflecting the unique processing and connectivity demands associated with the different types of information (e.g., action, social) different body parts (e.g., limbs, faces) convey. Significance statement: While the organization of body part representations in motor and somatosensory cortices has been well characterized, the principles underlying body part representations in visual cortex have not yet been explored. In the present fMRI study we used multivoxel pattern analysis and representational similarity analysis to characterize the organization of body maps in human occipitotemporal cortex (OTC). Results indicate that visual and shape dimensions do not fully account for the organization of body part representations in OTC. Instead, the representational structure of body maps in OTC appears strongly related to functional-semantic properties of body parts. We suggest that this organization reflects the unique processing and connectivity demands associated with the different types of information different body parts convey. Copyright © 2015 the authors 0270-6474/15/3512977-09$15.00/0.

Selective elimination of chromophoric and fluorescent dissolved organic matter in a full-scale municipal wastewater treatment plant.

PubMed

Yang, Xiaofang; Zhou, Zhongbo; Raju, Maddela Naga; Cai, Xiaoxuan; Meng, Fangang

2017-07-01

Effluent organic matter (EfOM) from municipal wastewater treatment plants potentially has a detrimental effect on both aquatic organisms and humans. This study evaluated the removal and transformation of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) in a full-scale wastewater treatment plant under different seasons. The results showed that bio-treatment was found to be more efficient in removing bulk DOM (in term of dissolved organic carbon, DOC) than CDOM and FDOM, which was contrary to the disinfection process. CDOM and FDOM were selectively removed at various stages during the treatment. Typically, the low molecular weight fractions of CDOM and protein-like FDOM were more efficiently removed during bio-treatment process, whereas the humic-like FDOM exhibited comparable decreases in both bio-treatment and disinfection processes. Overall, the performance of the WWTP was weak in terms of CDOM and FDOM removal, resulting in enrichment of CDOM and FDOM in effluent. Moreover, the total removal of the bulk DOM (P<0.05) and the protein-like FDOM (P<0.05) displayed a significant seasonal variation, with higher removal efficiencies in summer, whereas removal of CDOM and the humic-like FDOM showed little differences between summer and winter. In all, the results provide useful information for understanding the fate and transformation of DOM, illustrating that sub-fractions of DOM could be selectively removed depending on treatment processes and seasonality. Copyright © 2016. Published by Elsevier B.V.

Human beings' adaptability to extreme environmental changes from medical and physical points of view

NASA Astrophysics Data System (ADS)

Khabarova, Olga; Ragulskaya, Maria; Dimitrova, Svetla; Safaraly-Oghlu Babayev, Elchin; Samsonov, Sergey; Med. Dimitry Markov, Of; Nazarova, Of Med. Olga N.; Rudenchik, Evgeny

The question about features of human reaction on the sharp environmental physical activity (EPA) changes is considered by international group of physicists and physicians on the base of results of monitoring of human health state in different cities spread on latitude and longitude. The typical reaction of human body on the influences, exceeding the organisms' ability to adaptation, is of stress-reaction character. From medical point of view there is no significant difference for human body -what external (EPA) agent shocked an organism (emotional or some physical threats). First attempt of the organism to restore its homeostasis is stress-reaction, being universal for many stress-factors. Its main stages (such as alarm, resistance, and exhaustion) are detectable by different medical equipments, but we tried to find universal, non-traumatic method of daily measurements, enough sensitive and appropriate for observation of people reaction both on weather and space weather (geomagnetic activity) changes. The experiment was based on a method of electrical conductivity measurements of biologically active (acupunctural) points of human skin. The used method (electroacupunctural method by Dr. R.Voll) is very sensitive to current state of an organism and characterize the functional condition of different organs and systems of human body and allows to express so-called "group's health status" in the units, suitable for comparison with meteorological and heliogeophysical parameters. We conduct the parallel investigations as a part of collaborative study in different geographic latitudes-longitudes (Baku:40° 23'43"N -49° 52'56"E, Troitsk (Moscow region): 55° 28'40"N -37° 18'42"E, Yakutsk: 62° 02'00"N -129° 44'00"E). Measurements were carried out on daily basis with permanent group of functionally healthy persons (Moscow -19, Yakutsk -22, CityBaku -12 volunteers). Daily monitoring of nervous, endocrinological, lymphatic systems, blood, lungs, thick and thin intestine, heart and parenhimatic organs, allergy and hypophisis was conducted simultaneously with analyses of space weather (parameters of solar and geomagnetic activities) as well as local meteorological parameters (temperature, atmospheric pressure, humidity, wind speed, etc.). It was proved that it is possible to consider not only weather changes but also geomagnetic field variations as a stressor. It is concluded that : 1. human reaction on the sharp changes of selected external (environmental) physical activity parameters goes like typical stress-reaction; 2. features of stress-reaction depend on history of previous failures of an organism and on state of external background (frequent stresses deplete human organism possibility to adaptation); 3. features of stress-reaction depend on the geographic location (latitude). Possible physi-cal explanation of human organism stress-reaction on changes of geomagnetic oscillatory regime and atmospheric thermobaric variations is discussed.

Transport, behavior, and fate of volatile organic compounds in streams

USGS Publications Warehouse

Rathbun, R.E.

1998-01-01

Volatile organic compounds (VOCs) are compounds with chemical and physical properties that allow the compounds to move freely between the water and air phases of the environment. VOCs are widespread in the environment because of this mobility. Many VOCs have properties making them suspected or known hazards to the health of humans and aquatic organisms. Consequently, understanding the processes affecting the concentration and distribution VOCs in the environment is necessary. The U.S. Geological Survey selected 55 VOCs for study. This report reviews the characteristics of the various process that could affect the transport, behavior, and fate of these VOCs in streams.

Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip

PubMed Central

Musah, Samira; Mammoto, Akiko; Ferrante, Thomas C.; Jeanty, Sauveur S. F.; Hirano-Kobayashi, Mariko; Mammoto, Tadanori; Roberts, Kristen; Chung, Seyoon; Novak, Richard; Ingram, Miles; Fatanat-Didar, Tohid; Koshy, Sandeep; Weaver, James C.; Church, George M.; Ingber, Donald E.

2017-01-01

An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications. PMID:29038743

Microbial processes and organic priority substances in marine coastal sediments (Adriatic Sea, Italy)

NASA Astrophysics Data System (ADS)

Zoppini, Annamaria; Ademollo, Nicoletta; Amalfitano, Stefano; Dellisanti, Walter; Lungarini, Silvia; Miserocchi, Stefano; Patrolecco, Luisa; Langone, Leonardo

2015-04-01

PERSEUS EU FP7 Project aims to identify the interacting patterns of natural and human-derived pressures to assess their impact on marine ecosystems and, using the objectives and principles of the Marine Strategy Framework Directive (MSFD) as a vehicle, to design an effective and innovative research governance framework based on sound scientific knowledge. In the frame of this Project (subtask 1.3.3 ADREX: Adriatic and Ionian Seas Experiment), monitoring surveys were conducted in the Adriatic Sea (Italy) in order to study the variation of structural and functional characteristics of native bacterial communities and the occurrence of selected classes of organic priority substances in sediments. The study area represents a good natural laboratory sensitive to climate variability and human pressure, owing to the semi-enclosed nature of the Adriatic Sea and to the increasing trend of human activities in the coastal regions. During the cruise ADRI-13 (November 2013) and ADRI-14 (October 2014) we sampled several coastal sites from the mouth of the Po River to the Otranto strait. Surface sediments were collected in all areas, while sediment cores were sampled in selected sites. Microbes associated with marine sediments play an important role in the C-flux being responsible for the transformation of organic detritus (autochthonous and allochthonous) into biomass. The sediment bacterial abundance was determined by epifluorescence microscopy and the rate of bacterial carbon production by measuring the 3H-leucine uptake rates. The community respiration rate was estimated by the measurement of the electron transport system (ETS) activity. The sediment contamination level was determined by measuring the concentration of contaminants included in the list of organic priority substances: PAHs, bisphenol A (BPA), alkylphenols (APs). The extraction/clean-up of PAHs, BPA and APs was performed by ultrasonic bath with the appropriate solvents, followed by analytical determination with LC-MS or HPLC UV-fluorescence. The joint analysis of the microbial properties and the concentration of the organic pollutants reflects the impact of anthropic pressure on the selected coastal areas. At the surface layers, the microbial carbon assimilation and mineralization rates were affected by the increasing concentration of pollutants. The highest concentrations of organic pollutants were detected in the deeper sediment layers (20 cm) where a significant reduction of microbial metabolic activities was observed. The results of this study can contribute to acquire information to improve the MSFD and to reach the good environmental status.

Controlled activation of retrotransposition for plant breeding.

PubMed

Paszkowski, Jerzy

2015-04-01

Plant genomes consist to a large extent of transposable elements (TEs), predominantly retrotransposons. Their accumulation through periodic transposition bursts has shaped the structure and regulatory organization of plant genomes, often contributing to phenotypic traits. Transposon-generated phenotypes selected by humans during plant domestication have been maintained under strict selection during subsequent plant breeding. Our knowledge of the epigenetic, environmental, and developmental regulation of TE activity has advanced considerably in recent years. Here I will consider TEs as an attractive endogenous source of genetic variation that can be liberated in a controlled fashion and thus offer novel phenotypic diversity to be selected for crop improvement. Copyright © 2015 Elsevier Ltd. All rights reserved.

A single of MR sponge tactile sensor design for medical applications

NASA Astrophysics Data System (ADS)

Cha, Seung-Woo; Kang, Seok-Rae; Hwang, Yong-Hoon; Choi, Seung-Bok

2017-04-01

Recently, it is very popular in medical field to adopt robot surgery such as robot-assisted minimally invasive surgery (RMIS). However, there are some problems in the robot surgery. It is very hard to get the touch feeling of the organs during the surgical operation because the surgeons cannot touch and feel repulsive force from the organs directly. So, this work proposes a squeeze mode of single magneto-rheological (MR) sponge to realize viscoelastic property of human organs or skins and undertake a theoretical analysis of MR sponge. In addition, its effectiveness is verified through experimental tests. The similarity between MR sponge and real organs is identified and desired repulsive force of each organs can be achieved by proper selection of MR sponge cell associated with controlled input current.

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure

PubMed Central

Barbet, Anthony F.; Al-Khedery, Basima; Stuen, Snorre; Granquist, Erik G.; Felsheim, Roderick F.; Munderloh, Ulrike G.

2013-01-01

The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections. We analyzed the genome sequences of strains infecting humans, animals and ticks from diverse geographic locations. Despite extensive variability amongst these strains, those infecting humans had conserved genome structure including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen. These data provide potential targets to identify human-infective strains and have significance for understanding the selective pressures that lead to emergence of disease in new species. PMID:25437207

Reducing Wrong Patient Selection Errors: Exploring the Design Space of User Interface Techniques

PubMed Central

Sopan, Awalin; Plaisant, Catherine; Powsner, Seth; Shneiderman, Ben

2014-01-01

Wrong patient selection errors are a major issue for patient safety; from ordering medication to performing surgery, the stakes are high. Widespread adoption of Electronic Health Record (EHR) and Computerized Provider Order Entry (CPOE) systems makes patient selection using a computer screen a frequent task for clinicians. Careful design of the user interface can help mitigate the problem by helping providers recall their patients’ identities, accurately select their names, and spot errors before orders are submitted. We propose a catalog of twenty seven distinct user interface techniques, organized according to a task analysis. An associated video demonstrates eighteen of those techniques. EHR designers who consider a wider range of human-computer interaction techniques could reduce selection errors, but verification of efficacy is still needed. PMID:25954415

Reducing wrong patient selection errors: exploring the design space of user interface techniques.

PubMed

Sopan, Awalin; Plaisant, Catherine; Powsner, Seth; Shneiderman, Ben

2014-01-01

Wrong patient selection errors are a major issue for patient safety; from ordering medication to performing surgery, the stakes are high. Widespread adoption of Electronic Health Record (EHR) and Computerized Provider Order Entry (CPOE) systems makes patient selection using a computer screen a frequent task for clinicians. Careful design of the user interface can help mitigate the problem by helping providers recall their patients' identities, accurately select their names, and spot errors before orders are submitted. We propose a catalog of twenty seven distinct user interface techniques, organized according to a task analysis. An associated video demonstrates eighteen of those techniques. EHR designers who consider a wider range of human-computer interaction techniques could reduce selection errors, but verification of efficacy is still needed.

The Community Research Scholars Initiative: A Mid‐Project Assessment

PubMed Central

Pike, Earl; Sehgal, Ashwini R.; Fischer, Robert L.; Collins, Cyleste

2015-01-01

Abstract Community organizations addressing health and human service needs generally have minimal capacity for research and evaluation. As a result, they are often inadequately equipped to independently carry out activities that can be critical for their own success, such as conducting needs assessments, identifying best practices, and evaluating outcomes. Moreover, they are unable to develop equitable partnerships with academic researchers to conduct community‐based research. This paper reports on the progress of the Community Research Scholar Initiative (CRSI), a program that aims to enhance community research and evaluation capacity through training of selected employees from Greater Cleveland community organizations. The intensive 2‐year CRSI program includes didactic instruction, fieldwork, multiple levels of community and academic engagement, leadership training, and a mentored research project. The first cohort of CRSI Scholars, their community organizations, and other community stakeholders have incorporated program lessons into their practices and operations. The CRSI program evaluation indicates: the importance of careful Scholar selection; the need to engage executive leadership from Scholar organizations; the value of a curriculum integrating classwork, fieldwork, and community engagement; and the need for continual scholar skill and knowledge assessment. These findings and lessons learned guide other efforts to enhance community organization research and evaluation capacity. PMID:26073663

National Nutrition Policy: Nutrition and the Consumer--II. A Working Paper.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Nutrition and Human Needs.

This document is organized in four parts. Part One is a "State on the Needs for Nutrition Education" submitted by the Board of Directors, Society for Nutrition Education in connection with The Panel on Consumer Programs and Public Education, The National Nutrition Policy Study, to the Senate Select Committee on Nutrition and Human Needs. Part Two…

Use of Social Networking Sites by Academic Librarians in Six Selected States of Nigeria

ERIC Educational Resources Information Center

Tella, Adeyinka; Olarongbe, Shuaib Agboola; Akanbi-Ademolake, Hauwa Bolanle; Adisa, Mulikat Y.

2013-01-01

The attractiveness of social networking sites (SNSs) has extended to almost all professionals in numerous human organizations including the library. Librarians as a result of this development are now making use of these sites to connect to other libraries and librarians both within and outside their environment. However, it is observed that the…

Puzzles in modern biology. I. Male sterility, failure reveals design

PubMed Central

Frank, Steven A.

2016-01-01

Many human males produce dysfunctional sperm. Various plants frequently abort pollen. Hybrid matings often produce sterile males. Widespread male sterility is puzzling. Natural selection prunes reproductive failure. Puzzling failure implies something that we do not understand about how organisms are designed. Solving the puzzle reveals the hidden processes of design. PMID:28004842

Increasing seed size and quality by manipulating BIG SEEDS 1 in legume species

USDA-ARS?s Scientific Manuscript database

Plant organs such as seeds are primary sources of food for both humans and animals. Seed size is one of the major agronomic traits that have been selected in crop plants during their domestication. Legume seeds are a major source of dietary proteins and oils. Here, we report a novel and conserved ro...

Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain?

PubMed Central

Widomska, Justyna; Zareba, Mariusz; Subczynski, Witold Karol

2016-01-01

Epidemiological studies demonstrate that a high dietary intake of carotenoids may offer protection against age-related macular degeneration, cancer and cardiovascular and neurodegenerative diseases. Humans cannot synthesize carotenoids and depend on their dietary intake. Major carotenoids that have been found in human plasma can be divided into two groups, carotenes (nonpolar molecules, such as β-carotene, α-carotene or lycopene) and xanthophylls (polar carotenoids that include an oxygen atom in their structure, such as lutein, zeaxanthin and β-cryptoxanthin). Only two dietary carotenoids, namely lutein and zeaxanthin (macular xanthophylls), are selectively accumulated in the human retina. A third carotenoid, meso-zeaxanthin, is formed directly in the human retina from lutein. Additionally, xanthophylls account for about 70% of total carotenoids in all brain regions. Some specific properties of these polar carotenoids must explain why they, among other available carotenoids, were selected during evolution to protect the retina and brain. It is also likely that the selective uptake and deposition of macular xanthophylls in the retina and brain are enhanced by specific xanthophyll-binding proteins. We hypothesize that the high membrane solubility and preferential transmembrane orientation of macular xanthophylls distinguish them from other dietary carotenoids, enhance their chemical and physical stability in retina and brain membranes and maximize their protective action in these organs. Most importantly, xanthophylls are selectively concentrated in the most vulnerable regions of lipid bilayer membranes enriched in polyunsaturated lipids. This localization is ideal if macular xanthophylls are to act as lipid-soluble antioxidants, which is the most accepted mechanism through which lutein and zeaxanthin protect neural tissue against degenerative diseases. PMID:27030822

B. F. Skinner's Science and Human Behavior: its antecedents and its consequences.

PubMed

Catania, A Charles

2003-11-01

Skinner's Science and Human Behavior marked a transition from a treatment of behavior that took physics as its reference science to one that emphasized behavior as a fundamental part of the subject matter of biology. The book includes what may be Skinner's earliest statement about the similarity of operant selection to Darwinian natural selection in phylogeny. Other major topics discussed in the book included multiple causation, private events, the self, and social contingencies. Among the important antecedents were Skinner's own Behavior of Organisms and Keller & Schoenfeld's Pincinples of Psychology. Current developments in education, behavioral economics, and some behavior therapies can be attributed at least in part to Skinner's seminal work. The effective behavioral analysis of governmental and religious systems will probably depend on elaborations of our understanding of verbal behavior.

An application of adaption-innovation theory to bioremediation

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

Guerin, L.J.; Guerin, T.F.

1995-12-31

This paper provides a discussion of the potential application of the Kirton Adaption-Innovation Inventory (KAI) for assessing the adaptive-innovative cognitive style of individuals and organizations within the bioremediation industry. Human-resource and line managers, or other individuals responsible for staff evaluation, selection, and project planning, should consider using the KAI to assist them in selecting individuals for specific roles requiring either an innovative or adaptive style. The KAI, a measure for assessing adaption-innovation at the individual employee level, is introduced and its potential value in the bioremediation industry is discussed.

Selfish cellular networks and the evolution of complex organisms.

PubMed

Kourilsky, Philippe

2012-03-01

Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Risks from GMOs due to horizontal gene transfer.

PubMed

Keese, Paul

2008-01-01

Horizontal gene transfer (HGT) is the stable transfer of genetic material from one organism to another without reproduction or human intervention. Transfer occurs by the passage of donor genetic material across cellular boundaries, followed by heritable incorporation to the genome of the recipient organism. In addition to conjugation, transformation and transduction, other diverse mechanisms of DNA and RNA uptake occur in nature. The genome of almost every organism reveals the footprint of many ancient HGT events. Most commonly, HGT involves the transmission of genes on viruses or mobile genetic elements. HGT first became an issue of public concern in the 1970s through the natural spread of antibiotic resistance genes amongst pathogenic bacteria, and more recently with commercial production of genetically modified (GM) crops. However, the frequency of HGT from plants to other eukaryotes or prokaryotes is extremely low. The frequency of HGT to viruses is potentially greater, but is restricted by stringent selection pressures. In most cases the occurrence of HGT from GM crops to other organisms is expected to be lower than background rates. Therefore, HGT from GM plants poses negligible risks to human health or the environment.

A Potential Role for Drosophila Mucins in Development and Physiology

PubMed Central

Syed, Zulfeqhar A.; Härd, Torleif; Uv, Anne; van Dijk-Härd, Iris F.

2008-01-01

Vital vertebrate organs are protected from the external environment by a barrier that to a large extent consists of mucins. These proteins are characterized by poorly conserved repeated sequences that are rich in prolines and potentially glycosylated threonines and serines (PTS). We have now used the characteristics of the PTS repeat domain to identify Drosophila mucins in a simple bioinformatics approach. Searching the predicted protein database for proteins with at least 4 repeats and a high ST content, more than 30 mucin-like proteins were identified, ranging from 300–23000 amino acids in length. We find that Drosophila mucins are present at all stages of the fly life cycle, and that their transcripts localize to selective organs analogous to sites of vertebrate mucin expression. The results could allow for addressing basic questions about human mucin-related diseases in this model system. Additionally, many of the mucins are expressed in selective tissues during embryogenesis, thus revealing new potential functions for mucins as apical matrix components during organ morphogenesis. PMID:18725942

The Iodine Content in Urine, Faeces and Selected Organs of Rats Fed Lettuce Biofortified with Iodine Through Foliar Application.

PubMed

Rakoczy, Roksana; Kopeć, Aneta; Piątkowska, Ewa; Smoleń, Sylwester; Skoczylas, Łukasz; Leszczyńska, Teresa; Sady, Włodzimierz

2016-12-01

Iodine is an essential trace element for humans. Foliar application of micronutrients is successfully used in order to increase the concentration of essential elements in vegetables. The aim of this study was to evaluate the iodine absorption in the rat organism fed foliar biofortified lettuce. The presented study was consisted of the vegetative and animal experiment. In the vegetative experiment with lettuce, two combinations of foliar application were used: (1) control-without iodine application and (2) iodine application in the potassium iodide (KI) form. In the animal experiment, Wistar rats were divided to four groups, which received one of four diets: (1) C-control diet containing iodine in the KI form, (2) D-diet deficient in iodine, (3) D + BL-diet containing biofortified lettuce, and (4) D + CL-diet containing control lettuce (as the only source of iodine in diet, respectively). The diets contained 0.260, 0.060, 0.254 and 0.075 mg I/kg, respectively. In order to determine the iodine absorption in the rat organisms, the content of this trace element was measured in urine, faeces and in selected organs with the use of the ICP-OES technique. Foliar application of the KI increased the content of iodine in lettuce. The rats from the D + BL group excreted significantly less iodine in their urine and faeces and also accumulated more iodine in the organs than the rats from the C group. Iodine with biofortified lettuce was much bioavailable for rodents than iodine from control diet. Biofortified lettuce can be a source of iodine in a diet of human and can improve iodine nutrition.

Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut

PubMed Central

Underwood, Mark A.; German, J. Bruce; Lebrilla, Carlito B.; Mills, David A.

2015-01-01

Oligosaccharides are abundant in human milk. Production of these highly diverse structures requires significant energy expenditure by the mother and yet these human milk oligosaccharides offer no direct nutritive value to her infant. A primary function of human milk oligosaccharides is to shape the infant’s intestinal microbiota with life-long consequences. Bifidobacterium longum subspecies infantis (B. infantis) is unique among gut bacteria in its prodigious capacity to digest and consume any human milk oligosaccharide structure, the result of a large repertoire of bacterial genes encoding an array of glycosidases and oligosaccharide transporters not found in other bacterial species. In vitro, B. infantis grows better than other bacterial strains in the presence of human milk oligosaccharides, displays anti-inflammatory activity in premature intestinal cells, and decreases intestinal permeability. In premature infants, B. infantis given in combination with human milk increases B. infantis and decreases Enterobacteriaceae in the feces. Probiotics containing B. infantis decrease the risk of necrotizing enterocolitis in premature infants. Colonization with B. infantis is also associated with increased vaccine responses. Probiotic organisms have historically been selected based on ease of production and stability. The advantages of B. infantis, selected through coevolution with human milk glycans, present an opportunity for focused manipulation of the infant intestinal microbiota. PMID:25303277

Exceptional Evolutionary Expansion of Prefrontal Cortex in Great Apes and Humans.

PubMed

Smaers, Jeroen B; Gómez-Robles, Aida; Parks, Ashley N; Sherwood, Chet C

2017-03-06

One of the enduring questions that has driven neuroscientific enquiry in the last century has been the nature of differences in the prefrontal cortex of humans versus other animals [1]. The prefrontal cortex has drawn particular interest due to its role in a range of evolutionarily specialized cognitive capacities such as language [2], imagination [3], and complex decision making [4]. Both cytoarchitectonic [5] and comparative neuroimaging [6] studies have converged on the conclusion that the proportion of prefrontal cortex in the human brain is greatly increased relative to that of other primates. However, considering the tremendous overall expansion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal enlargement follows general allometric growth patterns, or whether it is exceptional [1]. Species' adherence to a common allometric relationship suggests conservation through phenotypic integration, while species' deviations point toward the occurrence of shifts in genetic and/or developmental mechanisms. Here we investigate prefrontal cortex scaling across anthropoid primates and find that great ape and human prefrontal cortex expansion are non-allometrically derived features of cortical organization. This result aligns with evidence for a developmental heterochronic shift in human prefrontal growth [7, 8], suggesting an association between neurodevelopmental changes and cortical organization on a macroevolutionary scale. The evolutionary origin of non-allometric prefrontal enlargement is estimated to lie at the root of great apes (∼19-15 mya), indicating that selection for changes in executive cognitive functions characterized both great ape and human cortical organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Domestication impacts on plant–herbivore interactions: a meta-analysis

PubMed Central

Poveda, Katja

2017-01-01

For millennia, humans have imposed strong selection on domesticated crops, resulting in drastically altered crop phenotypes compared with wild ancestors. Crop yields have increased, but a long-held hypothesis is that domestication has also unintentionally decreased plant defences against herbivores. To test this hypothesis, we conducted a phylogenetically controlled meta-analysis comparing insect herbivore resistance and putative plant defence traits between crops and their wild relatives. Our database included 2098 comparisons made across 73 crops in 89 studies. We found that domestication consistently reduced plant resistance to herbivores, although the magnitude of the effects varied across plant organs and depended on how resistance was measured. However, domestication had no consistent effects on the specific plant defence traits underlying resistance, including secondary metabolites and physical feeding barriers. The values of these traits sometimes increased and sometimes decreased during domestication. Consistent negative effects of domestication were observed only when defence traits were measured in reproductive organs or in the plant organ that was harvested. These results highlight the complexity of evolution under domestication and the need for an improved theoretical understanding of the mechanisms through which agronomic selection can influence the species interactions that impact both the yield and sustainability of our food systems. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920379

[The diagnostic usability of selected narrativity indices in stories about close relationships in the assessment of personality organization].

PubMed

Soroko, Emilia

2015-01-01

The aim of this study was to test the usability of selected narrativity indices identified from autobiographical accounts of important relationships in an assessment of neurotic (NPO) and borderline personality organization (BPO). Narrativity indices, both particular and generalized, were used to predict personality organization levels. Indices were derived from two separate layers of analysis: 1) lexical indices were counted with computer assistance; 2) evocative/reception indices dealing with coherence of the story were assessed using the competent judges method. It was found that the lexical narrativity index-the active "I"-was a good predictor of both BPO and NPO, while the human factor was a good predictor of BPO when low. Moreover, a generalized index was used to describe how stories are saturated with the narrativity indices of intentionality, concreteness, and active "I", but simultaneously deprived of human factor, and was found to be the best predictor of BPO. Furthermore, where the coherence of the story and of its subdimension (integration) rise, the probability of BPO diagnosis decreases. This research provides support for the thesis that surface narrativity indices may predict deeper personality structure. Its results are justified in the light of Kernberg's theory, and have the potential to become a useful tool in clinical practice as a supplementary source of information in diagnostic and psychotherapeutic processes.

Balancing selection on immunity genes: review of the current literature and new analysis in Drosophila melanogaster.

PubMed

Croze, Myriam; Živković, Daniel; Stephan, Wolfgang; Hutter, Stephan

2016-08-01

Balancing selection has been widely assumed to be an important evolutionary force, yet even today little is known about its abundance and its impact on the patterns of genetic diversity. Several studies have shown examples of balancing selection in humans, plants or parasites, and many genes under balancing selection are involved in immunity. It has been proposed that host-parasite coevolution is one of the main forces driving immune genes to evolve under balancing selection. In this paper, we review the literature on balancing selection on immunity genes in several organisms, including Drosophila. Furthermore, we performed a genome scan for balancing selection in an African population of Drosophila melanogaster using coalescent simulations of a demographic model with and without selection. We find very few genes under balancing selection and only one novel candidate gene related to immunity. Finally, we discuss the possible causes of the low number of genes under balancing selection. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

DETECTING SELECTION IN NATURAL POPULATIONS: MAKING SENSE OF GENOME SCANS AND TOWARDS ALTERNATIVE SOLUTIONS

PubMed Central

Haasl, Ryan J.; Payseur, Bret A.

2016-01-01

Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example FST, cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. PMID:26224644

Fifteen years of genomewide scans for selection: trends, lessons and unaddressed genetic sources of complication.

PubMed

Haasl, Ryan J; Payseur, Bret A

2016-01-01

Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example F(ST), cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. © 2015 John Wiley & Sons Ltd.

An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol.

PubMed

Bushee, Jennifer L; Dunne, Christine E; Argikar, Upendra A

2015-05-01

1. Topical glaucoma treatments have often been limited by poor absorption and bioavailability. Betaxolol, a selective β1-blocker, has been well studied for its pharmacokinetics and disposition. Limited ocular, betaxolol metabolism data is available despite a growing number of novel ocular treatments. 2. In vitro ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver. 3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human in vitro ocular data. M1 was specific to human and only captured by the liver data. 4. Liver S9 over predicted the extent of ocular metabolism compared to ocular fractions. Rabbit liver S9 fractions demonstrated extensive glucuronidation and higher parent turn-over in 1 h as compared to other matrices. 5. This research assesses in vitro species and organ differences across preclinical species and human. The complex data set highlights the need for an in vitro ocular system to explore poorly documented ocular metabolism.

Cellular automaton model of crowd evacuation inspired by slime mould

NASA Astrophysics Data System (ADS)

Kalogeiton, V. S.; Papadopoulos, D. P.; Georgilas, I. P.; Sirakoulis, G. Ch.; Adamatzky, A. I.

2015-04-01

In all the living organisms, the self-preservation behaviour is almost universal. Even the most simple of living organisms, like slime mould, is typically under intense selective pressure to evolve a response to ensure their evolution and safety in the best possible way. On the other hand, evacuation of a place can be easily characterized as one of the most stressful situations for the individuals taking part on it. Taking inspiration from the slime mould behaviour, we are introducing a computational bio-inspired model crowd evacuation model. Cellular Automata (CA) were selected as a fully parallel advanced computation tool able to mimic the Physarum's behaviour. In particular, the proposed CA model takes into account while mimicking the Physarum foraging process, the food diffusion, the organism's growth, the creation of tubes for each organism, the selection of optimum tube for each human in correspondence to the crowd evacuation under study and finally, the movement of all humans at each time step towards near exit. To test the model's efficiency and robustness, several simulation scenarios were proposed both in virtual and real-life indoor environments (namely, the first floor of office building B of the Department of Electrical and Computer Engineering of Democritus University of Thrace). The proposed model is further evaluated in a purely quantitative way by comparing the simulation results with the corresponding ones from the bibliography taken by real data. The examined fundamental diagrams of velocity-density and flow-density are found in full agreement with many of the already published corresponding results proving the adequacy, the fitness and the resulting dynamics of the model. Finally, several real Physarum experiments were conducted in an archetype of the aforementioned real-life environment proving at last that the proposed model succeeded in reproducing sufficiently the Physarum's recorded behaviour derived from observation of the aforementioned biological laboratory experiments.

Motion Direction Biases and Decoding in Human Visual Cortex

PubMed Central

Wang, Helena X.; Merriam, Elisha P.; Freeman, Jeremy

2014-01-01

Functional magnetic resonance imaging (fMRI) studies have relied on multivariate analysis methods to decode visual motion direction from measurements of cortical activity. Above-chance decoding has been commonly used to infer the motion-selective response properties of the underlying neural populations. Moreover, patterns of reliable response biases across voxels that underlie decoding have been interpreted to reflect maps of functional architecture. Using fMRI, we identified a direction-selective response bias in human visual cortex that: (1) predicted motion-decoding accuracy; (2) depended on the shape of the stimulus aperture rather than the absolute direction of motion, such that response amplitudes gradually decreased with distance from the stimulus aperture edge corresponding to motion origin; and 3) was present in V1, V2, V3, but not evident in MT+, explaining the higher motion-decoding accuracies reported previously in early visual cortex. These results demonstrate that fMRI-based motion decoding has little or no dependence on the underlying functional organization of motion selectivity. PMID:25209297

Optimized Periocular Template Selection for Human Recognition

PubMed Central

Sa, Pankaj K.; Majhi, Banshidhar

2013-01-01

A novel approach for selecting a rectangular template around periocular region optimally potential for human recognition is proposed. A comparatively larger template of periocular image than the optimal one can be slightly more potent for recognition, but the larger template heavily slows down the biometric system by making feature extraction computationally intensive and increasing the database size. A smaller template, on the contrary, cannot yield desirable recognition though the smaller template performs faster due to low computation for feature extraction. These two contradictory objectives (namely, (a) to minimize the size of periocular template and (b) to maximize the recognition through the template) are aimed to be optimized through the proposed research. This paper proposes four different approaches for dynamic optimal template selection from periocular region. The proposed methods are tested on publicly available unconstrained UBIRISv2 and FERET databases and satisfactory results have been achieved. Thus obtained template can be used for recognition of individuals in an organization and can be generalized to recognize every citizen of a nation. PMID:23984370

Soft fibrin gels promote selection and growth of tumorigenic cells

NASA Astrophysics Data System (ADS)

Liu, Jing; Tan, Youhua; Zhang, Huafeng; Zhang, Yi; Xu, Pingwei; Chen, Junwei; Poh, Yeh-Chuin; Tang, Ke; Wang, Ning; Huang, Bo

2012-08-01

The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.

Human hair follicle organ culture: theory, application and perspectives.

PubMed

Langan, Ewan A; Philpott, Michael P; Kloepper, Jennifer E; Paus, Ralf

2015-12-01

For almost a quarter of a century, ex vivo studies of human scalp hair follicles (HFs) have permitted major advances in hair research, spanning diverse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite this, a comprehensive methodological guide to serum-free human HF organ culture (HFOC) that facilitates the selection and analysis of standard HF biological parameters and points out both research opportunities and pitfalls to newcomers to the field is still lacking. The current methods review aims to close an important gap in the literature and attempts to promote standardisation of human HFOC. We provide basic information outlining the establishment of HFOC through to detailed descriptions of the analysis of standard read-out parameters alongside practical examples. The guide closes by pointing out how serum-free HFOC can be utilised optimally to obtain previously inaccessible insights into human HF biology and pathology that are of interest to experimental dermatologists, geneticists, developmental biologists and (neuro-) endocrinologists alike and by highlighting novel applications of the model, including gene silencing and gene expression profiling of defined, laser capture-microdissected HF compartments. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

PubMed

Ramot, Yuval; Bíró, Tamás; Tiede, Stephan; Tóth, Balázs I; Langan, Ewan A; Sugawara, Koji; Foitzik, Kerstin; Ingber, Arieh; Goffin, Vincent; Langbein, Lutz; Paus, Ralf

2010-06-01

The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.

Participatory planning of interventions to mitigate human-wildlife conflicts.

PubMed

Treves, Adrian; Wallace, R B; White, S

2009-12-01

Conservation of wildlife is especially challenging when the targeted species damage crops or livestock, attack humans, or take fish or game. Affected communities may retaliate and destroy wildlife or their habitats. We summarize recommendations from the literature for 13 distinct types of interventions to mitigate these human-wildlife conflicts. We classified eight types as direct (reducing the severity or frequency of encounters with wildlife) and five as indirect (raising human tolerance for encounters with wildlife) interventions. We analyzed general cause-and-effect relationships underlying human-wildlife conflicts to clarify the focal point of intervention for each type. To organize the recommendations on interventions we used three standard criteria for feasibility: cost-effective design, wildlife specificity and selectivity, and sociopolitical acceptability. The literature review and the feasibility criteria were integrated as decision support tools in three multistakeholder workshops. The workshops validated and refined our criteria and helped the participants select interventions. Our approach to planning interventions is systematic, uses standard criteria, and optimizes the participation of experts, policy makers, and affected communities. We argue that conservation action generally will be more effective if the relative merits of alternative interventions are evaluated in an explicit, systematic, and participatory manner.

When violence pays: a cost-benefit analysis of aggressive behavior in animals and humans.

PubMed

Georgiev, Alexander V; Klimczuk, Amanda C E; Traficonte, Daniel M; Maestripieri, Dario

2013-07-18

An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females.

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

PubMed

Jin, Yun; Ai, Junhua; Shi, Jun

2015-01-01

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

Measurement of volatile organic chemicals at selected sites in California

NASA Technical Reports Server (NTRS)

Singh, Hanwant B.; Salas, L.; Viezee, W.; Sitton, B.; Ferek, R.

1992-01-01

Urban air concentrations of 24 selected volatile organic chemicals that may be potentially hazardous to human health and environment were measured during field experiments conducted at two California locations, at Houston, and at Denver. Chemicals measured included chlorofluorocarbons, halomethanes, haloethanes, halopropanes, chloroethylenes, and aromatic hydrocarbons. With emphasis on California sites, data from these studies are analyzed and interpreted with respect to variabilities in ambient air concentrations, diurnal changes, relation to prevailing meteorology, sources and trends. Except in a few instances, mean concentrations are typically between 0 and 5 ppb. Significant variabilities in atmospheric concentrations associated with intense sources and adverse meteorological conditions are shown to exist. In addition to short-term variability, there is evidence of systematic diurnal and seasonal trends. In some instances it is possible to detect declining trends resulting from the effectiveness of control strategies.

Performance evaluation of the UV/H2O2 process on selected nitrogenous organic compounds: reductions of organic contents vs. corresponding C-, N-DBPs formations.

PubMed

Chen, Huei-Wen; Chen, Chia-Yang; Wang, Gen-Shuh

2011-10-01

The presence of various organic contaminants in water sources is of concern due to their direct threats to human health and potential to react with disinfectants to form carcinogenic byproducts including trihalomethanes, haloacetic acids and nitrosamines in finished water. This study applied both medium-pressure and low-pressure ultraviolet light coupled with hydrogen peroxide (UV/H2O2) to evaluate its efficacy for degradation of selected nitrogenous organic compounds and corresponding disinfection byproduct (DBP) formation. Six organic compounds were chosen as target precursors based on their nitrogen contents and molecular structures. The results showed that higher oxidation capacity resulted in better reduction of organic matters and DBP formation potentials (DBPFPs). However, insufficient contact time and oxidant doses could lead to a rise of DBPFPs in the early stages of UV/H2O2 reactions. A greater percentage removal was achieved for organic carbon than organic nitrogen after UV/H2O2 treatment, especially for compounds with complicated structure such as diltiazem. During the UV/H2O2 treatment, the intermediate products include tertiary amine, dimethyl amine (DMA) or DMA-like structures, which are N-nitrosodimethylamine (NDMA) precursors after chlorination or chloramination. Furthermore, it was observed that using dissolved organic nitrogen and DMA to predict NDMAFP could lead to biased conclusions because of the complex nature of nitrogenous matters in aqueous environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

Accelerated rates of protein evolution in barley grain and pistil biased genes might be legacy of domestication.

PubMed

Shi, Tao; Dimitrov, Ivan; Zhang, Yinling; Tax, Frans E; Yi, Jing; Gou, Xiaoping; Li, Jia

2015-10-01

Traits related to grain and reproductive organs in grass crops have been under continuous directional selection during domestication. Barley is one of the oldest domesticated crops in human history. Thus genes associated with the grain and reproductive organs in barley may show evidence of dramatic evolutionary change. To understand how artificial selection contributes to protein evolution of biased genes in different barley organs, we used Digital Gene Expression analysis of six barley organs (grain, pistil, anther, leaf, stem and root) to identify genes with biased expression in specific organs. Pairwise comparisons of orthologs between barley and Brachypodium distachyon, as well as between highland and lowland barley cultivars mutually indicated that grain and pistil biased genes show relatively higher protein evolutionary rates compared with the median of all orthologs and other organ biased genes. Lineage-specific protein evolutionary rates estimation showed similar patterns with elevated protein evolution in barley grain and pistil biased genes, yet protein sequences generally evolve much faster in the lowland barley cultivar. Further functional annotations revealed that some of these grain and pistil biased genes with rapid protein evolution are related to nutrient biosynthesis and cell cycle/division. Our analyses provide insights into how domestication differentially shaped the evolution of genes specific to different organs of a crop species, and implications for future functional studies of domestication genes.

Human Health Safety Evaluation of Halon Replacement Candidates

DTIC Science & Technology

2000-05-01

neurotoxicity, developmental neurotoxicity, immunotoxicity, and endocrine disruptor tests may be considered if there is reason to suspect alterations in...conclusion of the study), gross necropsy, and select organ weight measurements (e.g., liver, lungs, kidneys, adrenals, testes, brain) "* Preserve ...and evaluated in the study. The biological endpoints of a 90-day study include daily clinical observations; measurements of body weight, food

Changes in the genetic diversity of eastern hemlock as a result of different forest management practices

Treesearch

Gary J. Hawley; Donald H. DeHayes; John C. Brissette

2000-01-01

Loss of populations and individuals within species to human-induced selective forces can result in loss of specific genes and overall genetic diversity upon which productivity, ecosystem stability, long-term survival, and evolution depend. This is particularly true for long-lived organisms, such as forest trees, because genetic diversity confers adaptability necessary...

Switching on fluorescence for selective visual recognition of naringenin and morin with a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene

NASA Astrophysics Data System (ADS)

Zhao, Xi Juan; Wang, Hui Juan; Liang, Li Jiao; Li, Yuan Fang

2013-02-01

Flavonoids such as naringenin and morin are ubiquitous in a wide range of foods isolated from plants, and have diverse effects on plants even on human health. Here, we establish a selective visual method for recognition of aringenin and morin based on the "switched on" fluorescence induced by a metal-organic coordination polymer of Zn(bix) [bix = 1,4-bis(imidazol-1-ylmethyl)benzene]. Owing to the coordination interaction of aringenin and morin with Zn(II) from the polymeric structure of Zn(bix), the conformational free rotation of naringenin and morin is restricted leading to relatively rigid structures. And as a consequence, the fluorescence is switched on. While luteolin and quercetin, holding a very similar structure with naringenin and morin, have no such fluorescence enhancement most likely owing to the 3'-hydroxy substitution in the B ring. Under 365 nm UV lamp light, we can visually recognize and discriminate naringenin and morin from them each other and luteolin as well as quercetin based on the colors of their emission. With this recognition system, the detection of naringenin and morin in human urine was made with satisfactory results.

Inhibitory effect of selective cyclooxygenase-2 inhibitor lumiracoxib on human organic anion transporters hOAT1 and hOAT3.

