Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life.

PubMed

Kamminga, Tjerko; Koehorst, Jasper J; Vermeij, Paul; Slagman, Simen-Jan; Martins Dos Santos, Vitor A P; Bijlsma, Jetta J E; Schaap, Peter J

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the "minimal" synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life.

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life

PubMed Central

Kamminga, Tjerko; Koehorst, Jasper J.; Vermeij, Paul; Slagman, Simen-Jan; Martins dos Santos, Vitor A. P.; Bijlsma, Jetta J. E.; Schaap, Peter J.

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the “minimal” synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life. PMID:28224116

Attempts by one local health department to provide only essential public health services: a 10-year retrospective case study.

PubMed

Richardson, J Matthew; Pierce, J Rush; Lackan, Nuha

2012-01-01

Because of local political circumstances, in 1996, the local public health department in Amarillo, Texas, divested itself of almost all personal health services and chose to retain only essential population-based public health services. We analyzed function, funding, and staffing for various health department activities in FY 1997 and again in FY 2007. The figures were adjusted for inflation and population growth. We interviewed key personnel about the motivation and effects of the changes that occurred with this 10-year period. The local health department both transferred and reassumed some personal health services during this period. This was primarily in the area of immunization services and care for special population such as refugees. Public health preparedness also became a significant new area of activity. Most personal health services provided by the health department before 1996 remained the function of other health care entities in the community. When adjusted for inflation and population growth, most of the growth in the health department's personnel and budget was the result of state and federally mandated program changes. Growth in this local health department, which was committed to provide only essential health services, was driven primarily by state and federally mandated programs. Real growth for essential public health services did not occur over a 10-year period.

Chemical characterization (GC/MS and NMR Fingerprinting) and bioactivities of South-African Pelargonium capitatum (L.) L' Her. (Geraniaceae) essential oil.

PubMed

Guerrini, Alessandra; Rossi, Damiano; Paganetto, Guglielmo; Tognolini, Massimiliano; Muzzoli, Mariavittoria; Romagnoli, Carlo; Antognoni, Fabiana; Vertuani, Silvia; Medici, Alessandro; Bruni, Alessandro; Useli, Chiara; Tamburini, Elena; Bruni, Renato; Sacchetti, Gianni

2011-04-01

Chemical fingerprinting of commercial Pelargonium capitatum (Geraniaceae) essential oil samples of south African origin was performed by GC, GC/MS, and (13) C- and (1) H-NMR. Thirty-seven compounds were identified, among which citronellol (32.71%) and geraniol (19.58%) were the most abundant. NMR Spectra of characteristic chemicals were provided. Broad-spectrum bioactivity properties of the oil were evaluated and compared with those of commercial Thymus vulgaris essential oil with the aim to obtain a functional profile in terms of efficacy and safety. P. capitatum essential oil provides a good performance as antimicrobial, with particular efficacy against Candida albicans strains. Antifungal activity performed against dermatophyte and phytopathogen strains revealed the latter as more sensitive, while antibacterial activity was not remarkable against both Gram-positive and Gram-negative bacteria. P. capitatum oil provided a lower antioxidant activity (IC(50) ) than that expressed by thyme essential oil, both in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and β-carotene bleaching tests. Results in photochemiluminescence (PCL) assay were negligible. To test the safety aspects of P. capitatum essential oil, mutagenic and toxicity properties were assayed by Ames test, with and without metabolic activation. Possible efficacy of P. capitatum essential oil as mutagenic protective agent against NaN(3) , 2-nitrofluorene, and 2-aminoanthracene was also assayed, providing interesting and significant antigenotoxic properties. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

Insights into Human Behavior from Lesions to the Prefrontal Cortex

PubMed Central

Szczepanski, Sara M.; Knight, Robert T.

2014-01-01

SUMMARY The prefrontal cortex (PFC), a cortical region that was once thought to be functionally insignificant, is now known to play an essential role in the organization and control of goal-directed thought and behavior. Neuroimaging, neurophysiological, and modeling techniques have lead to tremendous advances in our understanding of PFC functions over the last few decades. It should be noted, however, that neurological, neuropathological, and neuropsychological studies have contributed some of the most essential, historical, and often prescient, conclusions regarding the functions of this region. Importantly, examination of patients with brain damage allows one to draw conclusions about whether a brain area is necessary for a particular function. Here, we provide a broad overview of PFC functions based upon behavioral and neural changes resulting from damage to PFC in both human patients and non-human primates. PMID:25175878

ASSESSING THE EFFECT OF HABITAT ALTERATION ON SHELLFISH POPULATIONS

EPA Science Inventory

Habitat provides a variety of life support functions for many species, such as providing shelter, substrate, food, and nursery areas. Habitat alteration is one of the most important causes of declines in ecological resources in North America, and habitats essential to the well b...

Requirements for clinical information modelling tools.

PubMed

Moreno-Conde, Alberto; Jódar-Sánchez, Francisco; Kalra, Dipak

2015-07-01

This study proposes consensus requirements for clinical information modelling tools that can support modelling tasks in medium/large scale institutions. Rather than identify which functionalities are currently available in existing tools, the study has focused on functionalities that should be covered in order to provide guidance about how to evolve the existing tools. After identifying a set of 56 requirements for clinical information modelling tools based on a literature review and interviews with experts, a classical Delphi study methodology was applied to conduct a two round survey in order to classify them as essential or recommended. Essential requirements are those that must be met by any tool that claims to be suitable for clinical information modelling, and if we one day have a certified tools list, any tool that does not meet essential criteria would be excluded. Recommended requirements are those more advanced requirements that may be met by tools offering a superior product or only needed in certain modelling situations. According to the answers provided by 57 experts from 14 different countries, we found a high level of agreement to enable the study to identify 20 essential and 21 recommended requirements for these tools. It is expected that this list of identified requirements will guide developers on the inclusion of new basic and advanced functionalities that have strong support by end users. This list could also guide regulators in order to identify requirements that could be demanded of tools adopted within their institutions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Functional domains of the human splicing factor ASF/SF2.

PubMed Central

Zuo, P; Manley, J L

1993-01-01

The human splicing factor ASF/SF2 displays two predominant activities in in vitro splicing assays: (i) it is an essential factor apparently required for all splices and (ii) it is able to switch utilization of alternative 5' splice sites in a concentration-dependent manner. ASF/SF2 is the prototype of a family of proteins typified by the presence of one or two RNP-type RNA binding domains (RBDs) and a region highly enriched in repeating arginine-serine dipeptides (RS regions). Here we describe a functional analysis of ASF/SF2, which defines several regions essential for one, or both, of its two principal activities, and provides insights into how this type of protein functions in splicing. Two isoforms of the protein, which arise from alternative splicing, are by themselves inactive, but each can block the activity of ASF/SF2, thereby functioning as splicing repressors. Some, but not all, mutations in the RS region prevent ASF/SF2 from functioning as an essential splicing factor. However, the entire RS region can be deleted without reducing splice site switching activity, indicating that it is not absolutely required for interaction with other splicing factors. Experiments with deletion and substitution mutants reveal that the protein contains two related, but highly diverged, RBDs, and that both are essential for activity. Each RBD by itself retains the ability to bind RNA, although optimal binding requires both domains. Images PMID:8223481

Effects of Economy Type and Nicotine on the Essential Value of Food in Rats

PubMed Central

Cassidy, Rachel N; Dallery, Jesse

2012-01-01

The exponential demand equation proposed by Hursh and Silberberg (2008) provides an estimate of the essential value of a good as a function of price. The model predicts that essential value should remain constant across changes in the magnitude of a reinforcer, but may change as a function of motivational operations. In Experiment 1, rats' demand for food across a sequence of fixed-ratio schedules was assessed during open and closed economy conditions and across one- and two-pellet per reinforcer delivery conditions. The exponential equation was fitted to the relation between fixed-ratio size and the logarithm of the absolute number of reinforcers. Estimates of the rate of change in elasticity of food, the proposed measure of essential value, were compared across conditions. Essential value was equivalent across magnitudes during the closed economy, but showed a slight decrease across magnitudes during the open economy. Experiment 2 explored the behavioral mechanisms of nicotine's effects on consumption with the results from Experiment 1 serving as a within-subject frame of reference. The same subjects were administered nicotine via subcutaneously implanted osmotic minipumps at a dose of 3 mg/kg/day and exposed to both the one- and two-pellet conditions under a closed economy. Although nicotine produced large decreases in demand, essential value was not significantly changed. The data from the present experiments provide further evidence for the adequacy of the exponential demand equation as a tool for quantifying the rate of change in elasticity of a good and for assessing behavioral mechanisms of drug action. PMID:22389525

Effects of economy type and nicotine on the essential value of food in rats.

PubMed

Cassidy, Rachel N; Dallery, Jesse

2012-03-01

The exponential demand equation proposed by Hursh and Silberberg (2008) provides an estimate of the essential value of a good as a function of price. The model predicts that essential value should remain constant across changes in the magnitude of a reinforcer, but may change as a function of motivational operations. In Experiment 1, rats' demand for food across a sequence of fixed-ratio schedules was assessed during open and closed economy conditions and across one- and two-pellet per reinforcer delivery conditions. The exponential equation was fitted to the relation between fixed-ratio size and the logarithm of the absolute number of reinforcers. Estimates of the rate of change in elasticity of food, the proposed measure of essential value, were compared across conditions. Essential value was equivalent across magnitudes during the closed economy, but showed a slight decrease across magnitudes during the open economy. Experiment 2 explored the behavioral mechanisms of nicotine's effects on consumption with the results from Experiment 1 serving as a within-subject frame of reference. The same subjects were administered nicotine via subcutaneously implanted osmotic minipumps at a dose of 3 mg/kg/day and exposed to both the one- and two-pellet conditions under a closed economy. Although nicotine produced large decreases in demand, essential value was not significantly changed. The data from the present experiments provide further evidence for the adequacy of the exponential demand equation as a tool for quantifying the rate of change in elasticity of a good and for assessing behavioral mechanisms of drug action.

Eco-logical successes : fourth edition, March 2013

DOT National Transportation Integrated Search

2013-03-01

Infrastructure facilities, such as roadways, transit lines, and communication systems, provide vital services that support the healthy functioning of a community. While essential, sometimes the development of these facilities has negative environment...

Preparing Transition-Age Students with High-Functioning Autism Spectrum Disorders for Meaningful Work

ERIC Educational Resources Information Center

Lee, Gloria K.; Carter, Erik W.

2012-01-01

This article provides an overview of promising essential elements for fostering vocational success among students with high-functioning autism spectrum disorders (HFASDs) by drawing literature from the fields of school-to-work transition for post-secondary students and vocational rehabilitation for individuals with disabilities. We highlight seven…

Communication and Diversity: Innovations in Teacher Education

ERIC Educational Resources Information Center

Simonds, Brent K.; Lippert, Lance R.; Hunt, Stephen K.; Angell, Maureen E.; Moore, Marilyn K.

2008-01-01

Teacher education programs have increasingly come under fire for not providing pre-service teachers communication skills training. Given that such training is essential to address diversity in the classroom and to meet the day-to-day functioning of teachers, higher education must provide communication skills training for teacher certification.…

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

PubMed Central

Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

2008-01-01

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

[The health system of Guatemala].

PubMed

Becerril-Montekio, Víctor; López-Dávila, Luis

2011-01-01

This paper describes the health conditions in Guatemala and, in more detail, the characteristics of the Guatemalan health system, including its structure en coverage, its financial sources, the stewardship functions developed by the Ministry of Health, as well as the generation of health information and the development of research activities. It also discusses the recent efforts to extend coverage of essential health services, mostly to poor rural areas.The most recent innovations also discussed in this paper include the Program for the Expansion of Coverage of Essential Services, the Program to Expand Access to Essential Drugs and the agreements between the Ministry of Health and several non-governmental organizations to provide essential services in rural settings.

30 CFR 822.11 - Essential hydrologic functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Essential hydrologic functions. 822.11 Section... IN ALLUVIAL VALLEY FLOORS § 822.11 Essential hydrologic functions. (a) The operator of a surface coal... throughout the mining and reclamation process the essential hydrologic functions of an alluvial valley floor...

Jamaican families.

PubMed

Miner, Dianne Cooney

2003-01-01

The study of the family in the Caribbean originated with European scholars who assumed the universality of the patriarchal nuclear family and the primacy of this structure to the healthy functioning of society. Matrifocal Caribbean families thus were seen as chaotic and disorganized and inadequate to perform the essential tasks of the social system. This article provides a more current discussion of the Jamaican family. It argues that its structure is the result of the agency and adaptation of its members and not the root cause of the increasing marginalization of peoples in the developing world. The article focuses on families living in poverty and how the family structure supports essential family functions, adaptations, and survival.

What's That You're Saying? Children with Better Executive Functioning Produce and Repair Communication More Effectively

ERIC Educational Resources Information Center

Bacso, Sarah A.; Nilsen, Elizabeth S.

2017-01-01

Young children often provide ambiguous referential statements. Thus, the ability to identify when miscommunication has occurred and subsequently repair messages is an essential component of communicative development. The present study examined the impact of listener feedback and children's executive functioning in influencing children's ability to…

Excellence in Career Counseling: Improving Services to Students Who Are Deaf or Hard of Hearing.

ERIC Educational Resources Information Center

Western Region Outreach Center and Consortia, Northridge, CA.

This booklet provides basic information on career counseling for deaf postsecondary students. and lists voice and TTY numbers for various federal resources related to the Americans with Disabilities Act. It also provides definitions of such terms as "reasonable accommodation" and "essential job functions." Basic information is…

Histone H2A.Z is essential for estrogen receptor signaling

PubMed Central

Gévry, Nicolas; Hardy, Sara; Jacques, Pierre-Étienne; Laflamme, Liette; Svotelis, Amy; Robert, François; Gaudreau, Luc

2009-01-01

Incorporation of H2A.Z into the chromatin of inactive promoters has been shown to poise genes for their expression. Here we provide strong evidence that H2A.Z is incorporated into the promoter regions of estrogen receptor (ERα) target genes only upon gene induction, and that, in a cyclic pattern. Moreover, members of the human H2A.Z-depositing complex, p400, also follow the same gene recruitment kinetics as H2A.Z. Importantly, cellular depletion of H2A.Z or p400 leads to a severe defect in estrogen signaling, including loss of estrogen-specific cell proliferation. We find that incorporation of H2A.Z within TFF1 promoter chromatin allows nucleosomes to adopt preferential positions along the DNA translational axis. Finally, we provide evidence that H2A.Z is essential to allow estrogen-responsive enhancer function. Taken together, our results provide strong mechanistic insight into how H2A.Z regulates ERα-mediated gene expression and provide a novel link between H2A.Z–p400 and ERα-dependent gene regulation and enhancer function. PMID:19515975

Segmenting healthcare terminology users: a strategic approach to large scale evolutionary development.

PubMed

Price, C; Briggs, K; Brown, P J

1999-01-01

Healthcare terminologies have become larger and more complex, aiming to support a diverse range of functions across the whole spectrum of healthcare activity. Prioritization of development, implementation and evaluation can be achieved by regarding the "terminology" as an integrated system of content-based and functional components. Matching these components to target segments within the healthcare community, supports a strategic approach to evolutionary development and provides essential product differentiation to enable terminology providers and systems suppliers to focus on end-user requirements.

Basic amino acid residues located in the N-terminal region of BEND3 are essential for its nuclear localization.

PubMed

Shiheido, Hirokazu; Shimizu, Jun

2015-02-20

BEN domain-containing protein 3 (BEND3) has recently been reported to function as a heterochromatin-associated protein in transcriptional repression in the nucleus. BEND3 should have nuclear localization signals (NLSs) to localize to the nucleus in light of its molecular weight, which is higher than that allowed to pass through nuclear pore complexes. We here analyzed the subcellular localization of deletion/site-directed mutants of human BEND3 by an immunofluorescence assay in an attempt to identify the amino acids essential for its nuclear localization. We found that three basic amino acid residues located in the N-terminal region of BEND3 (BEND356-58, KRK) are essential, suggesting that these residues play a role as a functional NLS. These results provide valuable information for progressing research on BEND3. Copyright © 2015 Elsevier Inc. All rights reserved.

Sustained choroid plexus function in human elderly and Alzheimer's disease patients.

PubMed

Spector, Reynold; Johanson, Conrad E

2013-09-24

We and other investigators have postulated deterioration of essential choroid plexus (CP) functions in some elderly and especially Alzheimer's disease patients based on apparent anatomical, histological and pathological changes in CP. We have termed this putative phenomenon CP failure. By focusing on four essential energy-requiring CP functions, specifically ascorbic acid (AA) and folate transport from blood into CSF, transthyretin synthesis and secretion into CSF, and electrolyte/acid-base balance in CSF, we were able to evaluate the hypothesis of CP failure by reviewing definitive human data. In both healthy elderly and Alzheimer's disease patients, the CP functions normally to transport AA and folates actively from blood into CSF, synthesize and secrete transthyretin into CSF, and maintain CSF acid-base balance and ion concentrations. These human CSF compositional data provide no support for the notion of CP failure in elderly humans and Alzheimer's disease patients.

Thermal-Diffusivity Measurements of Mexican Citrus Essential Oils Using Photoacoustic Methodology in the Transmission Configuration

NASA Astrophysics Data System (ADS)

Muñoz, G. A. López; González, R. F. López; López, J. A. Balderas; Martínez-Pérez, L.

2011-05-01

Photoacoustic methodology in the transmission configuration (PMTC) was used to study the thermophysical properties and their relation with the composition in Mexican citrus essential oils providing the viability of using photothermal techniques for quality control and for authentication of oils and their adulteration. Linear relations for the amplitude (on a semi-log scale) and phase, as functions of the sample's thickness, for the PMTC was obtained through a theoretical model fit to the experimental data for thermal-diffusivity measurements in Mexican orange, pink grapefruit, mandarin, lime type A, centrifuged essential oils, and Mexican distilled lime essential oil. Gas chromatography for distilled lime essential oil and centrifuged lime essential oil type A is reported to complement the study. Experimental results showed close thermal-diffusivity values between Mexican citrus essential oils obtained by centrifugation, but a significant difference of this physical property for distilled lime oil and the corresponding value obtained by centrifugation, which is due to their different chemical compositions involved with the extraction processes.

Oligomeric Status and Nucleotide Binding Properties of the Plastid ATP/ADP Transporter 1: Toward a Molecular Understanding of the Transport Mechanism

PubMed Central

Deniaud, Aurélien; Panwar, Pankaj; Frelet-Barrand, Annie; Bernaudat, Florent; Juillan-Binard, Céline; Ebel, Christine; Rolland, Norbert; Pebay-Peyroula, Eva

2012-01-01

Background Chloroplast ATP/ADP transporters are essential to energy homeostasis in plant cells. However, their molecular mechanism remains poorly understood, primarily due to the difficulty of producing and purifying functional recombinant forms of these transporters. Methodology/Principal Findings In this work, we describe an expression and purification protocol providing good yields and efficient solubilization of NTT1 protein from Arabidopsis thaliana. By biochemical and biophysical analyses, we identified the best detergent for solubilization and purification of functional proteins, LAPAO. Purified NTT1 was found to accumulate as two independent pools of well folded, stable monomers and dimers. ATP and ADP binding properties were determined, and Pi, a co-substrate of ADP, was confirmed to be essential for nucleotide steady-state transport. Nucleotide binding studies and analysis of NTT1 mutants lead us to suggest the existence of two distinct and probably inter-dependent binding sites. Finally, fusion and deletion experiments demonstrated that the C-terminus of NTT1 is not essential for multimerization, but probably plays a regulatory role, controlling the nucleotide exchange rate. Conclusions/Significance Taken together, these data provide a comprehensive molecular characterization of a chloroplast ATP/ADP transporter. PMID:22438876

Control of Spin Wave Dynamics in Spatially Twisted Magnetic Structures

DTIC Science & Technology

2017-06-27

realize high-performance spintronic and magnetic storage devices. 15. SUBJECT TERMS nano- electronics , spin, wave, magnetic, multi-functional, device 16... electronics has required us to develop high-performance and multi-functional electronic devices driven with extremely low power consumption...Spintronics”, simultaneously utilizing the charge and the spin of electrons , provides us with solutions to essential problems for semiconductor-based

What's at Stake in the Lives of People with Intellectual Disability? Part I: The Power of Naming, Defining, Diagnosing, Classifying, and Planning Supports

ERIC Educational Resources Information Center

Schalock, Robert L.; Luckasson, Ruth

2013-01-01

This article focuses on the power of naming, defining, diagnosing, classifying, and planning supports for people with intellectual disability. The article summarizes current thinking regarding these five functions, states the essential question addressed by the respective function, and provides an overview of the high stakes involved for people…

The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

PubMed

Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

2018-01-29

Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

HABITAT RELATIONSHIPS OF WATERFOWL WINTERING IN NARRAGANSTT BAY

EPA Science Inventory

Coastal marine habitats often provide essential structure and life support functions for estuarine-dependent wildlife such as wading birds, small mammals, and waterfowl. Unfortunately, these areas are increasingly being lost or degraded by watershed development and human disturb...

1997 Economic Census : transportation : 1997 Commodity Flow Survey : exports

DOT National Transportation Integrated Search

2000-04-01

The Commodity Flow Survey comprises one section of the 1997 Economic Census. The economic census is the major source of facts about the structure and functioning of the Nation's economy. It provides essential information for government, business, ind...

A Context-Aware Ubiquitous Learning Approach for Providing Instant Learning Support in Personal Computer Assembly Activities

ERIC Educational Resources Information Center

Hsu, Ching-Kun; Hwang, Gwo-Jen

2014-01-01

Personal computer assembly courses have been recognized as being essential in helping students understand computer structure as well as the functionality of each computer component. In this study, a context-aware ubiquitous learning approach is proposed for providing instant assistance to individual students in the learning activity of a…

Exploring Doctoral Students' Perceptions of Language Use in Supervisory Written Feedback Practices--Because "Feedback Is Hard to Have"

ERIC Educational Resources Information Center

Stracke, Elke; Kumar, Vijay

2016-01-01

The mastery of academic writing is essential in doctoral writing. Supervisory feedback provides opportunities for students to improve their writing. It is a communicative tool that can be categorised based on fundamental functions of speech: referential, directive, and expressive. This study provides some understanding of the impact that language…

Chapter 5. Essential equipment, pharmaceuticals and supplies. Recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza epidemic or mass disaster.

PubMed

Sprung, Charles L; Kesecioglu, Jozef

2010-04-01

To provide recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza pandemic or mass disaster with a specific focus on essential equipment, pharmaceuticals and supplies. Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including essential equipment, pharmaceuticals and supplies. Key recommendations include: (1) ensure that adequate essential medical equipment, pharmaceuticals and important supplies are available during a disaster; (2) develop a communication and coordination system between health care facilities and local/regional/state/country governmental authorities for the provision of additional support; (3) determine the required resources, order and stockpile adequate resources, and judiciously distribute them; (4) acquire additional mechanical ventilators that are portable, provide adequate gas exchange for a range of clinical conditions, function with low-flow oxygen and without high pressure, and are safe for patients and staff; (5) provide advanced ventilatory support and rescue therapies including high levels of inspired oxygen and positive end-expiratory pressure, volume and pressure control ventilation, inhaled nitric oxide, high-frequency ventilation, prone positioning ventilation and extracorporeal membrane oxygenation; (6) triage scarce resources including equipment, pharmaceuticals and supplies based on those who are likely to benefit most or on a 'first come, first served' basis. Judicious planning and adoption of protocols for providing adequate equipment, pharmaceuticals and supplies are necessary to optimize outcomes during a pandemic.

Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function

PubMed Central

Sokolovska, Anna; Becker, Christine E.; Eddie Ip, WK; Rathinam, Vijay A.K.; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Vanaja, Sivapriya K.; Moore, Kathryn J.; Fitzgerald, Katherine A.; Lacy-Hulbert, Adam; Stuart, Lynda M.

2013-01-01

Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates a number of functions of these organelles that allow them to participate in processes essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3-inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3-inflammasome and caspase-1 in host defense. PMID:23644505

1997 economic census : transportation 1997 commodity flow survey : United States

DOT National Transportation Integrated Search

1999-12-01

The 1997 Commodity Flow Survey is part of the 1997 Economic Census. The economic census is the major source of facts about the structure and functioning of the Nation's economy. It provides essential information for government, business, industry, an...

The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition

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

Zhang, Lei; Zhang, Qing; Yang, Yu

Highlights: • RNA recognition motif domains of RBM5 are essential for cell proliferation inhibition. • RNA recognition motif domains of RBM5 are essential for apoptosis induction. • RNA recognition motif domains of RBM5 are essential for RNA binding. • RNA recognition motif domains of RBM5 are essential for caspase-2 alternative splicing. - Abstract: RBM5 is a known putative tumor suppressor gene that has been shown to function in cell growth inhibition by modulating apoptosis. RBM5 also plays a critical role in alternative splicing as an RNA binding protein. However, it is still unclear which domains of RBM5 are required formore » RNA binding and related functional activities. We hypothesized the two putative RNA recognition motif (RRM) domains of RBM5 spanning from amino acids 98–178 and 231–315 are essential for RBM5-mediated cell growth inhibition, apoptosis regulation, and RNA binding. To investigate this hypothesis, we evaluated the activities of the wide-type and mutant RBM5 gene transfer in low-RBM5 expressing A549 cells. We found that, unlike wild-type RBM5 (RBM5-wt), a RBM5 mutant lacking the two RRM domains (RBM5-ΔRRM), is unable to bind RNA, has compromised caspase-2 alternative splicing activity, lacks cell proliferation inhibition and apoptosis induction function in A549 cells. These data provide direct evidence that the two RRM domains of RBM5 are required for RNA binding and the RNA binding activity of RBM5 contributes to its function on apoptosis induction and cell growth inhibition.« less

Essential basic and emergency obstetric and newborn care: from education and training to service delivery and quality of care.

PubMed

Otolorin, Emmanuel; Gomez, Patricia; Currie, Sheena; Thapa, Kusum; Dao, Blami

2015-06-01

Approximately 15% of expected births worldwide will result in life-threatening complications during pregnancy, delivery, or the postpartum period. Providers skilled in emergency obstetric and newborn care (EmONC) services are essential, particularly in countries with a high burden of maternal and newborn mortality. Jhpiego and its consortia partners have implemented three global programs to build provider capacity to provide comprehensive EmONC services to women and newborns in these resource-poor settings. Providers have been educated to deliver high-impact maternal and newborn health interventions, such as prevention and treatment of postpartum hemorrhage and pre-eclampsia/eclampsia and management of birth asphyxia, within the broader context of quality health services. This article describes Jhpiego's programming efforts within the framework of the basic and expanded signal functions that serve as indicators of high-quality basic and emergency care services. Lessons learned include the importance of health facility strengthening, competency-based provider education, global leadership, and strong government ownership and coordination as essential precursors to scale-up of high impact evidence-based maternal and newborn interventions in low-resource settings. Copyright © 2015. Published by Elsevier Ireland Ltd.

Drought impacts on ecosystem functions of the U.S. National Forests and Grasslands: Part II assessment results and management implications

Treesearch

Shanlei Sun; Ge Sun; Peter Caldwell; Steve McNulty; Erika Cohen; Jingfeng Xiao; Yang Zhang

2015-01-01

The 781,000 km2 (193 million acre) United States National Forests and Grasslands system (NF) provides important ecosystem services such as clean water supply, timber production, wildlife habitat, and recreation opportunities to the American public. Quantifying the historical impacts of climate change and drought on ecosystem functions at the national scale is essential...

Essential oils as natural food antimicrobial agents: a review.

PubMed

Vergis, Jess; Gokulakrishnan, P; Agarwal, R K; Kumar, Ashok

2015-01-01

Food-borne illnesses pose a real scourge in the present scenario as the consumerism of packaged food has increased to a great extend. Pathogens entering the packaged foods may survive longer, which needs a check. Antimicrobial agents either alone or in combination are added to the food or packaging materials for this purpose. Exploiting the antimicrobial property, essential oils are considered as a "natural" remedy to this problem other than its flavoring property instead of using synthetic agents. The essential oils are well known for its antibacterial, antiviral, antimycotic, antiparasitic, and antioxidant properties due to the presence of phenolic functional group. Gram-positive organisms are found more susceptible to the action of the essential oils. Essential oils improve the shelf-life of packaged products, control the microbial growth, and unriddle the consumer concerns regarding the use of chemical preservatives. This review is intended to provide an overview of the essential oils and their role as natural antimicrobial agents in the food industry.

What's at Stake in the Lives of People with Intellectual Disability? Part II: Recommendations for Naming, Defining, Diagnosing, Classifying, and Planning Supports

ERIC Educational Resources Information Center

Luckasson, Ruth; Schalock, Robert L.

2013-01-01

This article focuses on recommendations for naming, defining, diagnosing, classifying, and planning supports for individuals with intellectual disability (ID). The article provides an overview of the essential questions addressed by the respective functions and provides a series of specific recommendations that address the high stakes involved for…

7 CFR 1703.123 - Nonapproved purposes for grants.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., DEPARTMENT OF AGRICULTURE RURAL DEVELOPMENT Distance Learning and Telemedicine Grant Program § 1703.123...) To pay for medical equipment not having telemedicine as its essential function; (3) To pay salaries... the applicant. (6) To duplicate facilities providing distance learning or telemedicine services in...

7 CFR 1703.123 - Nonapproved purposes for grants.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., DEPARTMENT OF AGRICULTURE RURAL DEVELOPMENT Distance Learning and Telemedicine Grant Program § 1703.123...) To pay for medical equipment not having telemedicine as its essential function; (3) To pay salaries... the applicant. (6) To duplicate facilities providing distance learning or telemedicine services in...

7 CFR 1703.123 - Nonapproved purposes for grants.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., DEPARTMENT OF AGRICULTURE RURAL DEVELOPMENT Distance Learning and Telemedicine Grant Program § 1703.123...) To pay for medical equipment not having telemedicine as its essential function; (3) To pay salaries... the applicant. (6) To duplicate facilities providing distance learning or telemedicine services in...

7 CFR 1703.123 - Nonapproved purposes for grants.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., DEPARTMENT OF AGRICULTURE RURAL DEVELOPMENT Distance Learning and Telemedicine Grant Program § 1703.123...) To pay for medical equipment not having telemedicine as its essential function; (3) To pay salaries... the applicant. (6) To duplicate facilities providing distance learning or telemedicine services in...

Protein domains of unknown function are essential in bacteria.

PubMed

Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter

2013-12-31

More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.

Report of the workshop on evidence-based design of national wildlife health programs

USGS Publications Warehouse

Nguyen, Natalie T.; Duff, J. Paul; Gavier-Widén, Dolores; Grillo, Tiggy; He, Hongxuan; Lee, Hang; Ratanakorn, Parntep; Rijks, Jolianne M.; Ryser-Degiorgis, Marie-Pierre; Sleeman, Jonathan M.; Stephen, Craig; Tana, Toni; Uhart, Marcela; Zimmer , Patrick

2017-05-08

SummaryThis report summarizes a Wildlife Disease Association sponsored workshop held in 2016. The overall objective of the workshop was to use available evidence and selected subject matter expertise to define the essential functions of a National Wildlife Health Program and the resources needed to deliver a robust and reliable program, including the basic infrastructure, workforce, data and information systems, governance, organizational capacity, and essential features, such as wildlife disease surveillance, diagnostic services, and epidemiological investigation. This workshop also provided the means to begin the process of defining the essential attributes of a national wildlife health program that could be scalable and adaptable to each nation’s needs.

Septate Junction Proteins Play Essential Roles in Morphogenesis Throughout Embryonic Development in Drosophila

PubMed Central

Hall, Sonia; Ward, Robert E.

2016-01-01

The septate junction (SJ) is the occluding junction found in the ectodermal epithelia of invertebrate organisms, and is essential to maintain chemically distinct compartments in epithelial organs, to provide the blood–brain barrier in the nervous system, and to provide an important line of defense against invading pathogens. More than 20 genes have been identified to function in the establishment or maintenance of SJs in Drosophila melanogaster. Numerous studies have demonstrated the cell biological function of these proteins in establishing the occluding junction, whereas very few studies have examined further developmental roles for them. Here we examined embryos with mutations in nine different core SJ genes and found that all nine result in defects in embryonic development as early as germ band retraction, with the most penetrant defect observed in head involution. SJ genes are also required for cell shape changes and cell rearrangements that drive the elongation of the salivary gland during midembryogenesis. Interestingly, these developmental events occur at a time prior to the formation of the occluding junction, when SJ proteins localize along the lateral membrane and have not yet coalesced into the region of the SJ. Together, these observations reveal an underappreciated role for a large group of SJ genes in essential developmental events during embryogenesis, and suggest that the function of these proteins in facilitating cell shape changes and rearrangements is independent of their role in the occluding junction. PMID:27261004

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes.