PubMed

Uwai, Yuichi; Honjo, Hiroaki; Iwamoto, Kikuo

2010-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) delay renal excretion of antifolate methotrexate by inhibiting human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8). In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effect of selective cyclooxygenase-2 inhibitors on hOAT1 and hOAT3. The uptake of methotrexate into oocytes was increased by the injection of hOAT1 and hOAT3 cRNA, and transport was strongly inhibited by lumiracoxib. The apparent 50% inhibitory concentrations of lumiracoxib were estimated to be 3.3 µM and 1.9 µM for uptake of p-aminohippurate by hOAT1 and of estrone sulfate by hOAT3, respectively. Eadie-Hofstee plot analysis showed that lumiracoxib inhibited hOAT1 and hOAT3 in a competitive manner. For other cyclooxygenase-2 inhibitors celecoxib, etoricoxib, rofecoxib and valdecoxib, slight to moderate inhibition of hOAT3 only was observed. These findings show that lumiracoxib has inhibitory potential toward hOAT1 and hOAT3, comparable to that of nonselective NSAIDs.

Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol.

PubMed

Fili, S; Valmas, A; Norrman, M; Schluckebier, G; Beckers, D; Degen, T; Wright, J; Fitch, A; Gozzo, F; Giannopoulou, A E; Karavassili, F; Margiolaki, I

2015-09-01

This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

Liver transplantation: Fifty years of experience

PubMed Central

Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D’Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

2014-01-01

Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation. PMID:24833866

Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol

PubMed Central

Fili, S.; Valmas, A.; Norrman, M.; Schluckebier, G.; Beckers, D.; Degen, T.; Wright, J.; Fitch, A.; Gozzo, F.; Giannopoulou, A. E.; Karavassili, F.; Margiolaki, I.

2015-01-01

This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50–8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs. PMID:26306195

The ecology of human fear: survival optimization and the nervous system

PubMed Central

Mobbs, Dean; Hagan, Cindy C.; Dalgleish, Tim; Silston, Brian; Prévost, Charlotte

2015-01-01

We propose a Survival Optimization System (SOS) to account for the strategies that humans and other animals use to defend against recurring and novel threats. The SOS attempts to merge ecological models that define a repertoire of contextually relevant threat induced survival behaviors with contemporary approaches to human affective science. We first propose that the goal of the nervous system is to reduce surprise and optimize actions by (i) predicting the sensory landscape by simulating possible encounters with threat and selecting the appropriate pre-encounter action and (ii) prevention strategies in which the organism manufactures safe environments. When a potential threat is encountered the (iii) threat orienting system is engaged to determine whether the organism ignores the stimulus or switches into a process of (iv) threat assessment, where the organism monitors the stimulus, weighs the threat value, predicts the actions of the threat, searches for safety, and guides behavioral actions crucial to directed escape. When under imminent attack, (v) defensive systems evoke fast reflexive indirect escape behaviors (i.e., fight or flight). This cascade of responses to threat of increasing magnitude are underwritten by an interconnected neural architecture that extends from cortical and hippocampal circuits, to attention, action and threat systems including the amygdala, striatum, and hard-wired defensive systems in the midbrain. The SOS also includes a modulatory feature consisting of cognitive appraisal systems that flexibly guide perception, risk and action. Moreover, personal and vicarious threat encounters fine-tune avoidance behaviors via model-based learning, with higher organisms bridging data to reduce face-to-face encounters with predators. Our model attempts to unify the divergent field of human affective science, proposing a highly integrated nervous system that has evolved to increase the organism's chances of survival. PMID:25852451

Habituation of adult sea lamprey repeatedly exposed to damage-released alarm and predator cues

USGS Publications Warehouse

Imre, Istvan; Di Rocco, Richard T.; Brown, Grant E.; Johnson, Nicholas

2016-01-01

Predation is an unforgiving selective pressure affecting the life history, morphology and behaviour of prey organisms. Selection should favour organisms that have the ability to correctly assess the information content of alarm cues. This study investigated whether adult sea lamprey Petromyzon marinus habituate to conspecific damage-released alarm cues (fresh and decayed sea lamprey extract), a heterospecific damage-released alarm cue (white sucker Catostomus commersoniiextract), predator cues (Northern water snake Nerodia sipedon washing, human saliva and 2-phenylethylamine hydrochloride (PEA HCl)) and a conspecific damage-released alarm cue and predator cue combination (fresh sea lamprey extract and human saliva) after they were pre-exposed 4 times or 8 times, respectively, to a given stimulus the previous night. Consistent with our prediction, adult sea lamprey maintained an avoidance response to conspecific damage-released alarm cues (fresh and decayed sea lamprey extract), a predator cue presented at high relative concentration (PEA HCl) and a conspecific damage-released alarm cue and predator cue combination (fresh sea lamprey extract plus human saliva), irrespective of previous exposure level. As expected, adult sea lamprey habituated to a sympatric heterospecific damage-released alarm cue (white sucker extract) and a predator cue presented at lower relative concentration (human saliva). Adult sea lamprey did not show any avoidance of the Northern water snake washing and the Amazon sailfin catfish extract (heterospecific control). This study suggests that conspecific damage-released alarm cues and PEA HCl present the best options as natural repellents in an integrated management program aimed at controlling the abundance of sea lamprey in the Laurentian Great Lakes.

How institutions shaped the last major evolutionary transition to large-scale human societies

PubMed Central

Powers, Simon T.; van Schaik, Carel P.; Lehmann, Laurent

2016-01-01

What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default ‘Hobbesian’ rules of the ‘game of life’, determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter–gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization. PMID:26729937

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

PubMed Central

2017-01-01

Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS). Quantitative enzyme-linked immunoadsorption assays (ELISA) demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections. PMID:28972547

B. F. Skinner's Science and Human Behavior: its antecedents and its consequences.

PubMed Central

Catania, A Charles

2003-01-01

Skinner's Science and Human Behavior marked a transition from a treatment of behavior that took physics as its reference science to one that emphasized behavior as a fundamental part of the subject matter of biology. The book includes what may be Skinner's earliest statement about the similarity of operant selection to Darwinian natural selection in phylogeny. Other major topics discussed in the book included multiple causation, private events, the self, and social contingencies. Among the important antecedents were Skinner's own Behavior of Organisms and Keller & Schoenfeld's Pincinples of Psychology. Current developments in education, behavioral economics, and some behavior therapies can be attributed at least in part to Skinner's seminal work. The effective behavioral analysis of governmental and religious systems will probably depend on elaborations of our understanding of verbal behavior. PMID:14964711

Comparison of estimated human dose of (68)Ga-MAA with (99m)Tc-MAA based on rat data.

PubMed

Shanehsazzadeh, Saeed; Lahooti, Afsaneh; Yousefnia, Hassan; Geramifar, Parham; Jalilian, Amir Reza

2015-10-01

(99m)Tc macroaggregated albumin ((99m)Tc-MAA) that had been used as a perfusion agent has been evaluated. In this study, we tried to estimate human absorbed dose of ⁶⁸Ga-MAA via commercially available kit from Pars-Isotopes, based on biodistribution data in wild-type rats, and compare our estimation with the available absorbed dose data from (99m)Tc-MAA. For biodistribution of ⁶⁸Ga-MAA, three rats were sacrificed at each selected times after injection (15, 30, 45, 60, and 120 min) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 11 harvested organs. The medical internal radiation dose formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. The biodistribution data for ⁶⁸Ga-MAA showed that the most of the activity was taken up by the lung (more than 97 %) in no time. Our dose prediction shows that a 185-MBq injection of ⁶⁸Ga-MAA into humans might result in an estimated absorbed dose of 4.31 mGy in the whole body. The highest absorbed doses are observed in the adrenals, spleen, pancreas, and red marrow with 0.36, 0.34, 0.26, and 0.19 mGy, respectively. Since the (99m)Tc-MAA remains longer than ⁶⁸Ga-MAA in the lung and ⁶⁸Ga-MAA has good image qualities and results in lower amounts of dose delivery to the critical organs such as gonads, red marrow, and adrenals, the use of ⁶⁸Ga-MAA is recommended.

High-field fMRI unveils orientation columns in humans.

PubMed

Yacoub, Essa; Harel, Noam; Ugurbil, Kâmil

2008-07-29

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90 degrees (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

The Role of the Baldwin Effect in the Evolution of Human Musicality.

PubMed

Podlipniak, Piotr

2017-01-01

From the biological perspective human musicality is the term referred to as a set of abilities which enable the recognition and production of music. Since music is a complex phenomenon which consists of features that represent different stages of the evolution of human auditory abilities, the question concerning the evolutionary origin of music must focus mainly on music specific properties and their possible biological function or functions. What usually differentiates music from other forms of human sound expressions is a syntactically organized structure based on pitch classes and rhythmic units measured in reference to musical pulse. This structure is an auditory (not acoustical) phenomenon, meaning that it is a human-specific interpretation of sounds achieved thanks to certain characteristics of the nervous system. There is historical and cross-cultural diversity of this structure which indicates that learning is an important part of the development of human musicality. However, the fact that there is no culture without music, the syntax of which is implicitly learned and easily recognizable, suggests that human musicality may be an adaptive phenomenon. If the use of syntactically organized structure as a communicative phenomenon were adaptive it would be only in circumstances in which this structure is recognizable by more than one individual. Therefore, there is a problem to explain the adaptive value of an ability to recognize a syntactically organized structure that appeared accidentally as the result of mutation or recombination in an environment without a syntactically organized structure. The possible solution could be explained by the Baldwin effect in which a culturally invented trait is transformed into an instinctive trait by the means of natural selection. It is proposed that in the beginning musical structure was invented and learned thanks to neural plasticity. Because structurally organized music appeared adaptive (phenotypic adaptation) e.g., as a tool of social consolidation, our predecessors started to spend a lot of time and energy on music. In such circumstances, accidentally one individual was born with the genetically controlled development of new neural circuitry which allowed him or her to learn music faster and with less energy use.

The Role of the Baldwin Effect in the Evolution of Human Musicality

PubMed Central

Podlipniak, Piotr

2017-01-01

From the biological perspective human musicality is the term referred to as a set of abilities which enable the recognition and production of music. Since music is a complex phenomenon which consists of features that represent different stages of the evolution of human auditory abilities, the question concerning the evolutionary origin of music must focus mainly on music specific properties and their possible biological function or functions. What usually differentiates music from other forms of human sound expressions is a syntactically organized structure based on pitch classes and rhythmic units measured in reference to musical pulse. This structure is an auditory (not acoustical) phenomenon, meaning that it is a human-specific interpretation of sounds achieved thanks to certain characteristics of the nervous system. There is historical and cross-cultural diversity of this structure which indicates that learning is an important part of the development of human musicality. However, the fact that there is no culture without music, the syntax of which is implicitly learned and easily recognizable, suggests that human musicality may be an adaptive phenomenon. If the use of syntactically organized structure as a communicative phenomenon were adaptive it would be only in circumstances in which this structure is recognizable by more than one individual. Therefore, there is a problem to explain the adaptive value of an ability to recognize a syntactically organized structure that appeared accidentally as the result of mutation or recombination in an environment without a syntactically organized structure. The possible solution could be explained by the Baldwin effect in which a culturally invented trait is transformed into an instinctive trait by the means of natural selection. It is proposed that in the beginning musical structure was invented and learned thanks to neural plasticity. Because structurally organized music appeared adaptive (phenotypic adaptation) e.g., as a tool of social consolidation, our predecessors started to spend a lot of time and energy on music. In such circumstances, accidentally one individual was born with the genetically controlled development of new neural circuitry which allowed him or her to learn music faster and with less energy use. PMID:29056895

Supramolecular chemistry: from molecular information towards self-organization and complex matter

NASA Astrophysics Data System (ADS)

Lehn, Jean-Marie

2004-03-01

Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as supramolecular polymers and liquid crystals, and provide an original approach to nanoscience and nanotechnology. In particular, the spontaneous but controlled generation of well-defined, functional supramolecular architectures of nanometric size through self-organization represents a means of performing programmed engineering and processing of nanomaterials. Supramolecular chemistry is intrinsically a dynamic chemistry, in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when a molecular entity contains covalent bonds that may form and break reversibly, so as to make possible a continuous change in constitution and structure by reorganization and exchange of building blocks. This behaviour defines a constitutional dynamic chemistry that allows self-organization by selection as well as by design at both the molecular and supramolecular levels. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization by selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation in a Darwinistic fashion. The merging of the features, information and programmability, dynamics and reversibility, constitution and structural diversity, points towards the emergence of adaptative and evolutionary chemistry. Together with the corresponding fields of physics and biology, it constitutes a science of informed matter, of organized, adaptative complex matter. This article was originally published in 2003 by the Israel Academy of Sciences and Humanities in the framework of its Albert Einstein Memorial Lectures series. Reprinted by permission of the Israel Academy of Sciences and Humanities.

Monitoring of selected skin- and breath-borne volatile organic compounds emitted from the human body using gas chromatography ion mobility spectrometry (GC-IMS).

PubMed

Mochalski, Paweł; Wiesenhofer, Helmut; Allers, Maria; Zimmermann, Stefan; Güntner, Andreas T; Pineau, Nicolay J; Lederer, Wolfgang; Agapiou, Agapios; Mayhew, Christopher A; Ruzsanyi, Veronika

2018-02-15

Human smuggling and associated cross-border crimes have evolved as a major challenge for the European Union in recent years. Of particular concern is the increasing trend of smuggling migrants hidden inside shipping containers or trucks. Therefore, there is a growing demand for portable security devices for the non-intrusive and rapid monitoring of containers to detect people hiding inside. In this context, chemical analysis of volatiles organic compounds (VOCs) emitted from the human body is proposed as a locating tool. In the present study, an in-house made ion mobility spectrometer coupled with gas chromatography (GC-IMS) was used to monitor the volatile moieties released from the human body under conditions that mimic entrapment. A total of 17 omnipresent volatile compounds were identified and quantified from 35 ion mobility peaks corresponding to human presence. These are 7 aldehydes (acrolein, 2-methylpropanal, 3-methylbutanal, 2-ethacrolein, n-hexanal, n-heptanal, benzaldehyde), 3 ketones (acetone, 2-pentanone, 4-methyl-2-pentanone), 5 esters (ethyl formate, ethyl propionate, vinyl butyrate, butyl acetate, ethyl isovalerate), one alcohol (2-methyl-1-propanol) and one organic acid (acetic acid). The limits of detection (0.05-7.2 ppb) and relative standard deviations (0.6-11%) should be sufficient for detecting these markers of human presence in field conditions. This study shows that GC-IMS can be used as a portable field detector of hidden or entrapped people. Copyright © 2018 Elsevier B.V. All rights reserved.

Review of 'emerging' organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids.

PubMed

Clarke, Bradley O; Smith, Stephen R

2011-01-01

A broad spectrum of organic chemicals is essential to modern society. Once discharged from industrial, domestic and urban sources into the urban wastewater collection system they may transfer to the residual solids during wastewater treatment and assessment of their significance and implications for beneficial recycling of the treated sewage sludge biosolids is required. Research on organic contaminants (OCs) in biosolids has been undertaken for over thirty years and the increasing body of evidence demonstrates that the majority of compounds studied do not place human health at risk when biosolids are recycled to farmland. However, there are 143,000 chemicals registered in the European Union for industrial use and all could be potentially found in biosolids. Therefore, a literature review of 'emerging' OCs in biosolids has been conducted for a selection of chemicals of potential concern for land application based upon human toxicity, evidence of adverse effects on the environment and endocrine disruption. To identify monitoring and research priorities the selected chemicals were ranked using an assessment matrix approach. Compounds were evaluated based upon environmental persistence, human toxicity, evidence of bioaccumulation in humans and the environment, evidence of ecotoxicity and the number and quality of studies focussed on the contaminant internationally. The identified chemicals of concern were ranked in decreasing order of priority: perfluorinated chemicals (PFOS, PFOA); polychlorinated alkanes (PCAs), polychlorinated naphthalenes (PCNs); organotins (OTs), polybrominated diphenyl ethers (PBDEs), triclosan (TCS), triclocarban (TCC); benzothiazoles; antibiotics and pharmaceuticals; synthetic musks; bisphenol A, quaternary ammonium compounds (QACs), steroids; phthalate acid esters (PAEs) and polydimethylsiloxanes (PDMSs). A number of issues were identified and recommendations for the prioritisation of further research and monitoring of 'emerging' OCs for the agricultural use of biosolids are provided. In particular, a number of 'emerging' OCs (PFOS, PFOA and PCAs) were identified for priority attention that are environmentally persistent and potentially toxic with unique chemical properties, or are present in large concentrations in sludge, that make it theoretically possible for them to enter human and ecological food-chains from biosolids-amended soil. Copyright © 2010 Elsevier Ltd. All rights reserved.

Life cycle toxicity assessment of pesticides used in integrated and organic production of oranges in the Comunidad Valenciana, Spain.

PubMed

Juraske, Ronnie; Sanjuán, Neus

2011-02-01

The relative impacts of 25 pesticides including acaricides, fungicides, herbicides, insecticides, and post-harvest fungicides, used in the production of oranges in Spain were assessed with current life cycle impact assessment (LCIA) tools. Chemical specific concentrations were combined with pesticide emission data and information on chemical toxicity to assess human toxicity and freshwater ecotoxicity impacts. As a case study, the relative impacts of two orange production systems in the region of Valencia, integrated pest management (IP) and organic production (OP), were assessed. The evaluation of active ingredients showed that on average acaricides have the highest human toxicity impact scores, while for freshwater ecotoxicity insecticides show the highest impact. In both impact categories the lowest impact scores were calculated for herbicides. In the production of 1 kg of orange fruits, where several kinds of pesticides are combined, results show that post-harvest fungicides can contribute more than 95% to the aggregate human toxicity impacts. More than 85% of aquatic ecotoxicity is generated by fungicides applied before harvest. The potential to reduce impacts on freshwater ecosystems is seven orders of magnitude, while impacts on human health can be reduced by two orders of magnitude. Hence, this stresses the importance of a careful pre-selection of active ingredients. In both impact categories, organic production represents the least toxic pest-control method. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pu-239 organ specific dosimetric model applied to non-human biota

NASA Astrophysics Data System (ADS)

Kaspar, Matthew Jason

There are few locations throughout the world, like the Maralinga nuclear test site located in south western Australia, where sufficient plutonium contaminate concentration levels exist that they can be utilized for studies of the long-term radionuclide accumulation in non-human biota. The information obtained will be useful for the potential human users of the site while also keeping with international efforts to better understand doses to non-human biota. In particular, this study focuses primarily on a rabbit sample set collected from the population located within the site. Our approach is intended to employ the same dose and dose rate methods selected by the International Commission on Radiological Protection and adapted by the scientific community for similar research questions. These models rely on a series of simplifying assumptions on biota and their geometry; in particular; organisms are treated as spherical and ellipsoidal representations displaying the animal mass and volume. These simplifications assume homogeneity of all animal tissues. In collaborative efforts between Colorado State University and the Australian Nuclear Science and Technology Organisation (ANSTO), we are expanding current knowledge on radionuclide accumulation in specific organs causing organ-specific dose rates, such as Pu-239 accumulating in bone, liver, and lungs. Organ-specific dose models have been developed for humans; however, little has been developed for the dose assessment to biota, in particular rabbits. This study will determine if it is scientifically valid to use standard software, in particular ERICA Tool, as a means to determine organ-specific dosimetry due to Pu-239 accumulation in organs. ERICA Tool is normally applied to whole organisms as a means to determine radiological risk to whole ecosystems. We will focus on the aquatic model within ERICA Tool, as animal organs, like aquatic organisms, can be assumed to lie within an infinite uniform medium. This model would scientifically be valid for radionuclides emitting short-range radiation, as with Pu-239, where the energy is deposited locally. Two MCNPX models have been created and evaluated against ERICA Tool's aquatic model. One MCNPX model replicates ERICA Tool's intrinsic assumptions while the other uses a more realistic animal model adopted by ICRP Publication 108 and ERICA Tool for the organs "infinite" surrounding universe. In addition, the role of model geometry will be analyzed by focusing on four geometry sets for the same organ, including a spherical geometry. ERICA Tool will be compared to MCNPX results within and between each organ geometry set. In addition, the organ absorbed dose rate will be calculated for six rabbits located on the Maralinga nuclear test site as a preliminary test for further investigation. Data in all cases will be compared using percent differences and Student's t-test with respect to ERICA Tool's results and the overall average organ mean absorbed dose rate.

Darwin in Mind: New Opportunities for Evolutionary Psychology

PubMed Central

Bolhuis, Johan J.; Brown, Gillian R.; Richardson, Robert C.; Laland, Kevin N.

2011-01-01

Evolutionary Psychology (EP) views the human mind as organized into many modules, each underpinned by psychological adaptations designed to solve problems faced by our Pleistocene ancestors. We argue that the key tenets of the established EP paradigm require modification in the light of recent findings from a number of disciplines, including human genetics, evolutionary biology, cognitive neuroscience, developmental psychology, and paleoecology. For instance, many human genes have been subject to recent selective sweeps; humans play an active, constructive role in co-directing their own development and evolution; and experimental evidence often favours a general process, rather than a modular account, of cognition. A redefined EP could use the theoretical insights of modern evolutionary biology as a rich source of hypotheses concerning the human mind, and could exploit novel methods from a variety of adjacent research fields. PMID:21811401

Neurophysiological Organization of the Middle Face Patch in Macaque Inferior Temporal Cortex

PubMed Central

Aparicio, Paul L.; Issa, Elias B.

2016-01-01

While early cortical visual areas contain fine scale spatial organization of neuronal properties, such as orientation preference, the spatial organization of higher-level visual areas is less well understood. The fMRI demonstration of face-preferring regions in human ventral cortex and monkey inferior temporal cortex (“face patches”) raises the question of how neural selectivity for faces is organized. Here, we targeted hundreds of spatially registered neural recordings to the largest fMRI-identified face-preferring region in monkeys, the middle face patch (MFP), and show that the MFP contains a graded enrichment of face-preferring neurons. At its center, as much as 93% of the sites we sampled responded twice as strongly to faces than to nonface objects. We estimate the maximum neurophysiological size of the MFP to be ∼6 mm in diameter, consistent with its previously reported size under fMRI. Importantly, face selectivity in the MFP varied strongly even between neighboring sites. Additionally, extremely face-selective sites were ∼40 times more likely to be present inside the MFP than outside. These results provide the first direct quantification of the size and neural composition of the MFP by showing that the cortical tissue localized to the fMRI defined region consists of a very high fraction of face-preferring sites near its center, and a monotonic decrease in that fraction along any radial spatial axis. SIGNIFICANCE STATEMENT The underlying organization of neurons that give rise to the large spatial regions of activity observed with fMRI is not well understood. Neurophysiological studies that have targeted the fMRI identified face patches in monkeys have provided evidence for both large-scale clustering and a heterogeneous spatial organization. Here we used a novel x-ray imaging system to spatially map the responses of hundreds of sites in and around the middle face patch. We observed that face-selective signal localized to the middle face patch was characterized by a gradual spatial enrichment. Furthermore, strongly face-selective sites were ∼40 times more likely to be found inside the patch than outside of the patch. PMID:27810930

Neurophysiological Organization of the Middle Face Patch in Macaque Inferior Temporal Cortex.

PubMed

Aparicio, Paul L; Issa, Elias B; DiCarlo, James J

2016-12-14

While early cortical visual areas contain fine scale spatial organization of neuronal properties, such as orientation preference, the spatial organization of higher-level visual areas is less well understood. The fMRI demonstration of face-preferring regions in human ventral cortex and monkey inferior temporal cortex ("face patches") raises the question of how neural selectivity for faces is organized. Here, we targeted hundreds of spatially registered neural recordings to the largest fMRI-identified face-preferring region in monkeys, the middle face patch (MFP), and show that the MFP contains a graded enrichment of face-preferring neurons. At its center, as much as 93% of the sites we sampled responded twice as strongly to faces than to nonface objects. We estimate the maximum neurophysiological size of the MFP to be ∼6 mm in diameter, consistent with its previously reported size under fMRI. Importantly, face selectivity in the MFP varied strongly even between neighboring sites. Additionally, extremely face-selective sites were ∼40 times more likely to be present inside the MFP than outside. These results provide the first direct quantification of the size and neural composition of the MFP by showing that the cortical tissue localized to the fMRI defined region consists of a very high fraction of face-preferring sites near its center, and a monotonic decrease in that fraction along any radial spatial axis. The underlying organization of neurons that give rise to the large spatial regions of activity observed with fMRI is not well understood. Neurophysiological studies that have targeted the fMRI identified face patches in monkeys have provided evidence for both large-scale clustering and a heterogeneous spatial organization. Here we used a novel x-ray imaging system to spatially map the responses of hundreds of sites in and around the middle face patch. We observed that face-selective signal localized to the middle face patch was characterized by a gradual spatial enrichment. Furthermore, strongly face-selective sites were ∼40 times more likely to be found inside the patch than outside of the patch. Copyright © 2016 the authors 0270-6474/16/3612729-17$15.00/0.

α-Pinene, 3-carene and d-limonene in indoor air of Polish apartments: the impact on air quality and human exposure.

PubMed

Król, Sylwia; Namieśnik, Jacek; Zabiegała, Bożena

2014-01-15

Monoterpenes are among most ubiquitous volatile organic compounds (VOCs) to be detected in indoor air. Since the quality of indoor air is considered important for inhabitants' well-being, the present study aimed at investigating impact of human activity on levels of selected monoterpenes applying passive sampling technique followed by thermal desorption and gas chromatography coupled mass spectrometry. One of the objectives of the present work was to identify and characterize main emission sources as well as to investigate relationship between selected monoterpenes in indoor air. Concentration levels obtained for studied monoterpenes varied from 3 μg m(-3) for 3-carene to 1261 μg m(-3) for d-limonene. D-limonene was reported the most abundant of studied monoterpenes in indoor air. The strong correlation observed between monoterpenes suggests that studied compounds originate from same emission sources, while the I/O >1 proves the strong contribution of endogenous emission sources. The in-depth study of day-night fluctuations in concentrations of monoterpenes lead to the conclusion that human presence and specific pattern of behavior strongly influences presence and concentrations of VOCs in indoor environment. The evaluation of human exposure to selected monoterpenes via inhalation of air revealed that infants, toddlers and young children were the highly exposed individuals. © 2013.

Human rights and human dignity in the resolution of certain ethical questions in biomedicine.

PubMed

Wheatley, S

2001-01-01

As medical technology develops, new issues are raised as to how the use of this technology may comply or conflict with existing human rights standards and values. This article considers the application of human rights standards, and in particular the jurisprudence under Article 8 of the European Convention on Human Rights, to the trade in human body organs, the selection of the sex of prospective children, and human reproductive cloning. The current domestic law and regulatory framework is examined, as well as international regulation of this area by the Council of Europe Convention on Human Rights and Biomedicine. The author considers how the balance is to be struck between the ethical objections to many developments in biomedicine, and individual self-determination. It is suggested that, in order to be justified, any limitations on individual self-determination in the use of this new medical technology, should have a basis in the protection of human dignity.

Chemoselective Hydrodehalogenation of Organic Halides Utilizing Two-Dimensional Anionic Electrons of Inorganic Electride [Ca2N]+·e^.

PubMed

Kim, Ye Ji; Kim, Sun Min; Yu, Chunghyeon; Yoo, YoungMin; Cho, Eun Jin; Yang, Jung Woon; Kim, Sung Wng

2017-01-31

Halogenated organic compounds are important anthropogenic chemicals widely used in chemical industry, biology, and pharmacology; however, the persistence and inertness of organic halides cause human health problems and considerable environmental pollution. Thus, the elimination or replacement of halogen atoms with organic halides has been considered a central task in synthetic chemistry. In dehalogenation reactions, the consecutive single-electron transfer from reducing agents generates the radical and corresponding carbanion and thus removes the halogen atom as the leaving group. Herein, we report a new strategy for an efficient chemoselective hydrodehalogenation through the formation of stable carbanion intermediates, which are simply achieved by using highly mobile two-dimensional electrons of inorganic electride [Ca 2 N] + ·e - with effective electron transfer ability. The consecutive single-electron transfer from inorganic electride [Ca 2 N] + ·e - stabilized free carbanions, which is a key step in achieving the selective reaction. Furthermore, a determinant more important than leaving group ability is the stability control of free carbanions according to the s character determined by the backbone structure. We anticipate that this approach may provide new insight into selective chemical formation, including hydrodehalogenation.

Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

PubMed

Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

2016-10-01

The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

Different level of population differentiation among human genes.

PubMed

Wu, Dong-Dong; Zhang, Ya-Ping

2011-01-14

During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

Information Systems: How They Affect and Are Affected by Organization Structure

DTIC Science & Technology

1992-03-01

perceived managerial benefits of telecommuting were increased productivity, increased employee satisfaction, and decreased labor costs. Over 76 percent of...acceptable behavior, and provides fair treatment of employees. One drawback of this tool is that worker performance may actually decrease to the levels...of interpersonal relationships * Selection for employment and promotion based on technical competence. This style attempts to minimize human factors

WHO Atlas on Global Resources for Persons with Intellectual Disabilities 2007: Key Findings Relevant for Low- and Middle-Income Countries

ERIC Educational Resources Information Center

Mercier, Celine; Saxena, Shekhar; Lecomte, Jocelin; Cumbrera, Marco Garrido; Harnois, Gaston

2008-01-01

The World Health Organization (WHO) Atlas-ID project was designed to collect, compile, and disseminate information on intellectual disabilities (ID) services and resources from across the world. This paper aims at selecting findings in the Atlas-ID that can be used as a tool for advocacy, human rights awareness, development planning, and…

Advancement of Tools Supporting Improvement of Work Safety in Selected Industrial Company

NASA Astrophysics Data System (ADS)

Gembalska-Kwiecień, Anna

2018-03-01

In the presented article, the advancement of tools to improve the safety of work in the researched industrial company was taken into consideration. Attention was paid to the skillful analysis of the working environment, which includes the available technologies, work organization and human capital. These factors determine the development of the best prevention activities to minimize the number of accidents.

Construction of optical glucose nanobiosensor with high sensitivity and selectivity at physiological pH on the basis of organic-inorganic hybrid microgels.

PubMed

Wu, Weitai; Zhou, Ting; Aiello, Michael; Zhou, Shuiqin

2010-08-15

A new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological pH is described. To construct these glucose nanobiosensors, the fluorescent CdS quantum dots (QDs), serving as the optical code, were incorporated into the glucose-sensitive poly(N-isopropylacrylamide-acrylamide-2-acrylamidomethyl-5-fluorophenylboronic acid) copolymer microgels, via both in situ growth method and "breathing in" method, respectively. The polymeric gel can adapt to surrounding glucose concentrations, and regulate the fluorescence of the embedded QDs, converting biochemical signals into optical signals. The gradual swelling of the gel would lead to the quenching of the fluorescence at the elevated glucose concentrations. The hybrid microgels displayed high selectivity to glucose over the potential primary interferents of lactate and human serum albumin in the physiologically important glucose concentration range. The stability, reversibility, and sensitivity of the organic-inorganic hybrid microgel-based biosensors were also systematically studied. These general properties of our nanobiosensors are well tunable under appropriate tailor on the hybrid microgels, in particular, simply through the change in the crosslinking degree of the microgels. The optical glucose nanobiosensors based on the organic-inorganic hybrid microgels have shown the potential for a third generation fluorescent biosensor. Copyright 2010 Elsevier B.V. All rights reserved.

Just like the rest of evolution in Mother Nature, the evolution of cancers may be driven by natural selection, and not by haphazard mutations

PubMed Central

Zhang, Ju; Lou, Xiaomin; Zellmer, Lucas; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua

2014-01-01

Sporadic carcinogenesis starts from immortalization of a differentiated somatic cell or an organ-specific stem cell. The immortalized cell incepts a new or quasinew organism that lives like a parasite in the patient and usually proceeds to progressive simplification, constantly engendering intermediate organisms that are simpler than normal cells. Like organismal evolution in Mother Nature, this cellular simplification is a process of Darwinian selection of those mutations with growth- or survival-advantages, from numerous ones that occur randomly and stochastically. Therefore, functional gain of growth- or survival-sustaining oncogenes and functional loss of differentiation-sustaining tumor suppressor genes, which are hallmarks of cancer cells and contribute to phenotypes of greater malignancy, are not drivers of carcinogenesis but are results from natural selection of advantageous mutations. Besides this mutation-load dependent survival mechanism that is evolutionarily low and of an asexual nature, cancer cells may also use cell fusion for survival, which is an evolutionarily-higher mechanism and is of a sexual nature. Assigning oncogenes or tumor suppressor genes or their mutants as drivers to induce cancer in animals may somewhat coerce them to create man-made oncogenic pathways that may not really be a course of sporadic cancer formations in the human. PMID:25594068

Liver xenotransplantation.

PubMed

Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

1993-10-01

During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

A 90-Kilodalton Endothelial Cell Molecule Mediating Lymphocyte Binding in Humans

NASA Astrophysics Data System (ADS)

Salmi, Marko; Jalkanen, Sirpa

1992-09-01

Interactions between leukocyte surface receptors and their ligands on vascular endothelial cells control lymphocyte traffic between the blood and various lymphoid organs, as well as extravasation of leukocytes into sites of inflammation. A heretofore undescribed 90-kilodalton human endothelial cell adhesion molecule (VAP-1) defined by a monoclonal antibody 1B2 is described. The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes. VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man.

Highly Sensitive and Selective Sensing of Free Bilirubin Using Metal-Organic Frameworks-Based Energy Transfer Process.

PubMed

Du, Yaran; Li, Xiqian; Lv, Xueju; Jia, Qiong

2017-09-13

Free bilirubin, a key biomarker for jaundice, was detected with a newly designed fluorescent postsynthetically modified metal organic framework (MOF) (UIO-66-PSM) sensor. UiO-66-PSM was prepared based on the aldimine condensation reaction of UiO-66-NH 2 with 2,3,4-trihydroxybenzaldehyde. The fluorescence of UIO-66-PSM could be effectively quenched by free bilirubin via a fluorescent resonant energy transfer process, thus achieving its recognition of free bilirubin. It was the first attempt to design a MOF-based fluorescent probe for sensing free bilirubin. The probe exhibited fast response time, low detection limit, wide linear range, and high selectivity toward free bilirubin. The sensing system enabled the monitor of free bilirubin in real human serum. Hence, the reported free bilirubin sensing platform has potential applications for clinical diagnosis of jaundice.

Cancer: A disease at the crossroads of trade-offs.

PubMed

Jacqueline, Camille; Biro, Peter A; Beckmann, Christa; Moller, Anders Pape; Renaud, François; Sorci, Gabriele; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric

2017-03-01

Central to evolutionary theory is the idea that living organisms face phenotypic and/or genetic trade-offs when allocating resources to competing life-history demands, such as growth, survival, and reproduction. These trade-offs are increasingly considered to be crucial to further our understanding of cancer. First, evidences suggest that neoplastic cells, as any living entities subject to natural selection, are governed by trade-offs such as between survival and proliferation. Second, selection might also have shaped trade-offs at the organismal level, especially regarding protective mechanisms against cancer. Cancer can also emerge as a consequence of additional trade-offs in organisms (e.g., eco-immunological trade-offs). Here, we review the wide range of trade-offs that occur at different scales and their relevance for understanding cancer dynamics. We also discuss how acknowledging these phenomena, in light of human evolutionary history, may suggest new guidelines for preventive and therapeutic strategies.

The value of microgrants for community-based health promotion: two models for practice and policy.

PubMed

Hartwig, Kari A; Bobbitt-Cooke, Mary; Zaharek, Margot M; Nappi, Susan; Wykoff, Randolph F; Katz, David L

2006-01-01

In 2001, the Office of Disease Prevention and Health Promotion in the US Department of Health and Human Services announced its intention to (1) identify innovative ways to increase public awareness and focus on Healthy People 2010 objectives and (2) broaden the participation of community-based organizations, including agencies new to public health. The mechanism selected, microfinancing, was modeled after small venture loans for economic stimulus in developing countries. The Office of Disease Prevention and Health Promotion selected one state health department and one academic research organization from 80 applicants to test models of awarding "microgrants" of 2,010 dollars to community agencies. This article describes the two models, the types of agencies that were funded, the primary Healthy People 2010 objectives targeted, examples of how the monies were used and leveraged by grantees, and the implications of microgrants for public health practice and policy.

Efficient multi-atlas abdominal segmentation on clinically acquired CT with SIMPLE context learning.

PubMed

Xu, Zhoubing; Burke, Ryan P; Lee, Christopher P; Baucom, Rebeccah B; Poulose, Benjamin K; Abramson, Richard G; Landman, Bennett A

2015-08-01

Abdominal segmentation on clinically acquired computed tomography (CT) has been a challenging problem given the inter-subject variance of human abdomens and complex 3-D relationships among organs. Multi-atlas segmentation (MAS) provides a potentially robust solution by leveraging label atlases via image registration and statistical fusion. We posit that the efficiency of atlas selection requires further exploration in the context of substantial registration errors. The selective and iterative method for performance level estimation (SIMPLE) method is a MAS technique integrating atlas selection and label fusion that has proven effective for prostate radiotherapy planning. Herein, we revisit atlas selection and fusion techniques for segmenting 12 abdominal structures using clinically acquired CT. Using a re-derived SIMPLE algorithm, we show that performance on multi-organ classification can be improved by accounting for exogenous information through Bayesian priors (so called context learning). These innovations are integrated with the joint label fusion (JLF) approach to reduce the impact of correlated errors among selected atlases for each organ, and a graph cut technique is used to regularize the combined segmentation. In a study of 100 subjects, the proposed method outperformed other comparable MAS approaches, including majority vote, SIMPLE, JLF, and the Wolz locally weighted vote technique. The proposed technique provides consistent improvement over state-of-the-art approaches (median improvement of 7.0% and 16.2% in DSC over JLF and Wolz, respectively) and moves toward efficient segmentation of large-scale clinically acquired CT data for biomarker screening, surgical navigation, and data mining. Copyright © 2015 Elsevier B.V. All rights reserved.

Quinol derivatives as potential trypanocidal agents

PubMed Central

Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

2012-01-01

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

The Role of Organic Proteins on the Crack Growth Resistance of Human Enamel

PubMed Central

Yahyazadehfar, Mobin; Arola, Dwayne

2015-01-01

With only 1% protein by weight, tooth enamel is the most highly mineralized tissue in mammals. The focus of this study was to evaluate contributions of the proteins on the fracture resistance of this unique structural material. Sections of enamel were obtained from the cusps of human molars and the crack growth resistance was quantified using a conventional fracture mechanics approach with complementary finite element analysis. In selected specimens the proteins were extracted using a potassium hydroxide treatment. Removal of the proteins resulted in approximately 40% decrease in the fracture toughness with respect to the fully proteinized control. The loss of organic content was most detrimental to the extrinsic toughening mechanisms, causing over 80% reduction in their contribution to the total energy to fracture. This degradation occurred by embrittlement of the unbroken bridging ligaments and consequent reduction in the crack closure stress. Although the organic content of tooth enamel is very small, it is essential to crack growth toughening by facilitating the formation of unbroken ligaments and in fortifying their potency. Replicating functions of the organic content will be critical to the successful development of bio-inspired materials that are designed for fracture resistance. PMID:25805107

Self-organizing map classifier for stressed speech recognition

NASA Astrophysics Data System (ADS)

Partila, Pavol; Tovarek, Jaromir; Voznak, Miroslav

2016-05-01

This paper presents a method for detecting speech under stress using Self-Organizing Maps. Most people who are exposed to stressful situations can not adequately respond to stimuli. Army, police, and fire department occupy the largest part of the environment that are typical of an increased number of stressful situations. The role of men in action is controlled by the control center. Control commands should be adapted to the psychological state of a man in action. It is known that the psychological changes of the human body are also reflected physiologically, which consequently means the stress effected speech. Therefore, it is clear that the speech stress recognizing system is required in the security forces. One of the possible classifiers, which are popular for its flexibility, is a self-organizing map. It is one type of the artificial neural networks. Flexibility means independence classifier on the character of the input data. This feature is suitable for speech processing. Human Stress can be seen as a kind of emotional state. Mel-frequency cepstral coefficients, LPC coefficients, and prosody features were selected for input data. These coefficients were selected for their sensitivity to emotional changes. The calculation of the parameters was performed on speech recordings, which can be divided into two classes, namely the stress state recordings and normal state recordings. The benefit of the experiment is a method using SOM classifier for stress speech detection. Results showed the advantage of this method, which is input data flexibility.

Novel metals and metal complexes as platforms for cancer therapy.

PubMed

Frezza, Michael; Hindo, Sarmad; Chen, Di; Davenport, Andrew; Schmitt, Sara; Tomco, Dajena; Dou, Q Ping

2010-06-01

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[Pt(II) (NH(3))(2)Cl(2)], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed.

Expanding the eco-evolutionary context of herbicide resistance research.

PubMed

Neve, Paul; Busi, Roberto; Renton, Michael; Vila-Aiub, Martin M

2014-09-01

The potential for human-driven evolution in economically and environmentally important organisms in medicine, agriculture and conservation management is now widely recognised. The evolution of herbicide resistance in weeds is a classic example of rapid adaptation in the face of human-mediated selection. Management strategies that aim to slow or prevent the evolution of herbicide resistance must be informed by an understanding of the ecological and evolutionary factors that drive selection in weed populations. Here, we argue for a greater focus on the ultimate causes of selection for resistance in herbicide resistance studies. The emerging fields of eco-evolutionary dynamics and applied evolutionary biology offer a means to achieve this goal and to consider herbicide resistance in a broader and sometimes novel context. Four relevant research questions are presented, which examine (i) the impact of herbicide dose on selection for resistance, (ii) plant fitness in herbicide resistance studies, (iii) the efficacy of herbicide rotations and mixtures and (iv) the impacts of gene flow on resistance evolution and spread. In all cases, fundamental ecology and evolution have the potential to offer new insights into herbicide resistance evolution and management. © 2014 Society of Chemical Industry.

Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 in Cells

PubMed Central

Zhang, Feiran; Bhat, Shridhar; Gabelli, Sandra B.; Chen, Xiaochun; Miller, Michelle S.; Nacev, Benjamin A.; Cheng, Yim Ling; Meyers, David J.; Tenney, Karen; Shim, Joong Sup; Crews, Phillip; Amzel, L. Mario; Ma, Dawei; Liu, Jun O.