PubMed

Sidik, Saima M; Huet, Diego; Ganesan, Suresh M; Huynh, My-Hang; Wang, Tim; Nasamu, Armiyaw S; Thiru, Prathapan; Saeij, Jeroen P J; Carruthers, Vern B; Niles, Jacquin C; Lourido, Sebastian

2016-09-08

Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the parasite Toxoplasma gondii during infection of human fibroblasts. Our analysis defines ∼200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells. Secondary screens identify as an invasion factor the claudin-like apicomplexan microneme protein (CLAMP), which resembles mammalian tight-junction proteins and localizes to secretory organelles, making it critical to the initiation of infection. CLAMP is present throughout sequenced apicomplexan genomes and is essential during the asexual stages of the malaria parasite Plasmodium falciparum. These results provide broad-based functional information on T. gondii genes and will facilitate future approaches to expand the horizon of antiparasitic interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure and function of enzymes in heme biosynthesis.

PubMed

Layer, Gunhild; Reichelt, Joachim; Jahn, Dieter; Heinz, Dirk W

2010-06-01

Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the "Radical SAM enzyme" coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure-function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

Types, production and assessment of biobased food packaging materials

USDA-ARS?s Scientific Manuscript database

Food packaging performs an essential function, but packaging materials can have a negative impact on the environment. This book describes the latest advances in bio-based food packaging materials. Book provides a comprehensive review on bio-based, biodegradable and recycled materials and discusses t...

48 CFR 237.7601 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... provided by a firm or individual under contract to DoD to support mission-essential functions, such as support of vital systems, including ships owned, leased, or operated in support of military missions or roles at sea; associated support activities, including installation, garrison, and base support services...

Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

PubMed

Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

2014-08-12

The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

Emergency and trauma care in Pakistan: a cross-sectional study of healthcare levels

PubMed Central

Razzak, Junaid A; Baqir, Syed M; Khan, Uzma Rahim; Heller, David; Bhatti, Junaid; Hyder, Adnan A

2015-01-01

Background The importance of emergency medical care for the successful functioning of health systems has been increasingly recognised. This study aimed to evaluate emergency and trauma care facilities in four districts of the province of Sindh, Pakistan. Method We conducted a cross-sectional health facility survey in four districts of the province of Sindh in Pakistan using a modified version of WHO’s Guidelines for essential trauma care. 93 public health facilities (81 primary care facilities, nine secondary care hospitals, three tertiary hospitals) and 12 large private hospitals were surveyed. Interviews of healthcare providers and visual inspections of essential equipment and supplies as per guidelines were performed. A total of 141 physicians providing various levels of care were tested for their knowledge of basic emergency care using a validated instrument. Results Only 4 (44%) public secondary, 3 (25%) private secondary hospitals and all three tertiary care hospitals had designated emergency rooms. The majority of primary care health facilities had less than 60% of all essential equipments overall. Most of the secondary level public hospitals (78%) had less than 60% of essential equipments, and none had 80% or more. A fourth of private secondary care facilities and all tertiary care hospitals (n=3; 100%) had 80% or more essential equipments. The average percentage score on the physician knowledge test was 30%. None of the physicians scored above 60% correct responses. Conclusions The study findings demonstrated a gap in both essential equipment and provider knowledge necessary for effective emergency and trauma care. PMID:24157684

Remotely Sensed Information and Field Data are both Essential to Assess Biodiversity CONDITION!

NASA Astrophysics Data System (ADS)

Sparrow, B.; Schaefer, M.; Scarth, P.; Phinn, S. R.; Christensen, R.; Lowe, A. J.; O'Neill, S.; Thurgate, N.; Wundke, D.

2015-12-01

Over the past year the TERN Ausplots facility has hosted a process to determine the definition of Biodiversity Condition in an Australian Continental Context, and conducted a wide collaborative process to determine which environmental attributes are required to be measures to accurately inform on biodiversity condition. A major output from this work was the acknowledgement that good quality data from both remotely sensed sources and good quality field collected data are both essential to provide the best information possible on biodiversity condition. This poster details some background to the project, the assesment of which attributes to measure, and if the are sources primarily from field based or remotely sensed measures. It then proceeds to provide three examples of ways in which the combination of data types provides a superior product as output, with one example being provided for the three cornerstone areas of condition: Structure, Function and Composition.

An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes

PubMed Central

Kofoed, Megan; Milbury, Karissa L.; Chiang, Jennifer H.; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C.

2015-01-01

Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. PMID:26175450

An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

PubMed

Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

2015-07-14

Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. Copyright © 2015 Kofoed et al.

Mapping trees outside forests using high-resolution aerial imagery: a comparison of pixel- and object based classification approaches

Treesearch

Dacia M. Meneguzzo; Greg C. Liknes; Mark D. Nelson

2013-01-01

Discrete trees and small groups of trees in nonforest settings are considered an essential resource around the world and are collectively referred to as trees outside forests (ToF). ToF provide important functions across the landscape, such as protecting soil and water resources, providing wildlife habitat, and improving farmstead energy efficiency and aesthetics....

Rail-to-rail differential input amplification stage with main and surrogate differential pairs

DOEpatents

Britton, Jr., Charles Lanier; Smith, Stephen Fulton

2007-03-06

An operational amplifier input stage provides a symmetrical rail-to-rail input common-mode voltage without turning off either pair of complementary differential input transistors. Secondary, or surrogate, transistor pairs assume the function of the complementary differential transistors. The circuit also maintains essentially constant transconductance, constant slew rate, and constant signal-path supply current as it provides rail-to-rail operation.

PGI Bracket Positioner: A Novel Combination of Reverse Bracket Tweezer and Positioning Gauze.

PubMed

Singh, Sombir; Verma, Sanjeev; Bhupali, Nameksh Raj; Singh, Satinder Pal

2018-01-01

The accurate bracket positioning is essential for the expression of the bracket system that affects the treatment outcome considerably and is also essential for good functional occlusion as well as facial esthetics. The proper alignment cannot be achieved without proper bracket positioning. Thus, the brackets positioning devices are an integral part of orthodontic armamentarium. Here, we present a new innovation that provides a unique combination of reverse bracket tweezer and positioner and hence is very helpful in precise vertical positioning of brackets with increased efficiency.

Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement.

PubMed

Boesch, R Paul; Balakrishnan, Karthik; Acra, Sari; Benscoter, Dan T; Cofer, Shelagh A; Collaco, Joseph M; Dahl, John P; Daines, Cori L; DeAlarcon, Alessandro; DeBoer, Emily M; Deterding, Robin R; Friedlander, Joel A; Gold, Benjamin D; Grothe, Rayna M; Hart, Catherine K; Kazachkov, Mikhail; Lefton-Greif, Maureen A; Miller, Claire Kane; Moore, Paul E; Pentiuk, Scott; Peterson-Carmichael, Stacey; Piccione, Joseph; Prager, Jeremy D; Putnam, Philip E; Rosen, Rachel; Rutter, Michael J; Ryan, Matthew J; Skinner, Margaret L; Torres-Silva, Cherie; Wootten, Christopher T; Zur, Karen B; Cotton, Robin T; Wood, Robert E

2018-02-07

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients. Copyright © 2018 by the American Academy of Pediatrics.

Optical processing for future computer networks

NASA Technical Reports Server (NTRS)

Husain, A.; Haugen, P. R.; Hutcheson, L. D.; Warrior, J.; Murray, N.; Beatty, M.

1986-01-01

In the development of future data management systems, such as the NASA Space Station, a major problem represents the design and implementation of a high performance communication network which is self-correcting and repairing, flexible, and evolvable. To obtain the goal of designing such a network, it will be essential to incorporate distributed adaptive network control techniques. The present paper provides an outline of the functional and communication network requirements for the Space Station data management system. Attention is given to the mathematical representation of the operations being carried out to provide the required functionality at each layer of communication protocol on the model. The possible implementation of specific communication functions in optics is also considered.

Form and function in the Lower Palaeolithic: history, progress, and continued relevance.

PubMed

Key, Alastair; Stephen, Lycett

2017-12-30

Percussively flaked stone artefacts constitute a major source of evidence relating to hominin behavioural strategies and are, essentially, a product or byproduct of a past individual's decision to create a tool with respect to some broader goal. Moreover, it has long been noted that both differences and recurrent regularities exist within and between Palaeolithic stone artefact forms. Accordingly, archaeologists have frequently drawn links between form and functionality, with functional objectives and performance often being regarded consequential to a stone tool's morphological properties. Despite these factors, extensive reviews of the related concepts of form and function with respect to the Lower Palaeolithic remain surprisingly sparse. We attempt to redress this issue. First we stress the historical place of form-function concepts, and their role in establishing basic ideas that echo to this day. We then highlight methodological and conceptual progress in determining artefactual function in more recent years. Thereafter, we evaluate four specific issues that are of direct consequence for evaluating the ongoing relevance of form-function concepts, especially with respect to their relevance for understanding human evolution more generally. Our discussion highlights specifically how recent developments have been able to build on a long historical legacy, and demonstrate that direct, indirect, experimental, and evolutionary perspectives intersect in crucial ways, with each providing specific but essential insights for ongoing questions. We conclude by emphasising that our understanding of these issues and their interaction, has been, and will be, essential to accurately interpret the Lower Palaeolithic archaeological record, tool-form related behaviours of Lower Palaeolithic hominins, and their consequences for (and relationship to) wider questions of human evolution.

36 CFR 219.2 - Principles.

Code of Federal Regulations, 2010 CFR

2010-07-01

... increased human uses, it is essential that uses of today do not impair the functioning of ecological... achievement of goals. (b) Planning contributes to social and economic sustainability by providing for a wide... responsive to a broad range of ecological, social, and economic. (5) Planning acknowledges the limits and...

NIH Human Microbiome Project defines normal bacterial makeup of the body

Cancer.gov

Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for

The Americans with Disabilities Act: A Primer for Principals.

ERIC Educational Resources Information Center

Shelton, Maria M.

1993-01-01

The 1990 Americans with Disabilities Act bars discrimination against handicapped people who are otherwise qualified for a position. To comply, principals should be prepared to identify each job's essential functions, prepare a written description for each job, provide reasonable accommodations, establish job-related qualification standards, and…

Urbanization Affects the Extent and Hydrologic Permanence of Headwater Streams in a Midwestern US Metropolitan Area

EPA Science Inventory

Headwater streams dominate natural landscapes and provide essential functions for downstream waters. However, because of minimal legal protection, they often are piped or buried to accommodate urban growth. Urbanization also alters stream base flows. The combined impact of these ...

The Student-Teacher-Computer Team: Focus on the Computer.

ERIC Educational Resources Information Center

Ontario Inst. for Studies in Education, Toronto.

Descriptions of essential computer elements, logic and programing techniques, and computer applications are provided in an introductory handbook for use by educators and students. Following a brief historical perspective, the organization of a computer system is schematically illustrated, functions of components are explained in non-technical…

Sleep in vertebrate and invertebrate animals, and insights into the function and evolution of sleep.

PubMed

Miyazaki, Shinichi; Liu, Chih-Yao; Hayashi, Yu

2017-05-01

Many mammalian species, including humans, spend a substantial fraction of their life sleeping. Sleep deprivation in rats ultimately leads to death, indicating the essential role of sleep. Exactly why sleep is so essential, however, remains largely unknown. From an evolutionary point of view, almost all animal species that have been investigated exhibit sleep or sleep-like states, suggesting that sleep may benefit survival. In certain mammalian and avian species, sleep can be further divided into at least two stages, rapid eye movement (REM) sleep and non-REM sleep. In addition to a widely conserved role for sleep, these individual sleep stages may have roles unique to these animals. The recent use of state-of-the-art techniques, including optogenetics and chemogenetics, has greatly broadened our understanding of the neural mechanisms of sleep regulation, allowing us to address the function of sleep. Studies focusing on non-mammalian animals species have also provided novel insights into the evolution of sleep. This review provides a comprehensive overview regarding the current knowledge of the function and evolution of sleep. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Mutant power: using mutant allele collections for yeast functional genomics.

PubMed

Norman, Kaitlyn L; Kumar, Anuj

2016-03-01

The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Consensus recommendations for essential vascular care in low- and middle-income countries

PubMed Central

Stewart, Barclay T; Gyedu, Adam; Giannou, Christos; Mishra, Brijesh; Rich, Norman; Wren, Sherry; Mock, Charles; Kushner, Adam L

2016-01-01

Introduction Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income. Methods The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health, as well as with experience in LMIC healthcare. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources. Results The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs (i.e. primary health centers, and first-level, referral, and tertiary hospitals). The recommendations include both essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications. Conclusion The resources recommended have the potential to improve LMIC healthcare systems’ ability to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning pre- and inter-hospital transport system, and vascular training for both existing and future healthcare providers. PMID:27432199

VeriClick: an efficient tool for table format verification

NASA Astrophysics Data System (ADS)

Nagy, George; Tamhankar, Mangesh

2012-01-01

The essential layout attributes of a visual table can be defined by the location of four critical grid cells. Although these critical cells can often be located by automated analysis, some means of human interaction is necessary for correcting residual errors. VeriClick is a macro-enabled spreadsheet interface that provides ground-truthing, confirmation, correction, and verification functions for CSV tables. All user actions are logged. Experimental results of seven subjects on one hundred tables suggest that VeriClick can provide a ten- to twenty-fold speedup over performing the same functions with standard spreadsheet editing commands.

Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.

PubMed

Gramlich, Leah; Meddings, Liisa; Alberda, Cathy; Wichansawakun, Sanit; Robbins, Sarah; Driscoll, David; Bistrian, Bruce

2015-09-01

The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles. © 2015 American Society for Parenteral and Enteral Nutrition.

A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1

PubMed Central

de Berardinis, Véronique; Vallenet, David; Castelli, Vanina; Besnard, Marielle; Pinet, Agnès; Cruaud, Corinne; Samair, Sumitta; Lechaplais, Christophe; Gyapay, Gabor; Richez, Céline; Durot, Maxime; Kreimeyer, Annett; Le Fèvre, François; Schächter, Vincent; Pezo, Valérie; Döring, Volker; Scarpelli, Claude; Médigue, Claudine; Cohen, Georges N; Marlière, Philippe; Salanoubat, Marcel; Weissenbach, Jean

2008-01-01

We have constructed a collection of single-gene deletion mutants for all dispensable genes of the soil bacterium Acinetobacter baylyi ADP1. A total of 2594 deletion mutants were obtained, whereas 499 (16%) were not, and are therefore candidate essential genes for life on minimal medium. This essentiality data set is 88% consistent with the Escherichia coli data set inferred from the Keio mutant collection profiled for growth on minimal medium, while 80% of the orthologous genes described as essential in Pseudomonas aeruginosa are also essential in ADP1. Several strategies were undertaken to investigate ADP1 metabolism by (1) searching for discrepancies between our essentiality data and current metabolic knowledge, (2) comparing this essentiality data set to those from other organisms, (3) systematic phenotyping of the mutant collection on a variety of carbon sources (quinate, 2-3 butanediol, glucose, etc.). This collection provides a new resource for the study of gene function by forward and reverse genetic approaches and constitutes a robust experimental data source for systems biology approaches. PMID:18319726

Essentials of Risk Management. Strategic Decisions. Board Basics.

ERIC Educational Resources Information Center

Sonenstein, Burton; Kumin, Laura A.

1998-01-01

This booklet, intended for trustees of institutions of higher education, offers some instruction on the principles of risk management. Introductory information provides a definition of risk management, which is seen as a planning and strategic function, not solely as a financial or safety assessment. Individual sections then address the following…

SHALL CHILDREN, TOO, BE FREE.

ERIC Educational Resources Information Center

LANE, HOWARD A.

DEFECTS IN THE FUNCTIONING OF THE PERSONALITY CAN DEVELOP IN CHILDREN. TO KEEP HIS SPIRIT NOURISHED, THE CHILD NEEDS AFFECTION, FRIENDSHIP, FREEDOM, FAITH, AND CHALLENGE FROM HIS PARENTS. SELF-RESPECT IS ANOTHER QUALITY WHICH SHOULD BE DEVELOPED IN CHILDREN AS AN ESSENTIAL PART OF THEIR GOOD MENTAL HEALTH. PROVIDING WORK EXPERIENCES AROUND THE…

The functional analyses of the cis-prenyltransferase and the rubber elongation factor in rubber biosynthesis

USDA-ARS?s Scientific Manuscript database

Natural rubber (cis-1,4-polyisoprene) is an essential plant derived commodity required for the manufacture of numerous industrial, medical and household items. Rubber is synthesized and sequestered on cytsolic vesicles known as rubber particles. When provided with farnesyl pyrophosphate (FPP) and is...

The American Indian Digest.

ERIC Educational Resources Information Center

Russell, George

This guide provides a basic source of historical and contemporary Indian information from an American Indian perspective and includes study questions at the end of each section. The primary function of this guide is to be a quick-study reference handbook. Basic questions essential to understanding current problems and issues of American Indians…

Assessing the diversity and composition of bacterial communities across a wetland, transition, upland gradient in Macon County Alabama

USDA-ARS?s Scientific Manuscript database

Wetlands provide essential functions to the ecosphere that range from water filtration to flood control. Current methods of evaluating the quality of wetlands include assessing vegetation, soil type, and period of inundation. With recent advances in molecular and bioinformatic techniques, measuremen...

Evidence for the use of low-grade weirs in drainage ditches to improve nutrient reductions from agriculture

USDA-ARS?s Scientific Manuscript database

The essential function of drainage ditches is to remove water from the agricultural landscape to avoid crop senescence through flooding and soil saturation. Commonly used slotted board risers provide drainage management strategies over the dormant season; however, by introducing innovative, low-gra...

Brain Network Interactions in Auditory, Visual and Linguistic Processing

ERIC Educational Resources Information Center

Horwitz, Barry; Braun, Allen R.

2004-01-01

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are…

From theory to practice: what drives the core business of public health?

PubMed

Smith, Tina Anderson; Minyard, Karen J; Parker, Christopher A; Van Valkenburg, Rachel Ferencik; Shoemaker, John A

2007-01-01

In 1994, the Public Health Functions Steering Committee proffered a description of the Essential Public Health Services (Essential Services). Questions remain, however, about the relationship between the roles defined therein and current public health practice at state and local levels. This case study describes the core business of public health in Georgia relative to the theoretical ideal and elucidates the primary drivers of the core business, thus providing data to inform future efforts to strengthen practice in the state. The principal finding was that public health in Georgia is not aligned with the Essential Services. Further analysis revealed that the primary drivers or determinants of public health practice are finance-related rather than based in need or strategy, precluding an integrated and intentional focus on health improvement. This case study provides a systems context for public health financing discussions, suggests leverage points for public health system change, and furthers the examination of applications for systems thinking relative to public health finance, practice, and policy.

Bioinspired surface functionalization of metallic biomaterials.

PubMed

Su, Yingchao; Luo, Cheng; Zhang, Zhihui; Hermawan, Hendra; Zhu, Donghui; Huang, Jubin; Liang, Yunhong; Li, Guangyu; Ren, Luquan

2018-01-01

Metallic biomaterials are widely used for clinical applications because of their excellent mechanical properties and good durability. In order to provide essential biofunctionalities, surface functionalization is of particular interest and requirement in the development of high-performance metallic implants. Inspired by the functional surface of natural biological systems, many new designs and conceptions have recently emerged to create multifunctional surfaces with great potential for biomedical applications. This review firstly introduces the metallic biomaterials, important surface properties, and then elaborates some strategies on achieving the bioinspired surface functionalization for metallic biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model

PubMed Central

Chen, Song; Wang, Chenran; Yeo, Syn; Liang, Chun-Chi; Okamoto, Takako; Sun, Shaogang; Wen, Jian; Guan, Jun-Lin

2016-01-01

Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13. We found that residues 582–585 (LQFL) in FIP200 are required for interaction with Atg13, and mutation of these residues to AAAA (designated the FIP200-4A mutant) abolished its canonical autophagy function in vitro. Furthermore, we created a FIP200-4A mutant knock-in mouse model and found that specifically blocking FIP200 interaction with Atg13 abolishes autophagy in vivo, providing direct support for the essential role of the ULK1/Atg13/FIP200/Atg101 complex in the process beyond previous studies relying on the complete knockout of individual components. Analysis of the new mouse model showed that nonautophagic functions of FIP200 are sufficient to fully support embryogenesis by maintaining a protective role in TNFα-induced apoptosis. However, FIP200-mediated canonical autophagy is required to support neonatal survival and tumor cell growth. These studies provide the first genetic evidence linking an Atg's autophagy and nonautophagic functions to different biological processes in vivo. PMID:27013233

[Advance on genome research of Yersinia pestis bacteriophage].

PubMed

Tan, H L; Wang, P; Li, W

2017-04-10

Completion of the genome sequences on Yersinia pestis bacteriophage offered unprecedented opportunity for researchers to carry out related genomic studies. This review was based on the genomic sequences and provided a genomic perspective in describing the essential features of genome on Yersinia pestis bacteriophage. Based on the comparative genomics, genetic evolutionary relationship was discussed. Description of functions from the gene prediction and protein annotation provided evidence for further related studies.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

PubMed

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

2017-06-01

The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

PubMed Central

Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

2017-01-01

Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

Systems analysis in Cellvibrio japonicus resolves predicted redundancy of β-glucosidases and determines essential physiological functions: Functional analysis of C. japonicus β-glucosidases

DOE PAGES

Nelson, Cassandra E.; Rogowski, Artur; Morland, Carl; ...

2017-02-28

Degradation of polysaccharides forms an essential arc in the carbon cycle, provides a percentage of our daily caloric intake, and is a major driver in the renewable chemical industry. Microorganisms proficient at degrading insoluble polysaccharides possess large numbers of carbohydrate active enzymes, many of which have been categorized as functionally redundant. Here we present data that suggests that carbohydrate active enzymes that have overlapping enzymatic activities can have unique, non-overlapping biological functions in the cell. Our comprehensive study to understand cellodextrin utilization in the soil saprophyte Cellvibrio japonicus found that only one of four predicted β-glucosidases is required in amore » physiological context. Gene deletion analysis indicated that only the cel3B gene product is essential for efficient cellodextrin utilization in C. japonicus and is constitutively expressed at high levels. Interestingly, expression of individual β-glucosidases in Escherichia coli K-12 enabled this non-cellulolytic bacterium to be fully capable of using cellobiose as a sole carbon source. Furthermore, enzyme kinetic studies indicated that the Cel3A enzyme is significantly more active than the Cel3B enzyme on the oligosaccharides but not disaccharides. Finally, our approach for parsing related carbohydrate active enzymes to determine actual physiological roles in the cell can be applied to other polysaccharide-degradation systems.« less

A genetic replacement system for selection-based engineering of essential proteins

PubMed Central

2012-01-01

Background Essential genes represent the core of biological functions required for viability. Molecular understanding of essentiality as well as design of synthetic cellular systems includes the engineering of essential proteins. An impediment to this effort is the lack of growth-based selection systems suitable for directed evolution approaches. Results We established a simple strategy for genetic replacement of an essential gene by a (library of) variant(s) during a transformation. The system was validated using three different essential genes and plasmid combinations and it reproducibly shows transformation efficiencies on the order of 107 transformants per microgram of DNA without any identifiable false positives. This allowed for reliable recovery of functional variants out of at least a 105-fold excess of non-functional variants. This outperformed selection in conventional bleach-out strains by at least two orders of magnitude, where recombination between functional and non-functional variants interfered with reliable recovery even in recA negative strains. Conclusions We propose that this selection system is extremely suitable for evaluating large libraries of engineered essential proteins resulting in the reliable isolation of functional variants in a clean strain background which can readily be used for in vivo applications as well as expression and purification for use in in vitro studies. PMID:22898007

Architecture of conference control functions

NASA Astrophysics Data System (ADS)

Kausar, Nadia; Crowcroft, Jon

1999-11-01

Conference control is an integral part in many-to-many communications that is used to manage and co-ordinate multiple users in conferences. There are different types of conferences which require different types of control. Some of the features of conference control may be user invoked while others are for internal management of a conference. In recent years, ITU (International Telecommunication Union) and IETF (Internet Engineering Task Force) have standardized two main models of conferencing, each system providing a set of conference control functionalities that are not easily provided in the other one. This paper analyzes the main activities appropriate for different types of conferences and presents an architecture for conference control called GCCP (Generic Conference Control Protocol). GCCP interworks different types of conferencing and provides a set of conference control functions that can be invoked by users directly. As an example of interworking, interoperation of IETF's SIP and ITU's H.323 call control functions have been examined here. This paper shows that a careful analysis of a conferencing architecture can provide a set of control functions essential for any group communication model that can be extensible if needed.

Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

PubMed Central

Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

2014-01-01

ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral membrane. While it is known that the PtdSer binding is essential for the PVEER function of TIM-1, TIM-3 shares this binding activity but does not enhance virus entry. No comprehensive studies have been done to characterize the other domains of TIM-1. In this study, using a variety of chimeric proteins and deletion mutants, we define the features necessary for a functional PVEER. With these features in mind, we generated a TIM-1 mimic using functionally similar domains from other proteins. This mimic, like TIM-1, effectively enhanced transduction. These studies provide insight into the key features necessary for PVEERs and will allow for more effective identification of unknown PVEERs. PMID:24696470

Biomaterials and bone mechanotransduction

NASA Technical Reports Server (NTRS)

Sikavitsas, V. I.; Temenoff, J. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

2001-01-01

Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

Advances in magnetic resonance neuroimaging techniques in the evaluation of neonatal encephalopathy.

PubMed

Panigrahy, Ashok; Blüml, Stefan

2007-02-01

Magnetic resonance (MR) imaging has become an essential tool in the evaluation of neonatal encephalopathy. Magnetic resonance-compatible neonatal incubators allow sick neonates to be transported to the MR scanner, and neonatal head coils can improve signal-to-noise ratio, critical for advanced MR imaging techniques. Refinement of conventional imaging techniques include the use of PROPELLER techniques for motion correction. Magnetic resonance spectroscopic imaging and diffusion tensor imaging provide quantitative assessment of both brain development and brain injury in the newborn with respect to metabolite abnormalities and hypoxic-ischemic injury. Knowledge of normal developmental changes in MR spectroscopy metabolite concentration and diffusion tensor metrics is essential to interpret pathological cases. Perfusion MR and functional MR can provide additional physiological information. Both MR spectroscopy and diffusion tensor imaging can provide additional information in the differential of neonatal encephalopathy, including perinatal white matter injury, hypoxic-ischemic brain injury, metabolic disease, infection, and birth injury.

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

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

Hubin, Elizabeth A.; Fay, Allison; Xu, Catherine

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impedemore » transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD.« less

The structure of human SFPQ reveals a coiled-coil mediated polymer essential for functional aggregation in gene regulation

PubMed Central

Lee, Mihwa; Sadowska, Agata; Bekere, Indra; Ho, Diwei; Gully, Benjamin S.; Lu, Yanling; Iyer, K. Swaminathan; Trewhella, Jill; Fox, Archa H.; Bond, Charles S.

2015-01-01

SFPQ, (a.k.a. PSF), is a human tumor suppressor protein that regulates many important functions in the cell nucleus including coordination of long non-coding RNA molecules into nuclear bodies. Here we describe the first crystal structures of Splicing Factor Proline and Glutamine Rich (SFPQ), revealing structural similarity to the related PSPC1/NONO heterodimer and a strikingly extended structure (over 265 Å long) formed by an unusual anti-parallel coiled-coil that results in an infinite linear polymer of SFPQ dimers within the crystals. Small-angle X-ray scattering and transmission electron microscopy experiments show that polymerization is reversible in solution and can be templated by DNA. We demonstrate that the ability to polymerize is essential for the cellular functions of SFPQ: disruptive mutation of the coiled-coil interaction motif results in SFPQ mislocalization, reduced formation of nuclear bodies, abrogated molecular interactions and deficient transcriptional regulation. The coiled-coil interaction motif thus provides a molecular explanation for the functional aggregation of SFPQ that directs its role in regulating many aspects of cellular nucleic acid metabolism. PMID:25765647

The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.

PubMed

Klochendler-Yeivin, A; Fiette, L; Barra, J; Muchardt, C; Babinet, C; Yaniv, M

2000-12-01

The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types.

The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression

PubMed Central

Klochendler-Yeivin, Agnes; Fiette, Laurence; Barra, Jaqueline; Muchardt, Christian; Babinet, Charles; Yaniv, Moshe

2000-01-01

The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types. PMID:11263494

Supporting Patient Care in the Emergency Department with a Computerized Whiteboard System

PubMed Central

Aronsky, Dominik; Jones, Ian; Lanaghan, Kevin; Slovis, Corey M.

2008-01-01

Efficient information management and communication within the emergency department (ED) is essential to providing timely and high-quality patient care. The ED whiteboard (census board) usually serves as an ED’s central access point for operational and patient-related information. This article describes the design, functionality, and experiences with a computerized ED whiteboard, which has the ability to display relevant operational and patient-related information in real time. Embedded functionality, additional whiteboard views, and the integration with ED and institutional information system components, such as the computerized patient record or the provider order entry system, provide rapid access to more detailed information. As an information center, the computerized whiteboard supports our ED environment not only for providing patient care, but also for operational, educational, and research activities. PMID:18096913

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease.

PubMed

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K; Saudek, Vladimir; O'Rahilly, Stephen; Walther, Tobias C; Barroso, Inês; Savage, David B

2014-06-17

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

PubMed Central

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J.; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K.; Saudek, Vladimir; O’Rahilly, Stephen; Walther, Tobias C.; Barroso, Inês; Savage, David B.

2014-01-01

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action. PMID:24889630

Optical recording in functional polymer nanocomposites by multi-beam interference holography

NASA Astrophysics Data System (ADS)

Zhuk, Dmitrij; Burunkova, Julia; Kalabin, Viacheslav; Csarnovics, Istvan; Kokenyesi, Sandor

2017-05-01

Our investigations relate to the development of new polymer nanocomposite materials and technologies for fabrication of photonic elements like gratings, integrated elements, photonic crystals. The goal of the present work was the development and application of the multi-beam interference method for one step, direct formation of 1-, 2- or even 3D photonic structures in functional acrylate nanocomposites, which contain SiO2 and Au nanoparticles and which are sensitized to blue and green laser illumination. The presence of gold nanoparticles and possibility to excite plasmonic effects can essentially influence the polymerization processes and the spatial redistribution of nanoparticles in the nanocomposite during the recording. This way surface and volume phase reliefs can be recorded. It is essential, that no additional treatments of the material after the recording are necessary and the elements possess high transparency, are stable after some relaxation time. New functionalities can be provided to the recorded structures if luminescent materials are added to such materials.

Structure of human Cdc45 and implications for CMG helicase function

PubMed Central

Simon, Aline C.; Sannino, Vincenzo; Costanzo, Vincenzo; Pellegrini, Luca

2016-01-01

Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication. PMID:27189187

Two Closely Related Genes of Arabidopsis Encode Plastidial Cytidinediphosphate Diacylglycerol Synthases Essential for Photoautotrophic Growth1[C

PubMed Central

Haselier, André; Akbari, Hana; Weth, Agnes; Baumgartner, Werner; Frentzen, Margrit

2010-01-01

Cytidinediphosphate diacylglycerol synthase (CDS) catalyzes the formation of cytidinediphosphate diacylglycerol, an essential precursor of anionic phosphoglycerolipids like phosphatidylglycerol or -inositol. In plant cells, CDS isozymes are located in plastids, mitochondria, and microsomes. Here, we show that these isozymes are encoded by five genes in Arabidopsis (Arabidopsis thaliana). Alternative translation initiation or alternative splicing of CDS2 and CDS4 transcripts can result in up to 10 isoforms. Most of the cDNAs encoding the various plant isoforms were functionally expressed in yeast and rescued the nonviable phenotype of the mutant strain lacking CDS activity. The closely related genes CDS4 and CDS5 were found to encode plastidial isozymes with similar catalytic properties. Inactivation of both genes was required to obtain Arabidopsis mutant lines with a visible phenotype, suggesting that the genes have redundant functions. Analysis of these Arabidopsis mutants provided further independent evidence for the importance of plastidial phosphatidylglycerol for structure and function of thylakoid membranes and, hence, for photoautotrophic growth. PMID:20442275

Consensus recommendations for essential vascular care in low- and middle-income countries.

PubMed

Stewart, Barclay T; Gyedu, Adam; Giannou, Christos; Mishra, Brijesh; Rich, Norman; Wren, Sherry M; Mock, Charles; Kushner, Adam L

2016-12-01

Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income. The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health as well as with experience in LMIC health care. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources. The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs, comprising primary health centers and first-level, referral, and tertiary hospitals. The recommendations include essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications. The resources recommended have the potential to improve the ability of LMIC health care systems to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization, without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning prehospital and interhospital transport system, and vascular training for existing and future health care providers. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

APPLICATION OF SUSTAINABILITY CRITERIA TO STELLA, MISSOURI-ECONOMIC PLANNING-PRELIMINARY SITE INFORMATION AND ELEMENTS OF THE MASTER PLAN-16NOV2006 (1130)

EPA Science Inventory

Economic systems constraints and performance requirements that are essential to providing goods and services, jobs, and a functioning economic system form a list of criteria for planning a sustainable economy. This presentation places these economic criteria in the context of Ste...

Alaska: 2002 Economic Census. Educational Services, Geographic Area Series.

ERIC Educational Resources Information Center

US Department of Commerce, 2005

2005-01-01

The economic census is the major source of facts about the structure and functioning of the nation's economy. It provides essential information for government, business, industry, and the general public. The economic census furnishes an important part of the framework for such composite measures as the gross domestic product estimates, input…

New Mexico: 2002 Economic Census. Educational Services, Geographic Area Series.

ERIC Educational Resources Information Center

US Department of Commerce, 2005

2005-01-01

The economic census is the major source of facts about the structure and functioning of the nation's economy. It provides essential information for government, business, industry, and the general public. The economic census furnishes an important part of the framework for such composite measures as the gross domestic product estimates,…

CLEFT PALATE. FOUNDATIONS OF SPEECH PATHOLOGY SERIES.

ERIC Educational Resources Information Center

RUTHERFORD, DAVID; WESTLAKE, HAROLD

DESIGNED TO PROVIDE AN ESSENTIAL CORE OF INFORMATION, THIS BOOK TREATS NORMAL AND ABNORMAL DEVELOPMENT, STRUCTURE, AND FUNCTION OF THE LIPS AND PALATE AND THEIR RELATIONSHIPS TO CLEFT LIP AND CLEFT PALATE SPEECH. PROBLEMS OF PERSONAL AND SOCIAL ADJUSTMENT, HEARING, AND SPEECH IN CLEFT LIP OR CLEFT PALATE INDIVIDUALS ARE DISCUSSED. NASAL RESONANCE…

It's Different on the Inside: Creating an Organization to Study Organizations

ERIC Educational Resources Information Center

Walls, Celeste M.

2005-01-01

According to Corman (1995), theory and practice are two sides of the same coin. Each is essential for effective function in organizational contexts and effective teaching in organizational communication courses. However, the classroom experience can benefit from increased efforts to provide students with activities that allow them to apply theory…

77 FR 20872 - Intelligent Transportation Systems Program Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... organization, management, and mission; (5) Overview of the ITS Research Program; and (6) Brief ethics review... welcome new members and to provide the committee an overview of information essential to its functioning..., 2012, was created to advise the Secretary of Transportation on all matters relating to the study...

Thirteen is the lucky number for doublecortin.

PubMed

Akhmanova, Anna; Severin, Fedor

2004-07-01

Doublecortin is a microtubule-associated protein that is essential for normal brain development. A recent report published in Molecular Cell shows that doublecortin associates preferentially with microtubules made of 13 protofilaments, by recognizing a novel site between the protofilaments. These findings explain how doublecortin stabilizes microtubules and provide clues about its function during neuronal migration.

Predicting protein submitochondrial locations using a K-Nearest neighbor method based on the Bit-Score weighted euclidean distance

USDA-ARS?s Scientific Manuscript database

Mitochondria are essential subcellular organelles found in eukaryotic cells. Knowing information on a protein’s subcellular or sub subcellular location provides in-depth insights about the microenvironment where it interacts with other molecules and is crucial for inferring the protein’s function. T...

The Place of Behavioral Science in Medical Education and Practice.

ERIC Educational Resources Information Center

Bolman, William M.

1995-01-01

Technological and social changes have left the medical profession without theory and content needed to adapt, making it essential to upgrade teaching of behavioral sciences in medical education. Despite their breadth and lack of definition relative to medical science, behavioral sciences provide a functional area that mediates between the patient…

The Functions of Mass Media in the Political Socialization of Adolescents.

ERIC Educational Resources Information Center

Adoni, Hanna

1979-01-01

Suggests that the mass media serve as socializing agents by providing direct linkage to media and contents which are essential for the development of political values, and by contributing to the structuring of social contexts in which adolescents may exercise such value orientations and reinforce ties with primary socializing agents. (JMF)

Direct Observation of Teacher and Student Behavior in School Settings: Trends, Issues and Future Directions

ERIC Educational Resources Information Center

Lewis, Timothy J.; Scott, Terrance M.; Wehby, Joseph H.; Wills, Howard P.

2014-01-01

Across the modern history of the field of special education and emotional/behavioral disorders (EBD), direct observation of student and educator behavior has been an essential component of the diagnostic process, student progress monitoring, and establishing functional and statistical relationships within research. This article provides an…

Entrepreneurs and Producers: Identities of Finnish Farmers in 2001 and 2006

ERIC Educational Resources Information Center

Vesala, Hannu T.; Vesala, Kari Mikko

2010-01-01

The farmers' role within the EU has recently been under reconstruction: in addition to primary agricultural production farmers should fulfill multiple functions such as maintaining the rural landscape, conserving nature and providing services. One essential feature of this new role is the demand for entrepreneurship. Farmers should be capable of…

Should bioactive trace elements not recognized as essential, but with beneficial health effects, have intake recommendations.

PubMed

Nielsen, Forrest H

2014-10-01

Today, most nutritionists do not consider a trace element essential unless it has a defined biochemical function in higher animals or humans. As a result, even though it has been found that trace elements such as boron and silicon have beneficial bioactivity in higher animals and humans, they generally receive limited attention or mention when dietary guidelines or intake recommendations are formulated. Recently, the possibility of providing dietary intake recommendations such as an adequate intake (AI) for some bioactive food components (e.g., flavonoids) has been discussed. Boron, chromium, nickel, and silicon are bioactive food components that provide beneficial health effects by plausible mechanisms of action in nutritional and supra nutritional amounts, and thus should be included in the discussions. Although the science base may not be considered adequate for establishing AIs, a significant number of findings suggest that statements about these trace elements should be included when dietary intake guidance is formulated. An appropriate recommendation may be that diets should include foods that would provide trace elements not currently recognized as essential in amounts shown to reduce the risk of chronic disease and/or promote health and well-being. Published by Elsevier GmbH.

Psychosocial issues for children and adolescents with chronic illness: self-esteem, school functioning and sports participation.

PubMed

Vitulano, Lawrence A

2003-07-01

Self-esteem, school functioning, and sports participation are among the most significant psychosocial issues that affect children and adolescents with chronic illness. Although these capacities are essential components of development for all children, they present special concerns for children with limitations of health. Parents, teachers, and coaches play important roles in providing normalizing and gratifying opportunities for children who struggle to be competent and accepted by their peers. Much can be done to provide chronically ill children with experiences and support that will allow them to grow up happier, feel better about themselves, and enjoy more success.

Design development of the Apollo command and service module thrust vector attitude control systems

NASA Technical Reports Server (NTRS)

Peters, W. H.

1978-01-01

Development of the Apollo thrust vector control digital autopilot (TVC DAP) was summarized. This is the control system that provided pitch and yaw attitude control during velocity change maneuvers using the main rocket engine on the Apollo service module. A list of ten primary functional requirements for this control system are presented, each being subordinate to a more general requirement appearing earlier on the list. Development process functions were then identified and the essential information flow paths were explored. This provided some visibility into the particular NASA/contractor interface, as well as relationships between the many individual activities.

The joint fit of the BHMF and ERDF for the BAT AGN Sample

NASA Astrophysics Data System (ADS)

Weigel, Anna K.; Koss, Michael; Ricci, Claudio; Trakhtenbrot, Benny; Oh, Kyuseok; Schawinski, Kevin; Lamperti, Isabella

2018-01-01

A natural product of an AGN survey is the AGN luminosity function. This statistical measure describes the distribution of directly measurable AGN luminosities. Intrinsically, the shape of the luminosity function depends on the distribution of black hole masses and Eddington ratios. To constrain these fundamental AGN properties, the luminosity function thus has to be disentangled into the black hole mass and Eddington ratio distribution function. The BASS survey is unique as it allows such a joint fit for a large number of local AGN, is unbiased in terms of obscuration in the X-rays and provides black hole masses for type-1 and type-2 AGN. The black hole mass function at z ~ 0 represents an essential baseline for simulations and black hole growth models. The normalization of the Eddington ratio distribution function directly constrains the AGN fraction. Together, the BASS AGN luminosity, black hole mass and Eddington ratio distribution functions thus provide a complete picture of the local black hole population.

Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

PubMed

Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

2014-07-01

With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. © 2013 Wiley Periodicals, Inc.

RNA structures as mediators of neurological diseases and as drug targets

PubMed Central

Bernat, Viachaslau; Disney, Matthew D.

2015-01-01

RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. PMID:26139368

[Modes of action of agrochemicals against plant pathogenic organisms].

PubMed

Leroux, Pierre

2003-01-01

The chemical control of plant pathogens concerns mainly fungal diseases of crops. Most of the available fungicides act directly on essential fungal functions such as respiration, sterol biosynthesis or cell division. Consequently, these compounds can exhibit undesirable toxicological and environmental effects and sometimes select fungal resistant strains. Plant activators are expected to provide sustainable disease management in several crops because the development of resistance is not expected. Considering the future, the discovery of novel antifungal molecules will reap advantage from throughput screening methodologies and functional genomics.

Structural and functional diversity of cadherin at the adherens junction

PubMed Central

2011-01-01

Adhesion between cells is essential to the evolution of multicellularity. Indeed, morphogenesis in animals requires firm but flexible intercellular adhesions that are mediated by subcellular structures like the adherens junction (AJ). A key component of AJs is classical cadherins, a group of transmembrane proteins that maintain dynamic cell–cell associations in many animal species. An evolutionary reconstruction of cadherin structure and function provides a comprehensive framework with which to appreciate the diversity of morphogenetic mechanisms in animals. PMID:21708975

Properties of genes essential for mouse development

PubMed Central

Kabir, Mitra; Barradas, Ana; Tzotzos, George T.; Hentges, Kathryn E.

2017-01-01

Essential genes are those that are critical for life. In the specific case of the mouse, they are the set of genes whose deletion means that a mouse is unable to survive after birth. As such, they are the key minimal set of genes needed for all the steps of development to produce an organism capable of life ex utero. We explored a wide range of sequence and functional features to characterise essential (lethal) and non-essential (viable) genes in mice. Experimental data curated manually identified 1301 essential genes and 3451 viable genes. Very many sequence features show highly significant differences between essential and viable mouse genes. Essential genes generally encode complex proteins, with multiple domains and many introns. These genes tend to be: long, highly expressed, old and evolutionarily conserved. These genes tend to encode ligases, transferases, phosphorylated proteins, intracellular proteins, nuclear proteins, and hubs in protein-protein interaction networks. They are involved with regulating protein-protein interactions, gene expression and metabolic processes, cell morphogenesis, cell division, cell proliferation, DNA replication, cell differentiation, DNA repair and transcription, cell differentiation and embryonic development. Viable genes tend to encode: membrane proteins or secreted proteins, and are associated with functions such as cellular communication, apoptosis, behaviour and immune response, as well as housekeeping and tissue specific functions. Viable genes are linked to transport, ion channels, signal transduction, calcium binding and lipid binding, consistent with their location in membranes and involvement with cell-cell communication. From the analysis of the composite features of essential and viable genes, we conclude that essential genes tend to be required for intracellular functions, and viable genes tend to be involved with extracellular functions and cell-cell communication. Knowledge of the features that are over-represented in essential genes allows for a deeper understanding of the functions and processes implemented during mammalian development. PMID:28562614

X-ray crystallography and its impact on understanding bacterial cell wall remodeling processes.

PubMed

Büttner, Felix Michael; Renner-Schneck, Michaela; Stehle, Thilo

2015-02-01

The molecular structure of matter defines its properties and function. This is especially true for biological macromolecules such as proteins, which participate in virtually all biochemical processes. A three dimensional structural model of a protein is thus essential for the detailed understanding of its physiological function and the characterization of essential properties such as ligand binding and reaction mechanism. X-ray crystallography is a well-established technique that has been used for many years, but it is still by far the most widely used method for structure determination. A particular strength of this technique is the elucidation of atomic details of molecular interactions, thus providing an invaluable tool for a multitude of scientific projects ranging from the structural classification of macromolecules over the validation of enzymatic mechanisms or the understanding of host-pathogen interactions to structure-guided drug design. In the first part of this review, we describe essential methodological and practical aspects of X-ray crystallography. We provide some pointers that should allow researchers without a background in structural biology to assess the overall quality and reliability of a crystal structure. To highlight its potential, we then survey the impact X-ray crystallography has had on advancing an understanding of a class of enzymes that modify the bacterial cell wall. A substantial number of different bacterial amidase structures have been solved, mostly by X-ray crystallography. Comparison of these structures highlights conserved as well as divergent features. In combination with functional analyses, structural information on these enzymes has therefore proven to be a valuable template not only for understanding their mechanism of catalysis, but also for targeted interference with substrate binding. Copyright © 2015 Elsevier GmbH. All rights reserved.

When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases

PubMed Central

2011-01-01

Background Comprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data. Results Here, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus. Conclusions The Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology of human diseases. PMID:21255393

Functional Analysis of the Aspergillus nidulans Kinome

PubMed Central

De Souza, Colin P.; Hashmi, Shahr B.; Osmani, Aysha H.; Andrews, Peter; Ringelberg, Carol S.; Dunlap, Jay C.; Osmani, Stephen A.

2013-01-01

The filamentous fungi are an ecologically important group of organisms which also have important industrial applications but devastating effects as pathogens and agents of food spoilage. Protein kinases have been implicated in the regulation of virtually all biological processes but how they regulate filamentous fungal specific processes is not understood. The filamentous fungus Aspergillus nidulans has long been utilized as a powerful molecular genetic system and recent technical advances have made systematic approaches to study large gene sets possible. To enhance A. nidulans functional genomics we have created gene deletion constructs for 9851 genes representing 93.3% of the encoding genome. To illustrate the utility of these constructs, and advance the understanding of fungal kinases, we have systematically generated deletion strains for 128 A. nidulans kinases including expanded groups of 15 histidine kinases, 7 SRPK (serine-arginine protein kinases) kinases and an interesting group of 11 filamentous fungal specific kinases. We defined the terminal phenotype of 23 of the 25 essential kinases by heterokaryon rescue and identified phenotypes for 43 of the 103 non-essential kinases. Uncovered phenotypes ranged from almost no growth for a small number of essential kinases implicated in processes such as ribosomal biosynthesis, to conditional defects in response to cellular stresses. The data provide experimental evidence that previously uncharacterized kinases function in the septation initiation network, the cell wall integrity and the morphogenesis Orb6 kinase signaling pathways, as well as in pathways regulating vesicular trafficking, sexual development and secondary metabolism. Finally, we identify ChkC as a third effector kinase functioning in the cellular response to genotoxic stress. The identification of many previously unknown functions for kinases through the functional analysis of the A. nidulans kinome illustrates the utility of the A. nidulans gene deletion constructs. PMID:23505451

Novel functions for glycosyltransferases Jhp0562 and GalT in Lewis antigen synthesis and variation in Helicobacter pylori.

PubMed

Pohl, Mary Ann; Kienesberger, Sabine; Blaser, Martin J

2012-04-01

Lewis (Le) antigens are fucosylated oligosaccharides present in the Helicobacter pylori lipopolysaccharide. Expression of these antigens is believed to be important for H. pylori colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galT is essential for production of type 1 (Le(a) and Le(b)) antigens. The upstream gene jhp0562, which is present in many but not all H. pylori strains, is homologous to β-(1,3)galT but is of unknown function. Because H. pylori demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5' and 3' ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galT null mutant, but neither native nor recombinant jhp0562 can. Mutagenesis of jhp0562 revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galT expression in all wild-type (WT) and mutant strains tested, whereas jhp0562 was not expressed in jhp0562 null mutants, as expected. Since jhp0562 unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether galT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that galT is essential for Le(b) production. In total, these results demonstrate that galT and jhp0562 have functions that cross the expected Le synthesis pathways and that jhp0562 provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.

Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori

PubMed Central

Kienesberger, Sabine; Blaser, Martin J.

2012-01-01

Lewis (Le) antigens are fucosylated oligosaccharides present in the Helicobacter pylori lipopolysaccharide. Expression of these antigens is believed to be important for H. pylori colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galT is essential for production of type 1 (Lea and Leb) antigens. The upstream gene jhp0562, which is present in many but not all H. pylori strains, is homologous to β-(1,3)galT but is of unknown function. Because H. pylori demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galT null mutant, but neither native nor recombinant jhp0562 can. Mutagenesis of jhp0562 revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galT expression in all wild-type (WT) and mutant strains tested, whereas jhp0562 was not expressed in jhp0562 null mutants, as expected. Since jhp0562 unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether galT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that galT is essential for Leb production. In total, these results demonstrate that galT and jhp0562 have functions that cross the expected Le synthesis pathways and that jhp0562 provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes. PMID:22290141

Essential fats for future health. Proceedings of the 9th Unilever Nutrition Symposium, 26-27 May 2010.

PubMed

Calder, P C; Dangour, A D; Diekman, C; Eilander, A; Koletzko, B; Meijer, G W; Mozaffarian, D; Niinikoski, H; Osendarp, S J M; Pietinen, P; Schuit, J; Uauy, R

2010-12-01

The 9th Unilever Nutrition Symposium entitled 'Essential fats for future health', held on 26-27 May 2010, aimed to review the dietary recommendations for essential fatty acids (EFA); discuss the scientific evidence for the roles of EFA in cognition, immune function and cardiovascular health; and to identify opportunities for joint efforts by industry, academia, governmental and non-governmental organizations to effectively improve health behaviour. This paper summarizes the main conclusions of the presentations given at the symposium. Linoleic acid (LA) and α-linolenic acid (ALA) are EFA that cannot by synthesized by the human body. Docosahexaenoic acid (DHA) is considered as conditionally essential because of its limited formation from ALA in the human body and its critical role in early normal retinal and brain development and, jointly with eicosapentaenoic acid (EPA), in prevention of cardiovascular disease (CVD). Some evidence for possible beneficial roles of n-3 fatty acids for immune function and adult cognitive function is emerging. A higher consumption of polyunsaturated fatty acids (PUFA; >10%E), including LA, ALA and at least 250-500 mg per day of EPA+DHA, is recommended for prevention of coronary heart disease (CHD). Two dietary interventions suggest that EFA may affect CVD risk factors in children similarly as in adults. To ensure an adequate EFA intake of the population, including children, public health authorities should develop clear messages based on current science; ensure availability of healthy, palatable foods; and collaborate with scientists, the food industry, schools, hospitals, health-care providers and communities to encourage consumers to make healthy choices.

The Poly(C) Binding Protein Pcbp2 and Its Retrotransposed Derivative Pcbp1 Are Independently Essential to Mouse Development.

PubMed

Ghanem, Louis R; Kromer, Andrew; Silverman, Ian M; Chatterji, Priya; Traxler, Elizabeth; Penzo-Mendez, Alfredo; Weiss, Mitchell J; Stanger, Ben Z; Liebhaber, Stephen A

2016-01-15

RNA-binding proteins participate in a complex array of posttranscriptional controls essential to cell type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts mammalian embryonic development remains incompletely defined, and the level of functional redundancy among subsets of these proteins remains open to question. The poly(C) binding proteins, PCBPs (αCPs and hnRNP E proteins), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here, we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos undergo normal development until midgestation (12.5 to 13.5 days postcoitum), at which time they undergo a dramatic loss in viability associated with combined cardiovascular and hematopoietic abnormalities. Mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and nondisruptive defect in initial postpartum weight gain. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and have distinct impacts on embryonic viability and that Pcpb2 has a nonredundant in vivo role in hematopoiesis. These data further provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved an essential function(s) in the mammalian genome. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The anaplerotic node is essential for the intracellular survival of Mycobacterium tuberculosis

PubMed Central

Basu, Piyali; Sandhu, Noor; Bhatt, Apoorva; Singh, Albel; Balhana, Ricardo; Gobe, Irene; Crowhurst, Nicola A.; Mendum, Tom A.; Gao, Liang; Ward, Jane L.; Beale, Michael H.; McFadden, Johnjoe; Beste, Dany J. V.

2018-01-01

Enzymes at the phosphoenolpyruvate (PEP)–pyruvate–oxaloacetate or anaplerotic (ANA) node control the metabolic flux to glycolysis, gluconeogenesis, and anaplerosis. Here we used genetic, biochemical, and 13C isotopomer analysis to characterize the role of the enzymes at the ANA node in intracellular survival of the world's most successful bacterial pathogen, Mycobacterium tuberculosis (Mtb). We show that each of the four ANA enzymes, pyruvate carboxylase (PCA), PEP carboxykinase (PCK), malic enzyme (MEZ), and pyruvate phosphate dikinase (PPDK), performs a unique and essential metabolic function during the intracellular survival of Mtb. We show that in addition to PCK, intracellular Mtb requires PPDK as an alternative gateway into gluconeogenesis. Propionate and cholesterol detoxification was also identified as an essential function of PPDK revealing an unexpected role for the ANA node in the metabolism of these physiologically important intracellular substrates and highlighting this enzyme as a tuberculosis (TB)-specific drug target. We show that anaplerotic fixation of CO2 through the ANA node is essential for intracellular survival of Mtb and that Mtb possesses three enzymes (PCA, PCK, and MEZ) capable of fulfilling this function. In addition to providing a back-up role in anaplerosis we show that MEZ also has a role in lipid biosynthesis. MEZ knockout strains have an altered cell wall and were deficient in the initial entry into macrophages. This work reveals that the ANA node is a focal point for controlling the intracellular replication of Mtb, which goes beyond canonical gluconeogenesis and represents a promising target for designing novel anti-TB drugs. PMID:29475946

CTCF knockout reveals an essential role for this protein during the zebrafish development.

PubMed

Carmona-Aldana, Francisco; Zampedri, Cecilia; Suaste-Olmos, Fernando; Murillo-de-Ozores, Adrián; Guerrero, Georgina; Arzate-Mejía, Rodrigo; Maldonado, Ernesto; Navarro, Rosa; Chimal-Monroy, Jesús; Recillas-Targa, Félix

2018-05-01

Chromatin regulation and organization are essential processes that regulate gene activity. The CCCTC-binding factor (CTCF) is a protein with different and important molecular functions related with chromatin dynamics. It is conserved since invertebrates to vertebrates, posing it as a factor with an important role in the physiology. In this work, we aimed to understand the distribution and functional relevance of CTCF during the embryonic development of the zebrafish (Danio rerio). We generated a zebrafish specific anti-Ctcf antibody, and found this protein to be ubiquitous, through different stages and tissues. We used the CRISPR-Cas9 system to induce molecular alterations in the locus. This resulted in early lethality. We delayed the lethality performing knockdown morpholino experiments, and found an aberrant embryo morphology involving malformations in structures through all the length of the embryo. These phenotypes were rescued with human CTCF mRNA injections, showing the specificity of the morpholinos and a partial functional conservation between the fish and the human proteins. Lastly, we found that the pro-apoptotic genes p53 and bbc3/PUMA are deregulated in the ctcf morpholino-injected embryos. In conclusion, CTCF is a ubiquitous factor during the zebrafish development, which regulates the correct formation of different structures of the embryo, and its deregulation impacts on essential cell survival genes. Overall, this work provides a basis to look for the particular functions of CTCF in the different developing tissues and organs of the zebrafish. Copyright © 2018. Published by Elsevier B.V.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Resolving complex chromosome structures during meiosis: versatile deployment of Smc5/6.

PubMed

Verver, Dideke E; Hwang, Grace H; Jordan, Philip W; Hamer, Geert

2016-03-01

The Smc5/6 complex, along with cohesin and condensin, is a member of the structural maintenance of chromosome (SMC) family, large ring-like protein complexes that are essential for chromatin structure and function. Thanks to numerous studies of the mitotic cell cycle, Smc5/6 has been implicated to have roles in homologous recombination, restart of stalled replication forks, maintenance of ribosomal DNA (rDNA) and heterochromatin, telomerase-independent telomere elongation, and regulation of chromosome topology. The nature of these functions implies that the Smc5/6 complex also contributes to the profound chromatin changes, including meiotic recombination, that characterize meiosis. Only recently, studies in diverse model organisms have focused on the potential meiotic roles of the Smc5/6 complex. Indeed, Smc5/6 appears to be essential for meiotic recombination. However, due to both the complexity of the process of meiosis and the versatility of the Smc5/6 complex, many additional meiotic functions have been described. In this review, we provide a clear overview of the multiple functions found so far for the Smc5/6 complex in meiosis. Additionally, we compare these meiotic functions with the known mitotic functions in an attempt to find a common denominator and thereby create clarity in the field of Smc5/6 research.

The Essential Gene EMB1611 Maintains Shoot Apical Meristem Function During Arabidopsis Development

USDA-ARS?s Scientific Manuscript database

The Arabidopsis thaliana genome contains hundreds of genes essential for seed development. Because null mutations in these genes cause embryo lethality, their specific molecular and developmental functions are largely unknown. Here, we identify a role for EMB1611/MEE22, an essential gene in Arabidop...

Understanding the mind of a worm: hierarchical network structure underlying nervous system function in C. elegans.

PubMed

Chatterjee, Nivedita; Sinha, Sitabhra

2008-01-01

The nervous system of the nematode C. elegans provides a unique opportunity to understand how behavior ('mind') emerges from activity in the nervous system ('brain') of an organism. The hermaphrodite worm has only 302 neurons, all of whose connections (synaptic and gap junctional) are known. Recently, many of the functional circuits that make up its behavioral repertoire have begun to be identified. In this paper, we investigate the hierarchical structure of the nervous system through k-core decomposition and find it to be intimately related to the set of all known functional circuits. Our analysis also suggests a vital role for the lateral ganglion in processing information, providing an essential connection between the sensory and motor components of the C. elegans nervous system.

Human Gut Microbiome: Function Matters.

PubMed

Heintz-Buschart, Anna; Wilmes, Paul

2017-11-22

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Impact of Childhood Trauma on Brain Development: A Literature Review and Supporting Handouts

ERIC Educational Resources Information Center

Kirouac, Samantha; McBride, Dawn Lorraine

2009-01-01

This project provides a comprehensive overview of the research literature on the brain and how trauma impacts brain development, structures, and functioning. A basic exploration of childhood trauma is outlined in this project, as it is essential in making associations and connections to brain development. Childhood trauma is processed in the…

Peculiarities in the Gestural Repertoire: An Early Marker for Rett Syndrome?

ERIC Educational Resources Information Center

Marschik, Peter B.; Sigafoos, Jeff; Kaufmann, Walter E.; Wolin, Thomas; Talisa, Victor B.; Bartl-Pokorny, Katrin D.; Budimirovic, Dejan B.; Vollmann, Ralf; Einspieler, Christa

2012-01-01

We studied the gestures used by children with classic Rett syndrome (RTT) to provide evidence as to how this essential aspect of communicative functions develops. Seven participants with RTT were longitudinally observed between 9 and 18 months of life. The gestures used by these participants were transcribed and coded from a retrospective analysis…

Issues of Power and Equity in Two Models of Self-Assessment

ERIC Educational Resources Information Center

Taras, Maddalena

2008-01-01

The two models of self-assessment examined in this paper serve different functions and provide different skills and points of focus for both learners and tutors. The standard model focuses students on their own resources and knowledge in an essentially formative assessment context. Taras' model focuses on students' understanding, using the tutor's…

Stability of large-scale systems.

NASA Technical Reports Server (NTRS)

Siljak, D. D.

1972-01-01

The purpose of this paper is to present the results obtained in stability study of large-scale systems based upon the comparison principle and vector Liapunov functions. The exposition is essentially self-contained, with emphasis on recent innovations which utilize explicit information about the system structure. This provides a natural foundation for the stability theory of dynamic systems under structural perturbations.

Employment Selections of Resident and Non-Resident Graduates of Physical Therapy Programs in Underserved Western States

ERIC Educational Resources Information Center

Swart, Kathryn D.

2011-01-01

Background and Purpose: Physical therapy (PT) is an essential component of the healthcare system in providing a comprehensive treatment plan for patients with functional limitations. The demand for physical therapy services is projected to expand in the next eight years, leading to an increased need for practicing physical therapists. The Mountain…

The Role of Counseling Faculty and Delivery of Counseling Services in the California Community Colleges. Adopted Spring 2012

ERIC Educational Resources Information Center

Academic Senate for California Community Colleges, 2012

2012-01-01

The original paper, "The Role of Counseling Faculty in the California Community Colleges" (1994), provided principled positions of the Academic Senate regarding the essential functions of counselors and the delivery of counseling services in helping students achieve success. The paper concluded with specific guidance on appropriate roles…

Essential Role of Lymph Nodes in Contact Hypersensitivity Revealed in Lymphotoxin-α–Deficient Mice

PubMed Central

Rennert, Paul D.; Hochman, Paula S.; Flavell, Richard A.; Chaplin, David D.; Jayaraman, Sundararajan; Browning, Jeffrey L.; Fu, Yang-Xin

2001-01-01

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired immunity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs are absolutely required for generating contact hypersensitivity, a T cell–dependent cellular immune response induced by epicutaneous hapten. We show that the homing of epidermal Langerhans cells in response to hapten application is specifically directed to LNs, providing a cellular basis for this unique LN function. In contrast, the spleen cannot mediate contact hypersensitivity because antigen-bearing epidermal Langerhans cells do not access splenic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by reversing the LN defect in lymphotoxin-α−/− mice, thereby restoring the capacity for contact hypersensitivity. PMID:11390430

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

PubMed

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-07-12

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

Plants Consumption and Liver Health

PubMed Central

He, Qing

2015-01-01

The liver is a very important organ with a lot of functions for the host to survive. Dietary components are essential for and can be beneficial or detrimental to the healthy or diseased liver. Plants food is an essential part of the human diet and comprises various compounds which are closely related to liver health. Selected food plants can provide nutritional and medicinal support for liver disease. At the present, the knowledge of the effects of plants on the liver is still incomplete. The most urgent task at the present time is to find the best dietary and medicinal plants for liver health in an endless list of candidates. This review article updates the knowledge about the effects of plants consumption on the health of the liver, putting particular emphasis on the potential beneficial and harmful impact of dietary and medicinal plants on liver function. PMID:26221179

Expansion of Protein Farnesyltransferase Specificity Using “Tunable” Active Site Interactions

PubMed Central

Hougland, James L.; Gangopadhyay, Soumyashree A.; Fierke, Carol A.

2012-01-01

Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the creation of bioengineered parallel prenylation pathways with altered substrate selectivity within a cell. Engineered FTase variants provide a novel avenue for probing both the selectivity of prenylation pathway enzymes and the effects of prenylation pathway modifications on the cellular function of a protein. PMID:22992747

A Quaternary Mechanism Enables the Complex Biological Functions of Octameric Human UDP-glucose Pyrophosphorylase, a Key Enzyme in Cell Metabolism

PubMed Central

Führing, Jana Indra; Cramer, Johannes Thomas; Schneider, Julia; Baruch, Petra; Gerardy-Schahn, Rita; Fedorov, Roman

2015-01-01

In mammals, UDP-glucose pyrophosphorylase (UGP) is the only enzyme capable of activating glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc), a metabolite located at the intersection of virtually all metabolic pathways in the mammalian cell. Despite the essential role of its product, the molecular basis of UGP function is poorly understood. Here we report the crystal structure of human UGP in complex with its product UDP-Glc. Beyond providing first insight into the active site architecture, we describe the substrate binding mode and intermolecular interactions in the octameric enzyme that are crucial to its activity. Importantly, the quaternary mechanism identified for human UGP in this study may be common for oligomeric sugar-activating nucleotidyltransferases. Elucidating such mechanisms is essential for understanding nucleotide sugar metabolism and opens the perspective for the development of drugs that specifically inhibit simpler organized nucleotidyltransferases in pathogens. PMID:25860585

Treatment of Functional Impairment in Patients with Bipolar Disorder.

PubMed

Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Vieta, Eduard

2017-01-01

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

Cavin Family: New Players in the Biology of Caveolae.