2013-01-01

Methionine aminopeptidases (MetAPs) which remove the initiator methionine from nascent peptides are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1–4). But all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 1–4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells. PMID:23634668

Comparison of True and Smoothed Puff Profile Replication on Smoking Behavior and Mainstream Smoke Emissions

PubMed Central

2015-01-01

To estimate exposures to smokers from cigarettes, smoking topography is typically measured and programmed into a smoking machine to mimic human smoking, and the resulting smoke emissions are tested for relative levels of harmful constituents. However, using only the summary puff data—with a fixed puff frequency, volume, and duration—may underestimate or overestimate actual exposure to smoke toxins. In this laboratory study, we used a topography-driven smoking machine that faithfully reproduces a human smoking session and individual human topography data (n = 24) collected during previous clinical research to investigate if replicating the true puff profile (TP) versus the mathematically derived smoothed puff profile (SM) resulted in differences in particle size distributions and selected toxic/carcinogenic organic compounds from mainstream smoke emissions. Particle size distributions were measured using an electrical low pressure impactor, the masses of the size-fractionated fine and ultrafine particles were determined gravimetrically, and the collected particulate was analyzed for selected particle-bound, semivolatile compounds. Volatile compounds were measured in real time using a proton transfer reaction-mass spectrometer. By and large, TP levels for the fine and ultrafine particulate masses as well as particle-bound organic compounds were slightly lower than the SM concentrations. The volatile compounds, by contrast, showed no clear trend. Differences in emissions due to the use of the TP and SM profiles are generally not large enough to warrant abandoning the procedures used to generate the simpler smoothed profile in favor of the true profile. PMID:25536227

Proposed Project Selection Method for Human Support Research and Technology Development (HSR&TD)

NASA Technical Reports Server (NTRS)

Jones, Harry

2005-01-01

The purpose of HSR&TD is to deliver human support technologies to the Exploration Systems Mission Directorate (ESMD) that will be selected for future missions. This requires identifying promising candidate technologies and advancing them in technology readiness until they are acceptable. HSR&TD must select an may of technology development projects, guide them, and either terminate or continue them, so as to maximize the resulting number of usable advanced human support technologies. This paper proposes an effective project scoring methodology to support managing the HSR&TD project portfolio. Researchers strongly disagree as to what are the best technology project selection methods, or even if there are any proven ones. Technology development is risky and outstanding achievements are rare and unpredictable. There is no simple formula for success. Organizations that are satisfied with their project selection approach typically use a mix of financial, strategic, and scoring methods in an open, established, explicit, formal process. This approach helps to build consensus and develop management insight. It encourages better project proposals by clarifying the desired project attributes. We propose a project scoring technique based on a method previously used in a federal laboratory and supported by recent research. Projects are ranked by their perceived relevance, risk, and return - a new 3 R's. Relevance is the degree to which the project objective supports the HSR&TD goal of developing usable advanced human support technologies. Risk is the estimated probability that the project will achieve its specific objective. Return is the reduction in mission life cycle cost obtained if the project is successful. If the project objective technology performs a new function with no current cost, its return is the estimated cash value of performing the new function. The proposed project selection scoring method includes definitions of the criteria, a project evaluation questionnaire, and a scoring formula.

Agricultural use of Burkholderia (Pseudomonas) cepacia: a threat to human health?

PubMed Central

Holmes, A.; Govan, J.; Goldstein, R.

1998-01-01

In the past 2 decades, Burkholderia cepacia has emerged as a human pathogen causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. One highly transmissible strain has spread across North America and Britain, and another between hospitalized CF and non-CF patients. Meanwhile, the organism has been developed as a biopesticide for protecting crops against fungal diseases and has potential as a bioremediation agent for breaking down recalcitrant herbicides and pesticides. However, B. cepacia is inherently resistant to multiple antibiotics; selection of strains "safe" for environmental application is not at present possible phenotypically or genotypically; molecular epidemiology and phylogenetic studies demonstrate that highly transmissible strains emerge randomly; and the organism has a capacity for rapid mutation and adaptation (facilitated by numerous insertion sequences), and a large, complex genome divided into separate chromosomes. Therefore, the widespread agricultural use of B. cepacia should be approached with caution. PMID:9621192

The human resource information system: a rapid appraisal of Pakistan’s capacity to employ the tool

PubMed Central

2013-01-01

Background Human resources are an important building block of the health system. During the last decade, enormous investment has gone into the information systems to manage human resources, but due to the lack of a clear vision, policy, and strategy, the results of these efforts have not been very visible. No reliable information portal captures the actual state of human resources in Pakistan’s health sector. The World Health Organization (WHO) has provided technical support for the assessment of the existing system and development of a comprehensive Human Resource Information System (HRIS) in Pakistan. Methods The questions in the WHO-HRIS Assessment tool were distributed into five thematic groups. Purposively selected (n=65) representatives from the government, private sector, and development partners participated in this cross sectional study, based on their programmatic affiliations. Results Fifty-five percent of organizations and departments have an independent Human Resources (HR) section managed by an establishment branch and are fully equipped with functional computers. Forty-five organizations (70%) had HR rules, regulations and coordination mechanisms, yet these are not implemented. Data reporting is mainly in paper form, on prescribed forms (51%), registers (3%) or even plain papers (20%). Data analysis does not give inputs to the decision making process and dissemination of information is quite erratic. Most of the organizations had no feedback mechanism for cross checking the HR data, rendering it unreliable. Conclusion Pakistan is lacking appropriate HRIS management. The current HRIS indeed has a multitude of problems. In the wake of 2011 reforms within the health sector, provinces are even in a greater need for planning their respective health department services and must work on the deficiencies and inefficiencies of their HRIS so that the gaps and HR needs are better aligned for reaching the 2015 UN Millennium Development Goals (MDGs) targets. PMID:24016066

Natural protection from zoonosis by alpha-gal epitopes on virus particles in xenotransmission.

PubMed

Kim, Na Young; Jung, Woon-Won; Oh, Yu-Kyung; Chun, Taehoon; Park, Hong-Yang; Lee, Hoon-Taek; Han, In-Kwon; Yang, Jai Myung; Kim, Young Bong

2007-03-01

Clinical transplantation has become one of the preferred treatments for end-stage organ failure, and one of the novel approaches being pursued to overcome the limited supply of human organs involves the use of organs from other species. The pig appears to be a near ideal animal due to proximity to humans, domestication, and ability to procreate. The presence of Gal-alpha1,3-Gal residues on the surfaces of pig cells is a major immunological obstacle to xenotransplantation. Alpha1,3galactosyltransferase (alpha1,3GT) catalyzes the synthesis of Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-gal epitope) on the glycoproteins and glycolipids of non-primate mammals, but this does not occur in humans. Moreover, the alpha-gal epitope causes hyperacute rejection of pig organs in humans, and thus, the elimination of this antigen from pig tissues is highly desirable. Recently, concerns have been raised that the risk of virus transmission from such pigs may be increased due to the absence of alpha-gal on their viral particles. In this study, transgenic cells expressing alpha1,3GT were selected using 1.25 mg/ml neomycin. The development of HeLa cells expressing alpha1,3GT now allows accurate studies to be conducted on the function of the alpha-gal epitope in xenotransmission. The expressions of alpha-gal epitopes on HeLa/alpha-gal cells were demonstrated by flow cytometry and confocal microscopy using cells stained with IB4-fluorescein isothiocyanate lectin. Vaccinia viruses propagated in HeLa/alpha-gal cells also expressed alpha-gal on their viral envelopes and were more sensitive to inactivation by human sera than vaccinia virus propagated in HeLa cells. Moreover, neutralization of vaccinia virus was inhibited in human serum by 10 mm ethylene glycol bis(beta-aminoethylether)tetraacetic acid (EDTA) treatment. Our data indicated that alpha-gal epitopes are one of the major barriers to zoonosis via xenotransmission.

Immunophototherapy for the treatment of AIDS and AIDS-related infections

NASA Astrophysics Data System (ADS)

Schlager, Kenneth J.

1992-06-01

Immunophototherapy (IPT) is an experimental method of medical treatment that seeks to provide for the selective destruction of diseased cells and microbes such as human immunodeficiency virus (HIV)-T4 cells and the rapid elimination of their toxic by-products from the human body. Photosensitive monoclonal or polyclonal antibody fragments, which are specific to the diseased cell or microbe, will be used to treat acquired immunodeficiency syndrome (AIDS) and related infections. These antibody fragments are tagged with photosensitive compounds and metal colloids and then intravenously injected into the patient. The tagged antibodies quickly and selectively bind to the diseased cells or microbes in the blood stream and affected organs. These cells or microbes are then selectively destroyed by irradiation of these complexes with light of the proper wavelength. This light activates the photosensitive material which then creates singlet oxygen that destroys the microbe or cell. Toxic products of lysis are quickly discharged from the body by activation of the reticuloendothelial system. IPT has been demonstrated by Biotronics to be very effective in the in vitro selective destruction of specified cell types. In a proposed AIDS-treatment research program, IPT will be first demonstrated in vitro for a set of infected blood samples using commercially-available antibodies labeled with appropriate photosensitizers. Efficacy will be determined by a p24 antigen immunodiagnostic test that will indicate the % inhibition in comparison to controls and samples treated with the drug AZT. Subcontracted animal efficacy studies will use a SCID-hu mouse model and PCR/DNA-RNA for endpoint analysis. Toxicity studies of animal (rat) models will be based on post-treatment investigations of lymph nodes, spleen, liver and other organs.

World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies to Control Antimicrobial Resistance From Food Animal Production.

PubMed

Collignon, Peter C; Conly, John M; Andremont, Antoine; McEwen, Scott A; Aidara-Kane, Awa; Agerso, Yvonne; Andremont, Antoine; Collignon, Peter; Conly, John; Dang Ninh, Tran; Donado-Godoy, Pilar; Fedorka-Cray, Paula; Fernandez, Heriberto; Galas, Marcelo; Irwin, Rebecca; Karp, Beth; Matar, Gassan; McDermott, Patrick; McEwen, Scott; Mitema, Eric; Reid-Smith, Richard; Scott, H Morgan; Singh, Ruby; DeWaal, Caroline Smith; Stelling, John; Toleman, Mark; Watanabe, Haruo; Woo, Gun-Jo

2016-10-15

Antimicrobial use in food animals selects for antimicrobial resistance in bacteria, which can spread to people. Reducing use of antimicrobials-particularly those deemed to be critically important for human medicine-in food production animals continues to be an important step for preserving the benefits of these antimicrobials for people. The World Health Organization ranking of antimicrobials according to their relative importance in human medicine was recently updated. Antimicrobials considered the highest priority among the critically important antimicrobials were quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides. The updated ranking allows stakeholders in the agriculture sector and regulatory agencies to focus risk management efforts on drugs used in food animals that are the most important to human medicine. In particular, the current large-scale use of fluoroquinolones, macrolides, and third-generation cephalosporins and any potential use of glycopeptides and carbapenems need to be addressed urgently. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Evolution of direct reciprocity under uncertainty can explain human generosity in one-shot encounters

PubMed Central

Delton, Andrew W.; Krasnow, Max M.; Cosmides, Leda; Tooby, John

2011-01-01

Are humans too generous? The discovery that subjects choose to incur costs to allocate benefits to others in anonymous, one-shot economic games has posed an unsolved challenge to models of economic and evolutionary rationality. Using agent-based simulations, we show that such generosity is the necessary byproduct of selection on decision systems for regulating dyadic reciprocity under conditions of uncertainty. In deciding whether to engage in dyadic reciprocity, these systems must balance (i) the costs of mistaking a one-shot interaction for a repeated interaction (hence, risking a single chance of being exploited) with (ii) the far greater costs of mistaking a repeated interaction for a one-shot interaction (thereby precluding benefits from multiple future cooperative interactions). This asymmetry builds organisms naturally selected to cooperate even when exposed to cues that they are in one-shot interactions. PMID:21788489

Natural speech reveals the semantic maps that tile human cerebral cortex

PubMed Central

Huth, Alexander G.; de Heer, Wendy A.; Griffiths, Thomas L.; Theunissen, Frédéric E.; Gallant, Jack L.

2016-01-01

The meaning of language is represented in regions of the cerebral cortex collectively known as the “semantic system”. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modeling of fMRI data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that appear consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods—commonplace in studies of human neuroanatomy and functional connectivity—provide a powerful and efficient means for mapping functional representations in the brain. PMID:27121839

Evolution of direct reciprocity under uncertainty can explain human generosity in one-shot encounters.

PubMed

Delton, Andrew W; Krasnow, Max M; Cosmides, Leda; Tooby, John

2011-08-09

Are humans too generous? The discovery that subjects choose to incur costs to allocate benefits to others in anonymous, one-shot economic games has posed an unsolved challenge to models of economic and evolutionary rationality. Using agent-based simulations, we show that such generosity is the necessary byproduct of selection on decision systems for regulating dyadic reciprocity under conditions of uncertainty. In deciding whether to engage in dyadic reciprocity, these systems must balance (i) the costs of mistaking a one-shot interaction for a repeated interaction (hence, risking a single chance of being exploited) with (ii) the far greater costs of mistaking a repeated interaction for a one-shot interaction (thereby precluding benefits from multiple future cooperative interactions). This asymmetry builds organisms naturally selected to cooperate even when exposed to cues that they are in one-shot interactions.

Category-Selectivity in Human Visual Cortex Follows Cortical Topology: A Grouped icEEG Study

PubMed Central

Conner, Christopher Richard; Whaley, Meagan Lee; Baboyan, Vatche George; Tandon, Nitin

2016-01-01

Neuroimaging studies suggest that category-selective regions in higher-order visual cortex are topologically organized around specific anatomical landmarks: the mid-fusiform sulcus (MFS) in the ventral temporal cortex (VTC) and lateral occipital sulcus (LOS) in the lateral occipital cortex (LOC). To derive precise structure-function maps from direct neural signals, we collected intracranial EEG (icEEG) recordings in a large human cohort (n = 26) undergoing implantation of subdural electrodes. A surface-based approach to grouped icEEG analysis was used to overcome challenges from sparse electrode coverage within subjects and variable cortical anatomy across subjects. The topology of category-selectivity in bilateral VTC and LOC was assessed for five classes of visual stimuli—faces, animate non-face (animals/body-parts), places, tools, and words—using correlational and linear mixed effects analyses. In the LOC, selectivity for living (faces and animate non-face) and non-living (places and tools) classes was arranged in a ventral-to-dorsal axis along the LOS. In the VTC, selectivity for living and non-living stimuli was arranged in a latero-medial axis along the MFS. Written word-selectivity was reliably localized to the intersection of the left MFS and the occipito-temporal sulcus. These findings provide direct electrophysiological evidence for topological information structuring of functional representations within higher-order visual cortex. PMID:27272936

Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance.

PubMed

Mohana, Krishnamoorthy; Achary, Anant

2017-08-01

Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets. Structure analysis of various isoforms is carried out and literature mining has been performed to identify the differences in the active sites of the GSTs. The xenobiotic binding H site is classified into H1, H2, and H3 and the differences in the amino acid composition, the hydrophobicity and other structural features of H site of GSTs are discussed. The existing inhibition strategies are compared. The advent of rational drug design, mechanism-based inhibition strategies, availability of high-throughput screening, target specific, and selective inhibition of GST isoforms involved in drug resistance could be achieved for the reversal of drug resistance and aid in the treatment of diseases.

Assessment of human effective absorbed dose of 67 Ga-ECC based on biodistribution rat data.

PubMed

Shanehsazzadeh, Saeed; Yousefnia, Hassan; Lahooti, Afsaneh; Zolghadri, Samaneh; Jalilian, Amir Reza; Afarideh, Hossien

2015-02-01

In a diagnostic context, determination of absorbed dose is required before the introduction of a new radiopharmaceutical to the market to obtain marketing authorization from the relevant agencies. In this work, the absorbed dose of [67 Ga]-ethylenecysteamine cysteine [(67 Ga)ECC] to human organs was determined by using distribution data for rats. For biodistribution data, the animals were sacrificed by CO2 asphyxiation at selected times after injection (0.5, 2 and 48 h, n = 3 for each time interval), then the tissue (blood, heart, lung, brain, intestine, feces, skin, stomach, kidneys, liver, muscle and bone) were removed. The absorbed dose was determined by Medical Internal Radiation Dose (MIRD) method after calculating cumulated activities in each organ. Our prediction shows that a 185-MBq injection of (67)Ga-ECC into the humans might result in an estimated absorbed dose of 0.029 mGy in the whole body. The highest absorbed doses are observed in the spleen and liver with 33.766 and 16.847 mGy, respectively. The results show that this radiopharmaceutical can be a good SPECT tracer since it can be produced easily and also the absorbed dose in each organ is less than permitted absorbed dose.

The point-of-care colorimetric detection of the biomarker of phenylamine in the human urine based on Tb3+ functionalized metal-organic framework.

PubMed

Qin, Si-Jia; Yan, Bing

2018-07-05

Phenylamine has been recognized as one of the most important industrially relevant ingredient and a crucial intermediate in chemical products. Yet, its internal exposure detection in human remains largely elusive due to the lack of potent monitoring method. Hereby this issue is addressed with a probe based on lanthanide functionalized organic-inorganic hybrid material Al(OH)(bpydc) (1) through post-synthetically modified metal-organic framework. The as-synthesized Tb 3+ @1 exhibits the strong luminescence of Tb 3+ originated from efficient energy transfer from the ligand, which can sense the biological metabolite p-aminophenol (PAP) of the phenylamine in the human urine. Linear correlation between the integrated fluorescence intensity and the concentration of PAP was investigated, enabling quantitative analysis of PAP in physiologically ranges (0.005-5 mg mL -1 ) with low detection limit (5 μg mL -1 ). This probe demonstrates excellent sensitivity, high selectivity, good reusability and quick response to PAP. Furthermore, a simple and rapid smartphone-based medical portable test paper was developed, whose quantitative color change can be easily distinguished visually. Hence, the PAP sensing platform can serve as a potential diagnostic tool for home monitoring of PAP. Copyright © 2018 Elsevier B.V. All rights reserved.

Selective differential human blood bilayer media for isolation of Gardnerella (Haemophilus) vaginalis.

PubMed Central

Totten, P A; Amsel, R; Hale, J; Piot, P; Holmes, K K

1982-01-01

New selective and differential human blood bilayer agar media with Tween 80 (HBT medium) or without Tween 80 (HB medium), developed for the isolation of Gardnerella (Haemophilus) vaginalis, permitted significantly higher G. vaginalis isolation rates than have been obtained for other media used for this purpose. HB medium consists of a basal layer of Columbia agar base containing colistin and naladixic acid with added amphotericin B and an overlayer of the same composition plus 5% human blood. HBT agar also contains Proteose Peptone No. 3 (Difco Laboratories) and Tween 80 in the basal layer and the overlayer. Both Tween 80 and the bilayer composition enhanced G. vaginalis production of human blood hemolysis, permitting detection of this organism even in the presence of heavy growth of other vaginal flora. The use of HB or HBT medium thus permitted the demonstration that G. vaginalis was present in vaginal fluid from a large percentage (up to 68%) of normal women. However, the concentration of G. vaginalis was found by semiquantitative analysis to be significantly higher in vaginal fluid from women with nonspecific vaginitis than in fluid from normal women. Images PMID:6764766

The harmonic organization of auditory cortex.

PubMed

Wang, Xiaoqin

2013-12-17

A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds.

Replication of alpha-satellite DNA arrays in endogenous human centromeric regions and in human artificial chromosome

PubMed Central

Erliandri, Indri; Fu, Haiqing; Nakano, Megumi; Kim, Jung-Hyun; Miga, Karen H.; Liskovykh, Mikhail; Earnshaw, William C.; Masumoto, Hiroshi; Kouprina, Natalay; Aladjem, Mirit I.; Larionov, Vladimir

2014-01-01

In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed Human Artificial Chromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions. PMID:25228468

The costs and benefits of flexibility as an expression of behavioural plasticity: a primate perspective.

PubMed

van Schaik, Carel P

2013-05-19

Traditional neo-Darwinism ascribes geographical variation in morphology or in behaviour to varying selection on local genotypes. However, mobile and long-lived organisms cannot achieve local adaptation this way, leading to a renewed interest in plasticity. I examined geographical variation in orang-utan subsistence and social behaviour, and found this to be largely owing to behavioural plasticity, here called flexibility, both in the form of flexible individual decisions and of socially transmitted (cultural) innovations. Although comparison with other species is difficult, the extent of such flexibility is almost certainly limited by brain size. It is shown that brains can only increase relative to body size where the cognitive benefits they produce are reliably translated into improved survival rate. This means that organisms that are very small, face many predators, live in highly seasonal environments, or lack opportunities for social learning cannot evolve greater flexibility, and must achieve local adaptation through selection on specific genotypes. On the other hand, as body and brain size increase, local adaptation is increasingly achieved through selection on plasticity. The species involved are also generally those that most need it, being more mobile and longer-lived. Although high plasticity buffers against environmental change, the most flexible organisms face a clear limit because they respond slowly to selection. Thus, paradoxically, the largest-brained animals may actually be vulnerable to the more drastic forms of environmental change, such as those induced by human actions.

When Violence Pays: A Cost-Benefit Analysis of Aggressive Behavior in Animals and Humans

PubMed Central

Georgiev, Alexander V.; Klimczuk, Amanda C. E.; Traficonte, Daniel M.

2013-01-01

An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females. PMID:23864299

Multivariate Pattern Analysis Reveals Category-Related Organization of Semantic Representations in Anterior Temporal Cortex.

PubMed

Malone, Patrick S; Glezer, Laurie S; Kim, Judy; Jiang, Xiong; Riesenhuber, Maximilian

2016-09-28

The neural substrates of semantic representation have been the subject of much controversy. The study of semantic representations is complicated by difficulty in disentangling perceptual and semantic influences on neural activity, as well as in identifying stimulus-driven, "bottom-up" semantic selectivity unconfounded by top-down task-related modulations. To address these challenges, we trained human subjects to associate pseudowords (TPWs) with various animal and tool categories. To decode semantic representations of these TPWs, we used multivariate pattern classification of fMRI data acquired while subjects performed a semantic oddball detection task. Crucially, the classifier was trained and tested on disjoint sets of TPWs, so that the classifier had to use the semantic information from the training set to correctly classify the test set. Animal and tool TPWs were successfully decoded based on fMRI activity in spatially distinct subregions of the left medial anterior temporal lobe (LATL). In addition, tools (but not animals) were successfully decoded from activity in the left inferior parietal lobule. The tool-selective LATL subregion showed greater functional connectivity with left inferior parietal lobule and ventral premotor cortex, indicating that each LATL subregion exhibits distinct patterns of connectivity. Our findings demonstrate category-selective organization of semantic representations in LATL into spatially distinct subregions, continuing the lateral-medial segregation of activation in posterior temporal cortex previously observed in response to images of animals and tools, respectively. Together, our results provide evidence for segregation of processing hierarchies for different classes of objects and the existence of multiple, category-specific semantic networks in the brain. The location and specificity of semantic representations in the brain are still widely debated. We trained human participants to associate specific pseudowords with various animal and tool categories, and used multivariate pattern classification of fMRI data to decode the semantic representations of the trained pseudowords. We found that: (1) animal and tool information was organized in category-selective subregions of medial left anterior temporal lobe (LATL); (2) tools, but not animals, were encoded in left inferior parietal lobe; and (3) LATL subregions exhibited distinct patterns of functional connectivity with category-related regions across cortex. Our findings suggest that semantic knowledge in LATL is organized in category-related subregions, providing evidence for the existence of multiple, category-specific semantic representations in the brain. Copyright © 2016 the authors 0270-6474/16/3610089-08$15.00/0.

Color-Biased Regions of the Ventral Visual Pathway Lie between Face- and Place-Selective Regions in Humans, as in Macaques

PubMed Central

Conway, Bevil R.; Kanwisher, Nancy G.

2016-01-01

The existence of color-processing regions in the human ventral visual pathway (VVP) has long been known from patient and imaging studies, but their location in the cortex relative to other regions, their selectivity for color compared with other properties (shape and object category), and their relationship to color-processing regions found in nonhuman primates remain unclear. We addressed these questions by scanning 13 subjects with fMRI while they viewed two versions of movie clips (colored, achromatic) of five different object classes (faces, scenes, bodies, objects, scrambled objects). We identified regions in each subject that were selective for color, faces, places, and object shape, and measured responses within these regions to the 10 conditions in independently acquired data. We report two key findings. First, the three previously reported color-biased regions (located within a band running posterior–anterior along the VVP, present in most of our subjects) were sandwiched between face-selective cortex and place-selective cortex, forming parallel bands of face, color, and place selectivity that tracked the fusiform gyrus/collateral sulcus. Second, the posterior color-biased regions showed little or no selectivity for object shape or for particular stimulus categories and showed no interaction of color preference with stimulus category, suggesting that they code color independently of shape or stimulus category; moreover, the shape-biased lateral occipital region showed no significant color bias. These observations mirror results in macaque inferior temporal cortex (Lafer-Sousa and Conway, 2013), and taken together, these results suggest a homology in which the entire tripartite face/color/place system of primates migrated onto the ventral surface in humans over the course of evolution. SIGNIFICANCE STATEMENT Here we report that color-biased cortex is sandwiched between face-selective and place-selective cortex on the bottom surface of the brain in humans. This face/color/place organization mirrors that seen on the lateral surface of the temporal lobe in macaques, suggesting that the entire tripartite system is homologous between species. This result validates the use of macaques as a model for human vision, making possible more powerful investigations into the connectivity, precise neural codes, and development of this part of the brain. In addition, we find substantial segregation of color from shape selectivity in posterior regions, as observed in macaques, indicating a considerable dissociation of the processing of shape and color in both species. PMID:26843649

Hierarchical nanostructured WO3-SnO2 for selective sensing of volatile organic compounds

NASA Astrophysics Data System (ADS)

Nayak, Arpan Kumar; Ghosh, Ruma; Santra, Sumita; Guha, Prasanta Kumar; Pradhan, Debabrata

2015-07-01

It remains a challenge to find a suitable gas sensing material that shows a high response and shows selectivity towards various gases simultaneously. Here, we report a mixed metal oxide WO3-SnO2 nanostructured material synthesized in situ by a simple, single-step, one-pot hydrothermal method at 200 °C in 12 h, and demonstrate its superior sensing behavior towards volatile organic compounds (VOCs) such as ammonia, ethanol and acetone. SnO2 nanoparticles with controlled size and density were uniformly grown on WO3 nanoplates by varying the tin precursor. The density of the SnO2 nanoparticles on the WO3 nanoplates plays a crucial role in the VOC selectivity. The responses of the present mixed metal oxides are found to be much higher than the previously reported results based on single/mixed oxides and noble metal-doped oxides. In addition, the VOC selectivity is found to be highly temperature-dependent, with optimum performance obtained at 200 °C, 300 °C and 350 °C for ammonia, ethanol and acetone, respectively. The present results on the cost-effective noble metal-free WO3-SnO2 sensor could find potential application in human breath analysis by non-invasive detection.It remains a challenge to find a suitable gas sensing material that shows a high response and shows selectivity towards various gases simultaneously. Here, we report a mixed metal oxide WO3-SnO2 nanostructured material synthesized in situ by a simple, single-step, one-pot hydrothermal method at 200 °C in 12 h, and demonstrate its superior sensing behavior towards volatile organic compounds (VOCs) such as ammonia, ethanol and acetone. SnO2 nanoparticles with controlled size and density were uniformly grown on WO3 nanoplates by varying the tin precursor. The density of the SnO2 nanoparticles on the WO3 nanoplates plays a crucial role in the VOC selectivity. The responses of the present mixed metal oxides are found to be much higher than the previously reported results based on single/mixed oxides and noble metal-doped oxides. In addition, the VOC selectivity is found to be highly temperature-dependent, with optimum performance obtained at 200 °C, 300 °C and 350 °C for ammonia, ethanol and acetone, respectively. The present results on the cost-effective noble metal-free WO3-SnO2 sensor could find potential application in human breath analysis by non-invasive detection. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02571k

Self-Organization: Complex Dynamical Systems in the Evolution of Speech

NASA Astrophysics Data System (ADS)

Oudeyer, Pierre-Yves

Human vocalization systems are characterized by complex structural properties. They are combinatorial, based on the systematic reuse of phonemes, and the set of repertoires in human languages is characterized by both strong statistical regularities—universals—and a great diversity. Besides, they are conventional codes culturally shared in each community of speakers. What are the origins of the forms of speech? What are the mechanisms that permitted their evolution in the course of phylogenesis and cultural evolution? How can a shared speech code be formed in a community of individuals? This chapter focuses on the way the concept of self-organization, and its interaction with natural selection, can throw light on these three questions. In particular, a computational model is presented which shows that a basic neural equipment for adaptive holistic vocal imitation, coupling directly motor and perceptual representations in the brain, can generate spontaneously shared combinatorial systems of vocalizations in a society of babbling individuals. Furthermore, we show how morphological and physiological innate constraints can interact with these self-organized mechanisms to account for both the formation of statistical regularities and diversity in vocalization systems.

Lateral prefrontal cortex: architectonic and functional organization

PubMed Central

Petrides, Michael

2005-01-01

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012

Widespread Non-Hematopoietic Tissue Distribution by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity

PubMed Central

Hess, David A.; Craft, Timothy P.; Wirthlin, Louisa; Hohm, Sarah; Zhou, Ping; Eades, William C.; Creer, Michael H.; Sands, Mark S.; Nolta, Jan A.

2011-01-01

Transplanted adult progenitor cells distribute to peripheral organs and can promote endogenous cellular repair in damaged tissues. However, development of cell-based regenerative therapies has been hindered by the lack of pre-clinical models to efficiently assess multiple organ distribution and difficulty defining human cells with regenerative function. After transplantation into beta-glucuronidase (GUSB)-deficient NOD/SCID/MPSVII mice, we characterized the distribution of lineage depleted human umbilical cord blood-derived cells purified by selection using high aldehyde dehydrogenase activity (ALDH) with CD133 co-expression. ALDHhi or ALDHhiCD133+ cells produced robust hematopoietic reconstitution, and variable levels of tissue distribution in multiple organs. GUSB+ donor cells that co-expressed human (HLA-A,B,C) and hematopoietic (CD45+) cell surface markers were the primary cell phenotype found adjacent to the vascular beds of several tissues, including islet and ductal regions of mouse pancreata. In contrast, variable phenotypes were detected in the chimeric liver, with HLA+/CD45+ cells demonstrating robust GUSB expression adjacent to blood vessels, and CD45−/HLA− cells with diluted GUSB expression predominant in the liver parenchyma. However, true non-hematopoietic human (HLA+/CD45−) cells were rarely detected in other peripheral tissues, suggesting that these GUSB+/HLA−/CD45− cells in the liver were a result of downregulated human surface marker expression in vivo, not widespread seeding of non-hematopoietic cells. However, relying solely on continued expression of cell surface markers, as employed in traditional xenotransplantation models, may underestimate true tissue distribution. ALDH-expressing progenitor cells demonstrated widespread and tissue-specific distribution of variable cellular phenotypes, indicating that these adult progenitor cells should be explored in transplantation models of tissue damage. PMID:18055447

Evolution of the violin: The law of effect in action.

PubMed

Wasserman, Edward A; Cullen, Patrick

2016-01-01

As is true for most other human inventions, the origin of the violin is unknown. What is known is that this popular and versatile instrument has notably changed over the course of several hundred years. At issue is whether those evolutionary changes in the construction of the violin are the result of premeditated, intelligent design or whether they arose through a trial-and-error process. Recent scientific evidence favors the latter account. Our perspective piece puts these recent empirical findings into a comprehensive selectionist framework. According to this view, the many things we do and make--like violins--arise from a process of variation and selection which accords with the law of effect. Contrary to popular opinion, there is neither mystique nor romance in this process; it is as fundamental and ubiquitous as the law of natural selection. As with the law of natural selection in the evolution of organisms, there is staunch resistance to the role of the law of effect in the evolution of human inventions. We conclude our piece by considering several objections to our perspective. (c) 2016 APA, all rights reserved).

Apoptosis in the homeostasis of the immune system and in human immune mediated diseases.

PubMed

Giovannetti, A; Pierdominici, M; Di Iorio, A; Cianci, R; Murdaca, G; Puppo, F; Pandolfi, F; Paganelli, R

2008-01-01

The immune system has evolved sophisticated mechanisms controlling the development of responses to dangerous antigens while avoiding unnecessary attacks to innocuous, commensal or self antigens. The risk of autoimmunity is continuously checked and balanced against the risk of succumbing to exogenous infectious agents. It is therefore of paramount importance to understand the molecular events linking the breakdown of tolerance and the development of immunodeficiency. Apoptotic mechanisms are used to regulate the development of thymocytes, the shaping of T cell repertoire, its selection and the coordinate events leading to immune responses in the periphery. Moreover, they are at the heart of the homeostatic controls restoring T cell numbers and establishing T cell memory. T lymphocytes shift continuously from survival to death signals to ensure immune responsiveness without incurring in autoimmune damage. In this review we shall consider some key facts on the relationship of lymphopenia to autoreactivity, the mechanisms controlling positive and negative selection in the thymus, the role of apoptosis in selected primary immunodeficiency states and in systemic and organ-specific autoimmunity, with examples from human diseases and their animal models.

Tardigrades living in extreme environments have naturally selected prerequisites useful to space conquer

NASA Astrophysics Data System (ADS)

Guidetti, Roberto; Tiziana, Altiero; Cesari, Michele; Rizzo, Angela Maria; Bertolani, Roberto; Galletta, Giuseppe; Dalessandro, Maurizio; Rebecchi, Lorena

Extreme habitats are highly selective and can host only living organisms possessing specific adaptations to stressors. Among extreme habitats, space environment has particular charac-teristics of radiations, vacuum, microgravity and temperature, which induce rapid changes in living systems. Consequently, the response of multicellular complex organisms, able to colo-nize extreme environments, to space stresses can give very useful information on the ability to withstand a single stress or stress combinations. This knowledge on changes in living systems in space, with their similarity to the ageing processes, offers the opportunity to improve human life both on Earth and in space. Even though experimentation in space has often been carried out using unicellular organisms, multicellular organisms are very relevant in order to develop the appropriate countermeasures to avoid the risks imposed by environmental space in humans. The little attention received by multicellular organisms is probably due, other than to difficul-ties in the manipulation of biological materials in space, to the presence of only few organisms with the potential to tolerate environmental space stresses. Among them, tardigrades are small invertebrates representing an attractive animal model to study adaptive strategies for surviving extreme environments, including space environment. Tardigrades are little known microscopic aquatic animals (250-800 m in body length) distributed in different environments (from the deep sea to high mountains and deserts all over the world), and frequently inhabiting very unstable and unpredictable habitats (e.g. interstices of mosses, lichens, leaf litter, freshwater ponds, cryoconite holes). Their ability to live in the extreme environments is related to a wide variety of their life histories and adaptive strategies. A widespread and crucial strategy is cryptobiosis, a form of quiescence. It includes strategies such as anhydrobiosis and cryobiosis, characterized by a complete or almost complete metabolic standstill. The ability of tardigrades to colonize terrestrial habitats is linked to their well known ability to enter anhydrobiosis when their habi-tat desiccates. Tardigrades survive dehydration by entering a highly stable state of suspended animation due to complete desiccation (¿ 95Results on tardigrades open a window on the fu-ture perspective in astrobiology and in their applications. The discovery and identification of metabolites naturally synthesized by tardigrades to perform a remarkable protection against the damages to cellular components and DNA due to desiccation, radiation, microgravity and oxidation stresses, will be used to define the countermeasures to protect sensitive organisms, including humans, not naturally able to withstand extreme stresses under space conditions, for the future long-term explorations of our solar system, including Mars.

Novel kinin B1 receptor agonists with improved pharmacological profiles.

PubMed

Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

2009-04-01

There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

Mobility as an emergent property of biological organization: Insights from experimental evolution.

PubMed

Wallace, Ian J; Garland, Theodore

2016-05-06

Anthropologists accept that mobility is a critical dimension of human culture, one that links economy, technology, and social relations. Less often acknowledged is that mobility depends on complex and dynamic interactions between multiple levels of our biological organization, including anatomy, physiology, neurobiology, and genetics. Here, we describe a novel experimental approach to examining the biological foundations of mobility, using mice from a long-term artificial selection experiment for high levels of voluntary exercise on wheels. In this experiment, mice from selectively bred lines have evolved to run roughly three times as far per day as those from nonselected control lines. We consider three insights gleaned from this experiment as foundational principles for the study of mobility from the perspective of biological evolution. First, an evolutionary change in mobility will necessarily be associated with alterations in biological traits both directly and indirectly connected to mobility. Second, changing mobility will result in trade-offs and constraints among some of the affected traits. Third, multiple solutions exist to altering mobility, so that various combinations of adjustments to traits linked with mobility can achieve the same overall behavioral outcome. We suggest that anthropological knowledge of variation in human mobility might be improved by greater research attention to its biological dimensions. © 2016 Wiley Periodicals, Inc.

Anthropogenic ecosystem fragmentation drives shared and unique patterns of sexual signal divergence among three species of Bahamian mosquitofish.

PubMed

Giery, Sean T; Layman, Craig A; Langerhans, R Brian

2015-08-01

When confronted with similar environmental challenges, different organisms can exhibit dissimilar phenotypic responses. Therefore, understanding patterns of phenotypic divergence for closely related species requires considering distinct evolutionary histories. Here, we investigated how a common form of human-induced environmental alteration, habitat fragmentation, may drive phenotypic divergence among three closely related species of Bahamian mosquitofish (Gambusia spp.). Focusing on one phenotypic trait (male coloration), having a priori predictions of divergence, we tested whether populations persisting in fragmented habitats differed from those inhabiting unfragmented habitats and examined the consistency of the pattern across species. Species exhibited both shared and unique patterns of phenotypic divergence between the two types of habitats, with shared patterns representing the stronger effect. For all species, populations in fragmented habitats had fewer dorsal-fin spots. In contrast, the magnitude and trajectory of divergence in dorsal-fin color, a sexually selected trait, differed among species. We identified fragmentation-mediated increased turbidity as a possible driver of these trait shifts. These results suggest that even closely related species can exhibit diverse phenotypic responses when encountering similar human-mediated selection regimes. This element of unpredictability complicates forecasting the phenotypic responses of wild organisms faced with anthropogenic change - an important component of biological conservation and ecosystem management.

Anthropogenic ecosystem fragmentation drives shared and unique patterns of sexual signal divergence among three species of Bahamian mosquitofish

PubMed Central

Giery, Sean T; Layman, Craig A; Langerhans, R Brian

2015-01-01

When confronted with similar environmental challenges, different organisms can exhibit dissimilar phenotypic responses. Therefore, understanding patterns of phenotypic divergence for closely related species requires considering distinct evolutionary histories. Here, we investigated how a common form of human-induced environmental alteration, habitat fragmentation, may drive phenotypic divergence among three closely related species of Bahamian mosquitofish (Gambusia spp.). Focusing on one phenotypic trait (male coloration), having a priori predictions of divergence, we tested whether populations persisting in fragmented habitats differed from those inhabiting unfragmented habitats and examined the consistency of the pattern across species. Species exhibited both shared and unique patterns of phenotypic divergence between the two types of habitats, with shared patterns representing the stronger effect. For all species, populations in fragmented habitats had fewer dorsal-fin spots. In contrast, the magnitude and trajectory of divergence in dorsal-fin color, a sexually selected trait, differed among species. We identified fragmentation-mediated increased turbidity as a possible driver of these trait shifts. These results suggest that even closely related species can exhibit diverse phenotypic responses when encountering similar human-mediated selection regimes. This element of unpredictability complicates forecasting the phenotypic responses of wild organisms faced with anthropogenic change – an important component of biological conservation and ecosystem management. PMID:26240605

The compositional transition of vertebrate genomes: an analysis of the secondary structure of the proteins encoded by human genes.

PubMed

D'Onofrio, Giuseppe; Ghosh, Tapash Chandra

2005-01-17

Fluctuations and increments of both C(3) and G(3) levels along the human coding sequences were investigated comparing two sets of Xenopus/human orthologous genes. The first set of genes shows minor differences of the GC(3) levels, the second shows considerable increments of the GC(3) levels in the human genes. In both data sets, the fluctuations of C(3) and G(3) levels along the coding sequences correlated with the secondary structures of the encoded proteins. The human genes that underwent the compositional transition showed a different increment of the C(3) and G(3) levels within and among the structural units of the proteins. The relative synonymous codon usage (RSCU) of several amino acids were also affected during the compositional transition, showing that there exists a correlation between RSCU and protein secondary structures in human genes. The importance of natural selection for the formation of isochore organization of the human genome has been discussed on the basis of these results.

Alpha-beta and gamma rhythms subserve feedback and feedforward influences among human visual cortical areas

PubMed Central

Michalareas, Georgios; Vezoli, Julien; van Pelt, Stan; Schoffelen, Jan-Mathijs; Kennedy, Henry; Fries, Pascal

2016-01-01

Primate visual cortex is hierarchically organized. Bottom-up and top-down influences are exerted through distinct frequency channels, as was recently revealed in macaques by correlating inter-areal influences with laminar anatomical projection patterns. Because this anatomical data cannot be obtained in human subjects, we selected seven homologous macaque and human visual areas, and correlated the macaque laminar projection patterns to human inter-areal directed influences as measured with magnetoencephalography. We show that influences along feedforward projections predominate in the gamma band, whereas influences along feedback projections predominate in the alpha-beta band. Rhythmic inter-areal influences constrain a functional hierarchy of the seven homologous human visual areas that is in close agreement with the respective macaque anatomical hierarchy. Rhythmic influences allow an extension of the hierarchy to 26 human visual areas including uniquely human brain areas. Hierarchical levels of ventral and dorsal stream visual areas are differentially affected by inter-areal influences in the alpha-beta band. PMID:26777277

Synthetic PAMAM-RGD conjugates target and bind to odontoblast-like MDPC 23 cells and the predentin in tooth organ cultures.

PubMed

Hill, Elliott; Shukla, Rameshwer; Park, Steve S; Baker, James R

2007-01-01

Screening techniques now allow for the identification of small peptides that bind specifically to molecules like cells. However, despite the enthusiasm for this approach, single peptides often lack the binding affinity to target in vivo and regulate cell function. We took peptides containing the Arg-Gly Asp(RGD) motif that bind to the alpha Vbeta 3 integrin and have shown potential as therapeutics. To improve their binding affinity, we synthesized polyamidoamine (PAMAM) dendrimer-RGD conjugates that that contain 12-13 copies of the peptide. When cultured with human dermal microvessel endothelial cells (HDMEC), human vascular endothelial cells (HUVEC), or odontoblast-like MDPC-23 cells, the PAMAM dendrimer conjugate targets this receptor in a manner that is both time- and dose-dependent. Finally, this conjugate selectively targets RGD binding sites in the predentin of human tooth organ cultures. Taken together, these studies provide proof of principle that synthetic PAMAM-RGD conjugates could prove useful as carriers for the tissue-specific delivery of integrin-targeted therapeutics or imaging agents and could be used to engineer tissue regeneration.

CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription.

PubMed

Tang, Zhonghui; Luo, Oscar Junhong; Li, Xingwang; Zheng, Meizhen; Zhu, Jacqueline Jufen; Szalaj, Przemyslaw; Trzaskoma, Pawel; Magalska, Adriana; Wlodarczyk, Jakub; Ruszczycki, Blazej; Michalski, Paul; Piecuch, Emaly; Wang, Ping; Wang, Danjuan; Tian, Simon Zhongyuan; Penrad-Mobayed, May; Sachs, Laurent M; Ruan, Xiaoan; Wei, Chia-Lin; Liu, Edison T; Wilczynski, Grzegorz M; Plewczynski, Dariusz; Li, Guoliang; Ruan, Yijun

2015-12-17

Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF/cohesin-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes toward CTCF foci for coordinated transcription. Furthermore, we show that haplotype variants and allelic interactions have differential effects on chromosome configuration, influencing gene expression, and may provide mechanistic insights into functions associated with disease susceptibility. 3D genome simulation suggests a model of chromatin folding around chromosomal axes, where CTCF is involved in defining the interface between condensed and open compartments for structural regulation. Our 3D genome strategy thus provides unique insights in the topological mechanism of human variations and diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Reconsideration of the WHO NCTB Strategy and Test Selection

PubMed Central

Anger, W. Kent

2014-01-01

The World Health Organization-recommended Neurobehavioral Core Test Battery (NCTB) became the international standard for identifying adverse human behavioral effects due to neurotoxic chemical exposure when it was first proposed in 1983. Since then the WHO NCTB has been repeatedly cited as the basis for test selection in human neurotoxicology research. A Discussion Group was held before the International Symposium on Neurobehavioral Methods and effects in Occupational and Environmental Health to review the NCTB and reconsider it’s tests. The workshop made three consensus recommendations to the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP): a ‘screening’ battery of broadly sensitive tests is needed as guidance to the field of human neurotoxicologythe SCNP should convene a panel to reconsider the functions measured and the tests in the WHO NCTBThree disciplines should be represented in the panel recommending a revised NCTB: Neuropsychology; Experimental Psychology; Neurology This recommendation will be pursued at the next meeting of the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP). PMID:25172409

Molecularly imprinted microspheres synthesized by a simple, fast, and universal suspension polymerization for selective extraction of the topical anesthetic benzocaine in human serum and fish tissues.

PubMed

Sun, Hui; Lai, Jia-Ping; Chen, Fang; Zhu, De-Rong

2015-02-01

A simple, fast, and universal suspension polymerization method was used to synthesize the molecularly imprinted microspheres (MIMs) for the topical anesthetic benzocaine (BZC). The desired diameter (10-20 μm) and uniform morphology of the MIMs were obtained easily by changing one or more of the synthesis conditions, including type and amount of surfactant, stirring rate, and ratio of organic to water phase. The MIMs obtained were used as a molecular-imprinting solid-phase-extraction (MISPE) material for extraction of BZC in human serum and fish tissues. The MISPE results revealed that the BZC in these biosamples could be enriched effectively after the MISPE operation. The recoveries of BZC on MIMs cartridges were higher than 90% (n = 3). Finally, an MISPE-HPLC method with UV detection was developed for highly selective extraction and fast detection of trace BZC in human serum and fish tissues. The developed method could also be used for the enrichment and detection of BZC in other complex biosamples.

Amoeba provide insight into the origin of virulence in pathogenic fungi.

PubMed

Casadevall, Arturo

2012-01-01

Why are some fungi pathogenic while the majority poses no threat to humans or other hosts? Of the more than 1.5 million fungal species only about 150-300 are pathogenic for humans, and of these, only 10-15 are relatively common pathogens. In contrast, fungi are major pathogens for plants and insects. These facts pose several fundamental questions including the mechanisms responsible for the origin of virulence among the few pathogenic species and the high resistance of mammals to fungal diseases. This essay explores the origin of virulences among environmental fungi with no obvious requirement for animal association and proposes that selection pressures by amoeboid predators led to the emergence of traits that can also promote survival in mammalian hosts. In this regard, analysis of the interactions between the human pathogenic funges Cryptococcus neoformans and amoeba have shown a remarkable similarity with the interaction of this fungus with macrophages. Hence the virulence of environmental pathogenic fungi is proposed to originate from a combination of selection by amoeboid predators and perhaps other soil organism with thermal tolerance sufficient to allow survival in mammalian hosts.

An evolutionary perspective on human physical activity: implications for health.

PubMed

Eaton, S Boyd; Eaton, Stanley B

2003-09-01

At present, human genes and human lives are incongruent, especially in affluent Western nations. When our current genome was originally selected, daily physical exertion was obligatory; our biochemistry and physiology are designed to function optimally in such circumstances. However, today's mechanized, technologically oriented conditions allow and even promote an unprecedentedly sedentary lifestyle. Many important health problems are affected by this imbalance, including atherosclerosis, obesity, age-related fractures and diabetes, among others. Most physicians recognize that regular exercise is a critical component of effective health promotion regimens, but there is substantial disagreement about details, most importantly volume: how much daily caloric expenditure, as physical activity, is desirable. Because epidemiology-based recommendations vary, often confusing and alienating the health-conscious public, an independent estimate, arising from a separate scientific discipline, is desirable, at least for purposes of triangulation. The retrojected level of ancestral physical activity might meet this need. The best available such reconstruction suggests that the World Health Organization's recommendation, a physical activity level of 1.75 ( approximately 2.1 MJ (490 kcal)/d), most closely approximates the Paleolithic standard, that for which our genetic makeup was originally selected.

Copper hazards to fish, wildlife and invertebrates: a synoptic review

USGS Publications Warehouse

Eisler, Ronald

1998-01-01

Selective review and synthesis of the technical literature on copper and copper salts in the environment and their effects primarily on fishes, birds, mammals, terrestrial and aquatic invertebrates, and other natural resources. The subtopics include copper sources and uses; chemical and biochemical properties; concentrations of copper in field collections of abiotic materials and living organisms; effects of copper deficiency; lethal and sublethal effects on terrestrial plants and invertebrates, aquatic organisms, birds and mammals, including effects on survival, growth, reproduction, behavior, metabolism, carcinogenicity, matagenicity, and teratogenicity; proposed criteria for the protection of human health and sensitive natural resources; and recommendations for additional research.

Nanostructured Polypyrrole-Based Ammonia and Volatile Organic Compound Sensors

PubMed Central

Šetka, Milena; Drbohlavová, Jana; Hubálek, Jaromír

2017-01-01

The aim of this review is to summarize the recent progress in the fabrication of efficient nanostructured polymer-based sensors with special focus on polypyrrole. The correlation between physico-chemical parameters, mainly morphology of various polypyrrole nanostructures, and their sensitivity towards selected gas and volatile organic compounds (VOC) is provided. The different approaches of polypyrrole modification with other functional materials are also discussed. With respect to possible sensors application in medicine, namely in the diagnosis of diseases via the detection of volatile biomarkers from human breath, the sensor interaction with humidity is described as well. The major attention is paid to analytes such as ammonia and various alcohols. PMID:28287435

Photodetection of early cancer by laser-induced fluorescence of a tumor-selective dye: apparatus design and realization

NASA Astrophysics Data System (ADS)

Wagnieres, Georges A.; Depeursinge, Christian D.; Monnier, Philippe; Savary, Jean-Francois; Cornaz, Piet F.; Chatelain, Andre; van den Bergh, Hubert

1990-07-01

An apparatus is designed and realized to detect "early" cancer at the surface of the hollow organs in the human body by endoscopic means. The tumor is localized by the laser induced fluorescence of a dye (HPD) which concentrates selectively in the neoplastic tissue after intravenous injection. Fluorescence contrast between the tumor and its normal surroundings is enhanced by subtracting the background autofluorescence which occurs in both types of tissue. This is done by means of 2-color digital images manipulation in real-time. Preliminary clinical tests of the apparatus demonstrated the detection of carcinoma in situ in the esophagus.

Novel human-associated Lachnospiraceae genetic markers improve detection of fecal pollution sources in urban waters.

PubMed

Feng, Shuchen; Bootsma, Melinda; McLellan, Sandra L

2018-05-04

The human microbiome contains many organisms that could potentially be used as indicators of human fecal pollution. Here we report the development of two novel human-associated genetic marker assays that target organisms within the family Lachnospiraceae Next-generation sequencing of the V6 region of the 16S rRNA gene from sewage and animal stool samples identified 40 human-associated marker candidates with a robust signal in sewage and low or no occurrence in nonhuman hosts. Two were chosen for quantitative PCR (qPCR) assay development using longer sequences (V2 to V9 regions) generated from clone libraries. Validation of these assays, designated Lachno3 and Lachno12, was performed using fecal samples (n=55) from cat, dog, pig, cow, deer, and gull sources, and compared with established host-associated assays (Lachno2, and two Human Bacteroides assays; HB and HF183/BacR287). Each of the established assays cross-reacted with at least one other animal, including animals common in urban areas. Lachno3 and Lachno12 were primarily human-associated; however, Lachno12 demonstrated low levels of cross-reactivity with select cows, and non-specific amplification in pigs. This limitation may not be problematic when testing urban waters. These novel markers resolved ambiguous results from previous investigations in stormwater-impacted waters, demonstrating their utility. The complexity of the microbiome in humans and animals suggests no single organism is strictly specific to humans, and multiple complementary markers used in combination will provide the highest resolution and specificity for assessing fecal pollution sources. IMPORTANCE Traditional fecal indicator bacteria do not distinguish animal from human fecal pollution, which is necessary to evaluate health risks and mitigate pollution sources. Assessing urban areas is challenging since water can be impacted by sewage, which has a high likelihood of carrying human pathogens, as well as pet waste and urban wildlife. We demonstrate Lachno3 and Lachno12 assays are human-associated and highly specific for urban sources, offering reliable identification of fecal pollution sources in urban waters. Copyright © 2018 American Society for Microbiology.

SU-F-T-117: A Pilot Study of Organ Dose Reconstruction for Wilms Tumor Patients Treated with Radiation Therapy

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

Makkia, R; Pelletier, C; Jung, J

Purpose: To reconstruct major organ doses for the Wilms tumor pediatric patients treated with radiation therapy using pediatric computational phantoms, treatment planning system (TPS), and Monte Carlo (MC) dose calculation methods. Methods: A total of ten female and male pediatric patients (15–88 months old) were selected from the National Wilms Tumor Study cohort and ten pediatric computational phantoms corresponding to the patient’s height and weight were selected for the organ dose reconstruction. Treatment plans were reconstructed on the computational phantoms in a Pinnacle TPS (v9.10) referring to treatment records and exported into DICOM-RT files, which were then used to generatemore » the input files for XVMC MC code. The mean doses to major organs and the dose received by 50% of the heart were calculated and compared between TPS and MC calculations. The same calculations were conducted by replacing the computational human phantoms with a series of diagnostic patient CT images selected by matching the height and weight of the patients to validate the anatomical accuracy of the computational phantoms. Results: Dose to organs located within the treatment fields from the computational phantoms and the diagnostic patient CT images agreed within 2% for all cases for both TPS and MC calculations. The maximum difference of organ doses was 55.9 % (thyroid), but the absolute dose difference in this case was 0.33 Gy which was 0.96% of the prescription dose. The doses to ovaries and testes from MC in out-of-field provided more discrepancy (the maximum difference of 13.2% and 50.8%, respectively). The maximum difference of the 50% heart volume dose between the phantoms and the patient CT images was 40.0%. Conclusion: This study showed the pediatric computational phantoms are applicable to organ doses reconstruction for the radiotherapy patients whose three-dimensional radiological images are not available.« less

A novel route of transplantation of human cord blood stem cells in preimmune fetal sheep: the intracelomic cavity.

PubMed

Noia, Giuseppe; Pierelli, Luca; Bonanno, Giuseppina; Monego, Giovanni; Perillo, Alessandro; Rutella, Sergio; Cavaliere, Anna Franca; De Santis, Marco; Ligato, Maria Serena; Fortunato, Giuseppe; Scambia, Giovanni; Terzano, Giuseppina Maria; Iannace, Enrico; Zelano, Giovanni; Michetti, Fabrizio; Leone, Giuseppe; Mancuso, Salvatore; Terzano, Marinela; Fotunato, Giuseppe

2003-01-01

The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40-45 days) received intracelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human beta2-microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%-22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34-selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45(+) cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta2-microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.

Tilapia and human CLIC2 structures are highly conserved.

PubMed

Zeng, Jiao; Li, Zhengjun; Lui, Eei Yin; Lam, Siew Hong; Swaminathan, Kunchithapadam

2018-01-08

Chloride intracellular channels (CLICs) exist in soluble and membrane bound forms. We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. We have also compared the expression levels of clic2 in selected osmoregulatory organs of tilapia, acclimated to freshwater, seawater and hypersaline water. Structural conservation of vertebrate CLICs implies that they might play conserved roles. Also, tissue-specific responsiveness of clic2 suggests that it might be involved in iono-osmoregulation under extreme conditions in tilapia. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroanatomic organization of sound memory in humans.

PubMed

Kraut, Michael A; Pitcock, Jeffery A; Calhoun, Vince; Li, Juan; Freeman, Thomas; Hart, John

2006-11-01

The neural interface between sensory perception and memory is a central issue in neuroscience, particularly initial memory organization following perceptual analyses. We used functional magnetic resonance imaging to identify anatomic regions extracting initial auditory semantic memory information related to environmental sounds. Two distinct anatomic foci were detected in the right superior temporal gyrus when subjects identified sounds representing either animals or threatening items. Threatening animal stimuli elicited signal changes in both foci, suggesting a distributed neural representation. Our results demonstrate both category- and feature-specific responses to nonverbal sounds in early stages of extracting semantic memory information from these sounds. This organization allows for these category-feature detection nodes to extract early, semantic memory information for efficient processing of transient sound stimuli. Neural regions selective for threatening sounds are similar to those of nonhuman primates, demonstrating semantic memory organization for basic biological/survival primitives are present across species.

It matters how old you feel: Antecedents and performance consequences of average relative subjective age in organizations.

PubMed

Kunze, Florian; Raes, Anneloes M L; Bruch, Heike

2015-09-01

This article extends the conceptual knowledge of average relative subjective age in organizations by exploring organizational-level antecedents and consequences of employees, on average, feeling younger than their chronological age. We draw from the theories of selection-optimization-compensation and socioemotional selectivity to build a theoretical framework for relative subjective age in organizations. We hypothesize that companies in which employees, on average, perceive themselves to be younger than they actually are have a higher average individual goal accomplishment and, in turn, experience higher company performance. We further hypothesize that employees' average experience of high work-related meaning relates to a lower subjective age in organizations. In addition, we assess the role of environmental dynamism and age-inclusive human resource management as moderators in this theoretical model. Through empirically testing this model in a multisource dataset, including 107 companies with 15,164 participating employees, we received support for the hypothesized relationships. Our results contribute to current debates in the scientific literature on age and have important practical implications in light of the demographic changes faced by many companies. This research indicates to both researchers and practitioners that it is not employees' chronological age but their subjective age, a factor that can be influenced, which drives organizational performance outcomes. (c) 2015 APA, all rights reserved).

Endurance exercise and selective breeding for longevity extend Drosophila healthspan by overlapping mechanisms.

PubMed

Sujkowski, Alyson; Bazzell, Brian; Carpenter, Kylie; Arking, Robert; Wessells, Robert J

2015-08-01

Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity. Microarrays indicate that 65% of gene expression changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training. We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Both interventions generally upregulate stress defense, folate metabolism, and lipase activity, while downregulating carbohydrate metabolism and odorant receptor expression. Several members of the methuselah-like (mthl) gene family are downregulated by both interventions. Knockdown of mthl-3 was sufficient to provide extension of negative geotaxis behavior, endurance and cardiac stress resistance. These results provide support for endurance exercise as a broadly acting anti-aging intervention and confirm that exercise training acts in part by targeting longevity assurance pathways.

Review: The transcripts associated with organ allograft rejection.

PubMed

Halloran, Philip F; Venner, Jeffery M; Madill-Thomsen, Katelynn S; Einecke, Gunilla; Parkes, Michael D; Hidalgo, Luis G; Famulski, Konrad S

2018-04-01

The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG), activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR-selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and endothelial cells (eg, ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Image statistics underlying natural texture selectivity of neurons in macaque V4

PubMed Central

Okazawa, Gouki; Tajima, Satohiro; Komatsu, Hidehiko

2015-01-01

Our daily visual experiences are inevitably linked to recognizing the rich variety of textures. However, how the brain encodes and differentiates a plethora of natural textures remains poorly understood. Here, we show that many neurons in macaque V4 selectively encode sparse combinations of higher-order image statistics to represent natural textures. We systematically explored neural selectivity in a high-dimensional texture space by combining texture synthesis and efficient-sampling techniques. This yielded parameterized models for individual texture-selective neurons. The models provided parsimonious but powerful predictors for each neuron’s preferred textures using a sparse combination of image statistics. As a whole population, the neuronal tuning was distributed in a way suitable for categorizing textures and quantitatively predicts human ability to discriminate textures. Together, we suggest that the collective representation of visual image statistics in V4 plays a key role in organizing the natural texture perception. PMID:25535362

Mineral Composition of Organically Grown Wheat Genotypes: Contribution to Daily Minerals Intake

PubMed Central

Hussain, Abrar; Larsson, Hans; Kuktaite, Ramune; Johansson, Eva

2010-01-01

In this study, 321 winter and spring wheat genotypes were analysed for twelve nutritionally important minerals (B, Cu, Fe, Se, Mg, Zn, Ca, Mn, Mo, P, S and K). Some of the genotypes used were from multiple locations and years, resulting in a total number of 493 samples. Investigated genotypes were divided into six genotype groups i.e., selections, old landraces, primitive wheat, spelt, old cultivars and cultivars. For some of the investigated minerals higher concentrations were observed in selections, primitive wheat, and old cultivars as compared to more modern wheat material, e.g., cultivars and spelt wheat. Location was found to have a significant effect on mineral concentration for all genotype groups, although for primitive wheat, genotype had a higher impact than location. Spring wheat was observed to have significantly higher values for B, Cu, Fe, Zn, Ca, S and K as compared to winter wheat. Higher levels of several minerals were observed in the present study, as compared to previous studies carried out in inorganic systems, indicating that organic conditions with suitable genotypes may enhance mineral concentration in wheat grain. This study also showed that a very high mineral concentration, close to daily requirements, can be produced by growing specific primitive wheat genotypes in an organic farming system. Thus, by selecting genotypes for further breeding, nutritional value of the wheat flour for human consumption can be improved. PMID:20948934

Macromolecular networks and intelligence in microorganisms

PubMed Central

Westerhoff, Hans V.; Brooks, Aaron N.; Simeonidis, Evangelos; García-Contreras, Rodolfo; He, Fei; Boogerd, Fred C.; Jackson, Victoria J.; Goncharuk, Valeri; Kolodkin, Alexey

2014-01-01

Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence.” Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence,” all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence.” We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo. PMID:25101076

Novel Metals and Metal Complexes as Platforms for Cancer Therapy

PubMed Central

Frezza, Michael; Hindo, Sarmad; Chen, Di; Davenport, Andrew; Schmitt, Sara; Tomco, Dajena; Dou, Q. Ping

2013-01-01

Metals are essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms. Metals are endowed with unique characteristics that include redox activity, variable coordination modes, and reactivity towards organic substrates. Due to their reactivity, metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. For these reasons, coordination complexes, either as drugs or prodrugs, become very attractive probes as potential anticancer agents. The use of metals and their salts for medicinal purposes, from iatrochemistry to modern day, has been present throughout human history. The discovery of cisplatin, cis-[PtII(NH3)2Cl2], was a defining moment which triggered the interest in platinum(II)- and other metal-containing complexes as potential novel anticancer drugs. Other interests in this field address concerns for uptake, toxicity, and resistance to metallodrugs. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. The use of nonessential metals as probes to target molecular pathways as anticancer agents is also emphasized. Finally, based on the interface between molecular biology and bioinorganic chemistry the design of coordination complexes for cancer treatment is reviewed and design strategies and mechanisms of action are discussed. PMID:20337575

Older Veterans: Growing Numbers and Changing Needs. Hearing before the Subcommittee on Human Services of the Select Committee on Aging, House of Representatives, Ninety-Eighth Congress, Second Session (Bound Brook, New Jersey).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Aging.

This Congressional report contains the testimony presented at a hearing focusing on the need for expanding available medical facilities and services for older U.S. veterans in New Jersey. Included among those agencies and organizations represented at the hearing were the following: the Veterans Administration; the Division of Health Policy…

A Model of Human Variability in Viable Ship Design

DTIC Science & Technology

2014-02-21

when an organization is in a state of change. For example, an alternative to screening out individuals for a new job role is the self -selection of...being done and group members little care what happens beyond their self -imposed borders. The proposed extension addresses team decay with regard to the...these, the paygrade of team members probably reflects qualities of most interest from the authors’ point of 22 view. Paygrade is highly

The role of organic proteins on the crack growth resistance of human enamel.

PubMed

Yahyazadehfar, Mobin; Arola, Dwayne

2015-06-01

With only 1% protein by weight, tooth enamel is the most highly mineralized tissue in mammals. The focus of this study was to evaluate contributions of the proteins on the fracture resistance of this unique structural material. Sections of enamel were obtained from the cusps of human molars and the crack growth resistance was quantified using a conventional fracture mechanics approach with complementary finite element analysis. In selected specimens the proteins were extracted using a potassium hydroxide treatment. Removal of the proteins resulted in approximately 40% decrease in the fracture toughness with respect to the fully proteinized control. The loss of organic content was most detrimental to the extrinsic toughening mechanisms, causing over 80% reduction in their contribution to the total energy to fracture. This degradation occurred by embrittlement of the unbroken bridging ligaments and consequent reduction in the crack closure stress. Although the organic content of tooth enamel is very small, it is essential to crack growth toughening by facilitating the formation of unbroken ligaments and in fortifying their potency. Replicating functions of the organic content will be critical to the successful development of bio-inspired materials that are designed for fracture resistance. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Language and other artifacts: socio-cultural dynamics of niche construction

PubMed Central

Sinha, Chris

2015-01-01

Niche construction theory is a relatively new approach in evolutionary biology that seeks to integrate an ecological dimension into the Darwinian theory of evolution by natural selection. It is regarded by many evolutionary biologists as providing a significant revision of the Neo-Darwinian modern synthesis that unified Darwin’s theory of natural and sexual selection with 20th century population genetics. Niche construction theory has been invoked as a processual mediator of social cognitive evolution and of the emergence and evolution of language. I argue that language itself can be considered as a biocultural niche and evolutionary artifact. I provide both a general analysis of the cognitive and semiotic status of artifacts, and a formal analysis of language as a social and semiotic institution, based upon a distinction between the fundamental semiotic relations of “counting as” and “standing for.” I explore the consequences for theories of language and language learning of viewing language as a biocultural niche. I suggest that not only do niches mediate organism-organism interactions, but also that organisms mediate niche-niche interactions in ways that affect evolutionary processes, with the evolution of human infancy and childhood as a key example. I argue that language as a social and semiotic system is not only grounded in embodied engagements with the material and social-interactional world, but also grounds a sub-class of artifacts of particular significance in the cultural history of human cognition. Symbolic cognitive artifacts materially and semiotically mediate human cognition, and are not merely informational repositories, but co-agentively constitutive of culturally and historically emergent cognitive domains. I provide examples of the constitutive cognitive role of symbolic cognitive artifacts drawn from my research with my colleagues on cultural and linguistic conceptualizations of time, and their cultural variability. I conclude by reflecting on the philosophical and social implications of understanding artifacts co-agentively. PMID:26539144

Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs.

PubMed

Kim, Geon A; Lee, Eun Mi; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Hwang, Jong Ik; Alam, Zahid; Ahn, Curie; Lee, Byeong Chun

2017-08-01

As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans. Gal-deleted cells expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin -tagged-human heme oxygenase-1 (hHO-1) were transfected with a TALEN target for CMAH. Cells lacking CMAH were negatively selected using N-glyconeuraminic acid (Neu5Gc)/magnetic beads and the level of Neu5Gc expression of isolated cells were analyzed by FACS and DNA sequencing. Cloned embryos using 3 different genetically modified cell clones were respectively transferred into 3 recipients, with 55.6% (5/9) becoming pregnant and three cloned pigs were produced. Successful genetic disruption of the CMAH gene was confirmed by sequencing, showing lack of expression of CMAH in tail-derived fibroblasts of the cloned piglets. Besides decreased expression of Neu5Gc in piglets produced by SCNT, antibody-mediated complement-dependent cytotoxicity assays and natural antibody binding for examining immuno-reactivity of the quadruple gene modified pigs derived from endothelial cells and fibroblasts were reduced significantly compared to those of wild type animals. We conclude that by combining the TALEN system and transgenic cells, targeting of multiple genes could be useful for generating organs for xenotransplantation. We produced miniature pigs with quadruple modified genes CMAHKO/GTKO/shTNFRI-Fc/hHO-1 that will be suitable for xenotransplantation by overcoming hyperacute, acute and anti-inflammatory rejection.

Action semantics: A unifying conceptual framework for the selective use of multimodal and modality-specific object knowledge

NASA Astrophysics Data System (ADS)

van Elk, Michiel; van Schie, Hein; Bekkering, Harold

2014-06-01

Our capacity to use tools and objects is often considered one of the hallmarks of the human species. Many objects greatly extend our bodily capabilities to act in the physical world, such as when using a hammer or a saw. In addition, humans have the remarkable capability to use objects in a flexible fashion and to combine multiple objects in complex actions. We prepare coffee, cook dinner and drive our car. In this review we propose that humans have developed declarative and procedural knowledge, i.e. action semantics that enables us to use objects in a meaningful way. A state-of-the-art review of research on object use is provided, involving behavioral, developmental, neuropsychological and neuroimaging studies. We show that research in each of these domains is characterized by similar discussions regarding (1) the role of object affordances, (2) the relation between goals and means in object use and (3) the functional and neural organization of action semantics. We propose a novel conceptual framework of action semantics to address these issues and to integrate the previous findings. We argue that action semantics entails both multimodal object representations and modality-specific sub-systems, involving manipulation knowledge, functional knowledge and representations of the sensory and proprioceptive consequences of object use. Furthermore, we argue that action semantics are hierarchically organized and selectively activated and used depending on the action intention of the actor and the current task context. Our framework presents an integrative account of multiple findings and perspectives on object use that may guide future studies in this interdisciplinary domain.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Adaptation to fragmentation: evolutionary dynamics driven by human influences.

PubMed

Cheptou, Pierre-Olivier; Hargreaves, Anna L; Bonte, Dries; Jacquemyn, Hans

2017-01-19

Fragmentation-the process by which habitats are transformed into smaller patches isolated from each other-has been identified as a major threat for biodiversity. Fragmentation has well-established demographic and population genetic consequences, eroding genetic diversity and hindering gene flow among patches. However, fragmentation should also select on life history, both predictably through increased isolation, demographic stochasticity and edge effects, and more idiosyncratically via altered biotic interactions. While species have adapted to natural fragmentation, adaptation to anthropogenic fragmentation has received little attention. In this review, we address how and whether organisms might adapt to anthropogenic fragmentation. Drawing on selected case studies and evolutionary ecology models, we show that anthropogenic fragmentation can generate selection on traits at both the patch and landscape scale, and affect the adaptive potential of populations. We suggest that dispersal traits are likely to experience especially strong selection, as dispersal both enables migration among patches and increases the risk of landing in the inhospitable matrix surrounding them. We highlight that suites of associated traits are likely to evolve together. Importantly, we show that adaptation will not necessarily rescue populations from the negative effects of fragmentation, and may even exacerbate them, endangering the entire metapopulation.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

PeptidePicker: a scientific workflow with web interface for selecting appropriate peptides for targeted proteomics experiments.

PubMed

Mohammed, Yassene; Domański, Dominik; Jackson, Angela M; Smith, Derek S; Deelder, André M; Palmblad, Magnus; Borchers, Christoph H

2014-06-25

One challenge in Multiple Reaction Monitoring (MRM)-based proteomics is to select the most appropriate surrogate peptides to represent a target protein. We present here a software package to automatically generate these most appropriate surrogate peptides for an LC/MRM-MS analysis. Our method integrates information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM which is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our knowledge in choosing the best candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it previously has been observed. The modularity of the workflow allows further extension and additional selection criteria to be incorporated. We have developed a simple Web interface where the researcher provides the protein accession number, the subject organism, and peptide-specific options. Currently, the software is designed for human and mouse proteomes, but additional species can be easily be added. Our software improved the peptide selection by eliminating human error, considering multiple data sources and all of the isoforms of the protein, and resulted in faster peptide selection - approximately 50 proteins per hour compared to 8 per day. Compiling a list of optimal surrogate peptides for target proteins to be analyzed by LC/MRM-MS has been a cumbersome process, in which expert researchers retrieved information from different online repositories and used their own reasoning to find the most appropriate peptides. Our scientific workflow automates this process by integrating information from different data sources including UniProt, Global Proteome Machine, NCBI's dbSNP, and PeptideAtlas, simulating the researchers' reasoning, and incorporating their knowledge of how to select the best proteotypic peptides for an MRM analysis. The developed software can help to standardize the selection of peptides, eliminate human error, and increase productivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection.

PubMed

Lucotte, Elise A; Laurent, Romain; Heyer, Evelyne; Ségurel, Laure; Toupance, Bruno

2016-06-02

Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735-742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice's model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The child welfare system: through the eyes of public health nurses.

PubMed

Schneiderman, Janet U

2005-01-01

This qualitative descriptive study investigates how public health nurses working within the child welfare system view the organization and the organization's effect on their case management practice. Semistructured interviews were conducted utilizing the Bolman-Deal Organizational Model. This model identifies four frames of an organization: symbolic, human resources, political, and structural. A purposive sample of nine nurses and one social worker was selected to participate in comprehensive interviews. Data analysis identified two main themes. The first theme was the presence of organizational structural barriers to providing case management. The second theme was the lack of political influence by the nurses to change the structure of the organization; hence, their skills could be more completely utilized. Public health nurses who work in child welfare will need to systematically analyze their role within the organization and understand how to work in "host settings." Nursing educators need to prepare public health nurses to work in non-health care settings by teaching organizational analysis.

Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse.

PubMed

Kufaishi, Hala; Alarab, May; Drutz, Harold; Lye, Stephen; Shynlova, Oksana

2016-08-01

Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer-controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage ≥3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch-conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro mechanical stretch. Risk factors that induce stretch may alter ECM composition and cell-ECM interaction in pelvic floor tissue leading to the abatement of pelvic organ support and subsequent POP development. © The Author(s) 2016.

The importance of immune gene variability (MHC) in evolutionary ecology and conservation

PubMed Central

Sommer, Simone

2005-01-01

Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022

The harmonic organization of auditory cortex

PubMed Central

Wang, Xiaoqin

2013-01-01

A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds. PMID:24381544

Assignment of the human caltractin gene (CALT) to Xq28 by fluorescence in situ hybridization

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

Tanaka, Tanaka; Okui, Keiko; Nakamura, Yusuke

1994-12-01

The centrosome is the major microtubule-organizing center of interphase eukaryotic cells, an its duplication is essential to eukaryotic cell division. Caltractin, a structural component of centrosomes, is highly homologous in amino acid sequence to the product of the CDC31 gene of Saccharomyces cerevisiae. In S. cerevisiae, an important role for CDC31 in duplication of the spindle pole body (SPB), a kind of microtubule-organizing center, has been demonstrated by an experiment in which mutant CDC31 prevented SPB duplication and led to formation of a monopolar spindle. In view of the localization of human caltractin in centrosomes and the sequence homology itmore » bears to yeast CDC31, it is reasonable to assume that caltractin functions in humans as CDC31 does in yeast. As a part of the Human Genome Project, we have been determining nucleotide sequences of DNA clones randomly selected from a directionally cloned cDNA library constructed from fetal brain mRNA obtained from Clontech (La Jolla, CA). By comparing 5{prime} partial DNA sequences of these cDNA clones with known DNA sequences in the database, we found one clone that was highly homologous to the caltractin gene of Chlamydomonas, which turned out to be the same as a human gene identified recently. 4 refs., 1 fig.« less

Understanding Virulence in the Brucellae and Francisellae: Towards Efficacious Treatments for Two Potential Biothreat Agents

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

Rasley, A; Parsons, D A; El-Etr, S

2009-12-30

Francisella tularensis, Yersinia pestis and Brucellae species are highly infectious pathogens classified as select agents by the Centers for Disease Control and Prevention (CDC) with the potential for use in bioterrorism attacks. These organisms are known to be facultative intracellular pathogens that preferentially infect human monocytes. As such, understanding how the host responds to infection with these organisms is paramount in detecting and combating human disease. We have compared the ability of fully virulent strains of each pathogen and their non-pathogenic near neighbors to enter and survive inside the human monocytic cell line THP-1 and have quantified the cellular responsemore » to infection with the goal of identifying both unique and common host response patterns. We expanded the scope of these studies to include experiments with pathogenic and non-pathogenic strains of Y. pestis, the causative agent of plague. Nonpathogenic strains of each organism were impaired in their ability to survive intracellularly compared with their pathogenic counterparts. Furthermore, infection of THP-1 cells with pathogenic strains of Y. pestis and F. tularensis resulted in marked increases in the secretion of the inflammatory chemokines IL-8, RANTES, and MIP-1{beta}. In contrast, B. melitensis infection failed to elicit any significant increases in a panel of cytokines tested. These differences may underscore distinct strategies in pathogenic mechanisms employed by these pathogens.« less

Organic acids, sugars, vitamin C content and some pomological characteristics of eleven hawthorn species (Crataegus spp.) from Turkey.

PubMed

Gundogdu, Muttalip; Ozrenk, Koray; Ercisli, Sezai; Kan, Tuncay; Kodad, Ossama; Hegedus, Attila

2014-05-30

The Hawthorn (Crateagus sp.) mostly occurs around the temperate region of the world with a high number of species, producing a fruit with numerous beneficial effects for human health. The aim of the study was to determine organic acid and sugar contents in the fruit of a number of hawthorn species grown in Erzincan province of Turkey. Citric acid was the predominant organic acid in all hawthorn species and C. pseudoheterophylla had the highest citric acid content (23.688 g/100 g). There were not statistically significant differences among hawthorn species (except C. atrosanguinea Pojark) in terms of fumaric acid content. C.pontica C.Koch had a higher content of vitamin C (9.418 mg/100 g) compared to other species. Fructose was the predominant sugar component in all species and C. monogyna subsp. monogyna Joiq had the highest fructose content (18.378 g/100 g). The high fruit quality of the studied species indicates the importance of this fruit in human nutrition as a natural source. The study revealed that there were differences in terms of fruit characteristics among hawthorn species and thus better quality hawthorn genotypes can be selected within the species. Hence, this study is considered to be a valuable reference for forthcoming studies. The high fruit quality of the studied species indicates the importance of this fruit in human nutrition as a natural source.

Sex-dependent association of common variants of microcephaly genes with brain structure.

PubMed

Rimol, Lars M; Agartz, Ingrid; Djurovic, Srdjan; Brown, Andrew A; Roddey, J Cooper; Kähler, Anna K; Mattingsdal, Morten; Athanasiu, Lavinia; Joyner, Alexander H; Schork, Nicholas J; Halgren, Eric; Sundet, Kjetil; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A

2010-01-05

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

The Human Neonatal Gut Microbiome: A Brief Review

PubMed Central

Gritz, Emily C.; Bhandari, Vineet

2015-01-01

The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, has become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed) and gestational age (term versus preterm). We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field. PMID:25798435

Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution.

PubMed

Zihlman, Adrienne L; Bolter, Debra R

2015-06-16

The human body has been shaped by natural selection during the past 4-5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition.

Amphibian (Xenopus sp.) iodothyronine deiodinase ...

EPA Pesticide Factsheets

The U.S. EPA-MED amphibian thyroid group is currently screening chemicals for inhibition of human iodothyronine deiodinase activity as components of the thyroid system important in human development. Amphibians are a bellwether taxonomic group to gauge toxicity of chemicals in the environment. Amphibian thyroid function is not only important in development but also metamorphosis. Xenopus sp. have been used extensively as model organisms and are well characterized genetically. We propose to screen a list of chemicals (selected from the human DIO screening results) to test for inhibition of Xenopus deiodinases. Large quantities of the enzymes will be produced using an adenovirus system. Our preliminary results show that there may be catalytic differences between human and Xenopus deiodinases. The Twin Ports Early Career Scientists is a new group formed within the Duluth-Superior scientific community. This presentation will provide a basic introduction to my research and our mission at EPA, and help to establish networking and collaboration relationships across disciplines and institutions.

Body composition in Pan paniscus compared with Homo sapiens has implications for changes during human evolution

PubMed Central

Zihlman, Adrienne L.; Bolter, Debra R.

2015-01-01

The human body has been shaped by natural selection during the past 4–5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genus Pan provide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data with Homo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues between Pan and Homo provides new insights into the function and evolution of body composition. PMID:26034269

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

PubMed

Islam, Md Rafiqul; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Slater, Christine; Islam, Md Monirul; Akhter, Ayesha; d'Este, Catherine; Peel, Roseanne; Akter, Shahnaz; Smith, Wayne; Begg, Stephen; Milton, Abul Hasnat

2014-12-04

Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine. Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation. Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant's urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant's urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine. We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization's maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

KV7 channels in the human detrusor: channel modulator effects and gene and protein expression.

PubMed

Bientinesi, Riccardo; Mancuso, Cesare; Martire, Maria; Bassi, Pier Francesco; Sacco, Emilio; Currò, Diego

2017-02-01

Voltage-gated type 7 K + (K V 7 or KCNQ) channels regulate the contractility of various smooth muscles. With this study, we aimed to assess the role of K V 7 channels in the regulation of human detrusor contractility, as well as the gene and protein expression of K V 7 channels in this tissue. For these purposes, the isolated organ technique, RT-qPCR, and Western blot were used, respectively. XE-991, a selective K V 7 channel blocker, concentration-dependently contracted the human detrusor; mean EC 50 and E max of XE-991-induced concentration-response curve were 14.1 μM and 28.8 % of the maximal bethanechol-induced contraction, respectively. Flupirtine and retigabine, selective K V 7.2-7.5 channel activators, induced concentration-dependent relaxations of bethanechol-precontracted strips, with maximal relaxations of 51.6 and 51.8 % of the precontraction, respectively. XE-991 blocked the relaxations induced by flupirtine and retigabine. All five KCNQ genes were found to be expressed in the detrusor with KCNQ4 being the most expressed among them. Different bands, having sizes similar to some of reported K V 7.1, 7.4, and 7.5 channel subunit isoforms, were detected in the detrusor by Western blot with the K V 7.4 band being the most intense among them. In conclusion, K V 7 channels contribute to set the basal tone of the human detrusor. In addition, K V 7 channel activators significantly relax the detrusor. The K V 7.4 channels are probably the most important K V 7 channels expressed in the human detrusor. These data suggest that selective K V 7.4 channel activators might represent new pharmacological tools for inducing therapeutic relaxation of the detrusor.

Targeting the prostate for destruction through a vascular address

PubMed Central

Arap, Wadih; Haedicke, Wolfgang; Bernasconi, Michele; Kain, Renate; Rajotte, Daniel; Krajewski, Stanislaw; Ellerby, H. Michael; Bredesen, Dale E.; Pasqualini, Renata; Ruoslahti, Erkki

2002-01-01

Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10–15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk. PMID:11830668

Mate choice, sexual selection, and endocrine-disrupting chemicals.

PubMed

Gore, Andrea C; Holley, Amanda M; Crews, David

2018-05-01

Humans have disproportionately affected the habitat and survival of species through environmental contamination. Important among these anthropogenic influences is the proliferation of organic chemicals, some of which perturb hormone systems, the latter referred to as endocrine-disrupting chemicals (EDCs). EDCs are widespread in the environment and affect all levels of reproduction, including development of reproductive organs, hormone release and regulation through the life cycle, the development of secondary sexual characteristics, and the maturation and maintenance of adult physiology and behavior. However, what is not well-known is how the confluence of EDC actions on the manifestation of morphological and behavioral sexual traits influences mate choice, a process that requires the reciprocal evaluation of and/or acceptance of a sexual partner. Moreover, the outcomes of EDC-induced perturbations are likely to influence sexual selection; yet this has rarely been directly tested. Here, we provide background on the development and manifestation of sexual traits, reproductive competence, and the neurobiology of sexual behavior, and evidence for their perturbation by EDCs. Selection acts on individuals, with the consequences manifest in populations, and we discuss the implications for EDC contamination of these processes, and the future of species. Copyright © 2017 Elsevier Inc. All rights reserved.

Modification of visual function by early visual experience.

PubMed

Blakemore, C

1976-07-01

Physiological experiments, involving recording from the visual cortex in young kittens and monkeys, have given new insight into human developmental disorders. In the visual cortex of normal cats and monkeys most neurones are selectively sensitive to the orientation of moving edges and they receive very similar signals from both eyes. Even in very young kittens without visual experience, most neurones are binocularly driven and a small proportion of them are genuinely orientation selective. There is no passive maturation of the system in the absence of visual experience, but even very brief exposure to patterned images produces rapid emergence of the adult organization. These results are compared to observations on humans who have "recovered" from early blindness. Covering one eye in a kitten or a monkey, during a sensitive period early in life, produces a virtually complete loss of input from that eye in the cortex. These results can be correlated with the production of "stimulus deprivation amblyopia" in infants who have had one eye patched. Induction of a strabismus causes a loss of binocularity in the visual cortex, and in humans it leads to a loss of stereoscopic vision and binocular fusion. Exposing kittens to lines of one orientation modifies the preferred orientations of cortical cells and there is an analogous "meridional amblyopia" in astigmatic humans. The existence of a sensitive period in human vision is discussed, as well as the possibility of designing remedial and preventive treatments for human developmental disorders.

Selected Organochlorines in Human Blood and Urine in the South of the Russian Far East.

PubMed

Tsygankov, Vasiliy Yu; Khristoforova, Nadezhda K; Lukyanova, Olga N; Boyarova, Margarita D; Kiku, Pavel F; Yarygina, Marina V

2017-10-01

The trace OCP concentrations, such as α-, β-, and γ-HCH, DDT and its metabolites (DDD and DDE) in blood and urine of residents from the south of the Russian Far East was revealed. A large range of OCPs was found in the urine: α- and γ-isomers of HCH, DDT and DDE. The only β-HCH was detected in the blood; this indicates its persistence and the difficulty of excretion this substance from the organism. The total trace OCP concentration, found in the biological fluids of residents of the south of the Russian Far East, providing further evidence that these organic contaminants persist in the environment.

Marine products with anti-protozoal activity: a review.

PubMed

García, Marley; Monzote, Lianet

2014-01-01

The marine organisms are a rich source of varied natural products with unique functionality. A variety of natural products of new molecular structures with diverse biological activities have been reported from marine flora and fauna for treatment and/or prevention of human diseases. The present review briefly illustrates current status of marine products as antiprotozoal agents. The in vitro and in vivo studies of marine algae, invertebrates and micro-organism against different protozoa parasites are included. The marine products studied, according to international criterions for selection of more promisory products in the different models reported, demonstrated their potentialities as antiprozoal agents. Herein, the interest of scientific community to search new alternatives from marine environment has been demonstrated.

Endothelial function in pigs transgenic for human complement regulating factor.