PubMed

Nassar, Zeyad D; Parat, Marie-Odile

2015-01-01

Caveolae are specialized small plasma-membrane invaginations that play crucial cellular functions. Two essential protein families are required for caveola formation: membrane caveolin proteins and cytoplasmic cavin proteins. Each family includes members with specific tissue distribution, and their expression is altered under physiological and pathological conditions, implying highly specialized functions. Cavins not only stabilize caveolae, but modulate their morphology and functions as well. Before association with the plasma membrane, cavins form homo- and hetero-oligomers with strikingly strict stoichiometry in the cytosol. At the plasma membrane, they provide an outer peripheral cytosolic layer, necessary for caveola stability. Interestingly, upon stimulation, cavins can be released from caveolae into the cytoplasm in distinct subcomplexes, providing a rapid dynamic link between caveolae and cellular organelles including the nucleus. In this review, we detail the biology of cavins, their structural and functional roles, and their implication in pathophysiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Meta genome-wide network from functional linkages of genes in human gut microbial ecosystems.

PubMed

Ji, Yan; Shi, Yixiang; Wang, Chuan; Dai, Jianliang; Li, Yixue

2013-03-01

The human gut microbial ecosystem (HGME) exerts an important influence on the human health. In recent researches, meta-genomics provided deep insights into the HGME in terms of gene contents, metabolic processes and genome constitutions of meta-genome. Here we present a novel methodology to investigate the HGME on the basis of a set of functionally coupled genes regardless of their genome origins when considering the co-evolution properties of genes. By analyzing these coupled genes, we showed some basic properties of HGME significantly associated with each other, and further constructed a protein interaction map of human gut meta-genome to discover some functional modules that may relate with essential metabolic processes. Compared with other studies, our method provides a new idea to extract basic function elements from meta-genome systems and investigate complex microbial environment by associating its biological traits with co-evolutionary fingerprints encoded in it.

14 CFR 204.4 - Carriers proposing to provide essential air service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Carriers proposing to provide essential air... (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS DATA TO SUPPORT FITNESS DETERMINATIONS Filing Requirements § 204.4 Carriers proposing to provide essential air service. Applicants proposing to provide essential air...

Increased burden of deleterious variants in essential genes in autism spectrum disorder.

PubMed

Ji, Xiao; Kember, Rachel L; Brown, Christopher D; Bućan, Maja

2016-12-27

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

Increased burden of deleterious variants in essential genes in autism spectrum disorder

PubMed Central

Kember, Rachel L.; Brown, Christopher D.; Bućan, Maja

2016-01-01

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease. PMID:27956632

Probing for Binding Regions of the FtsZ Protein Surface through Site-Directed Insertions: Discovery of Fully Functional FtsZ-Fluorescent Proteins

PubMed Central

Moore, Desmond A.; Whatley, Zakiya N.; Joshi, Chandra P.; Osawa, Masaki

2016-01-01

ABSTRACT FtsZ, a bacterial tubulin homologue, is a cytoskeletal protein that assembles into protofilaments that are one subunit thick. These protofilaments assemble further to form a “Z ring” at the center of prokaryotic cells. The Z ring generates a constriction force on the inner membrane and also serves as a scaffold to recruit cell wall remodeling proteins for complete cell division in vivo. One model of the Z ring proposes that protofilaments associate via lateral bonds to form ribbons; however, lateral bonds are still only hypothetical. To explore potential lateral bonding sites, we probed the surface of Escherichia coli FtsZ by inserting either small peptides or whole fluorescent proteins (FPs). Among the four lateral surfaces on FtsZ protofilaments, we obtained inserts on the front and back surfaces that were functional for cell division. We concluded that these faces are not sites of essential interactions. Inserts at two sites, G124 and R174, located on the left and right surfaces, completely blocked function, and these sites were identified as possible sites for essential lateral interactions. However, the insert at R174 did not interfere with association of protofilaments into sheets and bundles in vitro. Another goal was to find a location within FtsZ that supported insertion of FP reporter proteins while allowing the FtsZ-FPs to function as the sole source of FtsZ. We discovered one internal site, G55-Q56, where several different FPs could be inserted without impairing function. These FtsZ-FPs may provide advances for imaging Z-ring structure by superresolution techniques. IMPORTANCE One model for the Z-ring structure proposes that protofilaments are assembled into ribbons by lateral bonds between FtsZ subunits. Our study excluded the involvement of the front and back faces of the protofilament in essential interactions in vivo but pointed to two potential lateral bond sites, on the right and left sides. We also identified an FtsZ loop where various fluorescent proteins could be inserted without blocking function; these FtsZ-FPs functioned as the sole source of FtsZ. This advance provides improved tools for all fluorescence imaging of the Z ring and may be especially important for superresolution imaging. PMID:27795325

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

PubMed Central

Hubin, Elizabeth A; Fay, Allison; Xu, Catherine; Bean, James M; Saecker, Ruth M; Glickman, Michael S; Darst, Seth A; Campbell, Elizabeth A

2017-01-01

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the −10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD. DOI: http://dx.doi.org/10.7554/eLife.22520.001 PMID:28067618

Orbit determination software development for microprocessor based systems: Evaluation and recommendations

NASA Technical Reports Server (NTRS)

Shenitz, C. M.; Mcgarry, F. E.; Tasaki, K. K.

1980-01-01

A guide is presented for National Aeronautics and Space Administration management personnel who stand to benefit from the lessons learned in developing microprocessor-based flight dynamics software systems. The essential functional characteristics of microprocessors are presented. The relevant areas of system support software are examined, as are the distinguishing characteristics of flight dynamics software. Design examples are provided to illustrate the major points presented, and actual development experience obtained in this area is provided as evidence to support the conclusions reached.

Retinoic acid signaling pathways in development and diseases.

PubMed

Das, Bhaskar C; Thapa, Pritam; Karki, Radha; Das, Sasmita; Mahapatra, Sweta; Liu, Ting-Chun; Torregroza, Ingrid; Wallace, Darren P; Kambhampati, Suman; Van Veldhuizen, Peter; Verma, Amit; Ray, Swapan K; Evans, Todd

2014-01-15

Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intraradical colonization by arbuscular mycorrhizal fungi triggers induction of a lipochitooligosaccharide receptor

NASA Astrophysics Data System (ADS)

Rasmussen, S. R.; Füchtbauer, W.; Novero, M.; Volpe, V.; Malkov, N.; Genre, A.; Bonfante, P.; Stougaard, J.; Radutoiu, S.

2016-07-01

Functional divergence of paralogs following gene duplication is one of the mechanisms leading to evolution of novel pathways and traits. Here we show that divergence of Lys11 and Nfr5 LysM receptor kinase paralogs of Lotus japonicus has affected their specificity for lipochitooligosaccharides (LCOs) decorations, while the innate capacity to recognize and induce a downstream signalling after perception of rhizobial LCOs (Nod factors) was maintained. Regardless of this conserved ability, Lys11 was found neither expressed, nor essential during nitrogen-fixing symbiosis, providing an explanation for the determinant role of Nfr5 gene during Lotus-rhizobia interaction. Lys11 was expressed in root cortex cells associated with intraradical colonizing arbuscular mycorrhizal fungi. Detailed analyses of lys11 single and nfr1nfr5lys11 triple mutants revealed a functional arbuscular mycorrhizal symbiosis, indicating that Lys11 alone, or its possible shared function with the Nod factor receptors is not essential for the presymbiotic phases of AM symbiosis. Hence, both subfunctionalization and specialization appear to have shaped the function of these paralogs where Lys11 acts as an AM-inducible gene, possibly to fine-tune later stages of this interaction.

A role for post-transcriptional control of endoplasmic reticulum dynamics and function in C. elegans germline stem cell maintenance.

PubMed

Maheshwari, Richa; Pushpa, Kumari; Subramaniam, Kuppuswamy

2016-09-01

Membrane-bound receptors, which are crucial for mediating several key developmental signals, are synthesized on endoplasmic reticulum (ER). The functional integrity of ER must therefore be important for the regulation of at least some developmental programs. However, the developmental control of ER function is not well understood. Here, we identify the C. elegans protein FARL-11, an ortholog of the mammalian STRIPAK complex component STRIP1/2 (FAM40A/B), as an ER protein. In the C. elegans embryo, we find that FARL-11 is essential for the cell cycle-dependent morphological changes of ER and for embryonic viability. In the germline, FARL-11 is required for normal ER morphology and for membrane localization of the GLP-1/Notch receptor involved in germline stem cell (GSC) maintenance. Furthermore, we provide evidence that PUF-8, a key translational regulator in the germline, promotes the translation of farl-11 mRNA. These findings reveal that ER form and function in the C. elegans germline are post-transcriptionally regulated and essential for the niche-GSC signaling mediated by GLP-1. © 2016. Published by The Company of Biologists Ltd.

Science and Measurement Requirements for a Plant Physiology and Functional Types Mission: Measuring the Composition, Function and Health of Global Land and Coastal Ocean Ecosystems

NASA Technical Reports Server (NTRS)

Green, Robert O.; Rogez, Francois; Green, Rob; Ungar, Steve; Knox, Robert; Asner, Greg; Muller-Karger, Frank; Bissett, Paul; Chekalyuk, Alex; Dierssen, Heidi;

Design of indoor furniture with acoustic insulation and noise reduction function

NASA Astrophysics Data System (ADS)

Chen, Ziqiang; Lyu, Jianhua; Chen, Ming

2018-05-01

In this article, the current status of noise pollution research is analyzed and indoor noise pollution hazard on human body is discussed taking noise pollution as entry point to better understand people's needs in this concern, and it comes to the conclusion that indoor furniture with noise insulation function is required; In addition, the design status and necessity of indoor furniture with noise insulation function are expounded and the material property, structure design essentials and form design are analyzed according to sound transmission principles. In the end, design case study is presented to provide an effective way for design of indoor furniture with acoustic insulation function that meets people's needs.

Microalgae as healthy ingredients for functional food: a review.

PubMed

Matos, J; Cardoso, C; Bandarra, N M; Afonso, C

2017-08-01

Microalgae are very interesting and valuable natural sources of highly valuable bioactive compounds, such as vitamins, essential amino acids, polyunsaturated fatty acids, minerals, carotenoids, enzymes and fibre. Due to their potential, microalgae have become some of the most promising and innovative sources of new food and functional products. Moreover, microalgae can be used as functional ingredients to enhance the nutritional value of foods and, thus, to favourably affect human health by improving the well-being and quality of life, but also by curtailing disease and illness risks. This review provides an overview of the current knowledge of the health benefits associated with the consumption of microalgae, bioactive compounds, functional ingredients, and health foods.

Chemical Composition of Essential Oils from Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis, and Their Effects on the HIV-1 Tat Protein Function.

PubMed

Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

2018-02-01

New drugs would be beneficial to fight resistant HIV strains, in particular those capable of interfering with essential viral functions other than those targeted by highly active antiretroviral therapy drugs. Despite the central role played by Tat protein in HIV transcription, a search for vegetable extracts able to hamper this important viral function was never carried out. In this work, we evaluated the chemical composition and possible interference of essential oil from Thymus vulgaris, Cananga odorata, Cymbopogon citratus, and Rosmarinus officinalis with the Tat/TAR-RNA interaction and with Tat-induced HIV-1 LTR transcription. GC/MS Analysis demonstrated the biodiversity of herbal species translated into essential oils composed of different blends of terpenes. In all of them, 4 - 6 constituents represent from 81.63% to 95.19% of the total terpenes. Essential oils of Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis were active in interfering with Tat functions, encouraging further studies to identify single terpenes responsible for the antiviral activity. In view of the quite different composition of these essential oils, we concluded that their interference on Tat function depends on specific terpene or a characteristic blend. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Predictive equation of state method for heavy materials based on the Dirac equation and density functional theory

NASA Astrophysics Data System (ADS)

Wills, John M.; Mattsson, Ann E.

2012-02-01

Density functional theory (DFT) provides a formally predictive base for equation of state properties. Available approximations to the exchange/correlation functional provide accurate predictions for many materials in the periodic table. For heavy materials however, DFT calculations, using available functionals, fail to provide quantitative predictions, and often fail to be even qualitative. This deficiency is due both to the lack of the appropriate confinement physics in the exchange/correlation functional and to approximations used to evaluate the underlying equations. In order to assess and develop accurate functionals, it is essential to eliminate all other sources of error. In this talk we describe an efficient first-principles electronic structure method based on the Dirac equation and compare the results obtained with this method with other methods generally used. Implications for high-pressure equation of state of relativistic materials are demonstrated in application to Ce and the light actinides. Sandia National Laboratories is a multi-program laboratory managed andoperated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila

PubMed Central

Genova, Jennifer L.; Fehon, Richard G.

2003-01-01

One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this study, we identify new proteins that are required for a functional paracellular barrier in Drosophila. In addition to the previously known components Coracle (COR) and Neurexin (NRX), we show that four other proteins, Gliotactin, Neuroglian (NRG), and both the α and β subunits of the Na+/K+ ATPase, are required for formation of the paracellular barrier. In contrast to previous reports, we demonstrate that the Na pump is not localized basolaterally in epithelial cells, but instead is concentrated at the SJ. Data from immunoprecipitation and somatic mosaic studies suggest that COR, NRX, NRG, and the Na+/K+ ATPase form an interdependent complex. Furthermore, the observation that NRG, a Drosophila homologue of vertebrate neurofascin, is an SJ component is consistent with the notion that the invertebrate SJ is homologous to the vertebrate paranodal SJ. These findings have implications not only for invertebrate epithelia and barrier functions, but also for understanding of neuron–glial interactions in the mammalian nervous system. PMID:12782686

Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila.

PubMed

Genova, Jennifer L; Fehon, Richard G

2003-06-09

One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this study, we identify new proteins that are required for a functional paracellular barrier in Drosophila. In addition to the previously known components Coracle (COR) and Neurexin (NRX), we show that four other proteins, Gliotactin, Neuroglian (NRG), and both the alpha and beta subunits of the Na+/K+ ATPase, are required for formation of the paracellular barrier. In contrast to previous reports, we demonstrate that the Na pump is not localized basolaterally in epithelial cells, but instead is concentrated at the SJ. Data from immunoprecipitation and somatic mosaic studies suggest that COR, NRX, NRG, and the Na+/K+ ATPase form an interdependent complex. Furthermore, the observation that NRG, a Drosophila homologue of vertebrate neurofascin, is an SJ component is consistent with the notion that the invertebrate SJ is homologous to the vertebrate paranodal SJ. These findings have implications not only for invertebrate epithelia and barrier functions, but also for understanding of neuron-glial interactions in the mammalian nervous system.

Mobile Phone-Based Joint Angle Measurement for Functional Assessment and Rehabilitation of Proprioception

PubMed Central

Mourcou, Quentin; Fleury, Anthony; Diot, Bruno; Franco, Céline; Vuillerme, Nicolas

2015-01-01

Assessment of joint functional and proprioceptive abilities is essential for balance, posture, and motor control rehabilitation. Joint functional ability refers to the capacity of movement of the joint. It may be evaluated thereby measuring the joint range of motion (ROM). Proprioception can be defined as the perception of the position and of the movement of various body parts in space. Its role is essential in sensorimotor control for movement acuity, joint stability, coordination, and balance. Its clinical evaluation is commonly based on the assessment of the joint position sense (JPS). Both ROM and JPS measurements require estimating angles through goniometer, scoliometer, laser-pointer, and bubble or digital inclinometer. With the arrival of Smartphones, these costly clinical tools tend to be replaced. Beyond evaluation, maintaining and/or improving joint functional and proprioceptive abilities by training with physical therapy is important for long-term management. This review aims to report Smartphone applications used for measuring and improving functional and proprioceptive abilities. It identifies that Smartphone applications are reliable for clinical measurements and are mainly used to assess ROM and JPS. However, there is lack of studies on Smartphone applications which can be used in an autonomous way to provide physical therapy exercises at home. PMID:26583101

Deletion of Selenoprotein M Leads to Obesity without Cognitive Deficits*

PubMed Central

Pitts, Matthew W.; Reeves, Mariclair A.; Hashimoto, Ann C.; Ogawa, Ashley; Kremer, Penny; Seale, Lucia A.; Berry, Marla J.

2013-01-01

Selenium is an essential trace element that is co-translationally incorporated into selenoproteins in the form of the 21st amino acid, selenocysteine. This class of proteins largely functions in oxidation-reduction reactions and is critically involved in maintaining proper redox balance essential to health. Selenoprotein M (SelM) is a thioredoxin-like endoplasmic reticulum-resident protein that is highly expressed in the brain and possesses neuroprotective properties. In this study, we first assessed the regional pattern of SelM expression in the mouse brain to provide insights into the potential functional implications of this protein in physiology and behavior. Next, we generated transgenic mice with a targeted deletion of the SelM gene and subjected them to a battery of neurobehavioral tests to evaluate motor coordination, locomotion, and cognitive function in comparison with wild-type controls. Finally, these mice were tested for several measures of metabolic function and body composition. Our results show that SelM knock-out (KO) mice display no deficits in measures of motor coordination and cognitive function but exhibit increased weight gain, elevated white adipose tissue deposition, and diminished hypothalamic leptin sensitivity. These findings suggest that SelM plays an important role in the regulation of body weight and energy metabolism. PMID:23880772

Decoupling catalytic activity from biological function of the ATPase that powers lipopolysaccharide transport

PubMed Central

Sherman, David J.; Lazarus, Michael B.; Murphy, Lea; Liu, Charles; Walker, Suzanne; Ruiz, Natividad; Kahne, Daniel

2014-01-01

The cell surface of Gram-negative bacteria contains lipopolysaccharides (LPS), which provide a barrier against the entry of many antibiotics. LPS assembly involves a multiprotein LPS transport (Lpt) complex that spans from the cytoplasm to the outer membrane. In this complex, an unusual ATP-binding cassette transporter is thought to power the extraction of LPS from the outer leaflet of the cytoplasmic membrane and its transport across the cell envelope. We introduce changes into the nucleotide-binding domain, LptB, that inactivate transporter function in vivo. We characterize these residues using biochemical experiments combined with high-resolution crystal structures of LptB pre- and post-ATP hydrolysis and suggest a role for an active site residue in phosphate exit. We also identify a conserved residue that is not required for ATPase activity but is essential for interaction with the transmembrane components. Our studies establish the essentiality of ATP hydrolysis by LptB to power LPS transport in cells and suggest strategies to inhibit transporter function away from the LptB active site. PMID:24639492

INPP5E Preserves Genomic Stability through Regulation of Mitosis.

PubMed

Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

2017-03-15

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

[Probiotics and prebiotics as a bioactive component of functional food].

PubMed

Kapka-Skrzypczak, Lucyna; Niedźwiecka, Joanna; Wojtyła, Andrzej; Kruszewski, Marcin

2012-01-01

The results of food science investigations have confirmed the relationship between the type of eaten food and health. Simultaneously, consumers are paying more and more attention to the kind of food they eat, as their awareness concerning the influence of proper food on health is increasing. On that base the conception of functional food has been created. This kind of food, besides being a source of essential macro- and micronutrients, exerts an additional positive influence on health. Probiotics and prebiotics containing products are a good example of functional food. These products provide not only essential nutrients but also microorganisms and polysaccharides, which are indigestible in the human alimentary tract, but exert a positive effect on human health. It may be a therapeutic or prophylactic effect due to specific affliction or may improve health in general. The paper - based on available literature - shows a positive influence of probiotics and prebiotics on human health, especially in the immunomodulation effect, an advantageous effect on the digestive system, antitumor activity and a possible therapeutic and prophylactic effect on cardiovascular diseases and obesity.

Maine: 2002 Economic Census. Educational Services, Geographic Area Series. EC02-61A-ME.

ERIC Educational Resources Information Center

US Department of Commerce, 2005

2005-01-01

The economic census is the major source of facts about the structure and functioning of the nation's economy. It provides essential information for government, business, industry, and the general public. Title 13 of the United States Code (Sections 131, 191, and 224) directs the Census Bureau to take the economic census every 5 years, covering…

Compelling Counternarratives to Deficit Discourses: An Investigation into the Funds of Knowledge of Culturally and Linguistically Diverse U.S. Elementary Students' Households

ERIC Educational Resources Information Center

Kinney, Angela

2015-01-01

This study focused on household funds of knowledge or "historically accumulated bodies of knowledge and skills essential for household functioning and well-being" (Gonzalez, Andrade, Civil, & Moll, 2001). A Funds of Knowledge approach provides both a methodological and theoretical lens for educators to understand both themselves and…

Virtual Environments for Soldier Training via Editable Demonstrations (VESTED)

DTIC Science & Technology

2011-04-01

demonstrations as visual depictions of task performance, though sound and especially verbal communications involved with the task can also be essential...or any component cue alone (e.g., Janelle, Champenoy, Coombes , & Mousseau, 2003). Neurophysiology. Recent neurophysiological research has...provides insight about how VESTED functions, what features to modify should it yield less than optimal results, and how to encode, communicate and

Real-Time Enzyme Kinetics by Quantitative NMR Spectroscopy and Determination of the Michaelis-Menten Constant Using the Lambert-W Function

ERIC Educational Resources Information Center

Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.

2015-01-01

Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…

Proceedings of the 1981 KL-ONE Workshop,

DTIC Science & Technology

1982-06-01

of stereotypical plans and provides friendly truth maintenance and choice generation. Among other facilities, the system responds to questions about...Role3t Relations, which express the interrelations among the [ functional Roles. A superConoept serves as proximate genus , while the internal...structure expresses essential eIifferences, as in classical classificatory definition [Sellars 17]. The sumum genus is represented by the Concept THING. THING

41 CFR Appendix A to Part 60 - 300-Guidelines on a Contractor's Duty To Provide Reasonable Accommodation

Code of Federal Regulations, 2010 CFR

2010-07-01

... performing his or her job. 1. A contractor is required to make reasonable accommodations to the known... qualified with respect to that process. One is “otherwise qualified” if he or she is qualified for a job... the job's essential functions. 2. Although the contractor would not be expected to accommodate...

Nerve growth factor, interoception, and sympathetic neuron: lesson from congenital insensitivity to pain with anhidrosis.

PubMed

Indo, Yasuhiro

2009-05-11

Nerve growth factor (NGF) is a well-known neurotrophic factor essential for the survival and maintenance of sensory and sympathetic neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is a genetic disorder due to loss-of-function mutations in the NTRK1 (also known as TRKA) gene encoding TrkA, a receptor tyrosine kinase for NGF. Patients with CIPA provide us a rare opportunity to explore the developmental and physiological function of the NGF-dependent neurons in behavior, cognitive, and mental activities that are not available in animal studies. Here, I discuss the significance of findings that patients with CIPA lack NGF-dependent neurons, including interoceptive polymodal receptors, sympathetic postganglionic neurons, and probably several types of neurons in the brain. They also exhibit characteristic emotional behavior or problems. Together, the NGF-TrkA system is essential for the establishment of a neural network for interoception and homeostasis that may underlie 'gut feelings'. Thus, NGF-dependent neurons play a crucial role in emotional experiences and decision-making processes. Prospective studies focused on these neurons might provide further insights into the neural basis of human emotion and feeling.

Strategic purchasing and health system efficiency: A comparison of two financing schemes in Thailand.

PubMed

Patcharanarumol, Walaiporn; Panichkriangkrai, Warisa; Sommanuttaweechai, Angkana; Hanson, Kara; Wanwong, Yaowaluk; Tangcharoensathien, Viroj

2018-01-01

Strategic purchasing is an essential health financing function. This paper compares the strategic purchasing practices of Thailand's two tax-financed health insurance schemes, the Universal Coverage Scheme (UCS) and the Civil Servant Medical Benefit Scheme (CSMBS), and identifies factors contributing to successful universal health coverage outcomes by analysing the relationships between the purchaser and government, providers and members. The study uses a cross-sectional mixed-methods design, including document review and interviews with 56 key informants. The Comptroller General Department (CGD) of Ministry of Finance manages CSMBS as one among civil servant welfare programmes. Their purchasing is passive. Fee for service payment for outpatient care has resulted in rapid cost escalation and overspending of their annual budget. In contrast, National Health Security Office (NHSO) manages purchasing for UCS, which undertakes a range of strategic purchasing actions, including applying closed ended provider payment, promoting primary healthcare's gate keeping functions, exercising collective purchasing power and engaging views of members in decision making process. This difference in purchasing arrangements resulted in expenditure per CSMBS member being 4 times higher than UCS in 2014. The governance of the purchaser organization, the design of the purchasing arrangements including incentives and use of information, and the institutional capacities to implement purchasing functions are essential for effective strategic purchasing which can improve health system efficiency as a whole.

Strategic purchasing and health system efficiency: A comparison of two financing schemes in Thailand

PubMed Central

2018-01-01

Strategic purchasing is an essential health financing function. This paper compares the strategic purchasing practices of Thailand’s two tax-financed health insurance schemes, the Universal Coverage Scheme (UCS) and the Civil Servant Medical Benefit Scheme (CSMBS), and identifies factors contributing to successful universal health coverage outcomes by analysing the relationships between the purchaser and government, providers and members. The study uses a cross-sectional mixed-methods design, including document review and interviews with 56 key informants. The Comptroller General Department (CGD) of Ministry of Finance manages CSMBS as one among civil servant welfare programmes. Their purchasing is passive. Fee for service payment for outpatient care has resulted in rapid cost escalation and overspending of their annual budget. In contrast, National Health Security Office (NHSO) manages purchasing for UCS, which undertakes a range of strategic purchasing actions, including applying closed ended provider payment, promoting primary healthcare’s gate keeping functions, exercising collective purchasing power and engaging views of members in decision making process. This difference in purchasing arrangements resulted in expenditure per CSMBS member being 4 times higher than UCS in 2014. The governance of the purchaser organization, the design of the purchasing arrangements including incentives and use of information, and the institutional capacities to implement purchasing functions are essential for effective strategic purchasing which can improve health system efficiency as a whole. PMID:29608610

FK506-Binding Proteins and Their Diverse Functions.

PubMed

Tong, Mingming; Jiang, Yu

2015-01-01

FK506 binding proteins (FKBPs) are a family of highly conserved proteins in eukaryotes. The prototype of this protein family, FKBP12, is the binding partner for immunosuppressive drugs FK506 and rapamycin. FKBP12 functions as a cis/trans peptidyl prolyl isomerase (PPIase) that catalyzes interconversion between prolyl cis/trans conformations. Members of the FKBP family contain one or several PPIase domains, which do not always exhibit PPIase activity yet are all essential for their function. FKBPs are involved in diverse cellular functions including protein folding, cellular signaling, apoptosis and transcription. They elicit their function through direct binding and altering conformation of their target proteins, hence acting as molecular switches. In this review, we provide a general summary for the structures and diverse functions of FKBPs found in mammalian cells.

Axonal transport: cargo-specific mechanisms of motility and regulation.

PubMed

Maday, Sandra; Twelvetrees, Alison E; Moughamian, Armen J; Holzbaur, Erika L F

2014-10-22

Axonal transport is essential for neuronal function, and many neurodevelopmental and neurodegenerative diseases result from mutations in the axonal transport machinery. Anterograde transport supplies distal axons with newly synthesized proteins and lipids, including synaptic components required to maintain presynaptic activity. Retrograde transport is required to maintain homeostasis by removing aging proteins and organelles from the distal axon for degradation and recycling of components. Retrograde axonal transport also plays a major role in neurotrophic and injury response signaling. This review provides an overview of axonal transport pathways and discusses their role in neuronal function.

Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

PubMed Central

Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

2014-01-01

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

Mitochondrial Ubiquitin Ligase in Cardiovascular Disorders.

PubMed

Yu, Tao; Zhang, Yinfeng; Li, Pei-Feng

2017-01-01

Mitochondrial dynamics play a critical role in cellular responses and physiological process. However, their dysregulation leads to a functional degradation, which results in a diverse array of common disorders, including cardiovascular disease. In this background, the mitochondrial ubiquitin ligase has been attracting substantial research interest in recent years. Mitochondrial ubiquitin ligase is localized in the mitochondrial outer membrane, where it plays an essential role in the regulation of mitochondrial dynamics and apoptosis. In this chapter, we provide a comprehensive overview of the functions of mitochondrial ubiquitin ligases identified hitherto, with a special focus on cardiovascular disorders.

Innovations in Functional Neurosurgery and Anesthetic Implications.

PubMed

Dunn, Lauren K; Durieux, Marcel E; Elias, W Jeffrey; Nemergut, Edward C; Naik, Bhiken I

2018-01-01

Functional neurosurgery has undergone rapid growth over the last few years fueled by advances in imaging technology and novel treatment modalities. These advances have led to new surgical treatments using minimally invasive and precise techniques for conditions such as Parkinson's disease, essential tremor, epilepsy, and psychiatric disorders. Understanding the goals and technological issues of these procedures is imperative for the anesthesiologist to ensure safe management of patients presenting for functional neurosurgical procedures. In this review, we discuss the advances in neurosurgical techniques for deep brain stimulation, focused ultrasound and minimally invasive laser-based treatment of refractory epilepsy and provide a guideline for anesthesiologists caring for patients undergoing these procedures.

How multi-partner endosymbioses function.

PubMed

Douglas, Angela E

2016-12-01

Various animals are associated with specific endosymbiotic microorganisms that provide the host with essential nutrients or confer protection against natural enemies. Genomic analyses of the many endosymbioses that are found in plant sap-feeding hemipteran insects have revealed independent acquisitions - and occasional replacements - of endosymbionts, such that many of these endosymbioses involve two or more microbial partners. In this Review, I discuss how partitioning of the genetic capacity for metabolic function between different endosymbionts has sustained nutritional function in multi-partner endosymbioses, and how the phenotypic traits of these endosymbionts can be shaped by co-evolutionary interactions with both co-occurring microbial taxa and the host, which often operate over long evolutionary timescales.

Repellent activity of essential oils: a review.

PubMed

Nerio, Luz Stella; Olivero-Verbel, Jesus; Stashenko, Elena

2010-01-01

Currently, the use of synthetic chemicals to control insects and arthropods raises several concerns related to environment and human health. An alternative is to use natural products that possess good efficacy and are environmentally friendly. Among those chemicals, essential oils from plants belonging to several species have been extensively tested to assess their repellent properties as a valuable natural resource. The essential oils whose repellent activities have been demonstrated, as well as the importance of the synergistic effects among their components are the main focus of this review. Essential oils are volatile mixtures of hydrocarbons with a diversity of functional groups, and their repellent activity has been linked to the presence of monoterpenes and sesquiterpenes. However, in some cases, these chemicals can work synergistically, improving their effectiveness. In addition, the use of other natural products in the mixture, such as vanillin, could increase the protection time, potentiating the repellent effect of some essential oils. Among the plant families with promising essential oils used as repellents, Cymbopogon spp., Ocimum spp. and Eucalyptus spp. are the most cited. Individual compounds present in these mixtures with high repellent activity include alpha-pinene, limonene, citronellol, citronellal, camphor and thymol. Finally, although from an economical point of view synthetic chemicals are still more frequently used as repellents than essential oils, these natural products have the potential to provide efficient, and safer repellents for humans and the environment.

General Toxicity and Antifungal Activity of a New Dental Gel with Essential Oil from Abies Sibirica L

PubMed Central

Noreikaitė, Aurelija; Ayupova, Rizvangul; Satbayeva, Elmira; Seitaliyeva, Aida; Amirkulova, Marzhan; Pichkhadze, Guram; Datkhayev, Ubaidilla; Stankeviandccaron;ius, Edgaras

2017-01-01

Background The aim of this study was to analyze the antifungal activity and the general toxicity of a new dental gel containing essential oil from the tree Abies sibirica L., which grows in the Republic of Kazakhstan. Material/Methods The essential oil from Abies sibirica L. was obtained by microwave heating method using the STARTE Microwave Extraction System. Adjutants used to prepare the oil were carbomer 974P, glycerin, polysorbate 80, xylitol, triethanolamine, and purified water, all allowed for medical usage. The antifungal activity of the essential oil was assessed by monitoring the optical density of Candida albicans in a microplate reader. The safety was determined by analyzing the acute and subacute toxicity. Results The essential oil obtained by the microwave heating method revealed a higher antifungal activity in comparison with the essential oil obtained by the steam distillation method. No obvious changes were detected in guinea pigs following cutaneous application of the gel. Enteral administration of the essential oil caused minimal functional and histological changes in mice after 4 weeks. The new harmless dental gel containing pine oil from Abies sibirica L. was provided for the purposes of this particular clinical research. Conclusions The high antifungal activity of the gel is the basis for more in-depth studies on its safety and pharmacological activity. PMID:28132065

General Toxicity and Antifungal Activity of a New Dental Gel with Essential Oil from Abies Sibirica L.