PubMed

Warnecke, Gregor; Severson, Sandra R; Ugurlu, Mustafa M; Taner, Cemal B; Logan, John S; Diamond, Lisa E; Miller, Virginia M; McGregor, Christopher G A

2002-04-15

Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. Experiments were designed to characterize endothelial and smooth muscle function of arteries from pigs transgenic for hCD46. Arterial blood from outbred pigs transgenic for hCD46 expression and nontransgenic animals of the same lineage was analyzed for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic endothelial cells were prepared for measurement of mRNA or activity for nitric oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were suspended in organ chambers for measurement of isometric tension. CNP was significantly greater, ACE was similar, and nitric oxide was significantly less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor activity of NOS differed between the groups. Endothelium-dependent relaxations to bradykinin and acetylcholine but not the calcium ionophore were shifted significantly to the left in femoral and pulmonary arteries from hCD46 transgenic pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did not inhibit relaxations in rings from transgenic pigs. Data suggest that expression of hCD46 on endothelium of pigs selectively augments endothelium-dependent relaxations to bradykinin by increased release of endothelium-derived factors other than nitric oxide. There does not seem to be any change in activity of ACE or NOS with expression of the human protein. Increased relaxations to bradykinin may be beneficial in lowering vascular resistance when transgenic organs are used for xenotransplantation.

The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment

PubMed Central

2011-01-01

Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies. PMID:21835012

Sediment quality in the north coastal basin of Massachusetts, 2003

USGS Publications Warehouse

Breault, Robert F.; Ashman, Mary S.; Heath, Douglas

2004-01-01

The U.S. Geological Survey, in cooperation with the Massachusetts Department of Environmental Protection, completed a reconnaissance-level study of bottom-sediment quality in selected lakes, rivers, and estuaries in the North Coastal Basin of Massachusetts. Bottom-sediment grab samples were collected from 20 sites in the North River, Lake Quannapowitt, Saugus River, Mill River, Shute Brook, Sea Plane Basin, Pines River, and Bear Creek. The samples were tested for various types of potentially harmful contaminants? including 33 elements, 17 polyaromatic hydrocarbons (PAHs), 22 organochlorine pesticides, and 7 polychlorinated biphenyl (PCB) mixtures (Aroclors)?to benthic organisms (bottom-dwelling) and humans. The results were compared among sampling sites, to background concentrations, and to concen-trations measured in other urban rivers, and sediment-quality guidelines were used to predict toxicity at the sampling sites to benthic organisms and humans. Because there are no standards for human toxicity for aquatic sediment, standards for contaminated upland soil were used. Contaminant concentrations measured in sediment collected from the North Coastal Basin generally were equal to or greater than concentrations in sediment from uncontaminated rivers throughout New England. Contaminants in North Coastal Basin sediment with elevated concentrations (above back-ground levels) included arsenic, chromium, copper, lead, nickel, and zinc, some of the PAHs, dichlorodiphenyltrichloro-ethane (DDT) and its metabolites, and dieldrin. No PCBs were measured above the detection limits. Measured concentrations of arsenic, chromium, and lead were also generally greater than those measured in other urban rivers throughout the conter-minous United States. With one exception (arsenic), local con-centrations measured in sediment samples collected from the North Coastal Basin were lower than concentrations measured in sediment collected from two of three urban rivers draining to Boston Harbor. The probable toxicity to benthic organisms ranged from about 33 to 91 percent across the study area. Of the elements analyzed, antimony, arsenic, beryllium, and lead exceeded the soil standards for risk to human health. Of the PAHs analyzed, four also exceeded soil standards. Organochlorine pesticide concentrations, however, were not high enough relative to the soil standards to pose a risk to human health. Some trace element and some organic compound concentrations in bottom sediment may be toxic to aquatic organisms and may pose a risk to human health.

3D Miniaturization of Human Organs for Drug Discovery.

PubMed

Park, Joseph; Wetzel, Isaac; Dréau, Didier; Cho, Hansang

2018-01-01

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues. Thus, engineered human organs can provide the microstructures and biological functions of target organs and advantageously substitute multiscaled drug-testing platforms including the current in vitro molecular assays, cell platforms, and in vivo models. This review provides an overview of advanced innovative designs based on the three main technologies used for organ construction leading to single and multiorgan systems useable for drug development. Current technological challenges and future perspectives are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

PubMed Central

Chiang, Annette N.; Valderramos, Juan-Carlos; Balachandran, Raghavan; Chovatiya, Raj J.; Mead, Brian P.; Schneider, Corinne; Bell, Samantha L.; Klein, Michael G.; Huryn, Donna M.; Chen, Xiaojiang S.; Day, Billy W.; Fidock, David A.; Wipf, Peter; Brodsky, Jeffrey L.

2009-01-01

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. PMID:19195901

Human induced rotation and reorganization of the brain of domestic dogs.

PubMed

Roberts, Taryn; McGreevy, Paul; Valenzuela, Michael

2010-07-26

Domestic dogs exhibit an extraordinary degree of morphological diversity. Such breed-to-breed variability applies equally to the canine skull, however little is known about whether this translates to systematic differences in cerebral organization. By looking at the paramedian sagittal magnetic resonance image slice of canine brains across a range of animals with different skull shapes (N = 13), we found that the relative reduction in skull length compared to width (measured by Cephalic Index) was significantly correlated to a progressive ventral pitching of the primary longitudinal brain axis (r = 0.83), as well as with a ventral shift in the position of the olfactory lobe (r = 0.81). Furthermore, these findings were independent of estimated brain size or body weight. Since brachycephaly has arisen from generations of highly selective breeding, this study suggests that the remarkable diversity in domesticated dogs' body shape and size appears to also have led to human-induced adaptations in the organization of the canine brain.

Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

PubMed

Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

2016-08-09

Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Metabolomics of human brain aging and age-related neurodegenerative diseases.

PubMed

Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

2014-07-01

Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

Increased Chain Length Promotes Pneumococcal Adherence and Colonization

PubMed Central

Rodriguez, Jesse L.; Dalia, Ankur B.

2012-01-01

Streptococcus pneumoniae is a mucosal pathogen that grows in chains of variable lengths. Short-chain forms are less likely to activate complement, and as a consequence they evade opsonophagocytic clearance more effectively during invasive disease. When grown in human nasal airway surface fluid, pneumococci exhibited both short- and long-chain forms. Here, we determined whether longer chains provide an advantage during colonization when the organism is attached to the epithelial surface. Chain-forming mutants and the parental strain grown under conditions to promote chain formation showed increased adherence to human epithelial cells (A549 cells) in vitro. Additionally, adherence to A549 cells selected for longer chains within the wild-type strain. In vivo in a murine model of colonization, chain-forming mutants outcompeted the parental strain. Together, our results demonstrate that morphological heterogeneity in the pneumococcus may promote colonization of the upper respiratory tract by enhancing the ability of the organism to bind to the epithelial surface. PMID:22825449

Functional Specialization and Flexibility in Human Association Cortex

PubMed Central

Yeo, B. T. Thomas; Krienen, Fenna M.; Eickhoff, Simon B.; Yaakub, Siti N.; Fox, Peter T.; Buckner, Randy L.; Asplund, Christopher L.; Chee, Michael W.L.

2015-01-01

The association cortex supports cognitive functions enabling flexible behavior. Here, we explored the organization of human association cortex by mathematically formalizing the notion that a behavioral task engages multiple cognitive components, which are in turn supported by multiple overlapping brain regions. Application of the model to a large data set of neuroimaging experiments (N = 10 449) identified complex zones of frontal and parietal regions that ranged from being highly specialized to highly flexible. The network organization of the specialized and flexible regions was explored with an independent resting-state fMRI data set (N = 1000). Cortical regions specialized for the same components were strongly coupled, suggesting that components function as partially isolated networks. Functionally flexible regions participated in multiple components to different degrees. This heterogeneous selectivity was predicted by the connectivity between flexible and specialized regions. Functionally flexible regions might support binding or integrating specialized brain networks that, in turn, contribute to the ability to execute multiple and varied tasks. PMID:25249407

Ergatic dynamic control systems

NASA Technical Reports Server (NTRS)

Pavlov, V. V. (Editor); Drozdova, T. I. (Editor); Antomonov, Y. G. (Editor); Golego, V. N. (Editor); Ivakhnenko, A. G. (Editor); Meleshev, A. M. (Editor)

1977-01-01

Synthesis and analysis of systems containing a man in their control circuits are considered. The concepts of ergonomics and ergatic systems are defined, and tasks and problems of ergonomics are outlined. The synthesis of the structure of an astronautic ergatic organism is presented, as well as the synthesis of nonstationary ergatic systems. Problems of selecting the criteria for complex systems are considered, and the results are presented from a study of ergatic control systems with any degree of human participation.

Health concerns and hazardous waste

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

Yassi, A.; Weeks, J.; Kraut, A.

1990-01-01

This report discusses health effects of hazardous waste and emphasizes human health concerns related to establishing a hazardous waste management facility. The study reviewed world epidemiological and public health literature to identify cases of suspected or substantiated claims of public health impacts associated with hazardous waste management facilities and potential products or emissions from such facilities, and placed them into perspective, including possible routes and consequences of exposure, risk assessment, and the toxicity of selected organic and inorganic compounds.

Use of anticoagulant rodenticides in outdoor urban areas: considerations and proposals for the protection of public health and non-target species.

PubMed

Dutto, M; Di Domenico, D; Rubbiani, M

2018-01-01

Rodent control operations represent an important tool for the prevention and management of infestations, in outdoor environments, by synanthropic rodents (Rattus rattus and R. norvegicus), which are a source of economic and environmental damage with significant sanitary implications. Although the use of anticoagulants is safer to humans and pets compared to the use of acute poisoning substances, an intrinsic hazard of the active ingredients exists, i.e. the possible poisoning of non-target organisms (e.g., children, pets and wildlife) following exposure. The risks arising from the use of anticoagulants for rodent control operations in anthropic contexts can therefore only be mitigated by a proper selection of the active ingredient, bait formulation and administration techniques, since an active ingredient with selective action towards non-target species does not currently exist on the market. This document lists practical proposals aimed at reducing the possibility of toxic exposure to anticoagulant rodenticides and mitigate the toxicological risk of human baits and non-target species.

Structures and mechanisms of antitumor agents: xestoquinones uncouple cellular respiration and disrupt HIF signaling in human breast tumor cells.

PubMed

Du, Lin; Mahdi, Fakhri; Datta, Sandipan; Jekabsons, Mika B; Zhou, Yu-Dong; Nagle, Dale G

2012-09-28

The organic extract of a marine sponge, Petrosia alfiani, selectively inhibited iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in a human breast tumor T47D cell-based reporter assay. Bioassay-guided fractionation yielded seven xestoquinones (1-7) including three new compounds: 14-hydroxymethylxestoquinone (1), 15-hydroxymethylxestoquinone (2), and 14,15-dihydroxestoquinone (3). Compounds 1-7 were evaluated for their effects on HIF-1 signaling, mitochondrial respiration, and tumor cell proliferation/viability. The known metabolites adociaquinones A (5) and B (6), which possess a 3,4-dihydro-2H-1,4-thiazine-1,1-dioxide moiety, potently and selectively inhibited iron chelator-induced HIF-1 activation in T47D cells, each with an IC(50) value of 0.2 μM. Mechanistic studies revealed that adociaquinones promote oxygen consumption without affecting mitochondrial membrane potential. Compound 1 both enhances respiration and decreases mitochondrial membrane potential, suggesting that it acts as a protonophore that uncouples mitochondrial respiration.

E-Waste Driven Pollution in Pakistan: The First Evidence of Environmental and Human Exposure to Flame Retardants (FRs) in Karachi City.

PubMed

Iqbal, Mehreen; Syed, Jabir Hussain; Breivik, Knut; Chaudhry, Muhammad Jamshed Iqbal; Li, Jun; Zhang, Gan; Malik, Riffat Naseem

2017-12-05

Informal e-waste recycling activities have been shown to be a major emitter of organic flame retardants (FRs), contributing to both environmental and human exposure to laborers at e-waste recycling sites in some West African countries, as well as in China and India. The main objective of this study was to determine the levels of selected organic FRs in both air and soil samples collected from areas with intensive informal e-waste recycling activities in Karachi, Pakistan. Dechlorane Plus (DP) and "novel" brominated flame retardants (NBFRs) were often detected in high concentrations in soils, while phosphorus-based FRs (OPFRs) dominated atmospheric samples. Among individual substances and substance groups, decabromodiphenyl ether (BDE-209) (726 ng/g), decabromodiphenyl ethane (DBDPE) (551 ng/g), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) (362 ng/g), and triphenyl-phosphate (∑TPP) (296 ng/g) were found to be prevalent in soils, while OPFR congeners (5903-24986 ng/m 3 ) were prevalent in air. The two major e-waste recycling areas (Shershah and Lyari) were highly contaminated with FRs, suggesting informal e-waste recycling activities as a major emission source of FRs in the environment in Karachi City. However, the hazards associated with exposure to PM 2.5 appear to exceed those attributed to exposure to selected FRs via inhalation and soil ingestion.

Microbial Communities as Experimental Units

PubMed Central

DAY, MITCH D.; BECK, DANIEL; FOSTER, JAMES A.

2011-01-01

Artificial ecosystem selection is an experimental technique that treats microbial communities as though they were discrete units by applying selection on community-level properties. Highly diverse microbial communities associated with humans and other organisms can have significant impacts on the health of the host. It is difficult to find correlations between microbial community composition and community-associated diseases, in part because it may be impossible to define a universal and robust species concept for microbes. Microbial communities are composed of potentially thousands of unique populations that evolved in intimate contact, so it is appropriate in many situations to view the community as the unit of analysis. This perspective is supported by recent discoveries using metagenomics and pangenomics. Artificial ecosystem selection experiments can be costly, but they bring the logical rigor of biological model systems to the emerging field of microbial community analysis. PMID:21731083

Structural and ultrastructural studies of the urinary tract of mice inoculated with Lactobacillus fermentum.

PubMed

Silva de Ruiz, C; del R Rey, M; Nader-Macías, M E

2003-06-01

To assess, using structural and ultrastructural studies of the urinary tract, the effects of the intraurethral inoculation of lactobacilli (probiotic treatment) as lactobacilli are the predominant micro-organisms of the urogenital tract of humans, monkeys and mice. Previous work showed the protective effect of Lactobacillus fermentum CRL 1058 intraurethrally inoculated against the challenge of uropathogenic Escherichia coli. There was also an effect of oestrogens and antibiotics in the kinetics of colonization of both micro-organisms in mice. In the present study L. fermentum was inoculated with agarose beads (107 colony-forming units) and the number of micro-organisms determined by plating in selective media, giving a high degree of colonization in all the organs studied. The urinary tract organs were processed by histological and electron microscopy techniques standardized in our laboratory. The intraurethral inoculation of lactobacilli produced no adverse effects or significant changes in any of the organs assessed (kidney, ureter, bladder or urethra), when evaluated by histological and ultrastructural techniques. The use of lactobacilli as a probiotic treatment is probably safe.

Relationship between organic precursors and N-nitrosodimethylamine (NDMA) formation in tropical water sources.

PubMed

Qi, Wang; Fang Yee, Lim; Jiangyong, Hu

2014-12-01

The presence of organic compounds in water sources is one of the concerns in water treatment. They are potential precursors of disinfection byproducts (DBPs) and thus induce health problems in humans. Among the emerging DBPs, carcinogenic compound N-nitrosodimethylamine (NDMA) has been receiving attention during the last decade. This study examined the characteristics of organic components in various water sources and investigated their relationships with NDMA formation. Experiments were carried out on selected water samples from both natural water and wastewater. Results showed similar NDMA formation kinetics for both water sources. However, more contribution of NDMA precursors was found to be from the wastewater due to its higher organic nitrogen content. NDMA formation potential (NDMAFP) of secondary effluent ranged from 264 to 530 ng/L. A correlation study between organic compound characteristics and NDMAFP indicated that the majority of NDMA precursors came from dissolved organic nitrogen (DON) compound with small molecular weight (smaller than 500 Da), with correlation R(2) = 0.898. Although secondary treatment removed more than 90% of NDMA precursors, the remaining precursors in secondary effluent would still pose a challenge for water quality.

Selective Distance-Based K+ Quantification on Paper-Based Microfluidics.

PubMed

Gerold, Chase T; Bakker, Eric; Henry, Charles S

2018-04-03

In this study, paper-based microfluidic devices (μPADs) capable of K + quantification in aqueous samples, as well as in human serum, using both colorimetric and distance-based methods are described. A lipophilic phase containing potassium ionophore I (valinomycin) was utilized to achieve highly selective quantification of K + in the presence of Na + , Li + , and Mg 2+ ions. Successful addition of a suspended lipophilic phase to a wax printed paper-based device is described and offers a solution to current approaches that rely on organic solvents, which damage wax barriers. The approach provides an avenue for future alkali/alkaline quantification utilizing μPADs. Colorimetric spot tests allowed for K + quantification from 0.1-5.0 mM using only 3.00 μL of sample solution. Selective distance-based quantification required small sample volumes (6.00 μL) and gave responses sensitive enough to distinguish between 1.0 and 2.5 mM of sample K + . μPADs using distance-based methods were also capable of differentiating between 4.3 and 6.9 mM K + in human serum samples. Distance-based methods required no digital analysis, electronic hardware, or pumps; any steps required for quantification could be carried out using the naked eye.

Computational approach for elucidating interactions of cross-species miRNAs and their targets in Flaviviruses.

PubMed

Shinde, Santosh P; Banerjee, Amit Kumar; Arora, Neelima; Murty, U S N; Sripathi, Venkateswara Rao; Pal-Bhadra, Manika; Bhadra, Utpal

2015-03-01

Combating viral diseases has been a challenging task since time immemorial. Available molecular approaches are limited and not much effective for this daunting task. MicroRNA based therapies have shown promise in recent times. MicroRNAs are tiny non-coding RNAs that regulate translational repression of target mRNA in highly specific manner. In this study, we have determined the target regions for human and viral microRNAs in the conserved genomic regions of selected viruses of Flaviviridae family using miRanda and performed a comparative target selectivity analysis among them. Specific target regions were determined and they were compared extensively among themselves by exploring their position to determine the vicinity. Based on the multiplicity and cooperativity analysis, interaction maps were developed manually to represent the interactions between top-ranking miRNAs and genomes of the viruses considered in this study. Self-organizing map (SOM) was used to cluster the best-ranked microRNAs based on the vital physicochemical properties. This study will provide deep insight into the interrelation of the viral and human microRNAs interactions with the selected Flaviviridae genomes and will help to identify cross-species microRNA targets on the viral genome.

Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

PubMed Central

Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

2014-01-01

Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

Crystal Structures of Trypanosoma brucei Sterol 14[alpha]-Demethylase and Implications for Selective Treatment of Human Infections

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

Lepesheva, Galina I.; Park, Hee-Won; Hargrove, Tatiana Y.

2010-01-25

Sterol 14{alpha}-demethylase (14DM, the CYP51 family of cytochrome P450) is an essential enzyme in sterol biosynthesis in eukaryotes. It serves as a major drug target for fungal diseases and can potentially become a target for treatment of human infections with protozoa. Here we present 1.9 {angstrom} resolution crystal structures of 14DM from the protozoan pathogen Trypanosoma brucei, ligand-free and complexed with a strong chemically selected inhibitor N-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(5-phenyl-1,3,4-oxadi-azol-2-yl)benzamide that we previously found to produce potent antiparasitic effects in Trypanosomatidae. This is the first structure of a eukaryotic microsomal 14DM that acts on sterol biosynthesis, and it differs profoundly from that ofmore » the water-soluble CYP51 family member from Mycobacterium tuberculosis, both in organization of the active site cavity and in the substrate access channel location. Inhibitor binding does not cause large scale conformational rearrangements, yet induces unanticipated local alterations in the active site, including formation of a hydrogen bond network that connects, via the inhibitor amide group fragment, two remote functionally essential protein segments and alters the heme environment. The inhibitor binding mode provides a possible explanation for both its functionally irreversible effect on the enzyme activity and its selectivity toward the 14DM from human pathogens versus the human 14DM ortholog. The structures shed new light on 14DM functional conservation and open an excellent opportunity for directed design of novel antiparasitic drugs.« less

Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.

PubMed

Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Zhou, Qing-Hui; Pardridge, William M

2010-03-01

Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics. Copyright 2010 Elsevier B.V. All rights reserved.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex

PubMed Central

Jonas, Jacques; Gomez, Jesse; Maillard, Louis; Brissart, Hélène; Hossu, Gabriela; Jacques, Corentin; Loftus, David; Colnat-Coulbois, Sophie; Stigliani, Anthony; Barnett, Michael A.; Grill-Spector, Kalanit; Rossion, Bruno

2016-01-01

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. SIGNIFICANCE STATEMENT Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks. PMID:27511014

Selective auditory grouping by zebra finches: testing the iambic-trochaic law.

PubMed

Spierings, Michelle; Hubert, Jeroen; Ten Cate, Carel

2017-07-01

Humans have a strong tendency to spontaneously group visual or auditory stimuli together in larger patterns. One of these perceptual grouping biases is formulated as the iambic/trochaic law, where humans group successive tones alternating in pitch and intensity as trochees (high-low and loud-soft) and alternating in duration as iambs (short-long). The grouping of alternations in pitch and intensity into trochees is a human universal and is also present in one non-human animal species, rats. The perceptual grouping of sounds alternating in duration seems to be affected by native language in humans and has so far not been found among animals. In the current study, we explore to which extent these perceptual biases are present in a songbird, the zebra finch. Zebra finches were trained to discriminate between short strings of pure tones organized as iambs and as trochees. One group received tones that alternated in pitch, a second group heard tones alternating in duration, and for a third group, tones alternated in intensity. Those zebra finches that showed sustained correct discrimination were next tested with longer, ambiguous strings of alternating sounds. The zebra finches in the pitch condition categorized ambiguous strings of alternating tones as trochees, similar to humans. However, most of the zebra finches in the duration and intensity condition did not learn to discriminate between training stimuli organized as iambs and trochees. This study shows that the perceptual bias to group tones alternating in pitch as trochees is not specific to humans and rats, but may be more widespread among animals.

Microtubule organization during human parthenogenesis.

PubMed

Terada, Yukihiro; Hasegawa, Hisataka; Ugajin, Tomohisa; Murakami, Takashi; Yaegashi, Nobuo; Okamura, Kunihiro

2009-04-01

In human fertilization, the sperm centrosome plays a crucial role as a microtubule organizing center (MTOC). We studied microtubule organization during human parthenogenesis, which occurs when a human egg undergoes cleavage without a sperm centrosome. Multiple cytoplasmic asters were organized in the human oocyte after parthenogenetic activation, indicating that multiple MTOC are present in the human oocyte cytoplasm and function like a human sperm centrosome during parthenogenesis.

Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice

PubMed Central

Zhang, Yong; Zhao, Ming; Yano, Shuya; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Toneri, Makoto; Bouvet, Michael; Matsubara, Hisahiro; Tsuchiya, Hiroyuki; Hoffman, Robert M.

2015-01-01

Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5×107 CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v. treatment. Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration. PMID:25957417

A tale of two species: neural integration in zebrafish and monkeys

PubMed Central

Joshua, Mati; Lisberger, Stephen G.

2014-01-01

Selection of a model organism creates a tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called “neural integration” that occurs in the brainstems of larval zebrafish, non-human primates, and species “in between”. We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for the details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone. PMID:24797331

Conciliatory gestures promote forgiveness and reduce anger in humans.

PubMed

McCullough, Michael E; Pedersen, Eric J; Tabak, Benjamin A; Carter, Evan C

2014-07-29

Conflict is an inevitable component of social life, and natural selection has exerted strong effects on many organisms to facilitate victory in conflict and to deter conspecifics from imposing harms upon them. Like many species, humans likely possess cognitive systems whose function is to motivate revenge as a means of deterring individuals who have harmed them from harming them again in the future. However, many social relationships often retain value even after conflicts have occurred between interactants, so natural selection has very likely also endowed humans with cognitive systems whose function is to motivate reconciliation with transgressors whom they perceive as valuable and nonthreatening, notwithstanding their harmful prior actions. In a longitudinal study with 337 participants who had recently been harmed by a relationship partner, we found that conciliatory gestures (e.g., apologies, offers of compensation) were associated with increases in victims' perceptions of their transgressors' relationship value and reductions in perceptions of their transgressors' exploitation risk. In addition, conciliatory gestures appeared to accelerate forgiveness and reduce reactive anger via their intermediate effects on relationship value and exploitation risk. These results strongly suggest that conciliatory gestures facilitate forgiveness and reduce anger by modifying victims' perceptions of their transgressors' value as relationship partners and likelihood of recidivism.

γS-Crystallin Proteins from the Antarctic Nototheniid Toothfish: A Model System for Investigating Differential Resistance to Chemical and Thermal Denaturation

PubMed Central

2015-01-01

The γS1- and γS2-crystallins, structural eye lens proteins from the Antarctic toothfish (Dissostichus mawsoni), are homologues of the human lens protein γS-crystallin. Although γS1 has the higher thermal stability of the two, it is more susceptible to chemical denaturation by urea. The lower thermodynamic stability of both toothfish crystallins relative to human γS-crystallin is consistent with the current picture of how proteins from organisms endemic to perennially cold environments have achieved low-temperature functionality via greater structural flexibility. In some respects, the sequences of γS1- and γS2-crystallin are typical of psychrophilic proteins; however, their amino acid compositions also reflect their selection for a high refractive index increment. Like their counterparts in the human lens and those of mesophilic fish, both toothfish crystallins are relatively enriched in aromatic residues and methionine and exiguous in aliphatic residues. The sometimes contradictory requirements of selection for cold tolerance and high refractive index make the toothfish crystallins an excellent model system for further investigation of the biophysical properties of structural proteins. PMID:25372016

Vasoactive mediators and splanchnic perfusion.

PubMed

Reilly, P M; Bulkley, G B

1993-02-01

To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes.

PubMed

Stachecka, Joanna; Walczak, Agnieszka; Kociucka, Beata; Ruszczycki, Błażej; Wilczyński, Grzegorz; Szczerbal, Izabela

2018-02-01

Differentiation of progenitor cells into adipocytes is accompanied by remarkable changes in cell morphology, cytoskeletal organization, and gene expression profile. Mature adipocytes are filled with a large lipid droplet and the nucleus tends to move to the cell periphery. It was hypothesized that the differentiation process is also associated with changes of nuclear organization. The aim of this study was to determine the number and distribution of selected components of nuclear architecture during porcine in vitro adipogenesis. The pig is an important animal model sharing many similarities to humans at the anatomical, physiological, and genetic levels and has been recognized as a good model for human obesity. Thus, understanding how cellular structures important for fundamental nuclear processes may be altered during adipocyte differentiation is of great importance. Mesenchymal stem cells (MSCs) were derived from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) and were cultured for 7 days in the adipogenic medium. A variable differentiation potential of these cell populations towards adipogenic lineage was observed, and for further study, a comparative characteristic of the nuclear organization in BM-MSCs and AD-MSCs was performed. Nuclear substructures were visualized by indirect immunofluorescence (nucleoli, nuclear speckles, PML bodies, lamins, and HP1α) or fluorescence in situ hybridization (telomeres) on fixed cells at 0, 3, 5, and 7 days of differentiation. Comprehensive characterization of these structures, in terms of their number, size, dynamics, and arrangement in three-dimensional space of the nucleus, was performed. It was found that during differentiation of porcine MSCs into adipocytes, changes of nuclear organization occurred and concerned: (1) the nuclear size and shape; (2) reduced lamin A/C expression; and (3) reorganization of chromocenters. Other elements of nuclear architecture such as nucleoli, SC-35 nuclear speckles, and telomeres showed no significant changes when compared to undifferentiated and mature fat cells. In addition, the presence of a low number of PML bodies was characteristic of the studied porcine mesenchymal stem cell adipogenesis system. It has been shown that the arrangement of selected components of nuclear architecture was very similar in MSCs derived from different sources, whereas adipocyte differentiation involves nuclear reorganization. This study adds new data on nuclear organization during adipogenesis using the pig as a model organism.

Intrinsic frequency biases and profiles across human cortex.

PubMed

Mellem, Monika S; Wohltjen, Sophie; Gotts, Stephen J; Ghuman, Avniel Singh; Martin, Alex

2017-11-01

Recent findings in monkeys suggest that intrinsic periodic spiking activity in selective cortical areas occurs at timescales that follow a sensory or lower order-to-higher order processing hierarchy (Murray JD, Bernacchia A, Freedman DJ, Romo R, Wallis JD, Cai X, Padoa-Schioppa C, Pasternak T, Seo H, Lee D, Wang XJ. Nat Neurosci 17: 1661-1663, 2014). It has not yet been fully explored if a similar timescale hierarchy is present in humans. Additionally, these measures in the monkey studies have not addressed findings that rhythmic activity within a brain area can occur at multiple frequencies. In this study we investigate in humans if regions may be biased toward particular frequencies of intrinsic activity and if a full cortical mapping still reveals an organization that follows this hierarchy. We examined the spectral power in multiple frequency bands (0.5-150 Hz) from task-independent data using magnetoencephalography (MEG). We compared standardized power across bands to find regional frequency biases. Our results demonstrate a mix of lower and higher frequency biases across sensory and higher order regions. Thus they suggest a more complex cortical organization that does not simply follow this hierarchy. Additionally, some regions do not display a bias for a single band, and a data-driven clustering analysis reveals a regional organization with high standardized power in multiple bands. Specifically, theta and beta are both high in dorsal frontal cortex, whereas delta and gamma are high in ventral frontal cortex and temporal cortex. Occipital and parietal regions are biased more narrowly toward alpha power, and ventral temporal lobe displays specific biases toward gamma. Thus intrinsic rhythmic neural activity displays a regional organization but one that is not necessarily hierarchical. NEW & NOTEWORTHY The organization of rhythmic neural activity is not well understood. Whereas it has been postulated that rhythms are organized in a hierarchical manner across brain regions, our novel analysis allows comparison of full cortical maps across different frequency bands, which demonstrate that the rhythmic organization is more complex. Additionally, data-driven methods show that rhythms of multiple frequencies or timescales occur within a particular region and that this nonhierarchical organization is widespread. Copyright © 2017 the American Physiological Society.

Partitioning of Organic Ions to Muscle Protein: Experimental Data, Modeling, and Implications for in Vivo Distribution of Organic Ions.

PubMed

Henneberger, Luise; Goss, Kai-Uwe; Endo, Satoshi

2016-07-05

The in vivo partitioning behavior of ionogenic organic chemicals (IOCs) is of paramount importance for their toxicokinetics and bioaccumulation. Among other proteins, structural proteins including muscle proteins could be an important sorption phase for IOCs, because of their high quantity in the human and other animals' body and their polar nature. Binding data for IOCs to structural proteins are, however, severely limited. Therefore, in this study muscle protein-water partition coefficients (KMP/w) of 51 systematically selected organic anions and cations were determined experimentally. A comparison of the measured KMP/w with bovine serum albumin (BSA)-water partition coefficients showed that anionic chemicals sorb more strongly to BSA than to muscle protein (by up to 3.5 orders of magnitude), while cations sorb similarly to both proteins. Sorption isotherms of selected IOCs to muscle protein are linear (i.e., KMP/w is concentration independent), and KMP/w is only marginally influenced by pH value and salt concentration. Using the obtained data set of KMP/w a polyparameter linear free energy relationship (PP-LFER) model was established. The derived equation fits the data well (R(2) = 0.89, RMSE = 0.29). Finally, it was demonstrated that the in vitro measured KMP/w values of this study have the potential to be used to evaluate tissue-plasma partitioning of IOCs in vivo.

Chlorine dioxide is a size-selective antimicrobial agent.

PubMed

Noszticzius, Zoltán; Wittmann, Maria; Kály-Kullai, Kristóf; Beregvári, Zoltán; Kiss, István; Rosivall, László; Szegedi, János

2013-01-01

ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e.g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic.

Individual improvements and selective mortality shape lifelong migratory performance.

PubMed

Sergio, Fabrizio; Tanferna, Alessandro; De Stephanis, Renaud; Jiménez, Lidia López; Blas, Julio; Tavecchia, Giacomo; Preatoni, Damiano; Hiraldo, Fernando

2014-11-20

Billions of organisms, from bacteria to humans, migrate each year and research on their migration biology is expanding rapidly through ever more sophisticated remote sensing technologies. However, little is known about how migratory performance develops through life for any organism. To date, age variation has been almost systematically simplified into a dichotomous comparison between recently born juveniles at their first migration versus adults of unknown age. These comparisons have regularly highlighted better migratory performance by adults compared with juveniles, but it is unknown whether such variation is gradual or abrupt and whether it is driven by improvements within the individual, by selective mortality of poor performers, or both. Here we exploit the opportunity offered by long-term monitoring of individuals through Global Positioning System (GPS) satellite tracking to combine within-individual and cross-sectional data on 364 migration episodes from 92 individuals of a raptorial bird, aged 1-27 years old. We show that the development of migratory behaviour follows a consistent trajectory, more gradual and prolonged than previously appreciated, and that this is promoted by both individual improvements and selective mortality, mainly operating in early life and during the pre-breeding migration. Individuals of different age used different travelling tactics and varied in their ability to exploit tailwinds or to cope with wind drift. All individuals seemed aligned along a race with their contemporary peers, whose outcome was largely determined by the ability to depart early, affecting their subsequent recruitment, reproduction and survival. Understanding how climate change and human action can affect the migration of younger animals may be the key to managing and forecasting the declines of many threatened migrants.

Distribution of heavy metals in internal organs and tissues of Korean molluscan shellfish and potential risk to human health.

PubMed

Mok, Jong Soo; Kwon, Ji Young; Son, Kwang Tae; Choi, Woo Seok; Kim, Poong Ho; Lee, Tae Seek; Kim, Ji Hoe

2015-09-01

Molluscan shellfish (gastropods and bivalves) were collected from major fish markets on the Korean coast and analyzed for mercury by direct Hg analyzer and for other metals, such as cadmium, lead, chromium, silver, nickel, copper and zinc, using inductively coupled plasma mass spectrometry. Distribution of heavy metals in muscles, internal organs and whole tissues were determined and a potential risk assessment was conducted to evaluate their hazard for human consumption. Heavy metals were accumulated significantly higher (P < 0.05) in internal organs than in muscles for all species. The mean Cd level, which had the highest level of three hazardous metals (Cd, Pb, and Hg) in all internal-organ samples were above the regulatory limit of Korea and the mean level in whole tissue samples of the selected gastropod species, bay scallop and comb pen shell, exceeded the limit (except in a few cases). The sum of the estimated dietary intake of Cd, Pb and Hg for each part of all tested species accounted for 1.59-16.94, 0.02-0.36, and 0.07-0.16% respectively, of the provisional tolerable daily intake adopted by the Joint FAO/WHO Expert Committee on Food Additives. The hazard index for each part of gastropods and bivalves was below 1.0, however, the maximum HI for internal organs of all analysed species was quite high (0.71). These results suggest that consumption of flesh after removing the internal organs of some molluscan shellfish (all gastropod species, bay scallop and comb pen shell) is a suitable way for reducing Cd exposure.

Organization-based self-development prescriptive model for the promotion of professional development of Iranian clinical nurses.

PubMed

Rahimaghaee, Flora; Nayeri, Nahid Dehghan; Mohammadi, Eesa; Salavati, Shahram

2015-01-01

Professional development is reiterated in the new definition of modern organizations as a serious undertaking of organizations. This article aims to present and describe a prescriptive model to increase the quality of professional development of Iranian nurses within an organization-based framework. This article is an outcome of the results of a study based on grounded theory describing how Iranian nurses develop. The present study adopted purposive sampling and the initial participants were experienced clinical nurses. Then, the study continued by theoretical sampling. The present study involved 21 participants. Data were mainly collected through interviews. Analysis began with open coding and continued with axial coding and selective coding. Trustworthiness was ensured by applying Lincoln and Guba criteria such as credibility, dependability, and conformability. Based on the data gathered in the study and a thorough review of related literature, a prescriptive model has been designed by use of the methodology of Walker and Avant (2005). In this model, the first main component is a three-part structure: Reformation to establish a value-assigning structure, a position for human resource management, and a job redesigning. The second component is certain of opportunities for organization-oriented development. These strategies are as follows: Raising the sensitivity of the organization toward development, goal setting and planning the development of human resources, and improving management practices. Through this model, clinical nurses' professional development can transform the profession from an individual, randomized activity into more planned and systematized services. This model can lead to a better quality of care.

Organization-based self-development prescriptive model for the promotion of professional development of Iranian clinical nurses

PubMed Central

Rahimaghaee, Flora; Nayeri, Nahid Dehghan; Mohammadi, Eesa; Salavati, Shahram

2015-01-01

Background: Professional development is reiterated in the new definition of modern organizations as a serious undertaking of organizations. This article aims to present and describe a prescriptive model to increase the quality of professional development of Iranian nurses within an organization-based framework. Materials and Methods: This article is an outcome of the results of a study based on grounded theory describing how Iranian nurses develop. The present study adopted purposive sampling and the initial participants were experienced clinical nurses. Then, the study continued by theoretical sampling. The present study involved 21 participants. Data were mainly collected through interviews. Analysis began with open coding and continued with axial coding and selective coding. Trustworthiness was ensured by applying Lincoln and Guba criteria such as credibility, dependability, and conformability. Based on the data gathered in the study and a thorough review of related literature, a prescriptive model has been designed by use of the methodology of Walker and Avant (2005). Results: In this model, the first main component is a three-part structure: Reformation to establish a value-assigning structure, a position for human resource management, and a job redesigning. The second component is certain of opportunities for organization-oriented development. These strategies are as follows: Raising the sensitivity of the organization toward development, goal setting and planning the development of human resources, and improving management practices. Conclusions: Through this model, clinical nurses’ professional development can transform the profession from an individual, randomized activity into more planned and systematized services. This model can lead to a better quality of care. PMID:26457100

Overview of Human-Centric Space Situational Awareness (SSA) Science and Technology (S&T)

NASA Astrophysics Data System (ADS)

Ianni, J.; Aleva, D.; Ellis, S.

2012-09-01

A number of organizations, within the government, industry, and academia, are researching ways to help humans understand and react to events in space. The problem is both helped and complicated by the fact that there are numerous data sources that need to be planned (i.e., tasked), collected, processed, analyzed, and disseminated. A large part of the research is in support of the Joint Space Operational Center (JSpOC), National Air and Space Intelligence Center (NASIC), and similar organizations. Much recent research has been specifically targeting the JSpOC Mission System (JMS) which has provided a unifying software architecture. This paper will first outline areas of science and technology (S&T) related to human-centric space situational awareness (SSA) and space command and control (C2) including: 1. Object visualization - especially data fused from disparate sources. Also satellite catalog visualizations that convey the physical relationships between space objects. 2. Data visualization - improve data trend analysis as in visual analytics and interactive visualization; e.g., satellite anomaly trends over time, space weather visualization, dynamic visualizations 3. Workflow support - human-computer interfaces that encapsulate multiple computer services (i.e., algorithms, programs, applications) into a 4. Command and control - e.g., tools that support course of action (COA) development and selection, tasking for satellites and sensors, etc. 5. Collaboration - improve individuals or teams ability to work with others; e.g., video teleconferencing, shared virtual spaces, file sharing, virtual white-boards, chat, and knowledge search. 6. Hardware/facilities - e.g., optimal layouts for operations centers, ergonomic workstations, immersive displays, interaction technologies, and mobile computing. Secondly we will provide a survey of organizations working these areas and suggest where more attention may be needed. Although no detailed master plan exists for human-centric SSA and C2, we see little redundancy among the groups supporting SSA human factors at this point.

Using image processing technology and mathematical algorithm in the automatic selection of vocal cord opening and closing images from the larynx endoscopy video.

PubMed

Kuo, Chung-Feng Jeffrey; Chu, Yueng-Hsiang; Wang, Po-Chun; Lai, Chun-Yu; Chu, Wen-Lin; Leu, Yi-Shing; Wang, Hsing-Won

2013-12-01

The human larynx is an important organ for voice production and respiratory mechanisms. The vocal cord is approximated for voice production and open for breathing. The videolaryngoscope is widely used for vocal cord examination. At present, physicians usually diagnose vocal cord diseases by manually selecting the image of the vocal cord opening to the largest extent (abduction), thus maximally exposing the vocal cord lesion. On the other hand, the severity of diseases such as vocal palsy, atrophic vocal cord is largely dependent on the vocal cord closing to the smallest extent (adduction). Therefore, diseases can be assessed by the image of the vocal cord opening to the largest extent, and the seriousness of breathy voice is closely correlated to the gap between vocal cords when closing to the smallest extent. The aim of the study was to design an automatic vocal cord image selection system to improve the conventional selection process by physicians and enhance diagnosis efficiency. Also, due to the unwanted fuzzy images resulting from examination process caused by human factors as well as the non-vocal cord images, texture analysis is added in this study to measure image entropy to establish a screening and elimination system to effectively enhance the accuracy of selecting the image of the vocal cord closing to the smallest extent. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Attentional selection in visual perception, memory and action: a quest for cross-domain integration

PubMed Central

Schneider, Werner X.; Einhäuser, Wolfgang; Horstmann, Gernot

2013-01-01

For decades, the cognitive and neural sciences have benefitted greatly from a separation of mind and brain into distinct functional domains. The tremendous success of this approach notwithstanding, it is self-evident that such a view is incomplete. Goal-directed behaviour of an organism requires the joint functioning of perception, memory and sensorimotor control. A prime candidate for achieving integration across these functional domains are attentional processes. Consequently, this Theme Issue brings together studies of attentional selection from many fields, both experimental and theoretical, that are united in their quest to find overreaching integrative principles of attention between perception, memory and action. In all domains, attention is understood as combination of competition and priority control (‘bias’), with the task as a decisive driving factor to ensure coherent goal-directed behaviour and cognition. Using vision as the predominant model system for attentional selection, many studies of this Theme Issue focus special emphasis on eye movements as a selection process that is both a fundamental action and serves a key function in perception. The Theme Issue spans a wide range of methods, from measuring human behaviour in the real word to recordings of single neurons in the non-human primate brain. We firmly believe that combining such a breadth in approaches is necessary not only for attentional selection, but also to take the next decisive step in all of the cognitive and neural sciences: to understand cognition and behaviour beyond isolated domains. PMID:24018715

Signatures of selection in the Iberian honey bee (Apis mellifera iberiensis) revealed by a genome scan analysis of single nucleotide polymorphisms.