PubMed

Noreikaitė, Aurelija; Ayupova, Rizvangul; Satbayeva, Elmira; Seitaliyeva, Aida; Amirkulova, Marzhan; Pichkhadze, Guram; Datkhayev, Ubaidilla; Stankevičius, Edgaras

2017-01-29

BACKGROUND The aim of this study was to analyze the antifungal activity and the general toxicity of a new dental gel containing essential oil from the tree Abies sibirica L., which grows in the Republic of Kazakhstan. MATERIAL AND METHODS The essential oil from Abies sibirica L. was obtained by microwave heating method using the STARTE Microwave Extraction System. Adjutants used to prepare the oil were carbomer 974P, glycerin, polysorbate 80, xylitol, triethanolamine, and purified water, all allowed for medical usage. The antifungal activity of the essential oil was assessed by monitoring the optical density of Candida albicans in a microplate reader. The safety was determined by analyzing the acute and subacute toxicity. RESULTS The essential oil obtained by the microwave heating method revealed a higher antifungal activity in comparison with the essential oil obtained by the steam distillation method. No obvious changes were detected in guinea pigs following cutaneous application of the gel. Enteral administration of the essential oil caused minimal functional and histological changes in mice after 4 weeks. The new harmless dental gel containing pine oil from Abies sibirica L. was provided for the purposes of this particular clinical research. CONCLUSIONS The high antifungal activity of the gel is the basis for more in-depth studies on its safety and pharmacological activity.

The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo

PubMed Central

Gubala, Anna M.; Schmitz, Jonathan F.; Kearns, Michael J.; Vinh, Tery T.; Bornberg-Bauer, Erich; Wolfner, Mariana F.

2017-01-01

New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. PMID:28104747

Functional characterization of the essential tail anchor of the herpes simplex virus type 1 nuclear egress protein pUL34.

PubMed

Ott, Melanie; Tascher, Georg; Hassdenteufel, Sarah; Zimmermann, Richard; Haas, Jürgen; Bailer, Susanne M

2011-12-01

Release of herpes simplex virus type 1 (HSV-1) nucleocapsids from the host nucleus relies on the nuclear egress complex consisting of the two essential proteins pUL34 and pUL31. The cytoplasmically exposed N-terminal region of pUL34 interacts with pUL31, while a hydrophobic region followed by a short luminal part mediates membrane association. Based on its domain organization, pUL34 was postulated to be a tail-anchor (TA) protein. We performed a coupled in vitro transcription/translation assay to show that membrane insertion of pUL34 occurs post-translationally. Transient transfection and localization experiments in mammalian cells were combined with HSV-1 bacterial artificial chromosome mutagenesis to reveal the functional properties of the essential pUL34 TA. Our data show that a minimal tail length of 15 residues is sufficient for nuclear envelope targeting and pUL34 function. Permutations of the pUL34 TA with orthologous regions of human cytomegalovirus pUL50 or Epstein-Barr virus pBFRF1 as well as the heterologous HSV-1 TA proteins pUL56 or pUS9 or the cellular TA proteins Bcl-2 and Vamp2 revealed that nuclear egress tolerates TAs varying in sequence and hydrophobicity, while a non-α-helical membrane anchor failed to complement the pUL34 function. In conclusion, this study provides the first mechanistic insights into the particular role of the TA of pUL34 in membrane curving and capsid egress from the host nucleus.

Review Article: Mapping of children's health and development data on population level using the classification system ICF-CY.

PubMed

Ståhl, Ylva; Granlund, Mats; Gäre-Andersson, Boel; Enskär, Karin

2011-02-01

The aim of this study was to investigate if essential health and development data of all children in Sweden in the Child Health Service (CHS) and School Health Service (SHS) can be linked to the classification system International Classification of Functioning, Disability and Health--Children and Youth (ICF-CY). Lists of essential health terms, compiled by professionals from CHS and SHS, expected to be used in the national standardised records form the basis for the analysis in this study. The essential health terms have been linked to the codes of ICF-CY by using linking rules and a verification procedure. After exclusion of terms not directly describing children's health, a majority of the health terms could be linked into the ICF-CY with a high proportion of terms in body functions and a lower proportion in activity/participation and environment respectively. Some health terms had broad description and were linked to several ICF-CY codes. The precision of the health terms was at a medium level of detail. ICF-CY can be useful as a tool for documenting child health. It provides not only a code useful for statistical purposes but also a language useful for the CHS and SHS in their work on individual as well as population levels. It was noted that the health terms used by services mainly focused on health related to body function. This indicates that more focus is needed on health data related to child's functioning in everyday life situations.

Chitosan-based microcapsules containing grapefruit seed extract grafted onto cellulose fibers by a non-toxic procedure.

PubMed

Alonso, Diana; Gimeno, Miquel; Sepúlveda-Sánchez, José D; Shirai, Keiko

2010-04-19

A novel non-toxic procedure is described for the grafting of chitosan-based microcapsules containing grapefruit seed oil extract onto cellulose. The cellulose was previously UV-irradiated and then functionalized from an aqueous emulsion of the chitosan with the essential oil. The novel materials are readily attained with durable fragrance and enhanced antimicrobial properties. The incorporation of chitosan as determined from the elemental analyses data was 16.08+/-0.29 mg/g of sample. Scanning electron microscopy (SEM) and gas chromatography-mass spectroscopy (GC-MS) provided further evidence for the successful attachment of chitosan microcapsules containing the essential oil to the treated cellulose fibers. The materials thus produced displayed 100% inhibition of Escherichia coli and Staphylococcus epidermidis up to 48 h of incubation. Inhibition of bacteria by the essential oil was also evaluated at several concentrations. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Vacuolar sequestration capacity and long-distance metal transport in plants

PubMed Central

Peng, Jia-Shi; Gong, Ji-Ming

2014-01-01

The vacuole is a pivotal organelle functioning in storage of metabolites, mineral nutrients, and toxicants in higher plants. Accumulating evidence indicates that in addition to its storage role, the vacuole contributes essentially to long-distance transport of metals, through the modulation of Vacuolar sequestration capacity (VSC) which is shown to be primarily controlled by cytosolic metal chelators and tonoplast-localized transporters, or the interaction between them. Plants adapt to their environments by dynamic regulation of VSC for specific metals and hence targeting metals to specific tissues. Study of VSC provides not only a new angle to understand the long-distance root-to-shoot transport of minerals in plants, but also an efficient way to biofortify essential mineral nutrients or to phytoremediate non-essential metal pollution. The current review will focus on the most recent proceedings on the interaction mechanisms between VSC regulation and long-distance metal transport. PMID:24550927

Vacuolar sequestration capacity and long-distance metal transport in plants.

PubMed

Peng, Jia-Shi; Gong, Ji-Ming

2014-01-01

The vacuole is a pivotal organelle functioning in storage of metabolites, mineral nutrients, and toxicants in higher plants. Accumulating evidence indicates that in addition to its storage role, the vacuole contributes essentially to long-distance transport of metals, through the modulation of Vacuolar sequestration capacity (VSC) which is shown to be primarily controlled by cytosolic metal chelators and tonoplast-localized transporters, or the interaction between them. Plants adapt to their environments by dynamic regulation of VSC for specific metals and hence targeting metals to specific tissues. Study of VSC provides not only a new angle to understand the long-distance root-to-shoot transport of minerals in plants, but also an efficient way to biofortify essential mineral nutrients or to phytoremediate non-essential metal pollution. The current review will focus on the most recent proceedings on the interaction mechanisms between VSC regulation and long-distance metal transport.

Workflow management in large distributed systems

NASA Astrophysics Data System (ADS)

Legrand, I.; Newman, H.; Voicu, R.; Dobre, C.; Grigoras, C.

2011-12-01

The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

High-throughput discovery of novel developmental phenotypes.

PubMed

Dickinson, Mary E; Flenniken, Ann M; Ji, Xiao; Teboul, Lydia; Wong, Michael D; White, Jacqueline K; Meehan, Terrence F; Weninger, Wolfgang J; Westerberg, Henrik; Adissu, Hibret; Baker, Candice N; Bower, Lynette; Brown, James M; Caddle, L Brianna; Chiani, Francesco; Clary, Dave; Cleak, James; Daly, Mark J; Denegre, James M; Doe, Brendan; Dolan, Mary E; Edie, Sarah M; Fuchs, Helmut; Gailus-Durner, Valerie; Galli, Antonella; Gambadoro, Alessia; Gallegos, Juan; Guo, Shiying; Horner, Neil R; Hsu, Chih-Wei; Johnson, Sara J; Kalaga, Sowmya; Keith, Lance C; Lanoue, Louise; Lawson, Thomas N; Lek, Monkol; Mark, Manuel; Marschall, Susan; Mason, Jeremy; McElwee, Melissa L; Newbigging, Susan; Nutter, Lauryl M J; Peterson, Kevin A; Ramirez-Solis, Ramiro; Rowland, Douglas J; Ryder, Edward; Samocha, Kaitlin E; Seavitt, John R; Selloum, Mohammed; Szoke-Kovacs, Zsombor; Tamura, Masaru; Trainor, Amanda G; Tudose, Ilinca; Wakana, Shigeharu; Warren, Jonathan; Wendling, Olivia; West, David B; Wong, Leeyean; Yoshiki, Atsushi; MacArthur, Daniel G; Tocchini-Valentini, Glauco P; Gao, Xiang; Flicek, Paul; Bradley, Allan; Skarnes, William C; Justice, Monica J; Parkinson, Helen E; Moore, Mark; Wells, Sara; Braun, Robert E; Svenson, Karen L; de Angelis, Martin Hrabe; Herault, Yann; Mohun, Tim; Mallon, Ann-Marie; Henkelman, R Mark; Brown, Steve D M; Adams, David J; Lloyd, K C Kent; McKerlie, Colin; Beaudet, Arthur L; Bućan, Maja; Murray, Stephen A

2016-09-22

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

High-throughput discovery of novel developmental phenotypes

PubMed Central

Dickinson, Mary E.; Flenniken, Ann M.; Ji, Xiao; Teboul, Lydia; Wong, Michael D.; White, Jacqueline K.; Meehan, Terrence F.; Weninger, Wolfgang J.; Westerberg, Henrik; Adissu, Hibret; Baker, Candice N.; Bower, Lynette; Brown, James M.; Caddle, L. Brianna; Chiani, Francesco; Clary, Dave; Cleak, James; Daly, Mark J.; Denegre, James M.; Doe, Brendan; Dolan, Mary E.; Edie, Sarah M.; Fuchs, Helmut; Gailus-Durner, Valerie; Galli, Antonella; Gambadoro, Alessia; Gallegos, Juan; Guo, Shiying; Horner, Neil R.; Hsu, Chih-wei; Johnson, Sara J.; Kalaga, Sowmya; Keith, Lance C.; Lanoue, Louise; Lawson, Thomas N.; Lek, Monkol; Mark, Manuel; Marschall, Susan; Mason, Jeremy; McElwee, Melissa L.; Newbigging, Susan; Nutter, Lauryl M.J.; Peterson, Kevin A.; Ramirez-Solis, Ramiro; Rowland, Douglas J.; Ryder, Edward; Samocha, Kaitlin E.; Seavitt, John R.; Selloum, Mohammed; Szoke-Kovacs, Zsombor; Tamura, Masaru; Trainor, Amanda G; Tudose, Ilinca; Wakana, Shigeharu; Warren, Jonathan; Wendling, Olivia; West, David B.; Wong, Leeyean; Yoshiki, Atsushi; MacArthur, Daniel G.; Tocchini-Valentini, Glauco P.; Gao, Xiang; Flicek, Paul; Bradley, Allan; Skarnes, William C.; Justice, Monica J.; Parkinson, Helen E.; Moore, Mark; Wells, Sara; Braun, Robert E.; Svenson, Karen L.; de Angelis, Martin Hrabe; Herault, Yann; Mohun, Tim; Mallon, Ann-Marie; Henkelman, R. Mark; Brown, Steve D.M.; Adams, David J.; Lloyd, K.C. Kent; McKerlie, Colin; Beaudet, Arthur L.; Bucan, Maja; Murray, Stephen A.

2016-01-01

Approximately one third of all mammalian genes are essential for life. Phenotypes resulting from mouse knockouts of these genes have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5000 knockout mouse lines, we have identified 410 lethal genes during the production of the first 1751 unique gene knockouts. Using a standardised phenotyping platform that incorporates high-resolution 3D imaging, we identified novel phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes identified in our screen, thus providing a novel dataset that facilitates prioritization and validation of mutations identified in clinical sequencing efforts. PMID:27626380

The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina.

PubMed

Connor, W E; Neuringer, M

1988-01-01

It is now apparent that both n-6 and n-3 fatty acids are essential for normal development in mammals, and that each has specific functions in the body. N-6 fatty acids are necessary primarily for growth, reproduction, and the maintenance of skin integrity, whereas n-3 fatty acids are involved in the development and function of the retina and cerebral cortex and perhaps other organs such as the testes. Fetal life and infancy are particularly critical for the nervous tissue development. Therefore, with respect to human nutrition, adequate amounts of omega-3 fatty acids should be provided during pregnancy, lactation and infancy, but probably throughout life. We estimate that adequate levels are provided by diets containing 6-8% kcals from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The essentiality of n-3 fatty acids resides in their presence as DHA in vital membranes of the photoreceptors of the retina and the synaptosomes and other subcellular membranes of the brain. The replacement of DHA in deficient animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the membranes for reasons as yet to be ascertained. Most significant is the lability of fatty acid composition in the retinal and brain of deficient animals. Dietary fish oil, which contains EPA and DHA, will readily lead to a change in the composition of the membrane of retina and brain, fatty acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships between the chemistry of neural and retinal membranes as affected by diet and their biological functioning provides an exciting prospect for future investigations.

FAPRS Manual: Manual for the Functional Analytic Psychotherapy Rating Scale

ERIC Educational Resources Information Center

Callaghan, Glenn M.; Follette, William C.

2008-01-01

The Functional Analytic Psychotherapy Rating Scale (FAPRS) is behavioral coding system designed to capture those essential client and therapist behaviors that occur during Functional Analytic Psychotherapy (FAP). The FAPRS manual presents the purpose and rules for documenting essential aspects of FAP. The FAPRS codes are exclusive and exhaustive…

Experimental characterization of a quantum many-body system via higher-order correlations.

PubMed

Schweigler, Thomas; Kasper, Valentin; Erne, Sebastian; Mazets, Igor; Rauer, Bernhard; Cataldini, Federica; Langen, Tim; Gasenzer, Thomas; Berges, Jürgen; Schmiedmayer, Jörg

2017-05-17

Quantum systems can be characterized by their correlations. Higher-order (larger than second order) correlations, and the ways in which they can be decomposed into correlations of lower order, provide important information about the system, its structure, its interactions and its complexity. The measurement of such correlation functions is therefore an essential tool for reading, verifying and characterizing quantum simulations. Although higher-order correlation functions are frequently used in theoretical calculations, so far mainly correlations up to second order have been studied experimentally. Here we study a pair of tunnel-coupled one-dimensional atomic superfluids and characterize the corresponding quantum many-body problem by measuring correlation functions. We extract phase correlation functions up to tenth order from interference patterns and analyse whether, and under what conditions, these functions factorize into correlations of lower order. This analysis characterizes the essential features of our system, the relevant quasiparticles, their interactions and topologically distinct vacua. From our data we conclude that in thermal equilibrium our system can be seen as a quantum simulator of the sine-Gordon model, relevant for diverse disciplines ranging from particle physics to condensed matter. The measurement and evaluation of higher-order correlation functions can easily be generalized to other systems and to study correlations of any other observable such as density, spin and magnetization. It therefore represents a general method for analysing quantum many-body systems from experimental data.

Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

PubMed Central

Samotus, Olivia; Rahimi, Fariborz; Lee, Jack; Jog, Mandar

2016-01-01

Objective Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection. Method Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant. Results Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (p<0.0005). UPDRS item 21 score rating action tremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST) significantly improved from 40.3±15.8 at week 0 to 31.1±15.3 (p = 0.035) at week 32 and to 27.8±15.3 (p = 0.028) at week 38. Kinematics provided an objective, secondary outcome measure, which showed a significant decrease in tremor amplitude in the wrist and shoulder joints (p<0.05). Eight participants (40%) self-reported mild weakness in injected muscles but had no interference in arm function. Conclusion Kinematic tremor assessments provide the injector unique insight to objectively individualize and personalize injection parameters demonstrating BoNT-A effectively alleviates functional disability caused by essential tremor. Kinematic technology is a promising method for standardizing assessments and for focal upper limb tremor treatment. Trial Registration ClinicalTrials.gov NCT02427646 PMID:27101283

Response diversity determines the resilience of ecosystems to environmental change.

PubMed

Mori, Akira S; Furukawa, Takuya; Sasaki, Takehiro

2013-05-01

A growing body of evidence highlights the importance of biodiversity for ecosystem stability and the maintenance of optimal ecosystem functionality. Conservation measures are thus essential to safeguard the ecosystem services that biodiversity provides and human society needs. Current anthropogenic threats may lead to detrimental (and perhaps irreversible) ecosystem degradation, providing strong motivation to evaluate the response of ecological communities to various anthropogenic pressures. In particular, ecosystem functions that sustain key ecosystem services should be identified and prioritized for conservation action. Traditional diversity measures (e.g. 'species richness') may not adequately capture the aspects of biodiversity most relevant to ecosystem stability and functionality, but several new concepts may be more appropriate. These include 'response diversity', describing the variation of responses to environmental change among species of a particular community. Response diversity may also be a key determinant of ecosystem resilience in the face of anthropogenic pressures and environmental uncertainty. However, current understanding of response diversity is poor, and we see an urgent need to disentangle the conceptual strands that pervade studies of the relationship between biodiversity and ecosystem functioning. Our review clarifies the links between response diversity and the maintenance of ecosystem functionality by focusing on the insurance hypothesis of biodiversity and the concept of functional redundancy. We provide a conceptual model to describe how loss of response diversity may cause ecosystem degradation through decreased ecosystem resilience. We explicitly explain how response diversity contributes to functional compensation and to spatio-temporal complementarity among species, leading to long-term maintenance of ecosystem multifunctionality. Recent quantitative studies suggest that traditional diversity measures may often be uncoupled from measures (such as response diversity) that may be more effective proxies for ecosystem stability and resilience. Certain conclusions and recommendations of earlier studies using these traditional measures as indicators of ecosystem resilience thus may be suspect. We believe that functional ecology perspectives incorporating the effects and responses of diversity are essential for development of management strategies to safeguard (and restore) optimal ecosystem functionality (especially multifunctionality). Our review highlights these issues and we envision our work generating debate around the relationship between biodiversity and ecosystem functionality, and leading to improved conservation priorities and biodiversity management practices that maximize ecosystem resilience in the face of uncertain environmental change. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

Financial and testamentary capacity evaluations: procedures and assessment instruments underneath a functional approach.

PubMed

Sousa, Liliana B; Simões, Mário R; Firmino, Horácio; Peisah, Carmelle

2014-02-01

Mental health professionals are frequently involved in mental capacity determinations. However, there is a lack of specific measures and well-defined procedures for these evaluations. The main purpose of this paper is to provide a review of financial and testamentary capacity evaluation procedures, including not only the traditional neuropsychological and functional assessment but also the more recently developed forensic assessment instruments (FAIs), which have been developed to provide a specialized answer to legal systems regarding civil competencies. Here the main guidelines, papers, and other references are reviewed in order to achieve a complete and comprehensive selection of instruments used in the assessment of financial and testamentary capacity. Although some specific measures for financial abilities have been developed recently, the same is not true for testamentary capacity. Here are presented several instruments or methodologies for assessing financial and testamentary capacity, including neuropsychological assessment, functional assessment scales, performance based functional assessment instruments, and specific FAIs. FAIs are the only specific instruments intended to provide a specific and direct answer to the assessment of financial capacity based on legal systems. Considering the need to move from a diagnostic to a functional approach in financial and testamentary capacity evaluations, it is essential to consider both general functional examination as well as cognitive functioning.

RNA Structures as Mediators of Neurological Diseases and as Drug Targets.

PubMed

Bernat, Viachaslau; Disney, Matthew D

2015-07-01

RNAs adopt diverse folded structures that are essential for function and thus play critical roles in cellular biology. A striking example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that orchestrates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have revealed other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures contribute to disease. In this Review, we provide a brief introduction into RNA structural biology and then describe how RNA structures function in cells and cause or contribute to neurological disease. Finally, we highlight successful applications of rational design principles to provide chemical probes and lead compounds targeting structured RNAs. Based on several examples of well-characterized RNA-driven neurological disorders, we demonstrate how designed small molecules can facilitate the study of RNA dysfunction, elucidating previously unknown roles for RNA in disease, and provide lead therapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Calculation of phonon dispersion relation using new correlation functional

NASA Astrophysics Data System (ADS)

Jitropas, Ukrit; Hsu, Chung-Hao

2017-06-01

To extend the use of Local Density Approximation (LDA), a new analytical correlation functional is introduced. Correlation energy is an essential ingredient within density functional theory and used to determine ground state energy and other properties including phonon dispersion relation. Except for high and low density limit, the general expression of correlation energy is unknown. The approximation approach is therefore required. The accuracy of the modelling system depends on the quality of correlation energy approximation. Typical correlation functionals used in LDA such as Vosko-Wilk-Nusair (VWN) and Perdew-Wang (PW) were obtained from parameterizing the near-exact quantum Monte Carlo data of Ceperley and Alder. These functionals are presented in complex form and inconvenient to implement. Alternatively, the latest published formula of Chachiyo correlation functional provides a comparable result for those much more complicated functionals. In addition, it provides more predictive power based on the first principle approach, not fitting functionals. Nevertheless, the performance of Chachiyo formula for calculating phonon dispersion relation (a key to the thermal properties of materials) has not been tested yet. Here, the implementation of new correlation functional to calculate phonon dispersion relation is initiated. The accuracy and its validity will be explored.

miRegulome: a knowledge-base of miRNA regulomics and analysis.

PubMed

Barh, Debmalya; Kamapantula, Bhanu; Jain, Neha; Nalluri, Joseph; Bhattacharya, Antaripa; Juneja, Lucky; Barve, Neha; Tiwari, Sandeep; Miyoshi, Anderson; Azevedo, Vasco; Blum, Kenneth; Kumar, Anil; Silva, Artur; Ghosh, Preetam

2015-08-05

miRNAs regulate post transcriptional gene expression by targeting multiple mRNAs and hence can modulate multiple signalling pathways, biological processes, and patho-physiologies. Therefore, understanding of miRNA regulatory networks is essential in order to modulate the functions of a miRNA. The focus of several existing databases is to provide information on specific aspects of miRNA regulation. However, an integrated resource on the miRNA regulome is currently not available to facilitate the exploration and understanding of miRNA regulomics. miRegulome attempts to bridge this gap. The current version of miRegulome v1.0 provides details on the entire regulatory modules of miRNAs altered in response to chemical treatments and transcription factors, based on validated data manually curated from published literature. Modules of miRegulome (upstream regulators, downstream targets, miRNA regulated pathways, functions, diseases, etc) are hyperlinked to an appropriate external resource and are displayed visually to provide a comprehensive understanding. Four analysis tools are incorporated to identify relationships among different modules based on user specified datasets. miRegulome and its tools are helpful in understanding the biology of miRNAs and will also facilitate the discovery of biomarkers and therapeutics. With added features in upcoming releases, miRegulome will be an essential resource to the scientific community. http://bnet.egr.vcu.edu/miRegulome.

A Qualitative Study of the Formation and Composition of Social Networks Among Homeless Youth

PubMed Central

Tyler, Kimberly A.; Melander, Lisa A.

2011-01-01

Although social networks are essential for explaining protective and risk factors among homeless youth, little is known about the formation and composition of these groups. In this study, we utilized 19 in-depth interviews with homeless youth to investigate their social network formation, role relationships, housing status, and network member functions. Our findings reveal that the formation of these networks occurred in different ways including meeting network members through others or in specific social situations. The majority of social network members were currently housed and provided various functions including instrumental and social support and protection. Responses from participants provide valuable insight into the formation of social networks and potentially explain their subsequent involvement in risky behaviors. PMID:22121330

Nuclear physics: quantitative single-cell approaches to nuclear organization and gene expression.

PubMed

Lionnet, T; Wu, B; Grünwald, D; Singer, R H; Larson, D R

2010-01-01

The internal workings of the nucleus remain a mystery. A list of component parts exists, and in many cases their functional roles are known for events such as transcription, RNA processing, or nuclear export. Some of these components exhibit structural features in the nucleus, regions of concentration or bodies that have given rise to the concept of functional compartmentalization--that there are underlying organizational principles to be described. In contrast, a picture is emerging in which transcription appears to drive the assembly of the functional components required for gene expression, drawing from pools of excess factors. Unifying this seemingly dual nature requires a more rigorous approach, one in which components are tracked in time and space and correlated with onset of specific nuclear functions. In this chapter, we anticipate tools that will address these questions and provide the missing kinetics of nuclear function. These tools are based on analyzing the fluctuations inherent in the weak signals of endogenous nuclear processes and determining values for them. In this way, it will be possible eventually to provide a computational model describing the functional relationships of essential components.

Insecticidal Activity of Melaleuca alternifolia Essential Oil and RNA-Seq Analysis of Sitophilus zeamais Transcriptome in Response to Oil Fumigation

PubMed Central

Liao, Min; Xiao, Jin-Jing; Zhou, Li-Jun; Liu, Yang; Wu, Xiang-Wei; Hua, Ri-Mao; Wang, Gui-Rong; Cao, Hai-Qun

2016-01-01

Background The cereal weevil, Sitophilus zeamais is one of the most destructive pests of stored cereals worldwide. Frequent use of fumigants for managing stored-product insects has led to the development of resistance in insects. Essential oils from aromatic plants including the tea oil plant, Melaleuca alternifolia may provide environmentally friendly alternatives to currently used pest control agents. However, little is known about molecular events involved in stored-product insects in response to plant essential oil fumigation. Results M. alternifolia essential oil was shown to possess the fumigant toxicity against S. zeamais. The constituent, terpinen-4-ol was the most effective compound for fumigant toxicity. M. alternifolia essential oil significantly inhibited the activity of three enzymes in S. zeamais, including two detoxifying enzymes, glutathione S-transferase (GST), and carboxylesterase (CarE), as well as a nerve conduction enzyme, acetylcholinesterase (AChE). Comparative transcriptome analysis of S. zeamais through RNA-Seq identified a total of 3,562 differentially expressed genes (DEGs), of which 2,836 and 726 were up-regulated and down-regulated in response to M. alternifolia essential oil fumigation, respectively. Based on gene ontology (GO) analysis, the majority of DEGs were involved in insecticide detoxification and mitochondrial function. Furthermore, an abundance of DEGs mapped into the metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were associated with respiration and metabolism of xenobiotics, including cytochrome P450s, CarEs, GSTs, and ATP-binding cassette transporters (ABC transporters). Some DEGs mapped into the proteasome and phagosome pathway were found to be significantly enriched. These results led us to propose a model of insecticide action that M. alternifolia essential oil likely directly affects the hydrogen carrier to block the electron flow and interfere energy synthesis in mitochondrial respiratory chain. Conclusion This is the first study to perform a comparative transcriptome analysis of S. zeamais in response to M. alternifolia essential oil fumigation. Our results provide new insights into the insecticidal mechanism of M. alternifolia essential oil fumigation against S. zeamais and eventually contribute to the management of this important agricultural pest. PMID:27936192

Insecticidal Activity of Melaleuca alternifolia Essential Oil and RNA-Seq Analysis of Sitophilus zeamais Transcriptome in Response to Oil Fumigation.

PubMed

Liao, Min; Xiao, Jin-Jing; Zhou, Li-Jun; Liu, Yang; Wu, Xiang-Wei; Hua, Ri-Mao; Wang, Gui-Rong; Cao, Hai-Qun

2016-01-01

The cereal weevil, Sitophilus zeamais is one of the most destructive pests of stored cereals worldwide. Frequent use of fumigants for managing stored-product insects has led to the development of resistance in insects. Essential oils from aromatic plants including the tea oil plant, Melaleuca alternifolia may provide environmentally friendly alternatives to currently used pest control agents. However, little is known about molecular events involved in stored-product insects in response to plant essential oil fumigation. M. alternifolia essential oil was shown to possess the fumigant toxicity against S. zeamais. The constituent, terpinen-4-ol was the most effective compound for fumigant toxicity. M. alternifolia essential oil significantly inhibited the activity of three enzymes in S. zeamais, including two detoxifying enzymes, glutathione S-transferase (GST), and carboxylesterase (CarE), as well as a nerve conduction enzyme, acetylcholinesterase (AChE). Comparative transcriptome analysis of S. zeamais through RNA-Seq identified a total of 3,562 differentially expressed genes (DEGs), of which 2,836 and 726 were up-regulated and down-regulated in response to M. alternifolia essential oil fumigation, respectively. Based on gene ontology (GO) analysis, the majority of DEGs were involved in insecticide detoxification and mitochondrial function. Furthermore, an abundance of DEGs mapped into the metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were associated with respiration and metabolism of xenobiotics, including cytochrome P450s, CarEs, GSTs, and ATP-binding cassette transporters (ABC transporters). Some DEGs mapped into the proteasome and phagosome pathway were found to be significantly enriched. These results led us to propose a model of insecticide action that M. alternifolia essential oil likely directly affects the hydrogen carrier to block the electron flow and interfere energy synthesis in mitochondrial respiratory chain. This is the first study to perform a comparative transcriptome analysis of S. zeamais in response to M. alternifolia essential oil fumigation. Our results provide new insights into the insecticidal mechanism of M. alternifolia essential oil fumigation against S. zeamais and eventually contribute to the management of this important agricultural pest.

Assessing Language Dominance with Functional MRI: The Role of Control Tasks and Statistical Analysis

ERIC Educational Resources Information Center

Dodoo-Schittko, Frank; Rosengarth, Katharina; Doenitz, Christian; Greenlee, Mark W.

2012-01-01

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic…

Survey of meshless and generalized finite element methods: A unified approach

NASA Astrophysics Data System (ADS)

Babuška, Ivo; Banerjee, Uday; Osborn, John E.

In the past few years meshless methods for numerically solving partial differential equations have come into the focus of interest, especially in the engineering community. This class of methods was essentially stimulated by difficulties related to mesh generation. Mesh generation is delicate in many situations, for instance, when the domain has complicated geometry; when the mesh changes with time, as in crack propagation, and remeshing is required at each time step; when a Lagrangian formulation is employed, especially with nonlinear PDEs. In addition, the need for flexibility in the selection of approximating functions (e.g., the flexibility to use non-polynomial approximating functions), has played a significant role in the development of meshless methods. There are many recent papers, and two books, on meshless methods; most of them are of an engineering character, without any mathematical analysis.In this paper we address meshless methods and the closely related generalized finite element methods for solving linear elliptic equations, using variational principles. We give a unified mathematical theory with proofs, briefly address implementational aspects, present illustrative numerical examples, and provide a list of references to the current literature.The aim of the paper is to provide a survey of a part of this new field, with emphasis on mathematics. We present proofs of essential theorems because we feel these proofs are essential for the understanding of the mathematical aspects of meshless methods, which has approximation theory as a major ingredient. As always, any new field is stimulated by and related to older ideas. This will be visible in our paper.

Bridging the Gap between Structures and Properties: An Investigation and Evaluation of Students' Representational Competence

ERIC Educational Resources Information Center

Underwood, Sonia Miller

2011-01-01

The heart of learning chemistry is the ability to connect a compound's structure to its function; Lewis structures provide an essential link in this process. In many cases, their construction is taught using an algorithmic approach, containing a set of step-by-step rules. We believe that this approach is in direct conflict with the precepts of…

Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo

PubMed Central

Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

2017-01-01

The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo. DOI: http://dx.doi.org/10.7554/eLife.28447.001 PMID:28699889

Evaluation of an affinity-amplified immunoassay of graphene oxide using surface plasmon resonance biosensors

NASA Astrophysics Data System (ADS)

Chiu, Nan-Fu; Huang, Teng-Yi; Kuo, Chun-Chuan

2015-05-01

We describe a fundamental study on the plasmonic properties and advanced biosensing mechanisms of functionalized graphene. We discuss a specific design using modified carboxyl groups, which can modulate surface plasmon (SP) coupling and provide an advantage for their binding to the sensing layer with high-performance affinity in an immunological reaction. The functionalized graphene-based surface plasmon resonance (SPR) biosensors have three advantages: high performance, high sensitivity, and excellent molecular kinetic response. In the future, functionalized graphene sheets will make a unique contribution to photonic and SPR diagnosis devices. We wish to highlight the essential characteristics of functionalized graphene-based SPR biosensors to assist researchers in developing and advancing suitable biosensors for unique applications.