PubMed

Chávez-Galarza, Julio; Henriques, Dora; Johnston, J Spencer; Azevedo, João C; Patton, John C; Muñoz, Irene; De la Rúa, Pilar; Pinto, M Alice

2013-12-01

Understanding the genetic mechanisms of adaptive population divergence is one of the most fundamental endeavours in evolutionary biology and is becoming increasingly important as it will allow predictions about how organisms will respond to global environmental crisis. This is particularly important for the honey bee, a species of unquestionable ecological and economical importance that has been exposed to increasing human-mediated selection pressures. Here, we conducted a single nucleotide polymorphism (SNP)-based genome scan in honey bees collected across an environmental gradient in Iberia and used four FST -based outlier tests to identify genomic regions exhibiting signatures of selection. Additionally, we analysed associations between genetic and environmental data for the identification of factors that might be correlated or act as selective pressures. With these approaches, 4.4% (17 of 383) of outlier loci were cross-validated by four FST -based methods, and 8.9% (34 of 383) were cross-validated by at least three methods. Of the 34 outliers, 15 were found to be strongly associated with one or more environmental variables. Further support for selection, provided by functional genomic information, was particularly compelling for SNP outliers mapped to different genes putatively involved in the same function such as vision, xenobiotic detoxification and innate immune response. This study enabled a more rigorous consideration of selection as the underlying cause of diversity patterns in Iberian honey bees, representing an important first step towards the identification of polymorphisms implicated in local adaptation and possibly in response to recent human-mediated environmental changes. © 2013 John Wiley & Sons Ltd.

Action semantics: A unifying conceptual framework for the selective use of multimodal and modality-specific object knowledge.

PubMed

van Elk, Michiel; van Schie, Hein; Bekkering, Harold

2014-06-01

Our capacity to use tools and objects is often considered one of the hallmarks of the human species. Many objects greatly extend our bodily capabilities to act in the physical world, such as when using a hammer or a saw. In addition, humans have the remarkable capability to use objects in a flexible fashion and to combine multiple objects in complex actions. We prepare coffee, cook dinner and drive our car. In this review we propose that humans have developed declarative and procedural knowledge, i.e. action semantics that enables us to use objects in a meaningful way. A state-of-the-art review of research on object use is provided, involving behavioral, developmental, neuropsychological and neuroimaging studies. We show that research in each of these domains is characterized by similar discussions regarding (1) the role of object affordances, (2) the relation between goals and means in object use and (3) the functional and neural organization of action semantics. We propose a novel conceptual framework of action semantics to address these issues and to integrate the previous findings. We argue that action semantics entails both multimodal object representations and modality-specific sub-systems, involving manipulation knowledge, functional knowledge and representations of the sensory and proprioceptive consequences of object use. Furthermore, we argue that action semantics are hierarchically organized and selectively activated and used depending on the action intention of the actor and the current task context. Our framework presents an integrative account of multiple findings and perspectives on object use that may guide future studies in this interdisciplinary domain. Copyright © 2013 Elsevier B.V. All rights reserved.

Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species.

PubMed

Contreras, Vanessa; Urien, Céline; Guiton, Rachel; Alexandre, Yannick; Vu Manh, Thien-Phong; Andrieu, Thibault; Crozat, Karine; Jouneau, Luc; Bertho, Nicolas; Epardaud, Mathieu; Hope, Jayne; Savina, Ariel; Amigorena, Sebastian; Bonneau, Michel; Dalod, Marc; Schwartz-Cornil, Isabelle

2010-09-15

The mouse lymphoid organ-resident CD8alpha(+) dendritic cell (DC) subset is specialized in Ag presentation to CD8(+) T cells. Recent evidence shows that mouse nonlymphoid tissue CD103(+) DCs and human blood DC Ag 3(+) DCs share similarities with CD8alpha(+) DCs. We address here whether the organization of DC subsets is conserved across mammals in terms of gene expression signatures, phenotypic characteristics, and functional specialization, independently of the tissue of origin. We study the DC subsets that migrate from the skin in the ovine species that, like all domestic animals, belongs to the Laurasiatheria, a distinct phylogenetic clade from the supraprimates (human/mouse). We demonstrate that the minor sheep CD26(+) skin lymph DC subset shares significant transcriptomic similarities with mouse CD8alpha(+) and human blood DC Ag 3(+) DCs. This allowed the identification of a common set of phenotypic characteristics for CD8alpha-like DCs in the three mammalian species (i.e., SIRP(lo), CADM1(hi), CLEC9A(hi), CD205(hi), XCR1(hi)). Compared to CD26(-) DCs, the sheep CD26(+) DCs show 1) potent stimulation of allogeneic naive CD8(+) T cells with high selective induction of the Ifngamma and Il22 genes; 2) dominant efficacy in activating specific CD8(+) T cells against exogenous soluble Ag; and 3) selective expression of functional pathways associated with high capacity for Ag cross-presentation. Our results unravel a unifying definition of the CD8alpha(+)-like DCs across mammalian species and identify molecular candidates that could be used for the design of vaccines applying to mammals in general.

EXOMARS IRAS (DOSE) radiation measurements.

NASA Astrophysics Data System (ADS)

Federico, C.; Di Lellis, A. M.; Fonte, S.; Pauselli, C.; Reitz, G.; Beaujean, R.

The characterization and the study of the radiations on their interaction with organic matter is of great interest in view of the human exploration on Mars. The Ionizing RAdiation Sensor (IRAS) selected in the frame of the ExoMars/Pasteur ESA mission is a lightweight particle spectrometer combining various techniques of radiation detection in space. It characterizes the first time the radiation environment on the Mars surface, and provide dose and dose equivalent rates as precursor information absolutely necessary to develop ways to mitigate the radiation risks for future human exploration on Mars. The Martian radiation levels are much higher than those found on Earth and they are relatively low for space. Measurements on the surface will show if they are similar or not to those seen in orbit (modified by the presence of ``albedo'' neutrons produced in the regolith and by the thin Martian atmosphere). IRAS consists of a telescope based on segmented silicon detectors of about 40\\userk\\milli\\metre\\user;k diameter and 300\\user;k\\micro\\metre\\user;k thickness, a segmented organic scintillator, and of a thermoluminescence dosimeter. The telescope will continuously monitor temporal variation of the particle count rate, the dose rate, particle and LET (Linear Energy Transfer) spectra. Tissue equivalent BC430 scintillator material will be used to measure the neutron dose. Neutrons are selected by a criteria requiring no signal in the anti-coincidence. Last, the passive thermoluminescence dosimeter, based on LiF:Mg detectors, regardless the on board operation timing, will measure the total dose accumulated during the exposure period and due to beta and gamma radiation, with a responsivity very close to that of a human tissue.

Natural and Human Influences on Water Quality in a Shallow Regional Unconsolidated Aquifer, Northern Atlantic Coastal Plain

USGS Publications Warehouse

Ator, Scott W.

2008-01-01

Data collected from more than 400 wells in the surficial unconfined aquifer in the Northern Atlantic Coastal Plain (New York through North Carolina) were compiled and analyzed to improve understanding of multiple natural and human influences on water quality in such shallow regional aquifers. Geochemical patterns were identified and described through principal components analysis on major ions, and correlation and logistic regression were used to relate observed concentrations of nitrate and selected pesticide compounds (atrazine, metolachlor, simazine, and deethylatrazine, an atrazine degradate) and volatile organic compounds (chloroform, 1,1,1-trichloroethane, tetrachlorethene, and methyl tert-butyl ether) to likely influences, such as observed geochemical patterns, land use, hydrogeology, and soils. Variability in major-ion concentrations is primarily related to ionic strength and redox condition. Concentrations of nitrate, pesticides, and volatile organic compounds are related to natural conditions, as well as the distribution of likely sources reflected in land use. Nitrate is most common in aerobic ground water and in relatively well-drained areas, for example; concentrations greater than 0.4 milligrams per liter may result from a variety of human activities, although concentrations greater than 3 milligrams per liter are more likely in agricultural areas. Atrazine, deethylatrazine, and metolachlor also are related to geochemical patterns, likely because ground-water geochemistry reflects hydrogeologic and soil conditions affecting pesticide transport to the water table. Results demonstrate the value of geochemical information along with the distribution of sources and other influences to understanding the regional occurrence of selected compounds in ground water. Such influences are not unique to the Northern Atlantic Coastal Plain, and thus observations and interpretations are relevant to broader areas.

National Nutrition Policy Study--1974. Hearings Before the Select Committee on Nutrition and Human Needs of the United States Senate Ninety-third Congress, Second Session. Part 4A--Appendix to Nutrition and Food Availability. Hearings Held Washington, D. C., June 20, 1974.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Nutrition and Human Needs.

These hearings on nutrition and food availability are comprised of the testimony of a number of experts and representatives of such organizations as the State of Washington Food and Nutrition Council; National Livestock and Meat Board; Bakery and Confectionery Workers' Union of America; Self Help and Rural Economic Support Inc.; North American…

Better Health for Our Children: A National Strategy. The Report of the Select Panel for the Promotion of Child Health to the United States Congress and the Secretary of Health and Human Services. Executive Summary.

ERIC Educational Resources Information Center

Public Health Service (DHEW), Rockville, MD.

This executive summary presents specific proposals to improve maternal and child health conditions in the United States. Contents of the summary are organized in 13 chapters. Five overriding concerns in the areas of health and health care are identified in Chapter One. Chapter Two focuses on the reduction of environmental risks; Chapter Three…

Coordination Mechanism in Fast Human Movements - Experimental and Modelling Studies. Volume 2.

DTIC Science & Technology

1982-02-01

1962. 11. Berger, R. "The Effects of Selected Progressive Resistance Exercise Programs on Strength, Hyper- tropny, and Strength Decrement." Master’s...Mathews, D.K. "Strength and Endurance (Conditioning) Effects of Exhaustive Exercise of the Elbow Flexor Muscles." Journal of the Association for Physical...13, 15, 19) the purpose of this study was to examine the effects of the TVR on the muscle spindle, not the Golgi tendon organ. Vibration at the

Selected elements and organic chemicals in streambed sediment in the Salem area, Oregon, 1999

USGS Publications Warehouse

Tanner, Dwight Q.

2002-09-13

The high levels of contaminants in some Salem area streams indicates the need for further study to assess the biological effects of these contaminants. Future monitoring in the Salem area could include bioassays using benthic invertebrates and the measurement of organochlorine compounds, including DDT, DDE, DDD, and dieldrin in fish tissue. Because resident fish may be consumed by humans and wildlife, fish tissue analyses would be helpful to determine the health risk associated with fish consumption.

Employee engagement: a prescription for organizational transformation.

PubMed

Halm, Barry

2011-01-01

Ivanitskaya, Glazer, and Erofeev (2009) suggest that "the most fundamental element of any organization that helps the organization to survive is the individual person" (p. 109). It is the motivation of human capital that makes a health-care organization come to life. Health-care is a unique industry; its accomplishments are directly dependent upon the competencies and technical skills of its employees. "When people in the workplace fulfill their organizational roles, then the organization thrives" (Ivanitskaya et al., 2009, p. 110). Health-care systems will require organizations that thrive and exhibit characteristics of continuous growth, expressing excessive levels of energy and an immense capacity for flourishing. Anticipating the challenges of the next decade, health-care organizations must achieve a higher degree of employee engagement to enhance organizational performance and profitability. The data analyzed for this chapter indicate that employees who are engaged are more enthusiastic and aspired to achieve both individual and organizational success. The chapter concludes by suggesting five operating practices to establish an employee engagement culture--defining the employee's role in fulfilling the organization's purpose, selecting employees with capability and passion, supporting and valuing the employee, creating sustainable reward systems, and developing feedback and reinforcement mechanisms.

Antimicrobial activity of an aspartic protease from Salpichroa origanifolia fruits.

PubMed

Díaz, M E; Rocha, G F; Kise, F; Rosso, A M; Guevara, M G; Parisi, M G

2018-05-08

Plant proteases play a fundamental role in several processes like growth, development and in response to biotic and abiotic stress. In particular, aspartic proteases (AP) are expressed in different plant organs and have antimicrobial activity. Previously, we purified an AP from Salpichroa origanifolia fruits called salpichroin. The aim of this work was to determine the cytotoxic activity of this enzyme on selected plant and human pathogens. For this purpose, the growth of the selected pathogens was analysed after exposure to different concentrations of salpichroin. The results showed that the enzyme was capable of inhibiting Fusarium solani and Staphylococcus aureus in a dose-dependent manner. It was determined that 1·2 μmol l -1 of salpichroin was necessary to inhibit 50% of conidial germination, and the minimal bactericidal concentration was between 1·9 and 2·5 μmol l -1 . Using SYTOX Green dye we were able to demonstrate that salpichroin cause membrane permeabilization. Moreover, the enzyme treated with its specific inhibitor pepstatin A did not lose its antibacterial activity. This finding demonstrates that the cytotoxic activity of salpichroin is due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of the AP could represent a potential alternative for the control of pathogens that affect humans or crops of economic interest. This study provides insights into the antimicrobial activity of an aspartic protease isolated from Salpichroa origanifolia fruits on plant and human pathogens. The proteinase inhibited Fusarium solani and Staphylococcus aureus in a dose-dependent manner due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of salpichroin suggests its potential applications as an important tool for the control of pathogenic micro-organisms affecting humans and crops of economic interest. Therefore, it would represent a new alternative to avoid the problems of environmental pollution and antimicrobial resistance. © 2018 The Society for Applied Microbiology.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

PubMed

Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

2009-03-11

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

49 CFR 604.7 - Qualified human service organizations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Qualified human service organizations. 604.7... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CHARTER SERVICE Exceptions § 604.7 Qualified human service organizations. (a) A recipient may provide charter service to a qualified human service organization (QHSO) for...

49 CFR 604.7 - Qualified human service organizations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Qualified human service organizations. 604.7... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CHARTER SERVICE Exceptions § 604.7 Qualified human service organizations. (a) A recipient may provide charter service to a qualified human service organization (QHSO) for...

49 CFR 604.7 - Qualified human service organizations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Qualified human service organizations. 604.7... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CHARTER SERVICE Exceptions § 604.7 Qualified human service organizations. (a) A recipient may provide charter service to a qualified human service organization (QHSO) for...

49 CFR 604.7 - Qualified human service organizations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Qualified human service organizations. 604.7... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CHARTER SERVICE Exceptions § 604.7 Qualified human service organizations. (a) A recipient may provide charter service to a qualified human service organization (QHSO) for...

Biological preservation of plant derived animal feed with antifungal microorganisms: safety and formulation aspects.

PubMed

Melin, Petter; Sundh, Ingvar; Håkansson, Sebastian; Schnürer, Johan

2007-08-01

During storage of moist animal feed, growth of detrimental fungi causing spoilage, or being mycotoxigenic or pathogenic, is a severe problem. Addition of biopreservative yeasts or lactic acid bacteria can significantly reduce this problem. However, their use requires several careful considerations. One is the safety to the animal, humans and the environment, tightly connected to legal aspects and the need for pre-market authorisation when supplementing feed with microorganisms. Although both yeasts and lactic acid bacteria are considered comparatively safe organisms due to low production of toxic metabolites, it is of great importance to understand the mechanisms behind the biopreservative abilities. Another important issue concerns practical aspects, such as the economic production of large amounts of the organisms and the development of a suitable formulation giving the organisms a long shelf life. These aspects are discussed and a recommendation of this review is that both safety and formulation aspects of a specific microbe should be considered at an early stage in the selection of new organisms with biopreservation potential.

Nontargeted metabolite profiles and sensory properties of strawberry cultivars grown both organically and conventionally.

PubMed

Kårlund, Anna; Hanhineva, Kati; Lehtonen, Marko; Karjalainen, Reijo O; Sandell, Mari

2015-01-28

Strawberry (Fragaria × ananassa Duch.) contains many secondary metabolites potentially beneficial for human health, and several of these compounds contribute to strawberry sensory properties, as well. In this study, three strawberry cultivars grown both conventionally and organically were subjected to nontargeted metabolite profiling analysis with LC-qTOF-ESI-MS and to descriptive sensory evaluation by a trained panel. Combined metabolome and sensory data (PLS model) revealed that 79% variation in the metabolome explained 88% variation in the sensory profiles. Flavonoids and condensed and hydrolyzable tannins determined the orosensory properties, and fatty acids contributed to the odor attributes of strawberry. Overall, the results indicated that the chemical composition and sensory quality of strawberries grown in different cultivation systems vary mostly according to cultivar. Organic farming practices may enhance the accumulation of some plant metabolites in specific strawberry genotypes. Careful cultivar selection is a key factor for the improvement of nutritional quality and marketing value of organic strawberries.

Specification of functional cranial placode derivatives from human pluripotent stem cells.

PubMed

Dincer, Zehra; Piao, Jinghua; Niu, Lei; Ganat, Yosif; Kriks, Sonja; Zimmer, Bastian; Shi, Song-Hai; Tabar, Viviane; Studer, Lorenz

2013-12-12

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

YamiPred: A Novel Evolutionary Method for Predicting Pre-miRNAs and Selecting Relevant Features.

PubMed

Kleftogiannis, Dimitrios; Theofilatos, Konstantinos; Likothanassis, Spiros; Mavroudi, Seferina

2015-01-01

MicroRNAs (miRNAs) are small non-coding RNAs, which play a significant role in gene regulation. Predicting miRNA genes is a challenging bioinformatics problem and existing experimental and computational methods fail to deal with it effectively. We developed YamiPred, an embedded classification method that combines the efficiency and robustness of support vector machines (SVM) with genetic algorithms (GA) for feature selection and parameters optimization. YamiPred was tested in a new and realistic human dataset and was compared with state-of-the-art computational intelligence approaches and the prevalent SVM-based tools for miRNA prediction. Experimental results indicate that YamiPred outperforms existing approaches in terms of accuracy and of geometric mean of sensitivity and specificity. The embedded feature selection component selects a compact feature subset that contributes to the performance optimization. Further experimentation with this minimal feature subset has achieved very high classification performance and revealed the minimum number of samples required for developing a robust predictor. YamiPred also confirmed the important role of commonly used features such as entropy and enthalpy, and uncovered the significance of newly introduced features, such as %A-U aggregate nucleotide frequency and positional entropy. The best model trained on human data has successfully predicted pre-miRNAs to other organisms including the category of viruses.

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity.

PubMed

Amacher, David E

2010-05-15

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other "omics" technologies can provide added selectivity and sensitivity in preclinical drug safety testing.

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

Amacher, David E.

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intendedmore » human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other 'omics' technologies can provide added selectivity and sensitivity in preclinical drug safety testing.« less

Characterize Behaviour of Emerging Pollutants in Artificial Recharge: Column Experiments - Experiment Design and Results of Preliminary Tests

NASA Astrophysics Data System (ADS)

Wang, H.; Carrera, J.; Ayora, C.; Licha, T.

2012-04-01

Emerging pollutants (EPs) have been detected in water resources as a result of human activities in recent years. They include pharmaceuticals, personal care products, dioxins, flame retardants, etc. They are a source of concern because many of them are resistant to conventional water treatment, and they are harmful to human health, even in low concentrations. Generally, this study aims to characterize the behaviour of emerging pollutants in reclaimed water in column experiments which simulates artificial recharge. One column set includes three parts: influent, reactive layer column (RLC) and aquifer column (AC). The main influent is decided to be Secondary Effluent (SE) of El Prat Wastewater Treatment Plant, Barcelona. The flow rate of the column experiment is 0.9-1.5 mL/min. the residence time of RLC is designed to be about 1 day and 30-40 days for AC. Both columns are made of stainless steel. Reactive layer column (DI 10cm * L55cm) is named after the filling material which is a mixture of organic substrate, clay and goethite. One purpose of the application of the mixture is to increase dissolve organic carbon (DOC). Leaching test in batchs and columns has been done to select proper organic substrate. As a result, compost was selected due to its long lasting of releasing organic matter (OM). The other purpose of the application of the mixture is to enhance adsorption of EPs. Partition coefficients (Kow) of EPs indicate the ability of adsorption to OM. EPs with logKow>2 could be adsorbed to OM, like Ibuprofen, Bezafibrate and Diclofenac. Moreover, some of EPs are charged in the solution with pH=7, according to its acid dissociation constant (Ka). Positively charged EPs, for example Atenolol, could adsorb to clay. In the opposite, negatively charged EPs, for example Gemfibrozil, could adsorb to goethite. Aquifer column (DI 35cm * L1.5m) is to simulate the processes taking place in aquifer in artificial recharge. The filling of AC has two parts: silica sand and compost. The grain size of the sand is about 0.5mm. Aquifer deposits usually contain some natural organic matter. Therefore, compost (<1mm) was selected to be mixed with sand with the ratio of 1:99. Long residence time of AC and high concentration of DOC are favourable to generate variable redox states, which favour EPs degradation.

Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition

PubMed Central

Norman-Haignere, Sam

2015-01-01

SUMMARY The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles (“components”) whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech. PMID:26687225

Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition.

PubMed

Norman-Haignere, Sam; Kanwisher, Nancy G; McDermott, Josh H

2015-12-16

The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles ("components") whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech. Copyright © 2015 Elsevier Inc. All rights reserved.

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition

PubMed Central

Stutz, Aaron J.

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment. PMID:25136323

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition.

PubMed

Stutz, Aaron J

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment.

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

Yang, Chung S., E-mail: csyang@rci.rutgers.edu; Lambert, Joshua D.; Ju Jihyeung

Tea made from the leaves of the plant Camellia sinensis is a popular beverage. The possible cancer-preventive activity of tea and tea polyphenols has been studied extensively. This article briefly reviews studies in animal models, cell lines, and possible relevance of these studies to the prevention of human cancer. The cancer-preventive activity of tea constituents have been demonstrated in many animal models including cancer of the skin, lung, oral cavity, esophagus, stomach, liver, pancreas, small intestine, colon, bladder, prostate, and mammary gland. The major active constituents are polyphenols, of which (-)-epigallocatechin-3-gallate (EGCG) is most abundant, most active, and most studied,more » and caffeine. The molecular mechanisms of the cancer-preventive action, however, are just beginning to be understood. Studies in cell lines led to the proposal of many mechanisms on the action of EGCG. However, mechanisms based on studies with very high concentrations of EGCG may not be relevant to cancer prevention in vivo. The autooxidation of EGCG in cell culture may also produce activities that do not occur in many internal organs. In contrast to the cancer prevention activity demonstrated in different animal models, no such conclusion can be convincingly drawn from epidemiological studies on tea consumption and human cancers. Even though the human data are inconclusive, tea constituents may still be used for the prevention of cancer at selected organ sites if sufficient concentrations of the agent can be delivered to these organs. Some interesting examples in this area are discussed.« less

Role of chromatography in the development of Standard Reference Materials for organic analysis.

PubMed

Wise, Stephen A; Phinney, Karen W; Sander, Lane C; Schantz, Michele M

2012-10-26

The certification of chemical constituents in natural-matrix Standard Reference Materials (SRMs) at the National Institute of Standards and Technology (NIST) can require the use of two or more independent analytical methods. The independence among the methods is generally achieved by taking advantage of differences in extraction, separation, and detection selectivity. This review describes the development of the independent analytical methods approach at NIST, and its implementation in the measurement of organic constituents such as contaminants in environmental materials, nutrients and marker compounds in food and dietary supplement matrices, and health diagnostic and nutritional assessment markers in human serum. The focus of this review is the important and critical role that separation science techniques play in achieving the necessary independence of the analytical steps in the measurement of trace-level organic constituents in natural matrix SRMs. Published by Elsevier B.V.

Feed-forward transcriptional programming by nuclear receptors: regulatory principles and therapeutic implications.

PubMed

Sasse, Sarah K; Gerber, Anthony N

2015-01-01

Nuclear receptors (NRs) are widely targeted to treat a range of human diseases. Feed-forward loops are an ancient mechanism through which single cell organisms organize transcriptional programming and modulate gene expression dynamics, but they have not been systematically studied as a regulatory paradigm for NR-mediated transcriptional responses. Here, we provide an overview of the basic properties of feed-forward loops as predicted by mathematical models and validated experimentally in single cell organisms. We review existing evidence implicating feed-forward loops as important in controlling clinically relevant transcriptional responses to estrogens, progestins, and glucocorticoids, among other NR ligands. We propose that feed-forward transcriptional circuits are a major mechanism through which NRs integrate signals, exert temporal control over gene regulation, and compartmentalize client transcriptomes into discrete subunits. Implications for the design and function of novel selective NR ligands are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

An effective method for the quantitative detection of porcine endogenous retrovirus in pig tissues.

PubMed

Zhang, Peng; Yu, Ping; Wang, Wei; Zhang, Li; Li, Shengfu; Bu, Hong

2010-05-01

Xenotransplantation shows great promise for providing a virtually limitless supply of cells, tissues, and organs for a variety of therapeutical procedures. However, the potential of porcine endogenous retrovirus (PERV) as a human-tropic pathogen, particularly as a public health risk, is a major concern for xenotransplantation. This study focus on the detection of copy number in various tissues and organs in Banna Minipig Inbreed (BMI) from 2006 to 2007 in West China Hospital, Sichuan University. Real-time quantitative polymerase chain reaction (SYBR Green I) was performed in this study. The results showed that the pol gene had the most copy number in tissues compared with gag, envA, and envB. Our experiment will offer a rapid and accurate method for the detection of the copy number in various tissues and was especially suitable for the selection of tissues or organs in future clinical xenotransplantation.

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

PubMed

Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

2016-09-01

Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

Prevalence of infectious diseases in feral cats in Northern Florida.

PubMed

Luria, Brian J; Levy, Julie K; Lappin, Michael R; Breitschwerdt, Edward B; Legendre, Alfred M; Hernandez, Jorge A; Gorman, Shawn P; Lee, Irene T

2004-10-01

Objectives of this study were to determine prevalence of infection in feral cats in Northern Florida with a select group of infectious organisms and to determine risk factors for infection. Blood samples or sera from 553 cats were tested with a panel of antibody, antigen or PCR assays. Male cats were at higher risk for FIV, Mycoplasma haemofelis, and M. haemominutum. Infection with either FeLV or FIV was associated with increased risk for coinfection with the other retrovirus, M. haemofelis, or M. haemominutum. Bartonella henselae had the highest prevalence and was the only organism that did not have any associated risk for coinfection with other organisms. Feral cats in this study had similar or lower prevalence rates of infections than those published for pet cats in the United States. Thus, feral cats assessed in this study appear to be of no greater risk to human beings or other cats than pet cats.

A Compendium of Canine Normal Tissue Gene Expression

PubMed Central

Chen, Qing-Rong; Wen, Xinyu; Khan, Javed; Khanna, Chand

2011-01-01

Background Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. Methodology/Principal Findings The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. Conclusions/Significance These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large. PMID:21655323

The neuropeptide galanin is a novel inhibitor of human hair growth.

PubMed

Holub, B S; Kloepper, J E; Tóth, B I; Bíro, T; Kofler, B; Paus, R

2012-07-01

Galanin is a trophic factor of the central and peripheral nervous system that shows widespread distribution in human skin. However, the exact localization and the role of galanin in the hair follicle (HF) remain to be clarified. To characterize galanin expression in human scalp HFs and to examine the effects of galanin on normal human scalp HF growth in organ culture. Immunohistochemistry was performed on cryosections of human female scalp skin. Anagen HFs were microdissected and cultured up to 9 days and treated with 100 nmol L(-1) galanin. Staining for Ki-67, TUNEL and Masson-Fontana were used to analyse proliferation, apoptosis and hair cycle staging of the HFs. Functional effects of galanin were tested in serum-free HF organ culture. Galanin-like immunoreactivity was detected in the outer root sheath (ORS) and inner root sheath. Additionally, galanin mRNA was detected in ORS keratinocytes and all HF samples tested. Galanin receptor transcripts (GalR2, GalR3) were also detected in selected samples. Galanin reduced proliferation of hair matrix keratinocytes in situ compared with vehicle-treated controls, shortened the hair growth phase (anagen) in vitro and reduced hair shaft elongation. This was accompanied by the premature development of a catagen-like morphology of galanin-treated HFs. We present the first evidence that human HFs are both a source and a functionally relevant target of galanin. Due to its hair growth-inhibitory properties in vitro, galanin application deserves further exploration as a potential new treatment strategy for unwanted hair growth (hirsutism, hypertrichosis). © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions.

PubMed

Nishizawa, M; Nishizawa, K

2000-10-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the 'between gene' GC content heterogeneity, which is linked to 'isochores', is a principal factor associated with the bias in substitution patterns in human, 'within gene' heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed.

Amino acid and nucleotide recurrence in aligned sequences: synonymous substitution patterns in association with global and local base compositions

PubMed Central

Nishizawa, Manami; Nishizawa, Kazuhisa

2000-01-01

The tendency for repetitiveness of nucleotides in DNA sequences has been reported for a variety of organisms. We show that the tendency for repetitive use of amino acids is widespread and is observed even for segments conserved between human and Drosophila melanogaster at the level of >50% amino acid identity. This indicates that repetitiveness influences not only the weakly constrained segments but also those sequence segments conserved among phyla. Not only glutamine (Q) but also many of the 20 amino acids show a comparable level of repetitiveness. Repetitiveness in bases at codon position 3 is stronger for human than for D.melanogaster, whereas local repetitiveness in intron sequences is similar between the two organisms. While genes for immune system-specific proteins, but not ancient human genes (i.e. human homologs of Escherichia coli genes), have repetitiveness at codon bases 1 and 2, repetitiveness at codon base 3 for these groups is similar, suggesting that the human genome has at least two mechanisms generating local repetitiveness. Neither amino acid nor nucleotide repetitiveness is observed beyond the exon boundary, denying the possibility that such repetitiveness could mainly stem from natural selection on mRNA or protein sequences. Analyses of mammalian sequence alignments show that while the ‘between gene’ GC content heterogeneity, which is linked to ‘isochores’, is a principal factor associated with the bias in substitution patterns in human, ‘within gene’ heterogeneity in nucleotide composition is also associated with such bias on a more local scale. The relationship amongst the various types of repetitiveness is discussed. PMID:11000273

Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor

PubMed Central

Liedtke, Wolfgang; Choe, Yong; Martí-Renom, Marc A.; Bell, Andrea M.; Denis, Charlotte S.; Šali, Andrej; Hudspeth, A. J.; Friedman, Jeffrey M.; Heller, Stefan

2008-01-01

SUMMARY The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nevous system, the channel is expressed neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells. PMID:11081638

Persistent organic pollutants in selected fishes of the Gulf of Finland

NASA Astrophysics Data System (ADS)

Järv, Leili; Kiviranta, Hannu; Koponen, Jani; Rantakokko, Panu; Ruokojärvi, Päivi; Radin, Maia; Raid, Tiit; Roots, Ott; Simm, Mart

2017-07-01

Fish samples of Baltic herring, sprat, flounder, perch, salmon, and river lamprey were collected from the Gulf of Finland in 2013 and 2014 with the aim to get an overview of the occurrence of pollutants in fish caught in Estonian waters. The content of non-dioxin-like polychlorinated biphenyls (ndl PCBs), polybrominated diphenyl ethers (PBDEs), organic tin (OT) and perfluorocompounds (PFAS) are examined and discussed in the study. The results revealed that potentially higher content of organo-tin compounds, perfluorocompounds and polybrominated diphenyl ethers in Baltic herring, salmon and river lamprey may cause concern regarding human exposure. It is important to link pollutant content to lipid content of fish taking into account their seasonal variation in different age classes.

Gas Separation Using Organic-Vapor-Resistent Membranes In Conjunctin With Organic-Vapor-Selective Membranes

DOEpatents

Baker, Richard W.; Pinnau, Ingo; He, Zhenjie; Da Costa, Andre R.; Daniels, Ramin; Amo, Karl D.; Wijmans, Johannes G.

2003-06-03

A process for treating a gas mixture containing at least an organic compound gas or vapor and a second gas, such as natural gas, refinery off-gas or air. The process uses two sequential membrane separation steps, one using membrane selective for the organic compound over the second gas, the other selective for the second gas over the organic vapor. The second-gas-selective membranes use a selective layer made from a polymer having repeating units of a fluorinated polymer, and demonstrate good resistance to plasticization by the organic components in the gas mixture under treatment, and good recovery after exposure to liquid aromatic hydrocarbons. The membrane steps can be combined in either order.

New copper(I) complexes bearing lomefloxacin motif: Spectroscopic properties, in vitro cytotoxicity and interactions with DNA and human serum albumin.

PubMed

Komarnicka, Urszula K; Starosta, Radosław; Kyzioł, Agnieszka; Płotek, Michał; Puchalska, Małgorzata; Jeżowska-Bojczuk, Małgorzata

2016-12-01

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar-phosphate backbone of plasmid DNA. The addition of H 2 O 2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of food, nutrition and functional substances, in the selected food materials for space agriculture

NASA Astrophysics Data System (ADS)

Tomita-Yokotani, Kaori; Kimura, Yasuko; Yamashita, Masamichi; Kimura, Shunta; Sato, Seigo; Katoh, Hiroshi

2016-07-01

We have been studying the evaluation of food, nutrition and functional substances, in the selected organic materials for useful life-support systems in closed bio-ecosystems for space agriculture on Mars in the future. We have already proposed several species as food materials; cyanobacterium, Nostoc sp. HK-01 and the Japanese cherry tree. Nostoc sp. HK-01 is a terrestrial cyanobacterium which has high tolerances to several space environments. In addition to its high tolerances to serious environments, HK-01 has a high protein content. Total protein per 100 g of the dried colony of Nostoc sp. HK-01 was approximately 50 g. Woody plant materials also have several properties which can be utilized in our habitation environment and as food. We have already found abilities to produce important functional substances for humans in the selected trees. Here, we show the extended results of our experiments.

Biomimetic virus-based colourimetric sensors.

PubMed

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

Biomimetic virus-based colourimetric sensors

NASA Astrophysics Data System (ADS)

Oh, Jin-Woo; Chung, Woo-Jae; Heo, Kwang; Jin, Hyo-Eon; Lee, Byung Yang; Wang, Eddie; Zueger, Chris; Wong, Winnie; Meyer, Joel; Kim, Chuntae; Lee, So-Young; Kim, Won-Geun; Zemla, Marcin; Auer, Manfred; Hexemer, Alexander; Lee, Seung-Wuk

2014-01-01

Many materials in nature change colours in response to stimuli, making them attractive for use as sensor platform. However, both natural materials and their synthetic analogues lack selectivity towards specific chemicals, and introducing such selectivity remains a challenge. Here we report the self-assembly of genetically engineered viruses (M13 phage) into target-specific, colourimetric biosensors. The sensors are composed of phage-bundle nanostructures and exhibit viewing-angle independent colour, similar to collagen structures in turkey skin. On exposure to various volatile organic chemicals, the structures rapidly swell and undergo distinct colour changes. Furthermore, sensors composed of phage displaying trinitrotoluene (TNT)-binding peptide motifs identified from a phage display selectively distinguish TNT down to 300 p.p.b. over similarly structured chemicals. Our tunable, colourimetric sensors can be useful for the detection of a variety of harmful toxicants and pathogens to protect human health and national security.

A Framework for Assessing Uncertainty Associated with Human Health Risks from MSW Landfill Leachate Contamination.

PubMed

Mishra, Harshit; Karmakar, Subhankar; Kumar, Rakesh; Singh, Jitendra

2017-07-01

Landfilling is a cost-effective method, which makes it a widely used practice around the world, especially in developing countries. However, because of the improper management of landfills, high leachate leakage can have adverse impacts on soils, plants, groundwater, aquatic organisms, and, subsequently, human health. A comprehensive survey of the literature finds that the probabilistic quantification of uncertainty based on estimations of the human health risks due to landfill leachate contamination has rarely been reported. Hence, in the present study, the uncertainty about the human health risks from municipal solid waste landfill leachate contamination to children and adults was quantified to investigate its long-term risks by using a Monte Carlo simulation framework for selected heavy metals. The Turbhe sanitary landfill of Navi Mumbai, India, which was commissioned in the recent past, was selected to understand the fate and transport of heavy metals in leachate. A large residential area is located near the site, which makes the risk assessment problem both crucial and challenging. In this article, an integral approach in the form of a framework has been proposed to quantify the uncertainty that is intrinsic to human health risk estimation. A set of nonparametric cubic splines was fitted to identify the nonlinear seasonal trend in leachate quality parameters. LandSim 2.5, a landfill simulator, was used to simulate the landfill activities for various time slices, and further uncertainty in noncarcinogenic human health risk was estimated using a Monte Carlo simulation followed by univariate and multivariate sensitivity analyses. © 2016 Society for Risk Analysis.

Darwin and sexual selection: One hundred years of misunderstanding.

PubMed

Veuille, Michel

2010-02-01

Darwin's book on the Descent of Man and Selection in Relation to Sex (1871) is often viewed as the continuation of The Origin of Species published 12 years earlier (1859), both because of the implicit parallelism between natural selection and sexual selection, and because Darwin himself presents the book as developing a subject (man) which he intentionally omitted in the Origin. But the Descent can also be viewed as the continuation of his book on Variation published three years earlier (1868). Firstly because Darwin's hypothesis of pangenesis links the selection process to the origin of variation through use and disuse, an idea underlying his speculations on the origin of moral sense in humans. Second because like the action of the horticulturist on his domestic crops, sexual selection exerted by one sex on the other sex can develop fancy traits that are not easily accounted for by their utility to the selected organism itself, such as artistic taste, pride, courage, and the morphological differences between human populations. These traits are difficult to reconcile with pangenesis. They add up to other contradictions of the book possibly resulting from Darwin's erroneous inference about the mechanism of inheritance, like those on the determination of sex-ratio, or the confusion between individual adaptation and the advantage to the species. These inconsistencies inaugurate a weakening of the Darwinian message, which will last 50 years after his death. They contributed to the neglect of sexual selection for a century. Darwin however maintained a logical distinction between evolutionary mechanisms and hereditary mechanisms, and an epistemological distinction between evolutionary theory and Pangenesis hypothesis. In the modern context of Mendelian genetics, Darwin's sexual selection retrospectively appears as luminous an idea in its pure principle as natural selection, even though the mechanisms governing the evolution of sexual choice in animals remain largely unresolved. 2009 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Race, genetics, and human reproductive strategies.

PubMed

Rushton, J P

1996-02-01

The international literature on racial differences is reviewed, novel data are reported, and a distinct pattern is found. People of east Asian ancestry and people of African ancestry average at opposite ends of a continuum, with people of European ancestry averaging intermediately, albeit with much variability within each major race. The racial matrix emerges from measures taken of reproductive behavior, sex hormones, twinning rate, speed of physical maturation, personality, family stability, brain size, intelligence, law abidingness, and social organization. An evolutionary theory of human reproduction is proposed, familiar to biologists as the r-K scale of reproductive strategies. At one end of this scale are r-strategies, which emphasize high reproductive rates; at the other end are K-strategies, which emphasize high levels of parental investment. This scale is generally used to compare the life histories of widely disparate species, but here it is used to describe the immensely smaller variations among human races. It is hypothesized that, again on average, Mongoloid people are more K-selected than Caucasoids, who are more K-selected than Negroids. The r-K scale of reproductive strategies is also mapped on to human evolution. Genetic distances indicate that Africans emerged from the ancestral hominid line about 200,000 years ago, with an African/non-African split about 110,000 years ago, and a Caucasoid/Mongoloid split about 41,000 years ago. Such an ordering fits with and explains how and why the variables cluster.

The niche construction of cultural complexity: interactions between innovations, population size and the environment.

PubMed

Fogarty, Laurel; Creanza, Nicole

2017-12-05

Niche construction is a process through which organisms alter their environments and, in doing so, influence or change the selective pressures to which they are subject. 'Cultural niche construction' refers specifically to the effect of cultural traits on the selective environments of other biological or cultural traits and may be especially important in human evolution. In addition, the relationship between population size and cultural accumulation has been the subject of extensive debate, in part because anthropological studies have demonstrated a significant association between population size and toolkit complexity in only a subset of studied cultures. Here, we review the role of cultural innovation in constructing human evolutionary niches and introduce a new model to describe the accumulation of human cultural traits that incorporates the effects of cultural niche construction. We consider the results of this model in light of available data on human toolkit sizes across populations to help elucidate the important differences between food-gathering societies and food-producing societies, in which niche construction may be a more potent force. These results support the idea that a population's relationship with its environment, represented here by cultural niche construction, should be considered alongside population size in studies of cultural complexity.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

Human exposure to Bisphenol A and liver health status: Quantification of urinary and circulating levels by LC-MS/MS.

PubMed

Nicolucci, Carla; Errico, Sonia; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Diano, Nadia

2017-06-05

A selective and highly sensitive analytical methodology for determination of Bisphenol A in human plasma was developed and validated. The method was based on selective liquid/solid extraction, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode and negative ionization. The linearity of the detector response was verified in human plasma over the concentration range 0.100-200ngmL -1 . The detection limit was 0.03ngmL -1 and the quantification limit was 0.100ngmL -1 . The analytical features of the proposed in-house validated method were satisfactory: precision was <10% and recoveries were around 84-104%. The matrix effect was studied and compensated using deuterated labeled standard. The applicability of the proposed method was demonstrated analyzing human plasma samples from individuals affected by non-alcoholic fatty liver disease. Bisphenol A was detected above the detection limit in all samples. The data show a persistence of unconjugated Bisphenol A levels in plasma and indicate a chronic Bisphenol A exposure of the target organ, suggesting an association between liver health status and Bisphenol A exposure. The results from our study are valuable for further investigation with large sample size and longitudinal study designs, necessary to confirm the observed association. Copyright © 2017 Elsevier B.V. All rights reserved.

The pore properties of human nociceptor channel TRPA1 evaluated in single channel recordings

PubMed Central

Bobkov, Y.V.; Corey, E.A.; Ache, B.W.

2011-01-01

TRPA channels detect stimuli of different sensory modalities, including a broad spectrum of chemosensory stimuli, noxious stimuli associated with tissue damage and inflammation, mechanical stimuli, and thermal stimuli. Despite a growing understanding of potential modulators, agonists, and antagonists for these channels, the exact mechanisms of channel regulation and activation remain mostly unknown or controversial and widely debated. Relatively little is also known about the basic biophysical parameters of both native and heterologously expressed TRPA channels. Here we use conventional single channel inside-out and outside-out patch recording from the human TRPA1 channel transiently expressed in human embryonic kidney 293T cells to characterize the selectivity of the channel for inorganic mono-/divalent and organic monovalent cations in the presence of Allylisothiocyanate (AITC). We show the relative permeability of the hTRPA1 channel to inorganic cations to be: Ca2+(5.1)>Ba2+(3.5)>Mg2+(2.8)>NH4+(1.5)>Li+(1.2)>Na+(1.0)≥K+(0.98)≥Rb+(0.98)>Cs+(0.95); and to organic cations: Na+(1.0)≥Dimethylamine(0.99)>Trimethylamine(0.7)>Tetramethylammonium(0.4)>N-methyl-d-glucamine(0.1). Activation of the hTRPA1 channels by AITC appears to recruit the channels to a conformational state with an increased permeability to large organic cations. The pore of the channels in this state can be characterized as dilated by approximately 1–2.5A. These findings provide important insight into the basic fundamental properties and function of TRPA1 channels in general and human TRPA1 channel in particular. PMID:21195050

Volatile organic compound mixing ratios above Beijing in November and December 2016

NASA Astrophysics Data System (ADS)

Acton, William; Shaw, Marvin; Huang, Zhonghui; Wang, Zhaoyi; Wang, Xinming; Zhang, Yanli; Davison, Brian; Langford, Ben; Mullinger, Neil; Nemitz, Eiko; Fu, Pingqing; Squires, Freya; Carpenter, Lucy; Lewis, Alastair; Hewitt, Nick

2017-04-01

Volatile organic compounds (VOCs) are emitted into the atmosphere from vegetation and anthropogenic sources such as fossil fuel combustion, biomass burning and the evaporation of petroleum products. These compounds play an important role in the chemistry of the lower atmosphere through secondary organic aerosol (SOA) formation and facilitating the formation of tropospheric ozone. As well as their indirect impact on human health via the formation of ozone and SOA, some VOCs, including benzene, directly affect human health adversely. Here we report VOC mixing ratios measured in Beijing during a 5 week intensive field campaign from the 7th November to the 10th December 2016. This work was carried out as part of the Sources and Emissions of Air Pollutants in Beijing (AIRPOLL-Beijing) work project within the Air Pollution and Human Health in a Developing Megacity (APHH-Beijing) research programme. APHH is a large multi-institutional study which aims to record the concentrations and identify the sources of urban air pollutants in Beijing, determine exposure, understand their effects on human health, and to identify solutions. VOC mixing ratios were recorded using a Proton Transfer Reaction-Time of Flight-Mass Spectrometer (PTR-ToF-MS, Ionicon Analytik) and a Selected Ion Flow Tube-Mass Spectrometer (SIFT-MS, SYFT Technologies). During the measurement period Beijing was subject to multiple pollution events that alternated with periods of relatively good air quality, allowing the VOCs within the polluted air masses to be identified and quantified. VOCs were sampled at 102 m with additional gradient measurements made at 3, 15, 32 and 64 m providing a vertical profile of VOC mixing ratios. Mixing ratios of methanol, acetonitrile, acetaldehyde, acetone, isoprene and aromatics species will be reported together with a discussion of potential sources. Comparisons will then be drawn with other large cities.

Chromosome segregation drives division site selection in Streptococcus pneumoniae.

PubMed

van Raaphorst, Renske; Kjos, Morten; Veening, Jan-Willem

2017-07-18

Accurate spatial and temporal positioning of the tubulin-like protein FtsZ is key for proper bacterial cell division. Streptococcus pneumoniae (pneumococcus) is an oval-shaped, symmetrically dividing opportunistic human pathogen lacking the canonical systems for division site control (nucleoid occlusion and the Min-system). Recently, the early division protein MapZ was identified and implicated in pneumococcal division site selection. We show that MapZ is important for proper division plane selection; thus, the question remains as to what drives pneumococcal division site selection. By mapping the cell cycle in detail, we show that directly after replication both chromosomal origin regions localize to the future cell division sites, before FtsZ. Interestingly, Z-ring formation occurs coincidently with initiation of DNA replication. Perturbing the longitudinal chromosomal organization by mutating the condensin SMC, by CRISPR/Cas9-mediated chromosome cutting, or by poisoning DNA decatenation resulted in mistiming of MapZ and FtsZ positioning and subsequent cell elongation. Together, we demonstrate an intimate relationship between DNA replication, chromosome segregation, and division site selection in the pneumococcus, providing a simple way to ensure equally sized daughter cells.

Selective aqueous extraction of organics coupled with trapping by membrane separation

DOEpatents

van Eikeren, Paul; Brose, Daniel J.; Ray, Roderick J.

1991-01-01

An improvement to processes for the selective extractation of organic solutes from organic solvents by water-based extractants is disclosed, the improvement comprising coupling various membrane separation processes with the organic extraction process, the membrane separation process being utilized to continuously recycle the water-based extractant and at the same time selectively remove or concentrate organic solute from the water-based extractant.

The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement.

PubMed

Toni, Roberto; Casa, Claudia Della; Spaletta, Giulia; Marchetti, Giacomo; Mazzoni, Perseo; Bodria, Monica; Ravera, Simone; Dallatana, Davide; Castorina, Sergio; Riccioli, Vincenzo; Castorina, Emilio Giovanni; Antoci, Salvatore; Campanile, Enrico; Raise, Gabriella; Scalise, Gabriella; Rossi, Raffaella; Rossio, Raffaella; Ugolotti, Giorgio; Ugolottio, Giorgio; Martorella, Andrew; Roti, Elio; Rot, Elio; Sgallari, Fiorella; Pinchera, Aldo

2007-01-01

A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable "putty", moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirementfor organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following implantation in animal hosts is proposed, with the intent to obtain a bioartificial thyroid gland morphologically and functionally adequate for transplantation. We believe that the biotechnological scenario proposed herein may provide a template to construct other, more complex and clinically-relevant bioartificial endocrine organs ex situ, such as human pancreatic islets and the liver, and perhaps a new approach to brain bioengineering.

The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

PubMed Central

Nakatsu, Fubito; Hase, Koji; Ohno, Hiroshi

2014-01-01

The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells. PMID:25387275

TBDQ: A Pragmatic Task-Based Method to Data Quality Assessment and Improvement

PubMed Central

Vaziri, Reza; Mohsenzadeh, Mehran; Habibi, Jafar

2016-01-01

Organizations are increasingly accepting data quality (DQ) as a major key to their success. In order to assess and improve DQ, methods have been devised. Many of these methods attempt to raise DQ by directly manipulating low quality data. Such methods operate reactively and are suitable for organizations with highly developed integrated systems. However, there is a lack of a proactive DQ method for businesses with weak IT infrastructure where data quality is largely affected by tasks that are performed by human agents. This study aims to develop and evaluate a new method for structured data, which is simple and practical so that it can easily be applied to real world situations. The new method detects the potentially risky tasks within a process, and adds new improving tasks to counter them. To achieve continuous improvement, an award system is also developed to help with the better selection of the proposed improving tasks. The task-based DQ method (TBDQ) is most appropriate for small and medium organizations, and simplicity in implementation is one of its most prominent features. TBDQ is case studied in an international trade company. The case study shows that TBDQ is effective in selecting optimal activities for DQ improvement in terms of cost and improvement. PMID:27192547

Modified clay minerals efficiency against chemical and biological warfare agents for civil human protection.

PubMed

Plachá, Daniela; Rosenbergová, Kateřina; Slabotínský, Jiří; Kutláková, Kateřina Mamulová; Studentová, Soňa; Martynková, Gražyna Simha

2014-04-30

Sorption efficiencies of modified montmorillonite and vermiculite of their mono ionic Na and organic HDTMA and HDP forms were studied against chemical and biological warfare agents such as yperite and selected bacterial strains. Yperite interactions with modified clay minerals were observed through its capture in low-density polyethylene foil-modified clay composites by measuring yperite gas permeation with using chemical indication and gas chromatography methods. The antibacterial activities of synthetized organoclays were tested against selected Gram-positive and Gram-negative bacterial species in minimum inhibitory concentration tests. The obtained results showed a positive influence of modified clay minerals on the significant yperite breakthrough-time increase. The most effective material was the polyethylene-Na form montmorillonite, while the polyethylene-Na form vermiculite showed the lowest efficiency. With increasing organic cations loading in the interlayer space the montmorillonite efficiency decreased, and in the case of vermiculite an opposite effect was observed. Generally the modified montmorillonites were more effective than modified vermiculites. The HDP cations seem to be more effective compare to the HDTMA. The antibacterial activity tests confirmed efficiency of all organically modified clay minerals against Gram-positive bacteria. The confirmation of antibacterial activity against Y. pestis, plague bacteria, is the most interesting result of this part of the study. Copyright © 2014 Elsevier B.V. All rights reserved.

Exobiological exploration of Mars.

PubMed

Klein, H P; DeVincenzi, D L

1995-03-01

Of all the other planets in the solar system, Mars remains the most promising for further elucidating concepts about chemical evolution and the origin of life. Strategies were developed to pursue three exobiological objectives for Mars exploration: determining the abundance and distribution of the biogenic elements and organic compounds, detecting evidence of an ancient biota on Mars, and determining whether indigenous organisms exist anywhere on the planet. The three strategies are quite similar and, in fact, share the same sequence of phases. In the first phase, each requires global reconnaissance and remote sensing by orbiters to select sites of interest for detailed in situ analyses. In the second phase, lander missions are conducted to characterize the chemical and physical properties of the selected sites. The third phase involves conducting "critical" experiments at sites whose properties make them particularly attractive for exobiology. These critical experiments would include, for example, identification of organics, detection of fossils, and detection of extant life. The fourth phase is the detailed analysis of samples returned from these sites in Earth-based laboratories to confirm and extend previous discoveries. Finally, in the fifth phase, human exploration is needed to establish the geological settings for the earlier findings or to discover and explore sites that are not accessible to robotic spacecraft.

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit

NASA Technical Reports Server (NTRS)

Yasuda, H.; Komiyama, T.; Fujitaka, K.; Badhwar, G. D. (Principal Investigator)

2002-01-01

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Environmental risk assessment of the use of different organic wastes as soil amendments

NASA Astrophysics Data System (ADS)

Alvarenga, Paula; Palma, Patrícia; Mourinha, Clarisse; Farto, Márcia; Cunha-Queda, Ana Cristina; Natal-da-Luz, Tiago; Sousa, José Paulo

2013-04-01

The use of organic wastes in agriculture is considered a way of maintaining or restoring the quality of soils, enlarging the slow cycling soil organic carbon pool. However, a wide variety of undesired substances, such as potentially trace elements and organic contaminants, can have adverse effects on the environment. That fact was highlighted by the Proposal for a Soil Framework Directive, which recognized that "soil degradation or soil improvements have a major impact on other areas, (…) such as surface waters and groundwater, human health, climate change, protection of nature and biodiversity, and food safety". Taking that into account, the research project "ResOrgRisk" aims to assess the environmental risk involved in the use of different organic wastes as soil amendments, evidencing their benefits and constraints, and defining the most suitable tests to reach such assessment. The organic wastes selected for this purpose were: sewage sludge, limed, not limed, and co-composted with agricultural wastes, agro-industrial sludge, mixed municipal solid waste compost, compost produced from organic farming residues, and pig slurry digestate. Whereas threshold values for heavy metals in sludge used for agriculture have been set by the European Commission, actually there is no definitive European legislation for organic contaminants. Guide values for some organic contaminants (e.g. polychlorinated biphenyls - PCBs, and polycyclic aromatic hydrocarbons - PAHs) have been adopted at national level by many European countries, such as Portugal. These values should be taken into account when assessing the risk involved in the use of organic wastes as soil amendments. However, chemical analysis of organic waste often gives scarce information because it does not include possible interactions between chemicals. Furthermore, an exhaustive identification and quantification of all substances is impractical. In this study, ecotoxicological tests (comprising solid and aquatic phases) were performed to obtain an integrated assessment on the effects of all contaminants from each organic waste, as a whole, to terrestrial systems. The results for the chemical and ecotoxicological characterization of the organic wastes selected in this study will be discussed, emphasizing the potential benefits and the risks of their use as soil amendments.

[Highly metastatic nude mouse model of human primary gastric lymphoma constructed by surgical orthotopic transplantation and in vivo continuous screening method].

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

2010-02-09

To develop a series of high metastatic models of human gastric malignant lymphoma in nude mice by orthotopic transplantation. Two histologically intact primary and hepatic metastatic fragments derived from surgical specimen of a patient with primary gastric lymphoma were implanted into the submucosa of stomach in nude mice. Highly metastatic and specific organ metastatic models were screened by selective orthotopic passage in nude mice. Transplantability, invasion, metastasis, morphological characteristics (light microscopy, electron microscopy and immunohistochemistry), karyotypic analysis and DNA content of orthotopically transplanted tumors were studied. Primary and hepatic metastatic fragments of primary gastric lymphoma were successfully transplanted in nude mice. Two nude mouse models of human primary gastric lymphoma, termed HGBL-0304 (hepatic metastasis model) and HGBL-0305 (high metastasis model), were developed, exhibiting different metastasis biology. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. Two models have been maintained for 45 generations by orthotopic passage in nude mice. A total of 419 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. Significant difference in metastasis biology was exhibited in four aspects of metastasis time, organ metastatic rate, the extent of hepatic metastasis and survival of cancer-bearing mice. The metastatic rates of liver, spleen, lymph nodes and peritoneal seeding in HGBL-0304 and HGBL-0305 models were 100% and 69.5%, 94.3% and 55.6%, 62.6% and 45.7%, and 43.5% and 30.5%. The onset time for metastases of liver, spleen, lymph nodes and peritoneal seeding was 2 w and 5 w, 3 w and 6 w, 2 w and 3 w, 3 w and 6 w respectively. The extent of hepatic metastasis in HGBL-0304 and HGBL-0305 models displayed diffuse involvement of the whole liver and mainly right lobe invasion of liver respectively. The mean survival time of HGBL-0304 and HGBL-0305 models was 54.3d and 106.9 d respectively. Surgical orthotopic implantation combined with in vivo selective passage screening is an effective method for establishing highly metastatic and specific organ metastatic models of human malignant lymphoma in nude mice. The study is the first time to establish hepatic metastasis and high metastasis nude mouse models of human primary gastric lymphoma with the same original patient and different potentials of invasion and metastasis.

Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin

PubMed Central

Nemudraya, Anna Andreevna; Kuligina, Elena Vladimirovna; Ilyichev, Alexandr Alexeevich; Fomin, Alexandr Sergeevich; Stepanov, Grigory Alexandrovich; Savelyeva, Anna Valentinovna; Koval, Olga Alexandrovna; Richter, Vladimir Alexandrovich

2016-01-01

It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cells in vitro and suppress the growth of HA-1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors. However, Lactaptin, as with the majority of protein-based therapeutic drugs, is distributed evenly throughout the organism, which reduces its antitumor efficacy. To develop the targeted delivery of lactaptin, the present study selected tumor-specific peptides by screening a phage display peptide library in vivo on A/Sn strain mice with subcutaneously transplanted HA-1 cells. Two genetic constructs were made for the production of recombinant fusion proteins composed of RL2 and the selected tumor-targeting peptide. In vitro experiments involving HA-1, MDA-MB-231 and MCF-7 cells cultures demonstrated that the fusion proteins induce apoptotic death in mouse and human tumor cells, as with RL2. The in vivo experiments involving the mouse HA-1 tumor model demonstrated that the tumor fluorescence intensity of the Cy5-fusion protein conjugates is higher than that of RL2-Cy5. As conjugation of the tumor-specific peptides to RL2 provided retention of RL2 in the tumor tissues, fusion proteins composed of lactaptin and peptides specific for human tumors are deemed promising to improve the antitumor efficiency of lactaptin. PMID:28105163

Interfacing sensory input with motor output: does the control architecture converge to a serial process along a single channel?

PubMed Central

van de Kamp, Cornelis; Gawthrop, Peter J.; Gollee, Henrik; Lakie, Martin; Loram, Ian D.

2013-01-01

Modular organization in control architecture may underlie the versatility of human motor control; but the nature of the interface relating sensory input through task-selection in the space of performance variables to control actions in the space of the elemental variables is currently unknown. Our central question is whether the control architecture converges to a serial process along a single channel? In discrete reaction time experiments, psychologists have firmly associated a serial single channel hypothesis with refractoriness and response selection [psychological refractory period (PRP)]. Recently, we developed a methodology and evidence identifying refractoriness in sustained control of an external single degree-of-freedom system. We hypothesize that multi-segmental whole-body control also shows refractoriness. Eight participants controlled their whole body to ensure a head marker tracked a target as fast and accurately as possible. Analysis showed enhanced delays in response to stimuli with close temporal proximity to the preceding stimulus. Consistent with our preceding work, this evidence is incompatible with control as a linear time invariant process. This evidence is consistent with a single-channel serial ballistic process within the intermittent control paradigm with an intermittent interval of around 0.5 s. A control architecture reproducing intentional human movement control must reproduce refractoriness. Intermittent control is designed to provide computational time for an online optimization process and is appropriate for flexible adaptive control. For human motor control we suggest that parallel sensory input converges to a serial, single channel process involving planning, selection, and temporal inhibition of alternative responses prior to low dimensional motor output. Such design could aid robots to reproduce the flexibility of human control. PMID:23675342

Similarity or dissimilarity in the relations between human service organizations.

PubMed

Bruynooghe, Kevin; Verhaeghe, Mieke; Bracke, Piet

2008-01-01

Exchange theory and homophily theory give rise to counteracting expectations for the interaction between human service organizations. Based on arguments of exchange theory, more interaction is expected between dissimilar organizations having complementary resources. Based on arguments of homophily theory, organizations having similar characteristics are expected to interact more. Interorganizational relations between human service organizations in two regional networks in Flanders are examined in this study. Results indicate that human service organizations tend to cooperate more with similar organizations as several homophily effects but not one effect of dissimilarity were found to be significant. The results of this study contribute to the understanding of interorganizational networks of human service organizations and have implications for the development of integrated care.

Midcingulate cortex: Structure, connections, homologies, functions and diseases.

PubMed

Vogt, Brent A

2016-07-01

Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC. Copyright © 2016 Elsevier B.V. All rights reserved.

49 CFR 604.15 - Registration of qualified human service organizations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Registration of qualified human service... Human Service Organizations and Duties for Recipients With Respect to Charter Registration Web site § 604.15 Registration of qualified human service organizations. (a) Qualified human service...

49 CFR 604.15 - Registration of qualified human service organizations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Registration of qualified human service... Human Service Organizations and Duties for Recipients With Respect to Charter Registration Web site § 604.15 Registration of qualified human service organizations. (a) Qualified human service...

49 CFR 604.15 - Registration of qualified human service organizations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Registration of qualified human service... Human Service Organizations and Duties for Recipients With Respect to Charter Registration Web site § 604.15 Registration of qualified human service organizations. (a) Qualified human service...

49 CFR 604.15 - Registration of qualified human service organizations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Registration of qualified human service... Human Service Organizations and Duties for Recipients With Respect to Charter Registration Web site § 604.15 Registration of qualified human service organizations. (a) Qualified human service...

Definition of the Cattle Killer Cell Ig–like Receptor Gene Family: Comparison with Aurochs and Human Counterparts

PubMed Central

Sanderson, Nicholas D.; Norman, Paul J.; Guethlein, Lisbeth A.; Ellis, Shirley A.; Williams, Christina; Breen, Matthew; Park, Steven D. E.; Magee, David A.; Babrzadeh, Farbod; Warry, Andrew; Watson, Mick; Bradley, Daniel G.; MacHugh, David E.; Parham, Peter

2014-01-01

Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig–like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle. PMID:25398326

Betacaryophyllene - A phytocannabinoid as potential therapeutic modality for human sepsis?

PubMed

Meza, Angel; Lehmann, Christian

2018-01-01

Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of estrogens on skin aging and the potential role of SERMs

PubMed Central

Stevenson, Susan; Thornton, Julie

2007-01-01

In humans, structural and functional changes attributable to aging are more visibly evident in the skin than in any other organ. Estrogens have significant effects on skin physiology and modulate epidermal keratinocytes, dermal fibroblasts and melanocytes, in addition to skin appendages including the hair follicle and the sebaceous gland. Importantly, skin aging can be significantly delayed by the administration of estrogen. This paper reviews the effects of estrogens on skin and the mechanisms by which estrogens can alleviate the changes due to aging that occur in human skin. The relevance of estrogen replacement therapy (HRT) in post-menopausal women and the potential value of selective estrogen receptor modulators (SERMs) as a therapy for diminishing skin aging are also highlighted. PMID:18044179

Automation literature: A brief review and analysis

NASA Technical Reports Server (NTRS)

Smith, D.; Dieterly, D. L.

1980-01-01

Current thought and research positions which may allow for an improved capability to understand the impact of introducing automation to an existing system are established. The orientation was toward the type of studies which may provide some general insight into automation; specifically, the impact of automation in human performance and the resulting system performance. While an extensive number of articles were reviewed, only those that addressed the issue of automation and human performance were selected to be discussed. The literature is organized along two dimensions: time, Pre-1970, Post-1970; and type of approach, Engineering or Behavioral Science. The conclusions reached are not definitive, but do provide the initial stepping stones in an attempt to begin to bridge the concept of automation in a systematic progression.

The Prehistory of Antibiotic Resistance.

PubMed

Perry, Julie; Waglechner, Nicholas; Wright, Gerard

2016-06-01

Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Regulating the sale of human organs: a discussion in context with the global market.

PubMed

Surman, Owen S; Saidi, Reza; Burke, Thomas F

2008-04-01

Insufficient availability of human organs for transplantation has given rise to a flourishing global market. This review addresses current thinking and practical considerations regarding legalization of organ sales. Increasing competition for human organs has led to egregious human rights violations. Governmental proscription of organ sales has failed to slow this process. Organ sales in China and the regulated market in Iran have received much attention. Some believe that a regulated market is an ethical vehicle for shortening waiting lists and decreasing illegal organ sales. Others consider it a blow to human dignity and to altruistic donation. There is alternative support toward reimbursing living donors for their financial losses. The World Health Organization advocates increased reliance on cadaver donor transplantation. Some countries have enacted presumed consent laws that have increased cadaver organ donation. In the USA an Organ Breakthrough Collaborative has generated comparable success. Serious discussion continues with regard to regulated sale of human organs. There is increased interest in reimbursement for living organ donation. Research is needed to elucidate workings of the global organ market, and to assess attitudes about stakeholders with regard to proposed changes in transplantation policy.

Acquired antibiotic resistance among wild animals: the case of Iberian Lynx (Lynx pardinus).

PubMed

Sousa, Margarida; Gonçalves, Alexandre; Silva, Nuno; Serra, Rodrigo; Alcaide, Eva; Zorrilla, Irene; Torres, Carmen; Caniça, Manuela; Igrejas, Gilberto; Poeta, Patrícia

2014-01-01

The selective pressure generated by the clinical misuse of antibiotics has been the major driving force leading to the emergence of antibiotic resistance among bacteria. Antibiotics or even resistant bacteria are released into the environment and contaminate the surrounding areas. Human and animal populations in contact with these sources are able to become reservoirs of these resistant organisms. Then, due to the convergence between habitats, the contact of wild animals with other animals, humans, or human sources is now more common and this leads to an increase in the exchange of resistance determinants between their microbiota. Indeed, it seems that wildlife populations living in closer proximity to humans have higher levels of antibiotic resistance. Now, the Iberian Lynx (Lynx pardinus) is a part of this issue, being suggested as natural reservoir of acquired resistant bacteria. The emerging public health concern regarding microbial resistance to antibiotics is becoming true: the bacteria are evolving and are now affecting unintentional hosts.

42 CFR 121.13 - Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended.

Code of Federal Regulations, 2010 CFR

2010-10-01

... National Organ Transplant Act, as amended. 121.13 Section 121.13 Public Health PUBLIC HEALTH SERVICE... NETWORK § 121.13 Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended. “Human organ,” as covered by section 301 of the National Organ Transplant Act, as amended, means...

42 CFR 121.13 - Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended.

Code of Federal Regulations, 2011 CFR

2011-10-01

... National Organ Transplant Act, as amended. 121.13 Section 121.13 Public Health PUBLIC HEALTH SERVICE... NETWORK § 121.13 Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended. “Human organ,” as covered by section 301 of the National Organ Transplant Act, as amended, means...

42 CFR 121.13 - Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended.

Code of Federal Regulations, 2012 CFR

2012-10-01

... National Organ Transplant Act, as amended. 121.13 Section 121.13 Public Health PUBLIC HEALTH SERVICE... NETWORK § 121.13 Definition of Human Organ Under section 301 of the National Organ Transplant Act, as amended. “Human organ,” as covered by section 301 of the National Organ Transplant Act, as amended, means...

Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells.

PubMed

Fernandez-Rebollo, Eduardo; Mentrup, Birgit; Ebert, Regina; Franzen, Julia; Abagnale, Giulio; Sieben, Torsten; Ostrowska, Alina; Hoffmann, Per; Roux, Pierre-François; Rath, Björn; Goodhardt, Michele; Lemaitre, Jean-Marc; Bischof, Oliver; Jakob, Franz; Wagner, Wolfgang

2017-07-11

Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have demonstrated that proliferation and cellular morphology are affected by these supplements - it is therefore important to determine if they favor outgrowth of different subpopulations and thereby impact on the heterogeneous composition of MSCs. We have isolated and expanded human bone marrow-derived MSCs in parallel with HPL or FCS and demonstrated that HPL significantly increases proliferation and leads to dramatic differences in cellular morphology. Remarkably, global DNA-methylation profiles did not reveal any significant differences. Even at the transcriptomic level, there were only moderate changes in pairwise comparison. Furthermore, the effects on proliferation, cytoskeletal organization, and focal adhesions were reversible by interchanging to opposite culture conditions. These results indicate that cultivation of MSCs with HPL or FCS has no systematic bias for specific cell types.

Life Support and Habitation and Planetary Protection Workshop

NASA Technical Reports Server (NTRS)

Hogan, John A. (Editor); Race, Margaret S. (Editor); Fisher, John W. (Editor); Joshi, Jitendra A. (Editor); Rummel, John D. (Editor)

2006-01-01

A workshop entitled "Life Support and Habitation and Planetary Protection Workshop" was held in Houston, Texas on April 27-29, 2005 to facilitate the development of planetary protection guidelines for future human Mars exploration missions and to identify the potential effects of these guidelines on the design and selection of related human life support, extravehicular activity and monitoring and control systems. This report provides a summary of the workshop organization, starting assumptions, working group results and recommendations. Specific result topics include the identification of research and technology development gaps, potential forward and back contaminants and pathways, mitigation alternatives, and planetary protection requirements definition needs. Participants concluded that planetary protection and science-based requirements potentially affect system design, technology trade options, development costs and mission architecture. Therefore early and regular coordination between the planetary protection, scientific, planning, engineering, operations and medical communities is needed to develop workable and effective designs for human exploration of Mars.

HSV as a vector in vaccine development and gene therapy.

PubMed

Marconi, Peggy; Argnani, Rafaela; Epstein, Alberto L; Manservigi, Roberto

2009-01-01

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), major human pathogen whose lifestyle is based on a long-term dual interaction with the infected host characterized by the existence of lytic and latent infections, has allowed the development of potential vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous system, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases and targeted infection of specific tissues or organs. Three different classes of vectors can be derived from HSV-1: replication-competent attenuated vectors, replication-incompetent recombinant vectors and defective helper-dependent vectors known as amplicons. This chapter highlights the current knowledge concerning design, construction and recent applications, as well as the potential and current limitations of the three different classes of HSV-1-based vectors.

Interdisciplinary education approach to the human science

NASA Astrophysics Data System (ADS)

Szu, Harold; Zheng, Yufeng; Zhang, Nian

2012-06-01

We introduced human sciences as components, and integrated them together as an interdisciplinary endeavor over decades. This year, we built a website to maintain systematically the educational research service. We captured the human sciences in various components in the SPIE proceedings over the last decades, which included: (i) ears & eyes like adaptive wavelets, (ii) brain-like unsupervised learning independent component analysis (ICA); (iii) compressive sampling spatiotemporal sparse information processing, (iv) nanoengineering approach to sensing components, (v) systems biology measurements, and (vi) biomedical wellness applications. In order to serve the interdisciplinary community better, our system approach is based on that the former recipients invited the next recipients to deliver their review talks and panel discussions. Since only the former recipients of each component can lead the nomination committees and make the final selections, we also create a leadership award which may be nominated by any conference attendance, to be approved by the conference organization committee.

Menstrual breakdown of human endometrium can be mimicked in vitro and is selectively and reversibly blocked by inhibitors of matrix metalloproteinases.

PubMed Central

Marbaix, E; Kokorine, I; Moulin, P; Donnez, J; Eeckhout, Y; Courtoy, P J

1996-01-01

The mechanisms underlying the menstrual lysis leading to shedding of the human endometrium and its accompanying bleeding are still largely unknown. In particular, whether breakdown of the endometrial fibrillar extra-cellular matrix that precedes bleeding depends on aspartic-, cysteine-, serine-, or metalloproteinases remains unclear. In the present study, menstrual regression of the human endometrium was mimicked in organ culture. Whereas sex steroids could preserve tissue integrity only in nonperimenstrual explants, matrix breakdown upon sex steroid deprivation was completely and reversibly inhibited at all stages of the menstrual cycle by specific inhibitors of matrix metalloproteinases, but not by inhibitors of the other classes of proteinases. Matrix metalloproteinases are thus identified as the key class of proteinases involved in the initiation of menstruation. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8799164

Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells.

PubMed

Vlastos, Dimitris; Antonopoulou, Maria; Konstantinou, Ioannis

2016-05-01

Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2-Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of the optimum location of external markers for patient setup accuracy enhancement at external beam radiotherapy

PubMed Central

Torshabi, Ahmad Esmaili; Nankali, Saber

2016-01-01

In external beam radiotherapy, one of the most common and reliable methods for patient geometrical setup and/or predicting the tumor location is use of external markers. In this study, the main challenging issue is increasing the accuracy of patient setup by investigating external markers location. Since the location of each external marker may yield different patient setup accuracy, it is important to assess different locations of external markers using appropriate selective algorithms. To do this, two commercially available algorithms entitled a) canonical correlation analysis (CCA) and b) principal component analysis (PCA) were proposed as input selection algorithms. They work on the basis of maximum correlation coefficient and minimum variance between given datasets. The proposed input selection algorithms work in combination with an adaptive neuro‐fuzzy inference system (ANFIS) as a correlation model to give patient positioning information as output. Our proposed algorithms provide input file of ANFIS correlation model accurately. The required dataset for this study was prepared by means of a NURBS‐based 4D XCAT anthropomorphic phantom that can model the shape and structure of complex organs in human body along with motion information of dynamic organs. Moreover, a database of four real patients undergoing radiation therapy for lung cancers was utilized in this study for validation of proposed strategy. Final analyzed results demonstrate that input selection algorithms can reasonably select specific external markers from those areas of the thorax region where root mean square error (RMSE) of ANFIS model has minimum values at that given area. It is also found that the selected marker locations lie closely in those areas where surface point motion has a large amplitude and a high correlation. PACS number(s): 87.55.km, 87.55.N PMID:27929479

49 CFR 604.7 - Qualified human service organizations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Qualified human service organizations. 604.7... organizations. (a) A recipient may provide charter service to a qualified human service organization (QHSO) for... disabilities; or (3) With low income. (b) If an organization serving persons described in paragraph (a) of this...

Selective recognition of 6-mercaptopurine based on luminescent metal-organic frameworks Fe-MIL-88NH₂.

PubMed

Sun, Zhengjuan; Liu, Yali; Li, Yuanfang

2015-03-15

A novel and rapid spectrofluorometry method for the recognition of 6-mercaptopurine (6-MP) has been developed based on luminescent metal-organic frameworks Fe-MIL-88NH2 as fluorescent probe. The strong fluorescence of Fe-MIL-88NH2 at 430 nm could be quenched by 6-MP directly, and the Fe-MIL-88NH2 shows high selectivity for 6-MP compared to other thiol-containing amino acids such as homocysteine (Hcy), cysteine (Cys), glutathione (GSH), etc. Under optimal conditions, the relative fluorescence intensity was linearly proportional to the concentration of 6-MP in the range of 5-600 μM with the detection limit at 1.17 μM (S/N=3). Furthermore, the present approach has been successfully applied to the determination of 6-MP in human serum samples. The possible fluorescence quenching mechanism has also been investigated, where it is revealed that the quenching was attributed to competition of absorption of the light source energy as well as electron transfer between Fe-MIL-88NH2 and 6-MP. Copyright © 2014 Elsevier B.V. All rights reserved.

A model of proto-object based saliency

PubMed Central

Russell, Alexander F.; Mihalaş, Stefan; von der Heydt, Rudiger; Niebur, Ernst; Etienne-Cummings, Ralph

2013-01-01

Organisms use the process of selective attention to optimally allocate their computational resources to the instantaneously most relevant subsets of a visual scene, ensuring that they can parse the scene in real time. Many models of bottom-up attentional selection assume that elementary image features, like intensity, color and orientation, attract attention. Gestalt psychologists, how-ever, argue that humans perceive whole objects before they analyze individual features. This is supported by recent psychophysical studies that show that objects predict eye-fixations better than features. In this report we present a neurally inspired algorithm of object based, bottom-up attention. The model rivals the performance of state of the art non-biologically plausible feature based algorithms (and outperforms biologically plausible feature based algorithms) in its ability to predict perceptual saliency (eye fixations and subjective interest points) in natural scenes. The model achieves this by computing saliency as a function of proto-objects that establish the perceptual organization of the scene. All computational mechanisms of the algorithm have direct neural correlates, and our results provide evidence for the interface theory of attention. PMID:24184601

Digestive enzymes of human and nonhuman primates.

PubMed

Janiak, Mareike Cora

2016-09-01

All living organisms need to consume nutrients to grow, survive, and reproduce, making the successful acquisition of food resources a powerful selective pressure. However, acquiring food is only part of the challenge. While all animals spend much of their daily activity budget hunting, searching for, or otherwise procuring food, a large part of what is involved in overall nutrition occurs once the meal has been swallowed. Most nutritional components are too complex for immediate use and must be broken down into simpler compounds, which can then be absorbed by the body. This process, digestion, is catalyzed by enzymes that are either endogenous or produced by the host's microbial population. 1 Research shows that the nutritional value of food is partially constrained by the digestive abilities of the microbial community present in the host's gut and that these microbes rapidly adapt to changes in diet and other environmental pressures. 2 An accumulating body of evidence suggests that endogenously produced digestive enzymes also have been, and still are, common targets of natural selection, further cementing their crucial role in an organism's digestive system. 3-5 . © 2016 Wiley Periodicals, Inc.

Analytical Chemical Sensing in the Submillimeter/terahertz Spectral Range

NASA Astrophysics Data System (ADS)

Moran, Benjamin L.; Fosnight, Alyssa M.; Medvedev, Ivan R.; Neese, Christopher F.

2012-06-01

Highly sensitive and selective Terahertz sensor utilized to quantitatively analyze a complex mixture of Volatile Organic Compounds is reported. To best demonstrate analytical capabilities of THz chemical sensors we chose to perform analytical quantitative analysis of a certified gas mixture using a novel prototype chemical sensor that couples a commercial preconcentration system (Entech 7100A) to a high resolution THz spectrometer. We selected Method TO-14A certified mixture of 39 volatile organic compounds (VOCs) diluted to 1 part per million (ppm) in nitrogen. 26 of the 39 chemicals were identified by us as suitable for THz spectroscopic detection. Entech 7100A system is designed and marketed as an inlet system for Gas Chromatography-Mass Spectrometry (GC-MS) instruments with a specific focus on TO-14 and TO-15 EPA sampling methods. Its preconcentration efficiency is high for the 39 chemicals in the mixture used for this study and our preliminary results confirm this. Here we present the results of this study which serves as basis for our ongoing research in environmental sensing and analysis of exhaled human breath.

Middle management of research

NASA Technical Reports Server (NTRS)

Graham, Robert W.

1990-01-01

The role of the middle manager in a research organization is discussed. The middle manager serves as a liaison between upper management and researchers to assure that individual research projects manifest the goals of the organization. The author draws on his long experience in this role to describe management practices that have proven successful. A general discussion is presented of the makeup of a research environment, derived from a study of a division involved in aerospace research and development (R and D). The study emphasized the importance of planning and management style in producing an attractive environment. Management practices are described, which include goal setting, planning, staffing, reviewing and evaluating, and rewarding. The importance of selecting and defining an appropriate research area is discussed. It is emphasized that in relating to the staff the middle manager must cultivate the human side of supervision, develop the art of delegating responsibility, judiciously select facilities, and provide recognition and meaningful rewards to develop a productive research staff. The development of the staff is probably the most important and challenging role of the manager.

An AOP analysis of selective serotonin reuptake inhibitors (SSRIs) for fish.

PubMed

McDonald, M Danielle

2017-07-01

Pharmaceuticals and personal care products (PPCPs) are found in measureable quantities within the aquatic environment. Selective serotonin reuptake inhibitor (SSRI) antidepressants are one class of pharmaceutical compound that has received a lot of attention. Consistent with most PPCPs, the pharmacokinetics and physiological impacts of SSRI treatment have been well-studied in small mammals and humans and this, combined with the evolutionary conservation of the serotonergic system across vertebrates, allows for the read-across of known SSRI effects in mammals to potential SSRI impacts on aquatic organisms. Using an Adverse Outcome Pathway (AOP) framework, this review examines the similarities and differences between the mammalian and teleost fish SSRI target, the serotonin transporter (SERT; SLC6A4), and the downstream impacts of elevated extracellular serotonin (5-HT; 5-hydroxytryptamine), the consequence of SERT inhibition, on organ systems and physiological processes within teleost fish. This review also intends to reveal potentially understudied endpoints for SSRI toxicity based on what is known to be controlled by 5-HT in fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical microsensors

DOEpatents

Li, DeQuan; Swanson, Basil I.

1995-01-01

An article of manufacture is provided including a substrate having an oxide surface layer and a selective thin film of a cyclodextrin derivative chemically bound upon said substrate, said film is adapted for the inclusion of a selected organic compound therewith. Such an article can be either a chemical sensor capable of detecting a resultant mass change from inclusion of the selected organic compound or a chemical separator capable of reversibly selectively separating a selected organic compound.

Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy.

PubMed

Cholewa, Jason; Guimarães-Ferreira, Lucas; da Silva Teixeira, Tamiris; Naimo, Marshall Alan; Zhi, Xia; de Sá, Rafaele Bis Dal Ponte; Lodetti, Alice; Cardozo, Mayara Quadros; Zanchi, Nelo Eidy

2014-09-01

Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. © 2013 Wiley Periodicals, Inc.

Drosophila as an In Vivo Model for Human Neurodegenerative Disease

PubMed Central

McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

2015-01-01

With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

Drosophila as an In Vivo Model for Human Neurodegenerative Disease.

PubMed

McGurk, Leeanne; Berson, Amit; Bonini, Nancy M

2015-10-01

With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. Copyright © 2015 by the Genetics Society of America.

Real-world volatile organic compound emission rates from seated adults and children for use in indoor air studies.

PubMed

Stönner, C; Edtbauer, A; Williams, J

2018-01-01

Human beings emit many volatile organic compounds (VOCs) of both endogenous (internally produced) and exogenous (external source) origin. Here we present real-world emission rates of volatile organic compounds from cinema audiences (50-230 people) as a function of time in multiple screenings of three films. The cinema location and film selection allowed high-frequency measurement of human-emitted VOCs within a room flushed at a known rate so that emissions rates could be calculated for both adults and children. Gas-phase emission rates are analyzed as a function of time of day, variability during the film, and age of viewer. The average emission rates of CO 2 , acetone, and isoprene were lower (by a factor of ~1.2-1.4) for children under twelve compared to adults while for acetaldehyde emission rates were equivalent. Molecules influenced by exogenous sources such as decamethylcyclopentasiloxanes and methanol tended to decrease over the course of day and then rise for late evening screenings. These results represent average emission rates of people under real-world conditions and can be used in indoor air quality assessments and building design. Averaging over a large number of people generates emission rates that are less susceptible to individual behaviors. © 2017 The Authors. Indoor Air published by John Wiley & Sons Ltd.

The future of human cerebral cartography: a novel approach

PubMed Central

Frackowiak, Richard; Markram, Henry

2015-01-01

Cerebral cartography can be understood in a limited, static, neuroanatomical sense. Temporal information from electrical recordings contributes information on regional interactions adding a functional dimension. Selective tagging and imaging of molecules adds biochemical contributions. Cartographic detail can also be correlated with normal or abnormal psychological or behavioural data. Modern cerebral cartography is assimilating all these elements. Cartographers continue to collect ever more precise data in the hope that general principles of organization will emerge. However, even detailed cartographic data cannot generate knowledge without a multi-scale framework making it possible to relate individual observations and discoveries. We propose that, in the next quarter century, advances in cartography will result in progressively more accurate drafts of a data-led, multi-scale model of human brain structure and function. These blueprints will result from analysis of large volumes of neuroscientific and clinical data, by a process of reconstruction, modelling and simulation. This strategy will capitalize on remarkable recent developments in informatics and computer science and on the existence of much existing, addressable data and prior, though fragmented, knowledge. The models will instantiate principles that govern how the brain is organized at different levels and how different spatio-temporal scales relate to each other in an organ-centred context. PMID:25823868

Literature review and global consensus on management of acute radiation syndrome affecting nonhematopoietic organ systems.

PubMed

Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

2011-10-01

The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.

Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

PubMed Central

Dainiak, Nicholas; Gent, Robert Nicolas; Carr, Zhanat; Schneider, Rita; Bader, Judith; Buglova, Elena; Chao, Nelson; Coleman, C. Norman; Ganser, Arnold; Gorin, Claude; Hauer-Jensen, Martin; Huff, L. Andrew; Lillis-Hearne, Patricia; Maekawa, Kazuhiko; Nemhauser, Jeffrey; Powles, Ray; Schünemann, Holger; Shapiro, Alla; Stenke, Leif; Valverde, Nelson; Weinstock, David; White, Douglas; Albanese, Joseph; Meineke, Viktor

2013-01-01

Objectives The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/ orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. Conclusions High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future. PMID:21986999

Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus.

PubMed

Hartmann-Fatu, Cristina; Trusch, Franziska; Moll, Carina N; Michin, Irina; Hassinen, Antti; Kellokumpu, Sakari; Bayer, Peter

2015-03-27

Tyrosine sulfation of proteins is an important post-translational modification shown to play a role in many membrane-associated or extracellular processes such as virus entry, blood clotting, antibody-mediated immune response, inflammation and egg fecundation. The sole two human enzymes that transfer sulfate moieties from 3'-phospho-adenosine-5'-phospho-sulfate onto tyrosine residues, TPST1 and TPST2, are anchored to the membranes of the trans-Golgi compartment with the catalytic domain oriented to the lumen. In contrast to the relatively well studied organization of medial Golgi enzymes, the organization of trans-Golgi transferases remains elusive. Although tyrosylprotein sulfotransferases are known to exist as homodimers in the Golgi membranes, this organization level may represent only a small piece of a puzzle that is linked to the entire picture. Here we report the formation of TPST1/TPST2 heterodimers and a novel interaction between either TPST1 or TPST2 and the α-2,6-sialyltransferase, indicating a higher organization level of tyrosylprotein sulfotransferases that may serve for substrate selectivity and/or effective organization of multiple post-translational modification of proteins. Copyright © 2015. Published by Elsevier Ltd.

Liquid-Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing.

PubMed

Zhang, Yu; Li, Jun; Li, Rui; Sbircea, Dan-Tiberiu; Giovannitti, Alexander; Xu, Junling; Xu, Huihua; Zhou, Guodong; Bian, Liming; McCulloch, Iain; Zhao, Ni

2017-11-08

Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid-liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the "sensing channel" can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?

PubMed Central

Temmam, Sarah; Davoust, Bernard; Berenger, Jean-Michel; Raoult, Didier; Desnues, Christelle

2014-01-01

Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases. PMID:24918293

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex.