The water-water cycle is essential for chloroplast protection in the absence of stress.

PubMed

Rizhsky, Ludmila; Liang, Hongjian; Mittler, Ron

2003-10-03

Maintaining electron flow through the photosynthetic apparatus, even in the absence of a sufficient amount of NADP+ as an electron acceptor, is essential for chloroplast protection from photooxidative stress. At least two different pathways are thought to participate in this process, i.e. cyclic electron flow and the water-water cycle. Although the function of the water-water cycle was inferred from a number of biochemical and physiological studies, genetic evidence for the function of this cycle is very limited. Here we show that knockdown Arabidopsis plants with suppressed expression of the key water-water cycle enzyme, thylakoid-attached copper/zinc superoxide dismutase (KD-SOD), are suppressed in their growth and development. Chloroplast size, chlorophyll content, and photosynthetic activity were also reduced in KD-SOD plants. Microarray analysis of KD-SOD plants, grown under controlled conditions, revealed changes in transcript expression consistent with an acclimation response to light stress. Although a number of transcripts involved in the defense of plants from oxidative stress were induced in KD-SOD plants, and seedlings of KD-SOD plants were more tolerant to oxidative stress, these mechanisms were unable to compensate for the suppression of the water-water cycle in mature leaves. Thus, the localization of copper/zinc superoxide dismutase at the vicinity of photosystem I may be essential for its function. Our studies provide genetic evidence for the importance of the water-water cycle in protecting the photosynthetic apparatus of higher plants from photooxidative damage.

Retinoblastoma function is essential for establishing lung epithelial quiescence after injury.

PubMed

Mason-Richie, Nicole A; Mistry, Meenakshi J; Gettler, Caitlin A; Elayyadi, Asmaa; Wikenheiser-Brokamp, Kathryn A

2008-06-01

The retinoblastoma gene product (RB) regulates cell cycle, quiescence, and survival in a cell type-dependent and environment-dependent manner. RB function is critical in the pulmonary epithelium, as evidenced by nearly universal RB inactivation in lung cancer and increased lung cancer risk in persons with germline RB gene mutations. Lung carcinomas occur in the context of epithelial remodeling induced by cytotoxic damage. Whereas the role of RB in development and normal organ homeostasis has been extensively studied, RB function in the context of cellular injury and repair has remained largely unexplored. In the current studies, the RB gene was selectively deleted in the respiratory epithelium of the mouse. Although RB was not required for establishing or maintaining quiescence during lung homeostasis, RB was essential for establishing quiescence during epithelial repair after injury. Notably, aberrant cell cycle progression was sustained for 9 months after injury in RB-deficient lungs. Prenatal and postnatal RB ablation had similar effects, providing evidence that timing of RB loss was not critical to the outcome and that the injury-induced phenotype was not secondary to compensatory alterations occurring during development. These data show that RB is essential for repair of the respiratory epithelium after cytotoxic damage and support a critical unique role for RB in the context of epithelial remodeling after injury. Because human cancers are associated with chronic cellular damage, these findings have important new implications for RB-mediated tumor suppression.

Valosin-containing protein VCP/p97 is essential for the intracellular development of Leishmania and its survival under heat stress.

PubMed

Guedes Aguiar, Bruno; Padmanabhan, Prasad K; Dumas, Carole; Papadopoulou, Barbara

2018-06-12

Valosin-containing protein (VCP)/p97/Cdc48 is one of the best-characterised type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homologue (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, Leishmania infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive (ts) LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity. Interestingly, these VCP mutants are also unable to survive heat stress, and a ts VCP mutant is defective in amastigote growth. Consistent with LiVCP's essential function in amastigotes, LiVCP messenger ribonucleic acid undergoes 3'Untranslated Region (UTR)-mediated developmental regulation, resulting in higher VCP expression in amastigotes. Furthermore, we show that parasite mutant lines expressing lower VCP levels or dominant negative VCP forms exhibit high accumulation of polyubiquitinated proteins and increased sensitivity to proteotoxic stress, supporting the ubiquitin-selective chaperone function of LiVCP. Together, these results emphasise the crucial role LiVCP plays under heat stress and during the parasite intracellular development. © 2018 John Wiley & Sons Ltd.

Mutant Huntingtin Impairs Axonal Trafficking in Mammalian Neurons In Vivo and In Vitro

PubMed Central

Trushina, Eugenia; Dyer, Roy B.; Badger, John D.; Ure, Daren; Eide, Lars; Tran, David D.; Vrieze, Brent T.; Legendre-Guillemin, Valerie; McPherson, Peter S.; Mandavilli, Bhaskar S.; Van Houten, Bennett; Zeitlin, Scott; McNiven, Mark; Aebersold, Ruedi; Hayden, Michael; Parisi, Joseph E.; Seeberg, Erling; Dragatsis, Ioannis; Doyle, Kelly; Bender, Anna; Chacko, Celin; McMurray, Cynthia T.

2004-01-01

Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence that htt is involved in fast axonal trafficking in mammals. Moreover, expression of full-length mutant htt (mhtt) impairs vesicular and mitochondrial trafficking in mammalian neurons in vitro and in whole animals in vivo. Particularly, mitochondria become progressively immobilized and stop more frequently in neurons from transgenic animals. These defects occurred early in development prior to the onset of measurable neurological or mitochondrial abnormalities. Consistent with a progressive loss of function, wild-type htt, trafficking motors, and mitochondrial components were selectively sequestered by mhtt in human Huntington's disease-affected brain. Data provide a model for how loss of htt function causes toxicity; mhtt-mediated aggregation sequesters htt and components of trafficking machinery leading to loss of mitochondrial motility and eventual mitochondrial dysfunction. PMID:15340079

Salt, chloride, bleach, and innate host defense

PubMed Central

Wang, Guoshun; Nauseef, William M.

2015-01-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979

Salt, chloride, bleach, and innate host defense.

PubMed

Wang, Guoshun; Nauseef, William M

2015-08-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.

Lipids, lysosomes, and autophagy

PubMed Central

2016-01-01

Lipids are essential components of a cell providing energy substrates for cellular processes, signaling intermediates, and building blocks for biological membranes. Lipids are constantly recycled and redistributed within a cell. Lysosomes play an important role in this recycling process that involves the recruitment of lipids to lysosomes via autophagy or endocytosis for their degradation by lysosomal hydrolases. The catabolites produced are redistributed to various cellular compartments to support basic cellular function. Several studies demonstrated a bidirectional relationship between lipids and lysosomes that regulate autophagy. While lysosomal degradation pathways regulate cellular lipid metabolism, lipids also regulate lysosome function and autophagy. In this review, we focus on this bidirectional relationship in the context of dietary lipids and provide an overview of recent evidence of how lipid-overload lipotoxicity, as observed in obesity and metabolic syndrome, impairs lysosomal function and autophagy that may eventually lead to cellular dysfunction or cell death. PMID:27330054

Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells

PubMed Central

Sullivan, Lucas B.; Gui, Dan Y.; Hosios, Aaron M.; Bush, Lauren N.; Freinkman, Elizaveta; Vander Heiden, Matthew G.

2015-01-01

Summary Mitochondrial respiration is important for cell proliferation, however the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis. PMID:26232225

14 CFR 272.9 - Selection of a carrier to provide essential air service and payment of compensation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS ESSENTIAL AIR SERVICE TO THE FREELY ASSOCIATED STATES § 272.9 Selection of a carrier to provide essential air service and... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Selection of a carrier to provide essential...

48 CFR 6.502 - Duties and responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of functions to be performed, performance required or essential physical characteristics, and... burdensome contract clauses. (b) Agency competition advocates shall— (1) Review the contracting operations of... functions to be performed, performance required or essential physical characteristics; (iv) Any condition or...

DISCOS- Current Status and Future Developments

NASA Astrophysics Data System (ADS)

Flohrer, T.; Lemmens, S.; Bastida Virgili, B.; Krag, H.; Klinkrad, H.; Parrilla, E.; Sanchez, N.; Oliveira, J.; Pina, F.

2013-08-01

We present ESA's Database and Information System Characterizing Objects in Space (DISCOS). DISCOS not only plays an essential role in the collision avoidance and re-entry prediction services provided by ESA's Space Debris Office, it is also providing input to numerous and very differently scoped engineering activities, within ESA and throughout industry. We introduce the central functionalities of DISCOS, present the available reporting capabilities, and describe selected data modelling features. Finally, we revisit the developments of the recent years and take a sneak preview of the on-going replacement of DISCOS web front-end.

The SCL gene specifies haemangioblast development from early mesoderm.

PubMed

Gering, M; Rodaway, A R; Göttgens, B; Patient, R K; Green, A R

1998-07-15

The SCL gene encodes a basic helix-loop-helix (bHLH) transcription factor that is essential for the development of all haematopoietic lineages. SCL is also expressed in endothelial cells, but its function is not essential for specification of endothelial progenitors and the role of SCL in endothelial development is obscure. We isolated the zebrafish SCL homologue and show that it was co-expressed in early mesoderm with markers of haematopoietic, endothelial and pronephric progenitors. Ectopic expression of SCL mRNA in zebrafish embryos resulted in overproduction of common haematopoietic and endothelial precursors, perturbation of vasculogenesis and concomitant loss of pronephric duct and somitic tissue. Notochord and neural tube formation were unaffected. These results provide the first evidence that SCL specifies formation of haemangioblasts, the proposed common precursor of blood and endothelial lineages. Our data also underline the striking similarities between the role of SCL in haematopoiesis/vasculogenesis and the function of other bHLH proteins in muscle and neural development.

mir-125a-5p-mediated Regulation of Lfng is Essential for the Avian Segmentation Clock

PubMed Central

Riley, Maurisa F.; Bochter, Matthew S.; Wahi, Kanu; Nuovo, Gerard J.; Cole, Susan E.

2013-01-01

Summary Somites are embryonic precursors of the axial skeleton and skeletal muscles, and establish the segmental vertebrate body plan. Somitogenesis is controlled in part by a segmentation clock that requires oscillatory expression of genes including Lunatic fringe (Lfng). Oscillatory genes must be tightly regulated both at the transcriptional and post-transcriptional levels for proper clock function. Here we demonstrate that microRNA-mediated regulation of Lfng is essential for proper segmentation during chick somitogenesis. We find that mir-125a-5p targets evolutionarily conserved sequences in the Lfng 3′UTR, and that preventing interactions between mir-125a-5p and Lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. This provides strong evidence that miRNAs function in the post-transcriptional regulation of oscillatory genes in the segmentation clock. Further, this demonstrates that the relatively subtle effects of miRNAs on target genes can have broad effects in developmental situations that have critical requirements for tight post-transcriptional regulation. PMID:23484856

Essential role for SUN5 in anchoring sperm head to the tail

PubMed Central

Wang, Lina; Ouyang, Ying-Chun; Dong, Ming-Zhe; Liu, Chao; Zhao, Haichao; Cui, Xiuhong; Ma, Dongyuan; Zhang, Zhiguo; Yang, Xiaoyu; Guo, Yueshuai; Liu, Feng; Yuan, Li

2017-01-01

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5−/− mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility. PMID:28945193

Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis.

PubMed

Wang, Weiye; Xu, Suowen; Yin, Meimei; Jin, Zheng Gen

2015-02-15

Growth factors and their downstream receptor tyrosine kinases (RTKs) mediate a number of biological processes controlling cell function. Adaptor (docking) proteins, which consist exclusively of domains and motifs that mediate molecular interactions, link receptor activation to downstream effectors. Recent studies have revealed that Grb2-associated-binders (Gab) family members (including Gab1, Gab2, and Gab3), when phosphorylated on tyrosine residues, provide binding sites for multiple effector proteins, such as Src homology-2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) and phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, thereby playing important roles in transducing RTKs-mediated signals into pathways with diversified biological functions. Here, we provide an up-to-date overview on the domain structure and biological functions of Gab1, the most intensively studied Gab family protein, in growth factor signaling and biological functions, with a special focus on angiogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Airborne Tactical Intent-Based Conflict Resolution Capability

NASA Technical Reports Server (NTRS)

Wing, David J.; Vivona, Robert A.; Roscoe, David A.

2009-01-01

Trajectory-based operations with self-separation involve the aircraft taking the primary role in the management of its own trajectory in the presence of other traffic. In this role, the flight crew assumes the responsibility for ensuring that the aircraft remains separated from all other aircraft by at least a minimum separation standard. These operations are enabled by cooperative airborne surveillance and by airborne automation systems that provide essential monitoring and decision support functions for the flight crew. An airborne automation system developed and used by NASA for research investigations of required functionality is the Autonomous Operations Planner. It supports the flight crew in managing their trajectory when responsible for self-separation by providing monitoring and decision support functions for both strategic and tactical flight modes. The paper focuses on the latter of these modes by describing a capability for tactical intent-based conflict resolution and its role in a comprehensive suite of automation functions supporting trajectory-based operations with self-separation.

Development and Pilot Testing of an Internet-Based Self-Help Intervention for Depression for Indian Users.

PubMed

Mehrotra, Seema; Sudhir, Paulomi; Rao, Girish; Thirthalli, Jagadisha; Srikanth, T K

2018-03-22

There is a dearth of published research on uptake and utility of mental health apps in India, despite a rising global trend in the application of technology in the field of mental health. We describe the development and pilot testing of a self-help intervention for depression, PUSH-D (Practice and Use Self-Help for Depression) for urban Indians. This guided self-help app, with essential and optional zone sections, was developed to provide a comprehensive coverage of therapeutic strategies drawn from cognitive behavior therapy, interpersonal therapy, supportive psychotherapy, and positive psychology. Pilot testing was carried out using a single group pre-, post- and follow-up design in 78 eligible participants. Participants were typically young adults with major depression or dysthymia and significant impairment in functioning. Almost two-thirds of the participants had never sought professional mental health help. Significant reductions in depression and improvement in the functioning and well-being were notedon standardized measures in participants completing all 10 essential zone sections. These gains were maintained at follow-up. The results were similar for partial completers, who completed fiveout of the 10 essential sections. PUSH-D is one of the first indigenously developed self-help apps for depression and it shows promise in reducing the treatment gap for depression in India.

An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

Disruption of the Mouse μ-Calpain Gene Reveals an Essential Role in Platelet Function

PubMed Central

Azam, Mohammad; Andrabi, Shaida S.; Sahr, Kenneth E.; Kamath, Lakshmi; Kuliopulos, Athan; Chishti, Athar H.

2001-01-01

Conventional calpains are ubiquitous calcium-regulated cysteine proteases that have been implicated in cytoskeletal organization, cell proliferation, apoptosis, cell motility, and hemostasis. There are two forms of conventional calpains: the μ-calpain, or calpain I, which requires micromolar calcium for half-maximal activation, and the m-calpain, or calpain II, which functions at millimolar calcium concentrations. We evaluated the functional role of the 80-kDa catalytic subunit of μ-calpain by genetic inactivation using homologous recombination in embryonic stem cells. The μ-calpain-deficient mice are viable and fertile. The complete deficiency of μ-calpain causes significant reduction in platelet aggregation and clot retraction but surprisingly the mutant mice display normal bleeding times. No detectable differences were observed in the cleavage pattern and kinetics of calpain substrates such as the β3 subunit of αIIbβ3 integrin, talin, and ABP-280 (filamin). However, μ-calpain null platelets exhibit impaired tyrosine phosphorylation of several proteins including the β3 subunit of αIIbβ3 integrin, correlating with the agonist-induced reduction in platelet aggregation. These results provide the first direct evidence that μ-calpain is essential for normal platelet function, not by affecting the cleavage of cytoskeletal proteins but by potentially regulating the state of tyrosine phosphorylation of the platelet proteins. PMID:11238954

Mechanisms Underlying the Essential Role of Mitochondrial Membrane Lipids in Yeast Chronological Aging

PubMed Central

Medkour, Younes; Dakik, Paméla; McAuley, Mélissa; Mohammad, Karamat; Mitrofanova, Darya

2017-01-01

The functional state of mitochondria is vital to cellular and organismal aging in eukaryotes across phyla. Studies in the yeast Saccharomyces cerevisiae have provided evidence that age-related changes in some aspects of mitochondrial functionality can create certain molecular signals. These signals can then define the rate of cellular aging by altering unidirectional and bidirectional communications between mitochondria and other organelles. Several aspects of mitochondrial functionality are known to impact the replicative and/or chronological modes of yeast aging. They include mitochondrial electron transport, membrane potential, reactive oxygen species, and protein synthesis and proteostasis, as well as mitochondrial synthesis of iron-sulfur clusters, amino acids, and NADPH. Our recent findings have revealed that the composition of mitochondrial membrane lipids is one of the key aspects of mitochondrial functionality affecting yeast chronological aging. We demonstrated that exogenously added lithocholic bile acid can delay chronological aging in yeast because it elicits specific changes in mitochondrial membrane lipids. These changes allow mitochondria to operate as signaling platforms that delay yeast chronological aging by orchestrating an institution and maintenance of a distinct cellular pattern. In this review, we discuss molecular and cellular mechanisms underlying the essential role of mitochondrial membrane lipids in yeast chronological aging. PMID:28593023

NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response.

PubMed

Xie, Xiaojun; Hu, Jack; Liu, Xiping; Qin, Hanjuan; Percival-Smith, Anthony; Rao, Yong; Li, Shawn S C

2010-05-11

NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1(st) larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. da(G32)-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29 degrees C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.

Molecular analysis of functional redundancy among anti-apoptotic Bcl-2 proteins and its role in cancer cell survival.

PubMed

Eichhorn, Joshua M; Alford, Sarah E; Sakurikar, Nandini; Chambers, Timothy C

2014-04-01

Bcl-2 family proteins act as essential regulators and mediators of intrinsic apoptosis. Several lines of evidence suggest that the anti-apoptotic members of the family, including Bcl-2, Bcl-xL and Mcl-1, exhibit functional redundancy. However, the current evidence is largely indirect, and based mainly on pharmacological data using small-molecule inhibitors. In order to study compensation and redundancy of anti-apoptotic Bcl-2 proteins at the molecular level, we used a combined knockdown/overexpression strategy to essentially replace the function of one member with another. The results show that HeLa cells are strictly dependent on Mcl-1 for survival and correspondingly refractory to the Bcl-2/Bcl-xL inhibitor ABT-263, and remain resistant to ABT-263 in the context of Bcl-xL overexpression because endogenous Mcl-1 continues to provide the primary guardian role. However, if Mcl-1 is knocked down in the context of Bcl-xL overexpression, the cells become Bcl-xL-dependent and sensitive to ABT-263. We also show that Bcl-xL compensates for loss of Mcl-1 by sequestration of two key pro-apoptotic Bcl-2 family members, Bak and Bim, normally bound to Mcl-1, and that Bim is essential for cell death induced by Mcl-1 knockdown. To our knowledge, this is the first example where cell death induced by loss of Mcl-1 was rescued by the silencing of a single BH3-only Bcl-2 family member. In colon carcinoma cell lines, Bcl-xL and Mcl-1 also play compensatory roles, and Mcl-1 knockdown sensitizes cells to ABT-263. The results, obtained employing a novel strategy of combining knockdown and overexpression, provide unique molecular insight into the mechanisms of compensation by pro-survival Bcl-2 family proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

Skilled Birth Attendants: who is who? A descriptive study of definitions and roles from nine Sub Saharan African countries.

PubMed

Adegoke, Adetoro; Utz, Bettina; Msuya, Sia E; van den Broek, Nynke

2012-01-01

Availability of a Skilled Birth Attendant (SBA) during childbirth is a key indicator for MDG5 and a strategy for reducing maternal and neonatal mortality in Africa. There is limited information on how SBAs and their functions are defined. The aim of this study was to map the cadres of health providers considered SBAs in Sub Saharan Africa (SSA); to describe which signal functions of Essential Obstetric Care (EmOC) they perform and assess whether they are legislated to perform these functions. Key personnel in the Ministries of Health, teaching institutions, referral, regional and district hospitals completed structured questionnaires in nine SSA countries in 2009-2011. A total of 21 different cadres of health care providers (HCP) were reported to be SBA. Type and number of EmOC signal functions reported to be provided, varied substantially between cadres and countries. Parenteral antibiotics, uterotonic drugs and anticonvulsants were provided by most SBAs. Removal of retained products of conception and assisted vaginal delivery were the least provided signal functions. Except for the cadres of obstetricians, medical doctors and registered nurse-midwives, there was lack of clarity regarding signal functions reported to be performed and whether they were legislated to perform these. This was particularly for manual removal of placenta, removal of retained products and assisted vaginal delivery. In some countries, cadres not considered SBA performed deliveries and provided EmOC signal functions. In other settings, cadres reported to be SBA were able to but not legislated to perform key EmOC signal functions. Comparison of cadres of HCPs reported to be SBA across countries is difficult because of lack of standardization in names, training, and functions performed. There is a need for countries to develop clear guidelines defining who is a SBA and which EmOC signal functions each cadre of HCP is expected to provide.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis.

PubMed

Du, Yushen; Wu, Nicholas C; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting; Sun, Ren

2016-11-01

Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. To fully comprehend the diverse functions of a protein, it is essential to understand the functionality of individual residues. Current methods are highly dependent on evolutionary sequence conservation, which is usually limited by sampling size. Sequence conservation-based methods are further confounded by structural constraints and multifunctionality of proteins. Here we present a method that can systematically identify and annotate functional residues of a given protein. We used a high-throughput functional profiling platform to identify essential residues. Coupling it with homologous-structure comparison, we were able to annotate multiple functions of proteins. We demonstrated the method with the PB1 protein of influenza A virus and identified novel functional residues in addition to its canonical function as an RNA-dependent RNA polymerase. Not limited to virology, this method is generally applicable to other proteins that can be functionally selected and about which homologous-structure information is available. Copyright © 2016 Du et al.

Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

PubMed Central

Siaud, Nicolas; Lam, Isabel; Christ, Nicole; Schlacher, Katharina; Xia, Bing; Jasin, Maria

2011-01-01

The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations. PMID:22194698

The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo.

PubMed

Gubala, Anna M; Schmitz, Jonathan F; Kearns, Michael J; Vinh, Tery T; Bornberg-Bauer, Erich; Wolfner, Mariana F; Findlay, Geoffrey D

2017-05-01

New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Complementary Information Derived from CRISPR Cas9 Mediated Gene Deletion and Suppression. | Office of Cancer Genomics

Cancer.gov

CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes.

Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and tight junctions with paracellular permselective barrier function.

PubMed

Tsukita, Sachiko; Katsuno, Tatsuya; Yamazaki, Yuji; Umeda, Kazuaki; Tamura, Atsushi; Tsukita, Shoichiro

2009-05-01

Tight junctions (TJs) create the primary permselective barrier to diffusion of solutes and ions through the paracellular pathway. The molecular architecture of TJs has gradually been unraveled in recent years, providing the basis for "barriology" (defined by Shoichiro Tsukita as the science of the barrier in multicellular organisms). Claudins are now considered to be the essential basic components of TJ strands, with which other integral membrane proteins, such as occludin, tricellulin, JAMs, and CAR, are associated. Peripherally associated scaffolding proteins are required for the organization of the integral membrane proteins. Among these, ZO-1, -2, and -3 have attracted a great deal of attention as TJ organizers, since ZO-1 (and in some cases, also ZO-2/3) was reported to be directly associated with claudins, occludin, and JAMs, as well as with AF-6/afadin and alpha-catenin. Here we summarize recent studies on ZO-1/2/3-deficiency in mice and cells, which have provided clear and important information regarding the functions of ZO-1/2/3 in vivo. In addition to the respective suppression of ZO-1/2/3 expression, simultaneous suppression of all three proteins has revealed the essential and nonessential in vivo roles of ZO-1/2 and ZO-3, respectively. ZO-3 shows an epithelial-specific TJ localization in a ZO-1/2-dependent fashion. ZO-1 and ZO-2 play pivotal roles in the final establishment of the belt-like adherens junctions (zonula adherens), followed by the formation of the belt-like TJs (zonula occludens) with paracellular barrier function, thereby providing the general basis for selective paracellular permeability in epithelial and endothelial cells.

Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

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

Lammerts van Bueren,A.; Higgins, M.; Wang, D.

2007-01-01

The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basismore » for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.« less

Alternative management and funding options for aeronautics programs, Task 1

NASA Technical Reports Server (NTRS)

1975-01-01

Research and technology will be at lower program levels with basic military research for aviation decreasing as fewer aircraft programs are initiated and the present new aircraft programs move into the prototype and production status. The key question is can industry take on the management and financing role and meet the criteria and characteristics considered essential for a viable research and technology program. The criteria for evaluating alternative approaches include an examination of the nature of the product to be provided, responsiveness to changing needs, efficiency in terms of costs, ability to provide leadership, and to provide impartial and independent evaluation of approaches, and to provide technological inputs for regulating functions.

Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making

PubMed Central

Thouvenot, Pierre; Ben Yamin, Barbara; Fourrière, Lou; Lescure, Aurianne; Boudier, Thomas; Del Nery, Elaine; Chauchereau, Anne; Goldgar, David E.; Stoppa-Lyonnet, Dominique; Nicolas, Alain; Millot, Gaël A.

2016-01-01

Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening. PMID:27272900

MEKK4 Signaling Regulates Sensory Cell Development and Function in the Mouse Inner Ear

PubMed Central

Haque, Khujista; Pandey, Atul K.; Zheng, Hong-Wei; Riazuddin, Saima; Sha, Su-Hua

2016-01-01

Mechanosensory hair cells (HCs) residing in the inner ear are critical for hearing and balance. Precise coordination of proliferation, sensory specification, and differentiation during development is essential to ensure the correct patterning of HCs in the cochlear and vestibular epithelium. Recent studies have revealed that FGF20 signaling is vital for proper HC differentiation. However, the mechanisms by which FGF20 signaling promotes HC differentiation remain unknown. Here, we show that mitogen-activated protein 3 kinase 4 (MEKK4) expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function. Mice homozygous for a kinase-inactive MEKK4 mutation exhibit significant hearing loss. Lack of MEKK4 activity in vivo also leads to a significant reduction in the number of cochlear and vestibular HCs, suggesting that MEKK4 activity is essential for overall development of HCs within the inner ear. Furthermore, we show that loss of FGF20 signaling in vivo inhibits MEKK4 activity, whereas gain of Fgf20 function stimulates MEKK4 expression, suggesting that Fgf20 modulates MEKK4 activity to regulate cellular differentiation. Finally, we demonstrate, for the first time, that MEKK4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence HC development and that FGFR1 signaling through activation of MEKK4 is necessary for outer hair cell differentiation. Collectively, this study provides compelling evidence of an essential role for MEKK4 in inner ear morphogenesis and identifies the requirement of MEKK4 expression in regulating the specific response of FGFR1 during HC development and FGF20/FGFR1 signaling activated MEKK4 for normal sensory cell differentiation. SIGNIFICANCE STATEMENT Sensory hair cells (HCs) are the mechanoreceptors within the inner ear responsible for our sense of hearing. HCs are formed before birth, and mammals lack the ability to restore the sensory deficits associated with their loss. In this study, we show, for the first time, that MEKK4 signaling is essential for the development of normal cytoarchitecture and hearing function as MEKK4 signaling-deficient mice exhibit a significant reduction of HCs and a hearing loss. We also identify MEKK4 as a critical hub kinase for FGF20-FGFR1 signaling to induce HC differentiation in the mammalian cochlea. These results reveal a new paradigm in the regulation of HC differentiation and provide significant new insights into the mechanism of Fgf signaling governing HC formation. PMID:26818521

The detailed balance requirement and general empirical formalisms for continuum absorption

NASA Technical Reports Server (NTRS)

Ma, Q.; Tipping, R. H.

1994-01-01

Two general empirical formalisms are presented for the spectral density which take into account the deviations from the Lorentz line shape in the wing regions of resonance lines. These formalisms satisfy the detailed balance requirement. Empirical line shape functions, which are essential to provide the continuum absorption at different temperatures in various frequency regions for atmospheric transmission codes, can be obtained by fitting to experimental data.

Bacillus subtilis ribonucleases J1 and J2 form a complex with altered enzyme behaviour.

PubMed

Mathy, Nathalie; Hébert, Agnès; Mervelet, Peggy; Bénard, Lionel; Dorléans, Audrey; Li de la Sierra-Gallay, Inés; Noirot, Philippe; Putzer, Harald; Condon, Ciarán

2010-01-01

Ribonucleases J1 and J2 are recently discovered enzymes with dual 5'-to-3' exoribonucleolytic/endoribonucleolytic activity that plays a key role in the maturation and degradation of Bacillus subtilis RNAs. RNase J1 is essential, while its paralogue RNase J2 is not. Up to now, it had generally been assumed that the two enzymes functioned independently. Here we present evidence that RNases J1 and J2 form a complex that is likely to be the predominant form of these enzymes in wild-type cells. While both RNase J1 and the RNase J1/J2 complex have robust 5'-to-3' exoribonuclease activity in vitro, RNase J2 has at least two orders of magnitude weaker exonuclease activity, providing a possible explanation for why RNase J1 is essential. The association of the two proteins also has an effect on the endoribonucleolytic properties of RNases J1 and J2. While the individual enzymes have similar endonucleolytic cleavage activities and specificities, as a complex they behave synergistically to alter cleavage site preference and to increase cleavage efficiency at specific sites. These observations dramatically change our perception of how these ribonucleases function and provide an interesting example of enzyme subfunctionalization after gene duplication.

The ubiquitin proteasome system in glia and its role in neurodegenerative diseases

PubMed Central

Jansen, Anne H. P.; Reits, Eric A. J.; Hol, Elly M.

2014-01-01

The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s, and Huntington’s disease, leading to the hypothesis that proteasomal impairment is contributing to these diseases. So far, most research related to the UPS in neurodegenerative diseases has been focused on neurons, while glial cells have been largely disregarded in this respect. However, glial cells are essential for proper neuronal function and adopt a reactive phenotype in neurodegenerative diseases, thereby contributing to an inflammatory response. This process is called reactive gliosis, which in turn affects UPS function in glial cells. In many neurodegenerative diseases, mostly neurons show accumulation and aggregation of ubiquitinated proteins, suggesting that glial cells may be better equipped to maintain proper protein homeostasis. During an inflammatory reaction, the immunoproteasome is induced in glia, which may contribute to a more efficient degradation of disease-related proteins. Here we review the role of the UPS in glial cells in various neurodegenerative diseases, and we discuss how studying glial cell function might provide essential information in unraveling mechanisms of neurodegenerative diseases. PMID:25152710

The essential role of endogenous ghrelin in growth hormone expression during zebrafish adenohypophysis development.

PubMed

Li, Xi; He, Jiangyan; Hu, Wei; Yin, Zhan

2009-06-01

Ghrelin, a multifunctional hormone, including potent GH stimulation activity, has been suggested to be important during embryonic development. Expression of ghrelin has been confirmed in the zebrafish pancreas during embryonic stages. Interfering with ghrelin function using two specific antisense morpholino oligonucleotides causes defects during zebrafish embryonic development. In ghrelin morphants the expression of GH was abolished in zebrafish somatotropes, whereas the expression patterns of the other key molecules involved in hypothalamic-pituitary development and distinct pituitary hormones genes remain largely intact at the appropriate time during zebrafish adenohypophysis development. Effective rescue of the ghrelin morphants with exogenous ghrelin mRNA showed that the correct gene had been targeted. Moreover, by analyzing the efficiencies of the ghrelin morphants rescue experiments with various forms of exogenous mutant ghrelin mRNAs, we also demonstrated the essentiality of the form acyl-ghrelin on GH stimulation during zebrafish adenohypophysis development. Our in vivo experiments, for the first time, also provided evidence of the existence of functional obestatin in the C-terminal part of zebrafish proghrelin peptides. Our research here has demonstrated that zebrafish is a unique model for functional studies of endogenous ghrelin, especially during embryonic development.

The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity*

PubMed Central

Peters, Diane E.; Szabo, Roman; Friis, Stine; Shylo, Natalia A.; Uzzun Sales, Katiuchia; Holmbeck, Kenn; Bugge, Thomas H.