PubMed

Weiner, Kevin S; Jonas, Jacques; Gomez, Jesse; Maillard, Louis; Brissart, Hélène; Hossu, Gabriela; Jacques, Corentin; Loftus, David; Colnat-Coulbois, Sophie; Stigliani, Anthony; Barnett, Michael A; Grill-Spector, Kalanit; Rossion, Bruno

2016-08-10

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks. Copyright © 2016 the authors 0270-6474/16/368426-16$15.00/0.

Effects of selection and training on unit-level performance over time: a latent growth modeling approach.

PubMed

Van Iddekinge, Chad H; Ferris, Gerald R; Perrewé, Pamela L; Blass, Fred R; Heetderks, Thomas D; Perryman, Alexa A

2009-07-01

Surprisingly few data exist concerning whether and how utilization of job-related selection and training procedures affects different aspects of unit or organizational performance over time. The authors used longitudinal data from a large fast-food organization (N = 861 units) to examine how change in use of selection and training relates to change in unit performance. Latent growth modeling analyses revealed significant variation in both the use and the change in use of selection and training across units. Change in selection and training was related to change in 2 proximal unit outcomes: customer service performance and retention. Change in service performance, in turn, was related to change in the more distal outcome of unit financial performance (i.e., profits). Selection and training also affected financial performance, both directly and indirectly (e.g., through service performance). Finally, results of a cross-lagged panel analysis suggested the existence of a reciprocal causal relationship between the utilization of the human resources practices and unit performance. However, there was some evidence to suggest that selection and training may be associated with different causal sequences, such that use of the training procedure appeared to lead to unit performance, whereas unit performance appeared to lead to use of the selection procedure.

Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model.

PubMed

Tan, Xiao; Gong, Zaiwu; Huang, Minji; Wang, Zhou-Jing

2017-02-14

Persistent organic pollutants (POPs) pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route), inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions ( I -consistency and I I -consistency) are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I -consistency results were more acceptable than the I I -consistency results.

Rational Design of Broad Spectrum Antibacterial Activity Based on a Clinically Relevant Enoyl-Acyl Carrier Protein (ACP) Reductase Inhibitor*

PubMed Central

Schiebel, Johannes; Chang, Andrew; Shah, Sonam; Lu, Yang; Liu, Li; Pan, Pan; Hirschbeck, Maria W.; Tareilus, Mona; Eltschkner, Sandra; Yu, Weixuan; Cummings, Jason E.; Knudson, Susan E.; Bommineni, Gopal R.; Walker, Stephen G.; Slayden, Richard A.; Sotriffer, Christoph A.; Tonge, Peter J.; Kisker, Caroline

2014-01-01

Determining the molecular basis for target selectivity is of particular importance in drug discovery. The ideal antibiotic should be active against a broad spectrum of pathogenic organisms with a minimal effect on human targets. CG400549, a Staphylococcus-specific 2-pyridone compound that inhibits the enoyl-acyl carrier protein reductase (FabI), has recently been shown to possess human efficacy for the treatment of methicillin-resistant Staphylococcus aureus infections, which constitute a serious threat to human health. In this study, we solved the structures of three different FabI homologues in complex with several pyridone inhibitors, including CG400549. Based on these structures, we rationalize the 65-fold reduced affinity of CG400549 toward Escherichia coli versus S. aureus FabI and implement concepts to improve the spectrum of antibacterial activity. The identification of different conformational states along the reaction coordinate of the enzymatic hydride transfer provides an elegant visual depiction of the relationship between catalysis and inhibition, which facilitates rational inhibitor design. Ultimately, we developed the novel 4-pyridone-based FabI inhibitor PT166 that retained favorable pharmacokinetics and efficacy in a mouse model of S. aureus infection with extended activity against Gram-negative and mycobacterial organisms. PMID:24739388

Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model

PubMed Central

Tan, Xiao; Gong, Zaiwu; Huang, Minji; Wang, Zhou-Jing

2017-01-01

Persistent organic pollutants (POPs) pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route), inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions (I-consistency and II-consistency) are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I-consistency results were more acceptable than the II-consistency results. PMID:28216589

Cadaver Thanatomicrobiome Signatures: The Ubiquitous Nature of Clostridium Species in Human Decomposition.

PubMed

Javan, Gulnaz T; Finley, Sheree J; Smith, Tasia; Miller, Joselyn; Wilkinson, Jeremy E

2017-01-01

Human thanatomicrobiome studies have established that an abundant number of putrefactive bacteria within internal organs of decaying bodies are obligate anaerobes, Clostridium spp. These microorganisms have been implicated as etiological agents in potentially life-threatening infections; notwithstanding, the scale and trajectory of these microbes after death have not been elucidated. We performed phylogenetic surveys of thanatomicrobiome signatures of cadavers' internal organs to compare the microbial diversity between the 16S rRNA gene V4 hypervariable region and V3-4 conjoined regions from livers and spleens of 45 cadavers undergoing forensic microbiological studies. Phylogenetic analyses of 16S rRNA gene sequences revealed that the V4 region had a significantly higher mean Chao1 richness within the total microbiome data. Permutational multivariate analysis of variance statistical tests, based on unweighted UniFrac distances, demonstrated that taxa compositions were significantly different between V4 and V3-4 hypervariable regions ( p < 0.001). Of note, we present the first study, using the largest cohort of criminal cases to date, that two hypervariable regions show discriminatory power for human postmortem microbial diversity. In conclusion, here we propose the impact of hypervariable region selection for the 16S rRNA gene in differentiating thanatomicrobiomic profiles to provide empirical data to explain a unique concept, the Postmortem Clostridium Effect.

Presence and distribution of organic wastewater compounds in wastewater, surface, ground, and drinking waters, Minnesota, 2000-02

USGS Publications Warehouse

Lee, Kathy E.; Barber, Larry B.; Furlong, Edward T.; Cahill, Jeffery D.; Kolpin, Dana W.; Meyer, Michael T.; Zaugg, Steven D.

2004-01-01

Results of this study indicate ubiquitous distribution of measured OWCs in the environment that originate from numerous sources and pathways. During this reconnaissance of OWCs in Minnesota it was not possible to determine the specific sources of OWCs to surface, ground, or drinking waters. The data indicate WWTP effluent is a major pathway of OWCs to surface waters and that landfill leachate at selected facilities is a potential source of OWCs to WWTPs. Aquatic organism or human exposure to some OWCs is likely based on OWC distribution. Few aquatic or human health standards or criteria exist for the OWCs analyzed, and the risks to humans or aquatic wildlife are not known. Some OWCs detected in this study are endocrine disrupters and have been found to disrupt or influence endocrine function in fish. Thirteen endocrine disrupters, 3-tert-butyl-4-hydoxyanisole (BHA), 4- cumylphenol, 4-normal-octylphenol, 4-tert-octylphenol, acetyl-hexamethyl-tetrahydro-naphthalene (AHTN), benzo[α]pyrene, beta-sitosterol, bisphenol-A, diazinon, nonylphenol diethoxylate (NP2EO), octyphenol diethoxylate (OP2EO), octylphenol monoethoxylate (OP1EO), and total para-nonylphenol (NP) were detected. Results of reconnaissance studies may help regulators who set water-quality standards begin to prioritize which OWCs to focus upon for given categories of water use.

Occupational Styrene Exposure on Auditory Function Among Adults: A Systematic Review of Selected Workers.

PubMed

Pleban, Francis T; Oketope, Olutosin; Shrestha, Laxmi

2017-12-01

A review study was conducted to examine the adverse effects of styrene, styrene mixtures, or styrene and/or styrene mixtures and noise on the auditory system in humans employed in occupational settings. The search included peer-reviewed articles published in English language involving human volunteers spanning a 25-year period (1990-2015). Studies included peer review journals, case-control studies, and case reports. Animal studies were excluded. An initial search identified 40 studies. After screening for inclusion, 13 studies were retrieved for full journal detail examination and review. As a whole, the results range from no to mild associations between styrene exposure and auditory dysfunction, noting relatively small sample sizes. However, four studies investigating styrene with other organic solvent mixtures and noise suggested combined exposures to both styrene organic solvent mixtures may be more ototoxic than exposure to noise alone. There is little literature examining the effect of styrene on auditory functioning in humans. Nonetheless, findings suggest public health professionals and policy makers should be made aware of the future research needs pertaining to hearing impairment and ototoxicity from styrene. It is recommended that chronic styrene-exposed individuals be routinely evaluated with a comprehensive audiological test battery to detect early signs of auditory dysfunction.

Rational design of broad spectrum antibacterial activity based on a clinically relevant enoyl-acyl carrier protein (ACP) reductase inhibitor.

PubMed

Schiebel, Johannes; Chang, Andrew; Shah, Sonam; Lu, Yang; Liu, Li; Pan, Pan; Hirschbeck, Maria W; Tareilus, Mona; Eltschkner, Sandra; Yu, Weixuan; Cummings, Jason E; Knudson, Susan E; Bommineni, Gopal R; Walker, Stephen G; Slayden, Richard A; Sotriffer, Christoph A; Tonge, Peter J; Kisker, Caroline

2014-06-06

Determining the molecular basis for target selectivity is of particular importance in drug discovery. The ideal antibiotic should be active against a broad spectrum of pathogenic organisms with a minimal effect on human targets. CG400549, a Staphylococcus-specific 2-pyridone compound that inhibits the enoyl-acyl carrier protein reductase (FabI), has recently been shown to possess human efficacy for the treatment of methicillin-resistant Staphylococcus aureus infections, which constitute a serious threat to human health. In this study, we solved the structures of three different FabI homologues in complex with several pyridone inhibitors, including CG400549. Based on these structures, we rationalize the 65-fold reduced affinity of CG400549 toward Escherichia coli versus S. aureus FabI and implement concepts to improve the spectrum of antibacterial activity. The identification of different conformational states along the reaction coordinate of the enzymatic hydride transfer provides an elegant visual depiction of the relationship between catalysis and inhibition, which facilitates rational inhibitor design. Ultimately, we developed the novel 4-pyridone-based FabI inhibitor PT166 that retained favorable pharmacokinetics and efficacy in a mouse model of S. aureus infection with extended activity against Gram-negative and mycobacterial organisms. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Multirobot Lunar Excavation and ISRU Using Artificial-Neural-Tissue Controllers

NASA Astrophysics Data System (ADS)

Thangavelautham, Jekanthan; Smith, Alexander; Abu El Samid, Nader; Ho, Alexander; Boucher, Dale; Richard, Jim; D'Eleuterio, Gabriele M. T.

2008-01-01

Automation of site preparation and resource utilization on the Moon with teams of autonomous robots holds considerable promise for establishing a lunar base. Such multirobot autonomous systems would require limited human support infrastructure, complement necessary manned operations and reduce overall mission risk. We present an Artificial Neural Tissue (ANT) architecture as a control system for autonomous multirobot excavation tasks. An ANT approach requires much less human supervision and pre-programmed human expertise than previous techniques. Only a single global fitness function and a set of allowable basis behaviors need be specified. An evolutionary (Darwinian) selection process is used to `breed' controllers for the task at hand in simulation and the fittest controllers are transferred onto hardware for further validation and testing. ANT facilitates `machine creativity', with the emergence of novel functionality through a process of self-organized task decomposition of mission goals. ANT based controllers are shown to exhibit self-organization, employ stigmergy (communication mediated through the environment) and make use of templates (unlabeled environmental cues). With lunar in-situ resource utilization (ISRU) efforts in mind, ANT controllers have been tested on a multirobot excavation task in which teams of robots with no explicit supervision can successfully avoid obstacles, interpret excavation blueprints, perform layered digging, avoid burying or trapping other robots and clear/maintain digging routes.

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

Thangavelautham, Jekanthan; Smith, Alexander; Abu El Samid, Nader

Automation of site preparation and resource utilization on the Moon with teams of autonomous robots holds considerable promise for establishing a lunar base. Such multirobot autonomous systems would require limited human support infrastructure, complement necessary manned operations and reduce overall mission risk. We present an Artificial Neural Tissue (ANT) architecture as a control system for autonomous multirobot excavation tasks. An ANT approach requires much less human supervision and pre-programmed human expertise than previous techniques. Only a single global fitness function and a set of allowable basis behaviors need be specified. An evolutionary (Darwinian) selection process is used to 'breed' controllersmore » for the task at hand in simulation and the fittest controllers are transferred onto hardware for further validation and testing. ANT facilitates 'machine creativity', with the emergence of novel functionality through a process of self-organized task decomposition of mission goals. ANT based controllers are shown to exhibit self-organization, employ stigmergy (communication mediated through the environment) and make use of templates (unlabeled environmental cues). With lunar in-situ resource utilization (ISRU) efforts in mind, ANT controllers have been tested on a multirobot excavation task in which teams of robots with no explicit supervision can successfully avoid obstacles, interpret excavation blueprints, perform layered digging, avoid burying or trapping other robots and clear/maintain digging routes.« less

Synergistic Disruption of External Male Sex Organ Development by a Mixture of Four Antiandrogens

PubMed Central

Christiansen, Sofie; Scholze, Martin; Dalgaard, Majken; Vinggaard, Anne Marie; Axelstad, Marta; Kortenkamp, Andreas; Hass, Ulla

2009-01-01

Background By disrupting the action of androgens during gestation, certain chemicals present in food, consumer products, and the environment can induce irreversible demasculinization and malformations of sex organs among male offspring. However, the consequences of simultaneous exposure to such chemicals are not well described, especially when they exert their actions by differing molecular mechanisms. Objectives To fill this gap, we investigated the effects of mixtures of a widely used plasticizer, di(2-ethylhexyl) phthalate (DEHP); two fungicides present in food, vinclozolin and prochloraz; and a pharmaceutical, finasteride, on landmarks of male sexual development in the rat, including changes in anogenital distance (AGD), retained nipples, sex organ weights, and malformations of genitalia. These chemicals were chosen because they disrupt androgen action with differing mechanisms of action. Results Strikingly, the effect of combined exposure to the selected chemicals on malformations of external sex organs was synergistic, and the observed responses were greater than would be predicted from the toxicities of the individual chemicals. In relation to other hallmarks of disrupted male sexual development, including changes in AGD, retained nipples, and sex organ weights, the combined effects were dose additive. When the four chemicals were combined at doses equal to no observed adverse effect levels estimated for nipple retention, significant reductions in AGD were observed in male offspring. Conclusions Because unhindered androgen action is essential for human male development in fetal life, these findings are highly relevant to human risk assessment. Evaluations that ignore the possibility of combination effects may lead to considerable underestimations of risks associated with exposures to chemicals that disrupt male sexual differentiation. PMID:20049201

Towards an evaluation framework for information quality management (IQM) practices for health information systems--evaluation criteria for effective IQM practices.

PubMed

Mohammed, Siti Asma; Yusof, Maryati Mohd

2013-04-01

Poor information quality (IQ) must be understood as a business problem rather than systems problem. In health care organization, what is required is an effective quality management that continuously manages and reviews the factors influencing IQ in health information systems (HIS) so as to achieve the desired outcomes. Hence, in order to understand the issues of information quality management (IQM) practices in health care organizations, a more holistic evaluation study should be undertaken to investigate the IQM practices in health care organizations. It is the aim of this paper to identify the significant evaluation criteria that influence the production of good IQ in HIS. Six selected frameworks and best practices both from health informatics and information systems literature have been reviewed to identify the evaluation criteria from the perspective of human, organizational and technological factors. From the review, it was found that human and organization factors are of greater significance in influencing HIS IQ. Our review depicts that there is still shortage in finding a comprehensive IQM evaluation framework. Thus, the criteria from the frameworks reviewed can be used in combination for more comprehensive evaluation criteria. Integrated IQM evaluation criteria for HIS are then proposed in this study. Poor IQ is the result of complex interdependency within sociotechnical factors in health care organization and lack of formal and structured IQM practices. Thus, a feedback mechanism such as evaluation is needed to understand the issues in depth in the future. © 2012 Blackwell Publishing Ltd.

The direction of evolution: the rise of cooperative organization.

PubMed

Stewart, John E

2014-09-01

Two great trends are evident in the evolution of life on Earth: towards increasing diversification and towards increasing integration. Diversification has spread living processes across the planet, progressively increasing the range of environments and free energy sources exploited by life. Integration has proceeded through a stepwise process in which living entities at one level are integrated into cooperative groups that become larger-scale entities at the next level, and so on, producing cooperative organizations of increasing scale (for example, cooperative groups of simple cells gave rise to the more complex eukaryote cells, groups of these gave rise to multi-cellular organisms, and cooperative groups of these organisms produced animal societies). The trend towards increasing integration has continued during human evolution with the progressive increase in the scale of human groups and societies. The trends towards increasing diversification and integration are both driven by selection. An understanding of the trajectory and causal drivers of the trends suggests that they are likely to culminate in the emergence of a global entity. This entity would emerge from the integration of the living processes, matter, energy and technology of the planet into a global cooperative organization. Such an integration of the results of previous diversifications would enable the global entity to exploit the widest possible range of resources across the varied circumstances of the planet. This paper demonstrates that it's case for directionality meets the tests and criticisms that have proven fatal to previous claims for directionality in evolution. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

SU-E-T-561: Monte Carlo-Based Organ Dose Reconstruction Using Pre-Contoured Human Model for Hodgkins Lymphoma Patients Treated by Cobalt-60 External Beam Therapy

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

Jung, J; Pelletier, C; Lee, C

Purpose: Organ doses for the Hodgkin’s lymphoma patients treated with cobalt-60 radiation were estimated using an anthropomorphic model and Monte Carlo modeling. Methods: A cobalt-60 treatment unit modeled in the BEAMnrc Monte Carlo code was used to produce phase space data. The Monte Carlo simulation was verified with percent depth dose measurement in water at various field sizes. Radiation transport through the lung blocks were modeled by adjusting the weights of phase space data. We imported a precontoured adult female hybrid model and generated a treatment plan. The adjusted phase space data and the human model were imported to themore » XVMC Monte Carlo code for dose calculation. The organ mean doses were estimated and dose volume histograms were plotted. Results: The percent depth dose agreement between measurement and calculation in water phantom was within 2% for all field sizes. The mean organ doses of heart, left breast, right breast, and spleen for the selected case were 44.3, 24.1, 14.6 and 3.4 Gy, respectively with the midline prescription dose of 40.0 Gy. Conclusion: Organ doses were estimated for the patient group whose threedimensional images are not available. This development may open the door to more accurate dose reconstruction and estimates of uncertainties in secondary cancer risk for Hodgkin’s lymphoma patients. This work was partially supported by the intramural research program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.« less

Predictive Management of Asian Carps in the Upper Mississippi River System

USGS Publications Warehouse

Vondracek, Bruce C.; Carlson, Andrew K.

2014-01-01

Prolific non-native organisms pose serious threats to ecosystems and economies worldwide. Nonnative bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix), collectively referred to as Asian carps, continue to colonize aquatic ecosystems throughout the central United States. These species are r-selected, exhibiting iteroparous spawning, rapid growth, broad environmental tolerance, high density, and long-distance movement. Hydrological, thermal, and physicochemical conditions are favorable for establishment beyond the current range, rendering containment and control imperative. Ecological approaches to confine Asian carp populations and prevent colonization characterize contemporary management in the United States. Foraging and reproduction of Asian carps govern habitat selection and movement, providing valuable insight for predictive control. Current management approaches are progressive and often anticipatory but deficient in human dimensions. We define predictive management of Asian carps as synthesis of ecology and human dimensions at regional and local scales to develop strategies for containment and control. We illustrate predictive management in the Upper Mississippi River System and suggest resource managers integrate predictive models, containment paradigms, and human dimensions to design effective, socially acceptable management strategies. Through continued research, university-agency collaboration, and public engagement, predictive management of Asian carps is an auspicious paradigm for preventing and alleviating consequences of colonization in the United States.

The Episodic Memory System: Neurocircuitry and Disorders

PubMed Central

Dickerson, Bradford C; Eichenbaum, Howard

2010-01-01

The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals. PMID:19776728

Screening of organic pollutants in pet hair samples and the significance of environmental factors.

PubMed

González-Gómez, Xiana; Cambeiro-Pérez, Noelia; Martínez-Carballo, Elena; Simal-Gándara, Jesús

2018-06-01

Organic pollutants (OPs) represent a wide range of chemicals that are potentially harmful for human and wildlife health. Many of these pollutants have been identified as endocrine disruptors that can alter hormonal balance producing adverse biological effects such as neurotoxicity, reproductive disorders, carcinogenicity and hepatotoxicity. For years, hair has been selected as a non-invasive source to assess levels of animal contamination. In the present study, a multiclass screening method for determining about 60 organic pollutants in pet hair was designed and validated for qualitative and quantitative purposes. Concentrations from different classes of organochlorine, and organophosphate pesticides (OCPs, and OPPs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (NDL-PCBs and DL-PCBs), polybrominated diphenyl ethers (PBDEs) and organophosphate esters (OPEs) were identified in the selected pet hair samples from Ourense (NW, Spain). We detected most of these pollutants in the selected hair pets. The mean concentrations found ranged from 89 to 6556ng/g for OPEs, from 8.6 to 1031ng/g for PAHs, from 8.6 to 256ng/g for PBDEs, from 29 to 184ng/g for OPPs, from 0.29 to 139 for OCPs, from 0.30 to 59ng/g for NDL-PCBs and from 1.2 to 14ng/g for DL-PCBs. To our knowledge, this is the first study to document the presence of OPs in pets from North-West Spain and it could provide baseline information for future monitoring of OPs in the area. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and ionic mimicry and the transport of toxic metals

PubMed Central

Bridges, Christy C.; Zalups, Rudolfs K.

2008-01-01

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues. PMID:15845419

Molecular and ionic mimicry and the transport of toxic metals

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

Bridges, Christy C.; Zalups, Rudolfs K.

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport ofmore » selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.« less

The use of crop rotation for mapping soil organic content in farmland

NASA Astrophysics Data System (ADS)

Yang, Lin; Song, Min; Zhu, A.-Xing; Qin, Chengzhi

2017-04-01

Most of the current digital soil mapping uses natural environmental covariates. However, human activities have significantly impacted the development of soil properties since half a century, and therefore become an important factor affecting soil spatial variability. Many researches have done field experiments to show how soil properties are impacted and changed by human activities, however, spatial variation data of human activities as environmental covariates have been rarely used in digital soil mapping. In this paper, we took crop rotation as an example of agricultural activities, and explored its effectiveness in characterizing and mapping the spatial variability of soil. The cultivated area of Xuanzhou city and Langxi County in Anhui Province was chosen as the study area. Three main crop rotations,including double-rice, wheat-rice,and oilseed rape-cotton were observed through field investigation in 2010. The spatial distribution of the three crop rotations in the study area was obtained by multi-phase remote sensing image interpretation using a supervised classification method. One-way analysis of variance (ANOVA) for topsoil organic content in the three crop rotation groups was performed. Factor importance of seven natural environmental covariates, crop rotation, Land use and NDVI were generated by variable importance criterion of Random Forest. Different combinations of environmental covariates were selected according to the importance rankings of environmental covariates for predicting SOC using Random Forest and Soil Landscape Inference Model (SOLIM). A cross validation was generated to evaluated the mapping accuracies. The results showed that there were siginificant differences of topsoil organic content among the three crop rotation groups. The crop rotation is more important than parent material, land use or NDVI according to the importance ranking calculated by Random Forest. In addition, crop rotation improved the mapping accuracy, especially for the flat clutivated area. This study demonstrates the usefulness of human activities in digital soil mapping and thus indicates the necessity for human activity factors in digital soil mapping studies.

High-performance workplace practices in nursing homes: an economic perspective.

PubMed

Bishop, Christine E

2014-02-01

To develop implications for research, practice and policy, selected economics and human resources management research literature was reviewed to compare and contrast nursing home culture change work practices with high-performance human resource management systems in other industries. The organization of nursing home work under culture change has much in common with high-performance work systems, which are characterized by increased autonomy for front-line workers, self-managed teams, flattened supervisory hierarchy, and the aspiration that workers use specific knowledge gained on the job to enhance quality and customization. However, successful high-performance work systems also entail intensive recruitment, screening, and on-going training of workers, and compensation that supports selective hiring and worker commitment; these features are not usual in the nursing home sector. Thus despite many parallels with high-performance work systems, culture change work systems are missing essential elements: those that require higher compensation. If purchasers, including public payers, were willing to pay for customized, resident-centered care, productivity gains could be shared with workers, and the nursing home sector could move from a low-road to a high-road employment system.

Personality and morphological traits affect pigeon survival from raptor attacks.

PubMed

Santos, Carlos D; Cramer, Julia F; Pârâu, Liviu G; Miranda, Ana C; Wikelski, Martin; Dechmann, Dina K N

2015-10-22

Personality traits have recently been shown to impact fitness in different animal species, potentially making them similarly relevant drivers as morphological and life history traits along the evolutionary pathways of organisms. Predation is a major force of natural selection through its deterministic effects on individual survival, but how predation pressure has helped to shape personality trait selection, especially in free-ranging animals, remains poorly understood. We used high-precision GPS tracking to follow whole flocks of homing pigeons (Columba livia) with known personalities and morphology during homing flights where they were severely predated by raptors. This allowed us to determine how the personality and morphology traits of pigeons may affect their risk of being predated by raptors. Our survival model showed that individual pigeons, which were more tolerant to human approach, slower to escape from a confined environment, more resistant to human handling, with larger tarsi, and with lighter plumage, were more likely to be predated by raptors. We provide rare empirical evidence that the personality of prey influences their risk of being predated under free-ranging circumstances.

Personality and morphological traits affect pigeon survival from raptor attacks

PubMed Central

Santos, Carlos D.; Cramer, Julia F.; Pârâu, Liviu G.; Miranda, Ana C.; Wikelski, Martin; Dechmann, Dina K. N.

2015-01-01

Personality traits have recently been shown to impact fitness in different animal species, potentially making them similarly relevant drivers as morphological and life history traits along the evolutionary pathways of organisms. Predation is a major force of natural selection through its deterministic effects on individual survival, but how predation pressure has helped to shape personality trait selection, especially in free-ranging animals, remains poorly understood. We used high-precision GPS tracking to follow whole flocks of homing pigeons (Columba livia) with known personalities and morphology during homing flights where they were severely predated by raptors. This allowed us to determine how the personality and morphology traits of pigeons may affect their risk of being predated by raptors. Our survival model showed that individual pigeons, which were more tolerant to human approach, slower to escape from a confined environment, more resistant to human handling, with larger tarsi, and with lighter plumage, were more likely to be predated by raptors. We provide rare empirical evidence that the personality of prey influences their risk of being predated under free-ranging circumstances. PMID:26489437

Multiple Click-Selective tRNA Synthetases Expand Mammalian Cell-Specific Proteomics.

PubMed

Yang, Andrew C; du Bois, Haley; Olsson, Niclas; Gate, David; Lehallier, Benoit; Berdnik, Daniela; Brewer, Kyle D; Bertozzi, Carolyn R; Elias, Joshua E; Wyss-Coray, Tony

2018-06-13

Bioorthogonal tools enable cell-type-specific proteomics, a prerequisite to understanding biological processes in multicellular organisms. Here we report two engineered aminoacyl-tRNA synthetases for mammalian bioorthogonal labeling: a tyrosyl ( ScTyr Y43G ) and a phenylalanyl ( MmPhe T413G ) tRNA synthetase that incorporate azide-bearing noncanonical amino acids specifically into the nascent proteomes of host cells. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. Both mutant synthetases label human, hamster, and mouse cell line proteins and selectively activate their azido-bearing amino acids over 10-fold above the canonical. ScTyr Y43G and MmPhe T413G label overlapping but distinct proteomes in human cell lines, with broader proteome coverage upon their coexpression. In mice, ScTyr Y43G and MmPhe T413G label the melanoma tumor proteome and plasma secretome. This work furnishes new tools for mammalian residue-specific bioorthogonal chemistry, and enables more robust and comprehensive cell-type-specific proteomics in live mammals.

Machine learning for the meta-analyses of microbial pathogens' volatile signatures.

PubMed

Palma, Susana I C J; Traguedo, Ana P; Porteira, Ana R; Frias, Maria J; Gamboa, Hugo; Roque, Ana C A

2018-02-20

Non-invasive and fast diagnostic tools based on volatolomics hold great promise in the control of infectious diseases. However, the tools to identify microbial volatile organic compounds (VOCs) discriminating between human pathogens are still missing. Artificial intelligence is increasingly recognised as an essential tool in health sciences. Machine learning algorithms based in support vector machines and features selection tools were here applied to find sets of microbial VOCs with pathogen-discrimination power. Studies reporting VOCs emitted by human microbial pathogens published between 1977 and 2016 were used as source data. A set of 18 VOCs is sufficient to predict the identity of 11 microbial pathogens with high accuracy (77%), and precision (62-100%). There is one set of VOCs associated with each of the 11 pathogens which can predict the presence of that pathogen in a sample with high accuracy and precision (86-90%). The implemented pathogen classification methodology supports future database updates to include new pathogen-VOC data, which will enrich the classifiers. The sets of VOCs identified potentiate the improvement of the selectivity of non-invasive infection diagnostics using artificial olfaction devices.

Learning through social interaction in game technology.

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

Waern, Annika; Raybourn, Elaine Marie

2005-05-01

The present ITSE journal special issue on 'Learning About Social Interaction through Gaming' is the result of an invitation to the attendees of a one-day workshop on 'Social Learning Through Gaming' co-organized by the guest editors and held at the Human Factors in Computing Systems (CHI) conference on April 26, 2004 in Vienna, Austria. CHI is one of the premiere conferences on human-computer interaction. CHI 2004 attracted hundreds of delegates from all over the world. The CHI workshop program results from a competitive selection process. The Social Learning through Gaming workshop was filled to capacity and attended by approximately 25more » participants from Europe and North America who submitted position papers that were refereed and selected for participation based on the relevancy and innovativeness of the research. The participants came together to share research on play, learning, games, interactive technologies, and what playing and designing games can teach us about social behaviors. The present special issue focuses on learning about social aspects through gaming: learning to socialize through games and learning games through social behavior.« less

An efficient ratiometric fluorescence sensor based on metal-organic frameworks and quantum dots for highly selective detection of 6-mercaptopurine.

PubMed

Jin, Meng; Mou, Zhao-Li; Zhang, Rui-Ling; Liang, Si-Si; Zhang, Zhi-Qi

2017-05-15

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed based on a dual-emission nanosensor. The nanosensor was fabricated by combining a blue-emission metal-organic framework (MOF) NH 2 -MIL-53(Al) (λ em =425nm) with green-emission 3-mercaptopropionic acid-capped CdTe quantum dots (MPA-CdTe QDs) (λ em =528nm) under a single excitation wavelength (335nm). Upon addition of 6-MP, the fluorescence of NH 2 -MIL-53(Al) in the nanohybrid was selectively quenched due to strong inner filter effects, while the fluorescence of the MPA-CdTe QDs was enhanced. The novel RF sensor exhibited higher selectivity towards 6-MP than CdTe QDs alone, and higher sensitivity than MOFs alone. 6-MP could be detected in the range of 0-50μM with a detection limit of 0.15μM (S/N=3). The developed sensor was applied for the determination of 6-MP in human urine samples and satisfactory results were obtained. Overall, a novel and efficient fluorescence-based method was developed for the detection of 6-MP in biosamples. Copyright © 2016 Elsevier B.V. All rights reserved.

Early valproic acid exposure alters functional organization in the primary visual cortex

PubMed Central

Pohl-Guimaraes, Fernanda; Krahe, Thomas E.; Medina, Alexandre E.

2018-01-01

Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200 mg/kg), Lev (100 mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42–P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val-but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. PMID:21215743

Early valproic acid exposure alters functional organization in the primary visual cortex.

PubMed

Pohl-Guimaraes, Fernanda; Krahe, Thomas E; Medina, Alexandre E

2011-03-01

Epilepsy is one of the most common neurologic disorders and affects 0.5 to 1% of pregnant women. The use of antiepileptic drugs, which is usually continued throughout pregnancy, can cause in offspring mild to severe sensory deficits. Neuronal selectivity to stimulus orientation is a basic functional property of the visual cortex that is crucial for perception of shapes and borders. Here we investigate the effects of early exposure to valproic acid (Val) and levetiracetam (Lev), commonly used antiepileptic drugs, on the development of cortical neuron orientation selectivity and organization of cortical orientation columns. Ferrets pups were exposed to Val (200mg/kg), Lev (100mg/kg) or saline every other day between postnatal day (P) 10 and P30, a period roughly equivalent to the third trimester of human gestation. Optical imaging of intrinsic signals or single-unit recordings were examined at P42-P84, when orientation selectivity in the ferret cortex has reached a mature state. Optical imaging of intrinsic signals revealed decreased contrast of orientation maps in Val- but not Lev- or saline-treated animals. Moreover, single-unit recordings revealed that early Val treatment also reduced orientation selectivity at the cellular level. These findings indicate that Val exposure during a brief period of development disrupts cortical processing of sensory information at a later age and suggest a neurobiological substrate for some types of sensory deficits in fetal anticonvulsant syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Human local adaptation of the TRPM8 cold receptor along a latitudinal cline

PubMed Central

Mundry, Roger; Peter, Benjamin M.; Sekar, Aarthi; D’Amato, Mauro; Dennis, Megan Y.; Andrés, Aida M.

2018-01-01

Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabit territories under a wide range of temperatures. Focusing on cold perception–which is central to thermoregulation and survival in cold environments–we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analyzed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent–precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today. PMID:29723195

Human local adaptation of the TRPM8 cold receptor along a latitudinal cline.

PubMed

Key, Felix M; Abdul-Aziz, Muslihudeen A; Mundry, Roger; Peter, Benjamin M; Sekar, Aarthi; D'Amato, Mauro; Dennis, Megan Y; Schmidt, Joshua M; Andrés, Aida M

2018-05-01

Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabit territories under a wide range of temperatures. Focusing on cold perception-which is central to thermoregulation and survival in cold environments-we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analyzed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent-precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today.

Antecedents of cell aging research.

PubMed

Hayflick, L

1989-01-01

Our observation that normal human and animal cells have a limited capacity to divide and function in vitro overturned a dogma held since the turn of the century. The dogma held that cultured normal cells are immortal and gerontologists interpreted this to mean that aging, therefore, could not be the result of intracellular events. We concluded that longevity and aging do result from intracellular events, and, in the subsequent 30 years, the validity of our finding has been widely confirmed. Other major findings have been made: (a) The number of population doublings and functional events that a cultured normal cell can undergo is inversely proportional to donor age and, probably, directly proportional to species longevity; (b) the limit on cell division and function also occurs in vivo when normal cells are transplanted seriatim; (c) as cell doublings or functional events reach their limit, changes occur in hundreds of variables from the molecular to the whole cell. Most importantly, many of these changes are identical to those seen in intact humans and animals as they age; (d) WI-38, the first widely distributed normal human cell strain has retained its memory of population doubling level during 27 years of cryogenic storage. This is the longest time that any normal human cell has ever been preserved. Evidence that longevity is determined by genetic events is overwhelming but evidence that age changes are the result of gene expression is not. Normal age changes must be distinguished from disease. Because few feral animals ever become old, natural selection could not have favored the development of a genetically programmed aging process. In the 2 or 3 million years of human existence, too few old humans existed to have provided a selective advantage favoring the development of a genetic program that would determine age changes. The selective advantage of maintaining physiological vigor for as long as possible in order to insure maximum reproductive success may be the essential indirect determinant of longevity. Natural selection has provided sexually mature animals with extraordinary reserve capacities in virtually all organs. After sexual maturation, animals continue to function by utilizing the reserve capacity that evolved to insure that they would attain reproductive success. The magnitude of reserve capacity is the essential element in determining postdevelopmental longevity. Thus "Why do we age?" may be the wrong question. The right question may be "Why do we live as long as we do?"

Using non-human primates to benefit humans: research and organ transplantation.

PubMed

Shaw, David; Dondorp, Wybo; de Wert, Guido

2014-11-01

Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

PubMed

Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

2018-01-01

Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

The potential of the combination of CRISPR/Cas9 and pluripotent stem cells to provide human organs from chimaeric pigs.

PubMed

Feng, Wanyou; Dai, Yifan; Mou, Lisha; Cooper, David K C; Shi, Deshun; Cai, Zhiming

2015-03-23

Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans as organs of any size would be available. Genome editing by RNA-guided endonucleases, also known as clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), in combination with induced pluripotent stem cells (iPSC), may have the potential to enable the creation of human organs from genetically-modified chimaeric pigs. These could potentially provide an unlimited supply of organs that would not be rejected by the recipient's immune system. However, substantial research is needed to prove that this approach will work. Genetic modification of chimaeric pigs could also provide useful models for developing therapies for various human diseases, especially in relation to drug development.

Pilot-scale UV/H2O2 study for emerging organic contaminants decomposition.

PubMed

Chu, Xiaona; Xiao, Yan; Hu, Jiangyong; Quek, Elaine; Xie, Rongjin; Pang, Thomas; Xing, Yongjie

2016-03-01

Human behaviors including consumption of drugs and use of personal care products, climate change, increased international travel, and the advent of water reclamation for direct potable use have led to the introduction of significant amounts of emerging organic contaminants into the aqueous environment. In addition, the lower detection limits associated with improved scientific methods of chemical analysis have resulted in a recent increase in documented incidences of these contaminants which previously were not routinely monitored in water. Such contaminants may cause known or suspected adverse ecological and/or human health effects at very low concentrations. Conventional drinking water treatment processes may not effectively remove these organic contaminants. Advanced oxidation process (AOP) is a promising treatment process for the removal of most of these emerging organic contaminants, and has been accepted worldwide as a suitable treatment process. In this study, different groups of emerging contaminants were studied for decomposition efficiency using pilot-scale UV/H2O2 oxidation setup, including EDCs, PPCPs, taste and odor (T&O), and perfluorinated compounds. Results found that MP UV/H2O2 AOP was efficient in removing all the selected contaminants except perfluorinated compounds. Study of the kinetics of the process showed that both light absorption and quantum yield of each compound affected the decomposition performance. Analysis of water quality parameters of the treated water indicated that the outcome of both UV photolysis and UV/H2O2 processes can be affected by changes in the feed water quality.

Explanation production by expert planners

NASA Technical Reports Server (NTRS)

Bridges, Susan; Jhannes, James D.

1988-01-01

Although the explanation capability of expert systems is usually listed as one of the distinguishing characteristics of these systems, the explanation facilities of most existing systems are quite primitive. Computer generated explanations are typically produced from canned text or by direct translation of the knowledge structures. Explanations produced in this manner bear little resemblance to those produced by humans for similar tasks. The focus of our research in explanation is the production of justifications for decisions by expert planning systems. An analysis of justifications written by people for planning tasks has been taken as the starting point. The purpose of this analysis is two-fold. First, analysis of the information content of the justifications will provide a basis for deciding what knowledge must be represented if human-like justifications are to be produced. Second, an analysis of the textual organization of the justifications will be used in the development of a mechanism for selecting and organizing the knowledge to be included in a computer-produced explanation. This paper describes a preliminary analysis done of justifications written by people for a planning task. It is clear that these justifications differ significantly from those that would be produced by an expert system by tracing the firing of production rules. The results from the text analysis have been used to develop an augmented phrase structured grammar (APSG) describing the organization of the justifications. The grammar was designed to provide a computationally feasible method for determining textual organization that will allow the necessary information to be communicated in a cohesive manner.

Freedom and purpose in biology.

PubMed

McShea, Daniel W

2016-08-01

All seemingly teleological systems share a common hierarchical structure. They consist of a small entity moving or changing within a larger field that directs it from above (what I call "upper direction"). This is true for organisms seeking some external resource, for the organized behavior of cells and other parts in organismal development, and for lineages evolving by natural selection. In all cases, the lower-level entity is partly "free," tending to wander under the influence of purely local forces, and partly directed by a larger enveloping field. The persistent and plastic behavior that characterizes goal-directedness arises, I argue, at intermediate levels of freedom and upper direction, when the two are in a delicate balance. I tentatively extend the argument to human teleology (wants, purposes). Copyright © 2015 Elsevier Ltd. All rights reserved.

Practical Strategies for Promoting Full Inclusion of Individuals with Disabilities in Community-Based Participatory Intervention Research

PubMed Central

Hassouneh, Dena; Alcala-Moss, Amana; McNeff, E.

2011-01-01

Community-based participatory research (CBPR) with disability communities is directed toward facilitating full inclusion of individuals with disabilities and disability community organizations in all aspects of the research process. Within the CBPR framework, academic-disability community partners may value and wish to use experimental designs to test interventions. Being aware of and proactively addressing barriers and challenges to inclusion in the areas of human resources, training, productivity, accommodation, and inadequate funding for disability community organizations are critical for success. Some of the strategies discussed in this paper for addressing these challenges include creating redundant systems, providing benefits counseling and individualized payment options for employment, designing trainings to be disability friendly, and carefully considering selection of partners in light of available community resources. PMID:21472736

Photosynthesis under artificial light: the shift in primary and secondary metabolism

PubMed Central

Darko, Eva; Heydarizadeh, Parisa; Schoefs, Benoît; Sabzalian, Mohammad R.

2014-01-01

Providing an adequate quantity and quality of food for the escalating human population under changing climatic conditions is currently a great challenge. In outdoor cultures, sunlight provides energy (through photosynthesis) for photosynthetic organisms. They also use light quality to sense and respond to their environment. To increase the production capacity, controlled growing systems using artificial lighting have been taken into consideration. Recent development of light-emitting diode (LED) technologies presents an enormous potential for improving plant growth and making systems more sustainable. This review uses selected examples to show how LED can mimic natural light to ensure the growth and development of photosynthetic organisms, and how changes in intensity and wavelength can manipulate the plant metabolism with the aim to produce functionalized foods. PMID:24591723

Neural network system and methods for analysis of organic materials and structures using spectral data

DOEpatents

Meyer, Bernd J.; Sellers, Jeffrey P.; Thomsen, Jan U.

1993-01-01

Apparatus and processes for recognizing and identifying materials. Characteristic spectra are obtained for the materials via spectroscopy techniques including nuclear magnetic resonance spectroscopy, infrared absorption analysis, x-ray analysis, mass spectroscopy and gas chromatography. Desired portions of the spectra may be selected and then placed in proper form and format for presentation to a number of input layer neurons in an offline neural network. The network is first trained according to a predetermined training process; it may then be employed to identify particular materials. Such apparatus and processes are particularly useful for recognizing and identifying organic compounds such as complex carbohydrates, whose spectra conventionally require a high level of training and many hours of hard work to identify, and are frequently indistinguishable from one another by human interpretation.

Human Resource Management in Virtual Organizations. Research in Human Resource Management Series.

ERIC Educational Resources Information Center

Heneman, Robert L., Ed.; Greenberger, David B., Ed.

This document contains 14 papers on human resources (HR) and human resource management (HRM) in virtual organizations. The following papers are included: "Series Preface" (Rodger Griffeth); "Volume Preface" (Robert L. Heneman, David B. Greenberger); "The Virtual Organization: Definition, Description, and…