2014-01-01

The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8−/−) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8Cat−/Cat− mice), develop barrier function and are healthy when followed for up to 20 weeks. This striking difference could not be explained by genetic modifiers or by maternal effects, as these divergent phenotypes were displayed by Prss8−/− and Prss8Cat−/Cat− mice born within the same litter. Furthermore, Prss8Cat−/Cat− mice were able to regenerate epidermal covering following cutaneous wounding. This study provides the first demonstration that essential in vivo functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease. PMID:24706745

Transcription Factors in Long-Term Memory and Synaptic Plasticity

PubMed Central

Alberini, Cristina M.

2013-01-01

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview of experimental work showing that several families of transcription factors, including CREB, C/EBP, Egr, AP-1, and Rel have essential functions in both processes. The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation. PMID:19126756

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia

PubMed Central

Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Willnecker, Vivienne; Schick, Bernhard; Zizzari, Philippe; Gossage, Samuel J.; Greer, Charles A.; Leinders-Zufall, Trese; Woods, C. Geoffrey; Wood, John N.; Zufall, Frank

2013-01-01

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Nav1.7, causes a congenital inability to experience pain in humans. Here we show that Nav1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Nav1.7 in odour perception, we generated conditional null mice in which Nav1.7 was removed from all olfactory sensory neurons. In the absence of Nav1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell. PMID:21441906

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.

PubMed

Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Willnecker, Vivienne; Schick, Bernhard; Zizzari, Philippe; Gossage, Samuel J; Greer, Charles A; Leinders-Zufall, Trese; Woods, C Geoffrey; Wood, John N; Zufall, Frank

2011-04-14

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.

E2F function in muscle growth is necessary and sufficient for viability in Drosophila

PubMed Central

Zappia, Maria Paula; Frolov, Maxim V.

2016-01-01

The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

Factors affecting the evolution of coastal wetlands of the Laurentian Great Lakes: An overview

USGS Publications Warehouse

Mayer, T.; Edsall, T.; Munawar, M.

2004-01-01

Coastal wetlands play a pivotal role in the Great Lakes ecosystem. As buffer zones between the land and open waters of the Great Lakes, they perform a variety of essential functions providing both direct and indirect anthropogenic benefits. Geology, morphology and climate are the dominant variables that influence Laurentian Great Lakes wetland development. However, anthropogenic factors are the major contributors to alteration of natural wetland processes. This paper provides an overview of natural and anthropogenic factors important in Great Lakes coastal wetland development and provides statistical information describing the Great Lakes Basin. A brief description of wetlands classification and research issues is also presented.

Relationship Between Soil and Essential Oil Profiles in Salvia desoleana Populations: Preliminary Results.

PubMed

Rapposelli, Emma; Melito, Sara; Barmina, Giovanni Gabriele; Foddai, Marzia; Azara, Emanuela; Scarpa, Grazia Maria

2015-09-01

Salvia desoleana is a herbaceous perennial shrub endemic of Sardinia (Italy). The leaves are a source of essential oil, used in pharmaceutical and cosmetic industries. The therapeutic function of this species has been associated to the presence of essential oils rich in α/β-pinene, p-cimene, linalool, linalyl acetate and 1,8-cineole. Today.the industrial request of Salvia essential oils is increasing and most of the biomass is exploited from the natural populations which are under severe risk of genetic erosion. In order to improve the essential oil production, the study of the environmental parameters that influence composition, quality and quantity of the essential oils, turns out to be necessary. Soil physical and chemical structure represents one of the determinant factors in secondary metabolites production, and could also be involved in volatiles fraction composition in the same species. The main aim of this research was to explore the relationship between essential oil profiles and soil characteristics in S. desoleana populations. GC/MS analysis performed on the essential oil extracts identified 22 principal compounds, which were extremely variable among the five S. desoleana populations studied. The analysis of the essential oils revealed different compositions in the terpenes fractions: 68.2% of monoterpenes, 27.3% of sesquiterpenes and 4.5% of diterpenes. Analysis of chemical and physical soil parameters at the collection sites revealed that silt and sand contents were correlated with α-pinene and sclareol fractions and the total K20 was significantly correlated to several compounds belonging to the three terpene fractions identified. These results will provide guidelines for the in site conservation and for the improvement of the commercial value of the species.

Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans

PubMed Central

Kowalski, Madzia P.; Baylis, Howard A.; Krude, Torsten

2015-01-01

ABSTRACT Stem bulge RNAs (sbRNAs) are a family of small non-coding stem-loop RNAs present in Caenorhabditis elegans and other nematodes, the function of which is unknown. Here, we report the first functional characterisation of nematode sbRNAs. We demonstrate that sbRNAs from a range of nematode species are able to reconstitute the initiation of chromosomal DNA replication in the presence of replication proteins in vitro, and that conserved nucleotide sequence motifs are essential for this function. By functionally inactivating sbRNAs with antisense morpholino oligonucleotides, we show that sbRNAs are required for S phase progression, early embryonic development and the viability of C. elegans in vivo. Thus, we demonstrate a new and essential role for sbRNAs during the early development of C. elegans. sbRNAs show limited nucleotide sequence similarity to vertebrate Y RNAs, which are also essential for the initiation of DNA replication. Our results therefore establish that the essential function of small non-coding stem-loop RNAs during DNA replication extends beyond vertebrates. PMID:25908866

The Americans with Disabilities Act: Using Job Analysis To Meet New Challenges.

ERIC Educational Resources Information Center

Lozada-Larsen, Susana R.

This paper focuses on the role that job analysis plays under the Americans with Disabilities Act (ADA). The most obvious use of job analysis data is in defining the essential functions of each job. The job analysis technique used should: list the functions of the job, define which functions are essential rather than marginal, and offer proof of…

Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.

PubMed

Mookerjee, Shona A; Lyon, Hiram D; Sia, Elaine A

2005-02-01

Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells

PubMed Central

Juliano, Celina E.; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A.; Wessel, Gary M.; Steele, Robert E.; Lin, Haifan

2014-01-01

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI–piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality. PMID:24367095

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells.

PubMed

Juliano, Celina E; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A; Wessel, Gary M; Steele, Robert E; Lin, Haifan

2014-01-07

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.

Insights into the evolution of enzyme substrate promiscuity after the discovery of (βα)₈ isomerase evolutionary intermediates from a diverse metagenome.

PubMed

Noda-García, Lianet; Juárez-Vázquez, Ana L; Ávila-Arcos, María C; Verduzco-Castro, Ernesto A; Montero-Morán, Gabriela; Gaytán, Paul; Carrillo-Tripp, Mauricio; Barona-Gómez, Francisco

2015-06-10

Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (βα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families. We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (βα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity. As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.

Structural and functional adaptations of the mammalian nuclear envelope to meet the meiotic requirements.

PubMed

Link, Jana; Jahn, Daniel; Alsheimer, Manfred

2015-01-01

Numerous studies in the past years provided definite evidence that the nuclear envelope is much more than just a simple barrier. It rather constitutes a multifunctional platform combining structural and dynamic features to fulfill many fundamental functions such as chromatin organization, regulation of transcription, signaling, but also structural duties like maintaining general nuclear architecture and shape. One additional and, without doubt, highly impressive aspect is the recently identified key function of selected nuclear envelope components in driving meiotic chromosome dynamics, which in turn is essential for accurate recombination and segregation of the homologous chromosomes. Here, we summarize the recent work identifying new key players in meiotic telomere attachment and movement and discuss the latest advances in our understanding of the actual function of the meiotic nuclear envelope.

Motor network disruption in essential tremor: a functional and effective connectivity study.

PubMed

Buijink, Arthur W G; van der Stouwe, A M Madelein; Broersma, Marja; Sharifi, Sarvi; Groot, Paul F C; Speelman, Johannes D; Maurits, Natasha M; van Rootselaar, Anne-Fleur

2015-10-01

Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective connectivity analysis, tremor variation during the motor task has an excitatory effect on both the extrinsic connection from cerebellar lobule V to the thalamus, and the intrinsic activity of cerebellar lobule V and thalamus. Second, the functional integrity of the motor network is affected in essential tremor, with a decrease in functional connectivity between cortical and cerebellar motor regions. This decrease in functional connectivity, related to the motor task, correlates with an increase in clinical tremor severity. Interestingly, increased functional connectivity between right cerebellar lobules I-IV and the left thalamus correlates with an increase in clinical tremor severity. In conclusion, our findings suggest that cerebello-dentato-thalamic activity and cerebello-cortical connectivity is disturbed in essential tremor, supporting previous evidence of functional cerebellar changes in essential tremor. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impact of Fermented Foods on Human Cognitive Function-A Review of Outcome of Clinical Trials.

PubMed

Sivamaruthi, Bhagavathi Sundaram; Kesika, Periyanaina; Chaiyasut, Chaiyavat

2018-05-31

Food is an essential need for all living creatures which provides the energy to maintain life and grow further. Fermentation is a process used to preserve and advance the quality of foods, and those foods are known as fermented foods. Some foods offer health benefits to consumers apart from nutrition, and such foods are called as functional foods. Most functional foods are fermented foods, and the fermenting microorganism plays a precious role in the functional property of the food. Cognitive decline is closely associated with the productivity of an individual and the society. Even though cognitive decline is connected to aging, dietary pattern influences memory, anxiety and other social behaviors. Many scientific studies have explained the link between food habits and cognitive functions by in vitro and in vivo models. The present review compiled the clinical data on the impact of fermented foods on human cognitive function.

Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

PubMed

Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

2015-01-01

Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

Provider perspectives on essential functions for care management in the collaborative treatment of hypertension: the P.A.R.T.N.E.R. framework.

PubMed

Hussain, Tanvir; Allen, Allyssa; Halbert, Jennifer; Anderson, Cheryl A M; Boonyasai, Romsai Tony; Cooper, Lisa A

2015-04-01

Care management has become a widespread strategy for improving chronic illness care. However, primary care provider (PCP) participation in programs has been poor. Because the success of care management relies on provider engagement, understanding provider perspectives is necessary. Our goal was to identify care management functions most valuable to PCPs in hypertension treatment. Six focus groups were conducted to discuss current challenges in hypertension care and identify specific functions of care management that would improve care. The study included 39 PCPs (participation rate: 83 %) representing six clinics, two of which care for large African American populations and four that are in underserved locations, in the greater Baltimore metropolitan area. This was a qualitative analysis of focus groups, using grounded theory and iterative coding. Providers desired achieving blood pressure control more rapidly. Collaborating with care managers who obtain ongoing patient data would allow treatment plans to be tailored to the changing life conditions of patients. The P.A.R.T.N.E.R. framework summarizes the care management functions that providers reported were necessary for effective collaboration: Partner with patients, providers, and the community; Arrange follow-up care; Resolve barriers to adherence; Track treatment response and progress; Navigate the health care system with patients; Educate patients & Engage patients in self-management; Relay information between patients and/or provider(s). The P.A.R.T.N.E.R. framework is the first to offer a checklist of care management functions that may promote successful collaboration with PCPs. Future research should examine the validity of this framework in various settings and for diverse patient populations affected by chronic diseases.

The potential of multiparametric MRI of the breast

PubMed Central

Pinker, Katja; Helbich, Thomas H

2017-01-01

MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5–7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer. PMID:27805423

WRF-TMH: predicting transmembrane helix by fusing composition index and physicochemical properties of amino acids.

PubMed

Hayat, Maqsood; Khan, Asifullah

2013-05-01

Membrane protein is the prime constituent of a cell, which performs a role of mediator between intra and extracellular processes. The prediction of transmembrane (TM) helix and its topology provides essential information regarding the function and structure of membrane proteins. However, prediction of TM helix and its topology is a challenging issue in bioinformatics and computational biology due to experimental complexities and lack of its established structures. Therefore, the location and orientation of TM helix segments are predicted from topogenic sequences. In this regard, we propose WRF-TMH model for effectively predicting TM helix segments. In this model, information is extracted from membrane protein sequences using compositional index and physicochemical properties. The redundant and irrelevant features are eliminated through singular value decomposition. The selected features provided by these feature extraction strategies are then fused to develop a hybrid model. Weighted random forest is adopted as a classification approach. We have used two benchmark datasets including low and high-resolution datasets. tenfold cross validation is employed to assess the performance of WRF-TMH model at different levels including per protein, per segment, and per residue. The success rates of WRF-TMH model are quite promising and are the best reported so far on the same datasets. It is observed that WRF-TMH model might play a substantial role, and will provide essential information for further structural and functional studies on membrane proteins. The accompanied web predictor is accessible at http://111.68.99.218/WRF-TMH/ .

Shoreline-crossing shear-velocity structure of the Juan de Fuca plate and Cascadia subduction zone from surface waves and receiver functions

NASA Astrophysics Data System (ADS)

Janiszewski, Helen; Gaherty, James; Abers, Geoffrey; Gao, Haiying

2017-04-01

The Cascadia subduction zone (CSZ) is the site of the onshore-offshore Cascadia Initiative, which deployed seismometers extending from the Juan de Fuca ridge to the subduction zone and onshore beyond the volcanic arc. This array allows the unique opportunity to seismically image the evolution and along-strike variation of the crust and mantle of the entire CSZ. We compare teleseismic receiver functions, ambient-noise Rayleigh-wave phase velocities in the 10-20 s period band, and earthquake-source Rayleigh-wave phase velocities from 20-100 s, to determine shear-velocity structure in the upper 200 km. Receiver functions from both onshore and shallow-water offshore sites provide constraints on crustal and plate interface structure. Spectral-domain fitting of ambient-noise empirical Green's functions constrains shear velocity of the crust and shallow mantle. An automated multi-channel cross-correlation analysis of teleseismic Rayleigh waves provides deeper lithosphere and asthenosphere constraints. The amphibious nature of the array means it is essential to examine the effect of noise variability on data quality. Ocean bottom seismometers (OBS) are affected by tilt and compliance noise. Removal of this noise from the vertical components of the OBS is essential for the teleseismic Rayleigh waves; this stabilizes the output phase velocity maps particularly along the coastline where observations are predominately from shallow water OBS. Our noise-corrected phase velocity maps reflect major structures and tectonic transitions including the transition from high-velocity oceanic lithosphere to low-velocity continental lithosphere, high velocities associated with the subducting slab, and low velocities beneath the ridge and arc. We interpret the resulting shear-velocity model in the context of temperature and compositional variation in the incoming plate and along the strike of the CSZ.

Shoreline-Crossing Shear-Velocity Structure of the Juan de Fuca Plate and Cascadia Subduction Zone from Surface Waves and Receiver Functions

NASA Astrophysics Data System (ADS)

Janiszewski, H. A.; Gaherty, J. B.; Abers, G. A.; Gao, H.

2016-12-01

The Cascadia subduction zone (CSZ) is the site of the onshore-offshore Cascadia Initiative, which deployed seismometers extending from the Juan de Fuca ridge to the subduction zone and onshore beyond the volcanic arc. This array allows the unique opportunity to seismically image the evolution and along-strike variation of the crust and mantle of the entire CSZ. We compare teleseismic receiver functions, ambient-noise Rayleigh-wave phase velocities in the 10-20 s period band, and earthquake-source Rayleigh-wave phase velocities from 20-100 s, to determine shear-velocity structure in the upper 200 km. Receiver functions from both onshore and shallow-water offshore sites provide constraints on crustal and plate interface structure. Spectral-domain fitting of ambient-noise empirical Green's functions constrains shear velocity of the crust and shallow mantle. An automated multi-channel cross-correlation analysis of teleseismic Rayleigh waves provides deeper lithosphere and asthenosphere constraints. The amphibious nature of the array means it is essential to examine the effect of noise variability on data quality. Ocean bottom seismometers (OBS) are affected by tilt and compliance noise. Removal of this noise from the vertical components of the OBS is essential for the teleseismic Rayleigh waves; this stabilizes the output phase velocity maps particularly along the coastline where observations are predominately from shallow water OBS. Our noise-corrected phase velocity maps reflect major structures and tectonic transitions including the transition from high-velocity oceanic lithosphere to low-velocity continental lithosphere, high velocities associated with the subducting slab, and low velocities beneath the ridge and arc. We interpret the resulting shear-velocity model in the context of temperature and compositional variation in the incoming plate and along the strike of the CSZ.

An assessment of the quality of care for children in eighteen randomly selected district and sub-district hospitals in Bangladesh

PubMed Central

2012-01-01

Background Quality hospital care is important in ensuring that the needs of severely ill children are met to avert child mortality. However, the quality of hospital care for children in developing countries has often been found poor. As the first step of a country road map for improving hospital care for children, we assessed the baseline situation with respect to the quality of care provided to children under-five years age in district and sub-district level hospitals in Bangladesh. Methods Using adapted World Health Organization (WHO) hospital assessment tools and standards, an assessment of 18 randomly selected district (n=6) and sub-district (n=12) hospitals was undertaken. Teams of trained assessors used direct case observation, record review, interviews, and Management Information System (MIS) data to assess the quality of clinical case management and monitoring; infrastructure, processes and hospital administration; essential hospital and laboratory supports, drugs and equipment. Results Findings demonstrate that the overall quality of care provided in these hospitals was poor. No hospital had a functioning triage system to prioritise those children most in need of immediate care. Laboratory supports and essential equipment were deficient. Only one hospital had all of the essential drugs for paediatric care. Less than a third of hospitals had a back-up power supply, and just under half had functioning arrangements for safe-drinking water. Clinical case management was found to be sub-optimal for prevalent illnesses, as was the quality of neonatal care. Conclusion Action is needed to improve the quality of paediatric care in hospital settings in Bangladesh, with a particular need to invest in improving newborn care. PMID:23268650

Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2.

PubMed

Logeman, Brandon L; Wood, L Kent; Lee, Jaekwon; Thiele, Dennis J

2017-07-07

Copper is an essential element for proper organismal development and is involved in a range of processes, including oxidative phosphorylation, neuropeptide biogenesis, and connective tissue maturation. The copper transporter (Ctr) family of integral membrane proteins is ubiquitously found in eukaryotes and mediates the high-affinity transport of Cu + across both the plasma membrane and endomembranes. Although mammalian Ctr1 functions as a Cu + transporter for Cu acquisition and is essential for embryonic development, a homologous protein, Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary relationship to Ctr1 is unclear. Here we report a biochemical, genetic, and phylogenetic comparison of metazoan Ctr1 and Ctr2, suggesting that Ctr2 arose over 550 million years ago as a result of a gene duplication event followed by loss of Cu + transport activity. Using a random mutagenesis and growth selection approach, we identified amino acid substitutions in human and mouse Ctr2 proteins that support copper-dependent growth in yeast and enhance copper accumulation in Ctr1 -/- mouse embryonic fibroblasts. These mutations revert Ctr2 to a more ancestral Ctr1-like state while maintaining endogenous functions, such as stimulating Ctr1 cleavage. We suggest key structural aspects of metazoan Ctr1 and Ctr2 that discriminate between their biological roles, providing mechanistic insights into the evolutionary, biochemical, and functional relationships between these two related proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Habitat and Biodiversity: One out of five essential soil functions for agricultural soils

NASA Astrophysics Data System (ADS)

Trinsoutrot Gattin, Isabelle; Creamer, Rachel; van Leeuwen, Jeroen; Vrebos, Dirk; Gatti, Fabio; Bampa, Francesca; Schulte, Rogier; Rutgers, Michiel

2017-04-01

Current agricultural challenges require developing new agricultural systems that can optimize the ecological functioning of soils in order to limit the use of chemical inputs (i.e. disease suppression) and maintain a high organic matter content. This implies our ability to evaluate the effects of management practices on immediate performance objectives (i.e. fertility linked to nutrient cycling) but also in longer-term objective (i.e. C cycling and storage) in a variety of agro-climatic conditions. These issues demand the development of systemic approaches for understanding the determinants of soil functioning. In ecology, it is generally accepted that there are many positive relationships between soil biodiversity indicators and the functioning of ecosystems. Indeed, soil organisms and their interactions are essential drivers of ecosystem processes and impact the response, resilience and adaptability of ecosystems to environmental pressures. Thus, maintaining soil biodiversity is a condition for the sustainability of cropping systems. In this new context, the European project Landmark considers soil functions as a key to the improvement of agricultural land management towards sustainable development goals, amongst the five functions is soil biodiversity and habitat provisioning. We propose to present how we manage within this project to deal with this challenging objective at three spatial scales : field, landscape (regional) and European (policy). We aim to define a link between the physical, chemical and biological soil properties and "habitat & biodiversity" soil function in order to identify key indicators which modulate biodiversity. This will allow us to quantify and assess this soil function, in order to provide insight in win wins and tradeoffs in soil functions to enhance management practices which optimise the biodiversity in European agricultural systems.

Enhancing bird banding information sharing across the western hemishpere

USGS Publications Warehouse

Rojo, A.; Berlanga, H.; Howes, L.; Tomosy, M.

2007-01-01

Bird banding and marking provide indispensable tools for ornithological research, management, and conservation of migratory birds and their habitats along migratory routes, breeding and non-breeding grounds. With the growing interest in international coordination of tracking bird movements, coordination amongst developing and existing programs is essential for effective data management. The North American Bird Banding Program (Canadian Bird Banding Office and U.S. Bird Banding Laboratory and the Mexican government) has been working to enhance collaboration with other Western Hemisphere countries to establish a voluntary bird banding communication network. This network addresses challenges, such as: demonstrating how sharing banding expertise and information management can support the stewardship of Western Hemisphere migratory birds, ensuring that valuable banding and encounter data are captured and shared. With increasing numbers of international scientific and conservation initiatives, bird banding and marking programs must provide essential international coordination functions as well as support local activities by facilitating access to bands, training, data management and encounter reporting.

A novel analysis method for near infrared spectroscopy based on Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Zhou, Zhenyu; Yang, Hongyu; Liu, Yun; Ruan, Zongcai; Luo, Qingming; Gong, Hui; Lu, Zuhong

2007-05-01

Near Infrared Imager (NIRI) has been widely used to access the brain functional activity non-invasively. We use a portable, multi-channel and continuous-wave NIR topography instrument to measure the concentration changes of each hemoglobin species and map cerebral cortex functional activation. By extracting some essential features from the BOLD signals, optical tomography is able to be a new way of neuropsychological studies. Fourier spectral analysis provides a common framework for examining the distribution of global energy in the frequency domain. However, this method assumes that the signal should be stationary, which limits its application in non-stationary system. The hemoglobin species concentration changes are of such kind. In this work we develop a new signal processing method using Hilbert-Huang transform to perform spectral analysis of the functional NIRI signals. Compared with wavelet based multi-resolution analysis (MRA), we demonstrated the extraction of task related signal for observation of activation in the prefrontal cortex (PFC) in vision stimulation experiment. This method provides a new analysis tool for functional NIRI signals. Our experimental results show that the proposed approach provides the unique method for reconstructing target signal without losing original information and enables us to understand the episode of functional NIRI more precisely.

Structural–Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work

PubMed Central

Kleinau, Gunnar; Worth, Catherine L.; Kreuchwig, Annika; Biebermann, Heike; Marcinkowski, Patrick; Scheerer, Patrick; Krause, Gerd

2017-01-01

The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to understand the molecular activation mechanisms of this receptor comprehensively. Finally, limitations of current knowledge and lack of information are discussed highlighting the need for intensified efforts toward TSHR structure elucidation. PMID:28484426

Evidence of Microbial Regulation of Biogeochemical Cycles from a Study on Methane Flux and Land Use Change

PubMed Central

Nazaries, Loïc; Pan, Yao; Bodrossy, Levente; Baggs, Elizabeth M.; Millard, Peter; Murrell, J. Colin

2013-01-01

Microbes play an essential role in ecosystem functions, including carrying out biogeochemical cycles, but are currently considered a black box in predictive models and all global biodiversity debates. This is due to (i) perceived temporal and spatial variations in microbial communities and (ii) lack of ecological theory explaining how microbes regulate ecosystem functions. Providing evidence of the microbial regulation of biogeochemical cycles is key for predicting ecosystem functions, including greenhouse gas fluxes, under current and future climate scenarios. Using functional measures, stable-isotope probing, and molecular methods, we show that microbial (community diversity and function) response to land use change is stable over time. We investigated the change in net methane flux and associated microbial communities due to afforestation of bog, grassland, and moorland. Afforestation resulted in the stable and consistent enhancement in sink of atmospheric methane at all sites. This change in function was linked to a niche-specific separation of microbial communities (methanotrophs). The results suggest that ecological theories developed for macroecology may explain the microbial regulation of the methane cycle. Our findings provide support for the explicit consideration of microbial data in ecosystem/climate models to improve predictions of biogeochemical cycles. PMID:23624469

Arabidopsis Chlorophyll Biosynthesis: An Essential Balance between the Methylerythritol Phosphate and Tetrapyrrole Pathways[C][W

PubMed Central

Kim, Se; Schlicke, Hagen; Van Ree, Kalie; Karvonen, Kristine; Subramaniam, Anant; Richter, Andreas; Grimm, Bernhard; Braam, Janet

2013-01-01

Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)–derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis. PMID:24363312

Arabidopsis chlorophyll biosynthesis: an essential balance between the methylerythritol phosphate and tetrapyrrole pathways.

PubMed

Kim, Se; Schlicke, Hagen; Van Ree, Kalie; Karvonen, Kristine; Subramaniam, Anant; Richter, Andreas; Grimm, Bernhard; Braam, Janet

2013-12-01

Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)-derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis.

Developing the public health workforce: training and recognizing specialists in public health from backgrounds other than medicine: experience in the UK.

PubMed

Gray, Selena F; Evans, David

2018-01-01

There is increasing recognition that improving health and tackling inequalities requires a strong public health workforce capable of delivering key public health functions across systems. The World Health Organization in Europe has identified securing the delivery of the Essential Public Health Operations and strengthening public health capacities within this as a priority.It is acknowledged that current public health capacities and arrangements of public health services vary considerably across the World Health Organization in European Region, and investment in multidisciplinary workforce with new skills is essential if public health services are to be delivered. This paper describes the current situation in the UK where there are nationally funded multidisciplinary programmes for training senior public health specialists. Uniquely, the UK provides public health registration for multidisciplinary as well as medical public health specialists. The transition from a predominantly medical to a multidisciplinary public health specialist workforce over a relatively short timescale is unprecedented globally and was the product of a sustained period of grass roots activism aligned with national policy innovation. the UK experience might provide a model for other countries seeking to develop public health specialist workforce capacity in line with the Essential Public Health Operations.

High-temperature protein G is essential for activity of the Escherichia coli clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system.

PubMed

Yosef, Ido; Goren, Moran G; Kiro, Ruth; Edgar, Rotem; Qimron, Udi

2011-12-13

Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3.

High-temperature protein G is essential for activity of the Escherichia coli clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system

PubMed Central

Yosef, Ido; Goren, Moran G.; Kiro, Ruth; Edgar, Rotem; Qimron, Udi

2011-01-01

Prokaryotic DNA arrays arranged as clustered regularly interspaced short palindromic repeats (CRISPR), along with their associated proteins, provide prokaryotes with adaptive immunity by RNA-mediated targeting of alien DNA or RNA matching the sequences between the repeats. Here, we present a thorough screening system for the identification of bacterial proteins participating in immunity conferred by the Escherichia coli CRISPR system. We describe the identification of one such protein, high-temperature protein G (HtpG), a homolog of the eukaryotic chaperone heat-shock protein 90. We demonstrate that in the absence of htpG, the E. coli CRISPR system loses its suicidal activity against λ prophage and its ability to provide immunity from lysogenization. Transcomplementation of htpG restores CRISPR activity. We further show that inactivity of the CRISPR system attributable to htpG deficiency can be suppressed by expression of Cas3, a protein that is essential for its activity. Accordingly, we also find that the steady-state level of overexpressed Cas3 is significantly enhanced following HtpG expression. We conclude that HtpG is a newly identified positive modulator of the CRISPR system that is essential for maintaining functional levels of Cas3. PMID:22114197

Perceptions on evaluative and formative functions of external supervision of Rwandan primary healthcare facilities: A qualitative study.

PubMed

Schriver, Michael; Cubaka, Vincent Kalumire; Itangishaka, Sylvere; Nyirazinyoye, Laetitia; Kallestrup, Per

2018-01-01

External supervision of primary healthcare facilities in low- and middle-income countries often has a managerial main purpose in which the role of support for professional development is unclear. To explore how Rwandan primary healthcare supervisors and providers (supervisees) perceive evaluative and formative functions of external supervision. Qualitative, exploratory study. Focus group discussions: three with supervisors, three with providers, and one mixed (n = 31). Findings were discussed with individual and groups of supervisors and providers. Evaluative activities occupied providers' understanding of supervision, including checking, correcting, marking and performance-based financing. These were presented as sources of motivation, that in self-determination theory indicate introjected regulation. Supervisors preferred to highlight their role in formative supervision, which may mask their own and providers' uncontested accounts that systematic performance evaluations predominated supervisors' work. Providers strongly requested larger focus on formative and supportive functions, voiced as well by most supervisors. Impact of performance evaluation on motivation and professional development is discussed. While external supervisors intended to support providers' professional development, our findings indicate serious problems with this in a context of frequent evaluations and performance marking. Separating the role of supporter and evaluator does not appear as the simple solution. If external supervision is to improve health care services, it is essential that supervisors and health centre managers are competent to support providers in a way that transparently accounts for various performance pressures. This includes delivery of proper formative supervision with useful feedback, maintaining an effective supervisory relationship, as well as ensuring providers are aware of the purpose and content of evaluative and formative supervision functions.

Essential oil of lavender in anxiety disorders: Ready for prime time?

PubMed Central

2017-01-01

Anxiety disorders are some of the most common psychiatric disorders, with potentially debilitating consequences on individual function. Existing pharmacotherapies for anxiety disorders are limited by delay to therapeutic effect, dependence, tolerance, withdrawal, and abuse potential. Therefore, safe and evidence-based complementary or alternative therapies may be important allies in the care of patients with anxiety disorders. Essential oils are lipophilic and concentrated botanical extracts that exhibit many properties of drugs, although they are not Food and Drug Administration approved and have limitations characteristic of herbal preparations. Lavender essential oil has an extensive anecdotal history of anxiolytic benefit that has recently been supported by clinical efficacy studies. The 2 primary terpenoid constituents of lavender essential oil, linalool and linalyl acetate, may produce an anxiolytic effect in combination via inhibition of voltage-gated calcium channels, reduction of 5HT1A receptor activity, and increased parasympathetic tone. The objectives of this article are to provide a brief overview of lavender oil in aromatherapy, explore variability in the constituents of lavender oil, summarize its pharmacology and safety profile, as well as describe its body of research that has been conducted for anxiety.

The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysis.

PubMed

Mao, Yimin; Kuo, Su-Wei; Chen, Le; Heckman, C J; Jiang, M C

2017-01-01

Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set (VCP, FUS, TDP-43 and hnRNPA1) but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins (22 out of 24) which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.

The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity.

PubMed

Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo; Schou, Julie; Nilsson, Jakob; Choudhary, Chunaram

2016-03-01

The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cost Estimating in the Department of Defense and Areas for Improvement

DTIC Science & Technology

2010-09-01

in reducing the overall projected cost to the agency without impairing essential functions or characteristics, provided that it does not involve a...government can obtain the “Best Value ” on both its competitive source selections and noncompetitive acquisitions. The reader will come away with a...so that the government can obtain the “Best Value ” on both its competitive source selections and noncompetitive acquisitions. The reader will come

Software Manages Documentation in a Large Test Facility

NASA Technical Reports Server (NTRS)

Gurneck, Joseph M.

2001-01-01

The 3MCS computer program assists and instrumentation engineer in performing the 3 essential functions of design, documentation, and configuration management of measurement and control systems in a large test facility. Services provided by 3MCS are acceptance of input from multiple engineers and technicians working at multiple locations;standardization of drawings;automated cross-referencing; identification of errors;listing of components and resources; downloading of test settings; and provision of information to customers.

IT Infrastructure Projects: A Framework for Analysis. ECAR Research Bulletin

ERIC Educational Resources Information Center

Grochow, Jerrold M.

2014-01-01

Just as maintaining a healthy infrastructure of water delivery and roads is essential to the functioning of cities and towns, maintaining a healthy infrastructure of information technology is essential to the functioning of universities. Deterioration in IT infrastructure can lead to deterioration in research, teaching, and administration. Given…

Designing sustainable soils in Earth's critical zone

NASA Astrophysics Data System (ADS)

Banwart, Steven Allan; de Souza, Danielle Maia; Menon, Manoj; Nikolaidis, Nikolaos; Panagos, Panos; Vala Ragnardsdottir, Kristin; Rousseva, Svelta; van Gaans, Pauline

2014-05-01

The demographic drivers of increasing human population and wealth are creating tremendous environmental pressures from growing intensity of land use, resulting in soil and land degradation worldwide. Environmental services are provided through multiple soil functions that include biomass production, water storage and transmission, nutrient transformations, contaminant attenuation, carbon and nitrogen storage, providing habitat and maintaining the genetic diversity of the land environment. One of the greatest challenges of the 21st century is to identify key risks to soil, and to design mitigation strategies to manage these risks and to enhance soil functions that can last into the future. The scientific study of Earth's Critical Zone (CZ), the thin surface layer that extends vertically from the top of the tree canopy to the bottom of aquifers, provides an essential integrating scientific framework to study, protect and enhance soil functions. The research hypothesis is that soil structure, the geometric architecture of solids, pores and biomass, is a critical indicator and essential factor of productive soil functions. The experimental design selects a network of Critical Zone Observatories (CZOs) as advanced field research sites along a gradient of land use intensity in order to quantify soil structure and soil processes that dictate the flows and transformations of material and energy as soil functions. The CZOs focus multidisciplinary expertise on soil processes, field observation and data interpretation, management science and ecological economics. Computational simulation of biophysical processes provides a quantitative method of integration for the range of theory and observations that are required to quantify the linkages between changes in soil structure and soil functions. Key results demonstrate that changes in soil structure can be quantified through the inputs of organic carbon and nitrogen from plant productivity and microbial activity, coupled with particle aggregation dynamics and organic matter mineralization. Simulation results show that soil structure is highly dynamic and is sensitive to organic matter production and minearlisation rates as influenced by vegetation, tillage and organic carbon amendments. These results point to a step-change in the capability to design soil management and land use through computational simulation. This approach of "sustainability by design" describes the mechanistic process linkages that exist between the above-ground inputs to the CZ and the internal processes that produce soil functions. This approach provides a rational, scientific approach to selecting points of intervention with the CZ in order to design methods to mitigate soil threats and to enhance and sustain vital soil functions. Furthermore, this approach provides a successful pilot study to the use of international networks of CZOs as a planetary-scale laboratory to test the response of CZ process rates along gradients of global environmental change - and to test adaptation strategies to manage the risks arising from the CZ impacts. Acknowledgements. The authors acknowledge the substantial contributions of the entire team of investigators and funding of the SoilTrEC project (EC FP7, agreement no. 244118; www.soiltrec.eu).

Social outcomes in children with autism spectrum disorder: a review of music therapy outcomes

PubMed Central

LaGasse, A Blythe

2017-01-01

Autism spectrum disorder (ASD) affects approximately one in 68 children, substantially affecting the child’s ability to acquire social skills. The application of effective interventions to facilitate and develop social skills is essential due to the lifelong impact that social skills may have on independence and functioning. Research indicates that music therapy can improve social outcomes in children with ASD. Outcome measures are primarily assessed using standardized nonmusical scales of social functioning from the parent or clinician perspective. Certified music therapists may also assess musical engagement and outcomes as a part of the individual’s profile. These measures provide an assessment of the individual’s social functioning within the music therapy session and generalizability to nonmusical settings. PMID:28260959

Neutralizing antibody and functional mapping of Bacillus anthracis protective antigen-The first step toward a rationally designed anthrax vaccine.

PubMed

McComb, Ryan C; Martchenko, Mikhail

2016-01-02

Anthrax is defined by the Centers for Disease Control and Prevention as a Category A pathogen for its potential use as a bioweapon. Current prevention treatments include Anthrax Vaccine Adsorbed (AVA). AVA is an undefined formulation of Bacillus anthracis culture supernatant adsorbed to aluminum hydroxide. It has an onerous vaccination schedule, is slow and cumbersome to produce and is slightly reactogenic. Next-generation vaccines are focused on producing recombinant forms of anthrax toxin in a well-defined formulation but these vaccines have been shown to lose potency as they are stored. In addition, studies have shown that a proportion of the antibody response against these vaccines is focused on non-functional, non-neutralizing regions of the anthrax toxin while some essential functional regions are shielded from eliciting an antibody response. Rational vaccinology is a developing field that focuses on designing vaccine antigens based on structural information provided by neutralizing antibody epitope mapping, crystal structure analysis, and functional mapping through amino acid mutations. This information provides an opportunity to design antigens that target only functionally important and conserved regions of a pathogen in order to make a more optimal vaccine product. This review provides an overview of the literature related to functional and neutralizing antibody epitope mapping of the Protective Antigen (PA) component of anthrax toxin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Environmental Impact on Intestinal Stem Cell Functions in Mucosal Homeostasis and Tumorigenesis.

PubMed

Augenlicht, Leonard H

2017-05-01

Multiple cell compartments at or near the base of the intestinal crypt have been identified as contributing intestinal stem cells for homeostasis of the rapidly turning over intestinal mucosa and cells that can initiate tumor development upon appropriate genetic changes. There is a strong literature establishing the importance of the frequently dividing Lgr5+ crypt base columnar cells as the fundamental cell in providing these stem cell-associated functions, but there are also clear data that more quiescent cells from other compartments can be mobilized to provide these stem cell functions upon compromise of Lgr5+ cells. We review the data that vitamin D, a pleiotropic hormone, is essential for Lgr5 stem cell functions by signaling through the vitamin D receptor. Moreover, we discuss the implications of this role of vitamin D and its impact on relatively long-lived stem cells in regards to the fact that virtually all the data on normal functioning of mouse Lgr5 stem cells is derived from mice exposed to vitamin D levels well above those that characterize the human population. Thus, there are still many questions regarding how dietary and environmental factors influence the complement of cells providing stem cell functions and the mechanisms by which this is determined, and the importance of this in human colorectal tumor development. J. Cell. Biochem. 118: 943-952, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Connexins and Pannexins in Vascular Function and Disease.

PubMed

Molica, Filippo; Figueroa, Xavier F; Kwak, Brenda R; Isakson, Brant E; Gibbins, Jonathan M

2018-06-05

Connexins (Cxs) and pannexins (Panxs) are ubiquitous membrane channel forming proteins that are critically involved in many aspects of vascular physiology and pathology. The permeation of ions and small metabolites through Panx channels, Cx hemichannels and gap junction channels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function. The essential nature of these membrane proteins in vascular homeostasis is further emphasized by the pathologies that are linked to mutations and polymorphisms in Cx and Panx genes.

Organelle communication: signaling crossroads between homeostasis and disease.

PubMed

Bravo-Sagua, Roberto; Torrealba, Natalia; Paredes, Felipe; Morales, Pablo E; Pennanen, Christian; López-Crisosto, Camila; Troncoso, Rodrigo; Criollo, Alfredo; Chiong, Mario; Hill, Joseph A; Simmen, Thomas; Quest, Andrew F; Lavandero, Sergio

2014-05-01

Cellular organelles do not function as isolated or static units, but rather form dynamic contacts between one another that can be modulated according to cellular needs. The physical interfaces between organelles are important for Ca2+ and lipid homeostasis, and serve as platforms for the control of many essential functions including metabolism, signaling, organelle integrity and execution of the apoptotic program. Emerging evidence also highlights the importance of organelle communication in disorders such as Alzheimer's disease, pulmonary arterial hypertension, cancer, skeletal and cardiac muscle dysfunction. Here, we provide an overview of the current literature on organelle communication and the link to human pathologies. Copyright © 2014 Elsevier Ltd. All rights reserved.

INSECT FAT BODY: ENERGY, METABOLISM, AND REGULATION

PubMed Central

Arrese, Estela L.; Soulages, Jose L.

2010-01-01

The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release energy in response to the energy demands of the insect. Insects store energy reserves in the form of glycogen and triglycerides in the adipocytes, the main fat body cell. Insect adipocytes can store a great amount of lipid reserves as cytoplasmic lipid droplets. Lipid metabolism is essential for growth and reproduction and provides energy needed during extended nonfeeding periods. This review focuses on energy storage and release and summarizes current understanding of the mechanisms underlying these processes in insects. PMID:19725772

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., function, or reproduction, e.g., vitamins, essential minerals, essential amino acids, and essential fatty acids. These compounds must be supplied from external sources. FDA means the Food and Drug... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., function, or reproduction, e.g., vitamins, essential minerals, essential amino acids, and essential fatty acids. These compounds must be supplied from external sources. FDA means the Food and Drug... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

Characterization of STIP, a multi-domain nuclear protein, highly conserved in metazoans, and essential for embryogenesis in Caenorhabditis elegans.

PubMed

Ji, Qiongmei; Huang, Cheng-Han; Peng, Jianbin; Hashmi, Sarwar; Ye, Tianzhang; Chen, Ying

2007-04-15

We report here the identification and characterization of STIP, a multi-domain nuclear protein that contains a G-patch, a coiled-coil, and several short tryptophan-tryptophan repeats highly conserved in metazoan species. To analyze their functional role in vivo, we cloned nematode stip-1 genes and determined the spatiotemporal pattern of Caenorhabditis elegans STIP-1 protein. RNA analyses and Western blots revealed that stip-1 mRNA was produced via trans-splicing and translated as a 95-kDa protein. Using reporter constructs, we found STIP-1 to be expressed at all developmental stages and in many tissue/cell types including worm oocyte nuclei. We found that STIP-1 is targeted to the nucleus and forms large polymers with a rod-like shape when expressed in mammalian cells. Using deletion mutants, we mapped the regions of STIP-1 involved in nuclear import and polymer assembly. We further showed that knockdown of C. elegans stip-1 by RNA interference arrested development and resulted in morphologic abnormalities around the 16-cell stage followed by 100% lethality, suggesting its essential role in worm embryogenesis. Importantly, the embryonic lethal phenotype could be faithfully rescued with Drosophila and human genes via transgenic expression. Our data provide the first direct evidence that STIP have a conserved essential nuclear function across metazoans from worms to humans.

Free radical-mediated systemic immunity in plants.

PubMed

Wendehenne, David; Gao, Qing-Ming; Kachroo, Aardra; Kachroo, Pradeep

2014-08-01

Systemic acquired resistance (SAR) is a form of defense that protects plants against a broad-spectrum of secondary infections by related or unrelated pathogens. SAR related research has witnessed considerable progress in recent years and a number of chemical signals and proteins contributing to SAR have been identified. All of these diverse constituents share their requirement for the phytohormone salicylic acid, an essential downstream component of the SAR pathway. However, recent work demonstrating the essential parallel functioning of nitric oxide (NO)-derived and reactive oxygen species (ROS)-derived signaling together with SA provides important new insights in the overlapping pathways leading to SAR. This review discusses the potential significance of branched pathways and the relative contributions of NO/ROS-derived and SA-derived pathways in SAR. Copyright © 2014 Elsevier Ltd. All rights reserved.

Person-Centered Care: A Definition and Essential Elements.

PubMed

2016-01-01

Improving healthcare safety, quality, and coordination, as well as quality of life, are important aims of caring for older adults with multiple chronic conditions and/or functional limitations. Person-centered care is an approach to meeting these aims, but there are no standardized, agreed-upon parameters for delivering such care. The SCAN Foundation charged a team from the American Geriatrics Society (AGS) in collaboration with a research and clinical team from the Keck School of Medicine of the University of Southern California to provide the evidence base to support a definition of person-centered care and its essential elements. An interprofessional panel of experts in person-centered care principles and practices that the AGS convened developed this statement. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Quality of trauma care and trauma registries.

PubMed

Pino Sánchez, F I; Ballesteros Sanz, M A; Cordero Lorenzana, L; Guerrero López, F

2015-03-01

Traumatic disease is a major public health concern. Monitoring the quality of services provided is essential for the maintenance and improvement thereof. Assessing and monitoring the quality of care in trauma patient through quality indicators would allow identifying opportunities for improvement whose implementation would improve outcomes in hospital mortality, functional outcomes and quality of life of survivors. Many quality indicators have been used in this condition, although very few ones have a solid level of scientific evidence to recommend their routine use. The information contained in the trauma registries, spread around the world in recent decades, is essential to know the current health care reality, identify opportunities for improvement and contribute to the clinical and epidemiological research. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

The Small GTPase Rif Is Dispensable for Platelet Filopodia Generation in Mice

PubMed Central

Goggs, Robert; Savage, Joshua S.; Mellor, Harry; Poole, Alastair W.

2013-01-01

Background Formation of filopodia and other shape change events are vital for platelet hemostatic function. The mechanisms regulating filopodia formation by platelets are incompletely understood however. In particular the small GTPase responsible for initiating filopodia formation by platelets remains elusive. The canonical pathway involving Cdc42 is not essential for filopodia formation in mouse platelets. The small GTPase Rif (RhoF) provides an alternative route to filopodia generation in other cell types and is expressed in both human and mouse platelets. Hypothesis/Objective We hypothesized that Rif might be responsible for generating filopodia by platelets and generated a novel knockout mouse model to investigate the functional role of Rif in platelets. Methodology/Principal Findings Constitutive RhoF−/− mice are viable and have normal platelet, leukocyte and erythrocyte counts and indices. RhoF−/− platelets form filopodia and spread normally on various agonist surfaces in static conditions and under arterial shear. In addition, RhoF−/− platelets have normal actin dynamics, are able to activate and aggregate normally and secrete from alpha and dense granules in response to collagen related peptide and thrombin stimulation. Conclusions The small GTPase Rif does not appear to be critical for platelet function in mice. Functional overlap between Rif and other small GTPases may be responsible for the non-essential role of Rif in platelets. PMID:23359340

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

PubMed Central

Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

2015-01-01

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

Functional Interaction between Phosducin-like Protein 2 and Cytosolic Chaperonin Is Essential for Cytoskeletal Protein Function and Cell Cycle Progression

PubMed Central

Stirling, Peter C.; Srayko, Martin; Takhar, Karam S.; Pozniakovsky, Andrei; Hyman, Anthony A.

2007-01-01

The C haperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2. PMID:17429077

The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence

PubMed Central

Geisberger, Roland; Rada, Cristina; Neuberger, Michael S.

2009-01-01

The carboxyterminal region of activation-induced deaminase (AID) is required for its function in Ig class switch recombination (CSR) and also contains a nuclear-export sequence (NES). Here, based on an extensive fine-structure mutation analysis of the AID NES, as well as from AID chimeras bearing heterologous NESs, we show that while a functional NES is indeed essential for CSR, it is not sufficient. The precise nature of the NES is critical both for AID stabilization and CSR function: minor changes in the NES can perturb stabilization and CSR without jeopardizing nuclear export. The results indicate that the AID NES fulfills a function beyond simply providing a signal for nuclear export and suggest the possibility that the quality of exportin-binding may be critical to the stabilization of AID and its activity in CSR. PMID:19351893

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

PubMed Central

Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

2015-01-01

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

Clinical and surgical anatomy of the liver: a review for clinicians.

PubMed

Juza, Ryan M; Pauli, Eric M

2014-07-01

The liver is the largest gland in the body occupying 2.5% of total body weight and providing a host of functions necessary for maintaining normal physiological homeostasis. Despite the complexity of its functions, the liver has a homogenous appearance, making hepatic anatomy a challenging topic of discussion. To address this issue, scholars have devoted time to establishing a framework for describing hepatic anatomy to aid clinicians. Work by the anatomist Sir James Cantlie provided the first accurate division between the right and left liver in 1897. The French surgeon and anatomist Claude Couinaud provided additional insight by introducing the Couinaud segments on the basis of hepatic vasculature. These fundamental studies provided a framework for medical and surgical discussions of hepatic anatomy and were essential for the advancement of modern medicine. In this article, the authors review the normal anatomy and physiology of the liver with a view to enhancing the clinician's knowledge base. They also provide a convenient model to assist with understanding and discussion of liver anatomy. Copyright © 2014 Wiley Periodicals, Inc.

Tetrazine ligation for chemical proteomics.

PubMed

Kang, Kyungtae; Park, Jongmin; Kim, Eunha

2016-01-01

Determining small molecule-target protein interaction is essential for the chemical proteomics. One of the most important keys to explore biological system in chemical proteomics field is finding first-class molecular tools. Chemical probes can provide great spatiotemporal control to elucidate biological functions of proteins as well as for interrogating biological pathways. The invention of bioorthogonal chemistry has revolutionized the field of chemical biology by providing superior chemical tools and has been widely used for investigating the dynamics and function of biomolecules in live condition. Among 20 different bioorthogonal reactions, tetrazine ligation has been spotlighted as the most advanced bioorthogonal chemistry because of their extremely faster kinetics and higher specificity than others. Therefore, tetrazine ligation has a tremendous potential to enhance the proteomic research. This review highlights the current status of tetrazine ligation reaction as a molecular tool for the chemical proteomics.

Retinal vessel enhancement based on the Gaussian function and image fusion

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Obreja, Cristian Dragoş

2017-01-01

The Gaussian function is essential in the construction of the Frangi and COSFIRE (combination of shifted filter responses) filters. The connection of the broken vessels and an accurate extraction of the vascular structure is the main goal of this study. Thus, the outcome of the Frangi and COSFIRE edge detection algorithms are fused using the Dempster-Shafer algorithm with the aim to improve detection and to enhance the retinal vascular structure. For objective results, the average diameters of the retinal vessels provided by Frangi, COSFIRE and Dempster-Shafer fusion algorithms are measured. These experimental values are compared to the ground truth values provided by manually segmented retinal images. We prove the superiority of the fusion algorithm in terms of image quality by using the figure of merit objective metric that correlates the effects of all post-processing techniques.

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

PubMed

Chabiniok, Radomir; Wang, Vicky Y; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A; Moireau, Philippe; Nash, Martyn P; Chapelle, Dominique; Nordsletten, David A

2016-04-06

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.

Communication in autism spectrum disorder: a guide for pediatric nurses.

PubMed

Brown, Amanda B; Elder, Jennifer H

2014-01-01

In the United States, one in every 68 children has autism spectrum disorder (ASD) (Centers for Disease Control and Prevention, 2014). ASD is a developmental disorder of the brain that is characterized by impairments in social interaction, communication, and repetitive patterns of behavior (American Psychiatric Association [APA], 2013). Nurses have a duty to provide high quality care to children with ASD. Effective communication is essential to providing quality care. Three main theories attempt to explain how the ASD brain functions and the implications on communication: lack of theory of mind, weak central coherence, and lack of executive function. Children with ASD have difficulties in vocalic, kinesthetic, and proxemic aspects of communication (Notbhom, 2006). Simple adaptations to environment and style can make the communication between nurses and children with ASD easier and more effective (Aylott, 2000; Green et al., 2010).

In vivo RNAi: Today and Tomorrow

PubMed Central

Perrimon, Norbert; Ni, Jian-Quan; Perkins, Lizabeth

2010-01-01

SUMMARY RNA interference (RNAi) provides a powerful reverse genetics approach to analyze gene functions both in tissue culture and in vivo. Because of its widespread applicability and effectiveness it has become an essential part of the tool box kits of model organisms such as Caenorhabditis elegans, Drosophila, and the mouse. In addition, the use of RNAi in animals in which genetic tools are either poorly developed or nonexistent enables a myriad of fundamental questions to be asked. Here, we review the methods and applications of in vivo RNAi to characterize gene functions in model organisms and discuss their impact to the study of developmental as well as evolutionary questions. Further, we discuss the applications of RNAi technologies to crop improvement, pest control and RNAi therapeutics, thus providing an appreciation of the potential for phenomenal applications of RNAi to agriculture and medicine. PMID:20534712

Wound care in the neonatal intensive care unit.

PubMed

Fox, Miriam D

2011-01-01

The skin is a vital organ with key protective functions. Infants in the NICU are at risk for skin injury because of developmental immaturity and intensive care treatments. When skin injury occurs, the neonatal nurse is challenged to provide wound care to optimize functional and cosmetic healing. Optimal wound care requires basic knowledge of the mechanisms of injury, physiology of wound healing, host factors affecting wound healing, and wound assessment. This knowledge provides the basis for determining appropriate wound treatment, including dressing selection. Attention to pain issues associated with wound care is difficult because of the infant's developmental stage, but is essential because of the potentially negative life-long impact of pain. The premature infant's propensity for skin stripping limits the selection of appropriate dressing, as does the paucity of research examining wound care products in this population.

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

Pre-Participation Screening: The Use of Fundamental Movements as an Assessment of Function – Part 1

PubMed Central

Burton, Lee; Hoogenboom, Barb

2006-01-01

To prepare an athlete for the wide variety of activities needed to participate in their sport, the analysis of fundamental movements should be incorporated into pre-participation screening in order to determine who possesses, or lacks, the ability to perform certain essential movements. In a series of two articles, the background and rationale for the analysis of fundamental movement will be provided. In addition, one such evaluation tool that attempts to assess the fundamental movement patterns performed by an individual, the Functional Movement Screen (FMS™), will be described. Three of the seven fundamental movement patterns that comprise the FMS™ are described in detail in Part I: deep squat, hurdle step, and in-line lunge. Part II of this series, which will be published in the August issue of NAJSPT, will provide a brief review of the analysis of fundamental movements, as well a detailed description of the four additional patterns that complement those presented in Part I (to complete the total of seven fundamental movement patterns which comprise the FMS™): shoulder mobility, active straight leg raise, trunk stability push-up, and rotary stability. The intent of this two part series is to introduce the concept of the evaluation of fundamental movements, whether it is the FMS™ system or a different system devised by another clinician. Such a functional assessment should be incorporated into pre-participation screening in order to determine whether the athlete has the essential movements needed to participate in sports activities with a decreased risk of injury. PMID:21522216

Role of the ECM in notochord formation, function and disease.

PubMed

Trapani, Valeria; Bonaldo, Paolo; Corallo, Diana

2017-10-01

The notochord is a midline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function. Work carried out in the past two decades has allowed researchers to dissect the contribution of different ECM components to this embryonic tissue. Here, we will provide an overview of these genetic and mechanistic studies. In particular, we highlight the specific functions of distinct matrix molecules in regulating notochord development and notochord-derived signals. Moreover, we also discuss the involvement of ECM synthesis and its remodeling in the pathogenesis of chordoma, a malignant bone cancer that originates from remnants of notochord remaining after embryogenesis. © 2017. Published by The Company of Biologists Ltd.

GExplore: a web server for integrated queries of protein domains, gene expression and mutant phenotypes

PubMed Central

2009-01-01

Background The majority of the genes even in well-studied multi-cellular model organisms have not been functionally characterized yet. Mining the numerous genome wide data sets related to protein function to retrieve potential candidate genes for a particular biological process remains a challenge. Description GExplore has been developed to provide a user-friendly database interface for data mining at the gene expression/protein function level to help in hypothesis development and experiment design. It supports combinatorial searches for proteins with certain domains, tissue- or developmental stage-specific expression patterns, and mutant phenotypes. GExplore operates on a stand-alone database and has fast response times, which is essential for exploratory searches. The interface is not only user-friendly, but also modular so that it accommodates additional data sets in the future. Conclusion GExplore is an online database for quick mining of data related to gene and protein function, providing a multi-gene display of data sets related to the domain composition of proteins as well as expression and phenotype data. GExplore is publicly available at: http://genome.sfu.ca/gexplore/ PMID:19917126

Secondary Plastids of Euglenids and Chlorarachniophytes Function with a Mix of Genes of Red and Green Algal Ancestry.

PubMed

Ponce-Toledo, Rafael I; Moreira, David; López-García, Purificación; Deschamps, Philippe

2018-06-19

Endosymbiosis has been common all along eukaryotic evolution, providing opportunities for genomic and organellar innovation. Plastids are a prominent example. After the primary endosymbiosis of the cyanobacterial plastid ancestor, photosynthesis spread in many eukaryotic lineages via secondary endosymbioses involving red or green algal endosymbionts and diverse heterotrophic hosts. However, the number of secondary endosymbioses and how they occurred remain poorly understood. In particular, contrasting patterns of endosymbiotic gene transfer (EGT) have been detected and subjected to various interpretations. In this context, accurate detection of EGTs is essential to avoid wrong evolutionary conclusions. We have assembled a strictly selected set of markers that provides robust phylogenomic evidence suggesting that nuclear genes involved in the function and maintenance of green secondary plastids in chlorarachniophytes and euglenids have unexpected mixed red and green algal origins. This mixed ancestry contrasts with the clear red algal origin of most nuclear genes carrying similar functions in secondary algae with red plastids.

Looking at the Disordered Proteins through the Computational Microscope.

PubMed

Das, Payel; Matysiak, Silvina; Mittal, Jeetain

2018-05-23

Intrinsically disordered proteins (IDPs) have attracted wide interest over the past decade due to their surprising prevalence in the proteome and versatile roles in cell physiology and pathology. A large selection of IDPs has been identified as potential targets for therapeutic intervention. Characterizing the structure-function relationship of disordered proteins is therefore an essential but daunting task, as these proteins can adapt transient structure, necessitating a new paradigm for connecting structural disorder to function. Molecular simulation has emerged as a natural complement to experiments for atomic-level characterizations and mechanistic investigations of this intriguing class of proteins. The diverse range of length and time scales involved in IDP function requires performing simulations at multiple levels of resolution. In this Outlook, we focus on summarizing available simulation methods, along with a few interesting example applications. We also provide an outlook on how these simulation methods can be further improved in order to provide a more accurate description of IDP structure, binding, and assembly.

Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.

PubMed

Sullivan, Lucas B; Gui, Dan Y; Hosios, Aaron M; Bush, Lauren N; Freinkman, Elizaveta; Vander Heiden, Matthew G

2015-07-30

Mitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Dendritic cell targeted vaccines: Recent progresses and challenges

PubMed Central

Chen, Pengfei; Liu, Xinsheng; Sun, Yuefeng; Zhou, Peng; Wang, Yonglu; Zhang, Yongguang

2016-01-01

ABSTRACT Dendritic cells (DCs) are known to be a set of morphology, structure and function of heterogeneous professional antigen presenting cells (APCs), as well as the strongest functional antigen presenting cells, which can absorb, process and present antigens. As the key regulators of innate and adaptive immune responses, DCs are at the center of the immune system and capable of interacting with both B cells and T cells, thereby manipulating the humoral and cellular immune responses. DCs provide an essential link between the innate and adaptive immunity, and the strong immune activation function of DCs and their properties of natural adjuvants, make them a valuable target for antigen delivery. Targeting antigens to DC-specific endocytic receptors in combination with the relevant antibodies or ligands along with immunostimulatory adjuvants has been recently recognized as a promising strategy for designing an effective vaccine that elicits a strong and durable T cell response against intracellular pathogens and cancer. This opinion article provides a brief summary of the rationales, superiorities and challenges of existing DC-targeting approaches. PMID:26513200

On the logistic equation subject to uncertainties in the environmental carrying capacity and initial population density

NASA Astrophysics Data System (ADS)

Dorini, F. A.; Cecconello, M. S.; Dorini, L. B.

2016-04-01

It is recognized that handling uncertainty is essential to obtain more reliable results in modeling and computer simulation. This paper aims to discuss the logistic equation subject to uncertainties in two parameters: the environmental carrying capacity, K, and the initial population density, N0. We first provide the closed-form results for the first probability density function of time-population density, N(t), and its inflection point, t*. We then use the Maximum Entropy Principle to determine both K and N0 density functions, treating such parameters as independent random variables and considering fluctuations of their values for a situation that commonly occurs in practice. Finally, closed-form results for the density functions and statistical moments of N(t), for a fixed t > 0, and of t* are provided, considering the uniform distribution case. We carried out numerical experiments to validate the theoretical results and compared them against that obtained using Monte Carlo simulation.

Looking at the Disordered Proteins through the Computational Microscope

PubMed Central

2018-01-01

Intrinsically disordered proteins (IDPs) have attracted wide interest over the past decade due to their surprising prevalence in the proteome and versatile roles in cell physiology and pathology. A large selection of IDPs has been identified as potential targets for therapeutic intervention. Characterizing the structure–function relationship of disordered proteins is therefore an essential but daunting task, as these proteins can adapt transient structure, necessitating a new paradigm for connecting structural disorder to function. Molecular simulation has emerged as a natural complement to experiments for atomic-level characterizations and mechanistic investigations of this intriguing class of proteins. The diverse range of length and time scales involved in IDP function requires performing simulations at multiple levels of resolution. In this Outlook, we focus on summarizing available simulation methods, along with a few interesting example applications. We also provide an outlook on how these simulation methods can be further improved in order to provide a more accurate description of IDP structure, binding, and assembly.

Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice.

PubMed

Loftus, Róisín M; Assmann, Nadine; Kedia-Mehta, Nidhi; O'Brien, Katie L; Garcia, Arianne; Gillespie, Conor; Hukelmann, Jens L; Oefner, Peter J; Lamond, Angus I; Gardiner, Clair M; Dettmer, Katja; Cantrell, Doreen A; Sinclair, Linda V; Finlay, David K

2018-06-14

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked. We identify SLC7A5 as the predominant system L-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function.

Programming of the complex logarithm function in the solution of the cracked anisotropic plate loaded by a point force

NASA Astrophysics Data System (ADS)

Zaal, K. J. J. M.

1991-06-01

In programming solutions of complex function theory, the complex logarithm function is replaced by the complex logarithmic function, introducing a discontinuity along the branch cut into the programmed solution which was not present in the mathematical solution. Recently, Liaw and Kamel presented their solution of the infinite anisotropic centrally cracked plate loaded by an arbitrary point force, which they used as Green's function in a boundary element method intended to evaluate the stress intensity factor at the tip of a crack originating from an elliptical home. Their solution may be used as Green's function of many more numerical methods involving anisotropic elasticity. In programming applications of Liaw and Kamel's solution, the standard definition of the logarithmic function with the branch cut at the nonpositive real axis cannot provide a reliable computation of the displacement field for Liaw and Kamel's solution. Either the branch cut should be redefined outside the domain of the logarithmic function, after proving that the domain is limited to a part of the plane, or the logarithmic function should be defined on its Riemann surface. A two dimensional line fractal can provide the link between all mesh points on the plane essential to evaluate the logarithm function on its Riemann surface. As an example, a two dimensional line fractal is defined for a mesh once used by Erdogan and Arin.

[Advanced organ failure in the elderly. Some issues from a geriatrics, palliative medicine and bioethics perspectives].

PubMed

Alonso-Renedo, Francisco Javier; González-Ercilla, Leire; Iráizoz-Apezteguía, Itziar

2014-01-01

To analyze the literature as regards the knowledge, skills and attitudes that these disciplines can provide in improving technical, ethical and human quality health care in the elderly with advanced organ failure, multimorbidity, frailty and progressive dementia. A comprehensive review focused on available references on the interrelationship between geriatric medicine and palliative medicine, education in bioethics, prognostic tools, functional status, and the humanization of health care. Advance care planning, comprehensive geriatric assessment, the study of the values of the patient and their introduction in decision-making process, as well as the need to promote moral, care, and healthcare organizational ethics, are essential elements to achieve this objective. Practitioners and healthcare organizations should seek excellence as a moral requirement. To achieve this, there is a priority to acquire virtues of care and fundamental concepts of geriatric and palliative medicine, assessing functional status, advance care planning and patient/family needs as essential issues to protect, care for and promote them in all care settings. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

A Rare SNP Identified a TCP Transcription Factor Essential for Tendril Development in Cucumber.

PubMed

Wang, Shenhao; Yang, Xueyong; Xu, Mengnan; Lin, Xingzhong; Lin, Tao; Qi, Jianjian; Shao, Guangjin; Tian, Nana; Yang, Qing; Zhang, Zhonghua; Huang, Sanwen

2015-12-07

Rare genetic variants are abundant in genomes but less tractable in genome-wide association study. Here we exploit a strategy of rare variation mapping to discover a gene essential for tendril development in cucumber (Cucumis sativus L.). In a collection of >3000 lines, we discovered a unique tendril-less line that forms branches instead of tendrils and, therefore, loses its climbing ability. We hypothesized that this unusual phenotype was caused by a rare variation and subsequently identified the causative single nucleotide polymorphism. The affected gene TEN encodes a TCP transcription factor conserved within the cucurbits and is expressed specifically in tendrils, representing a new organ identity gene. The variation occurs within a protein motif unique to the cucurbits and impairs its function as a transcriptional activator. Analyses of transcriptomes from near-isogenic lines identified downstream genes required for the tendril's capability to sense and climb a support. This study provides an example to explore rare functional variants in plant genomes. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I

DOE PAGES

Tan, Kemin; Zhou, Qingxuan; Cheng, Bokun; ...

2015-10-20

Escherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain andmore » zinc ribbon-like domain bind ssDNA with primarily π -stacking interactions. Finally, this novel structure, in combination with new biochemical data, provides important insights into the mechanism of genome regulation by type IA topoisomerases that is essential for life, as well as the structures of homologous type IA TOP3α and TOP3β from higher eukaryotes that also have multiple 4-Cys zinc ribbon domains required for their physiological functions.« less

Mechanisms of Divalent Metal Toxicity in Affective Disorders

PubMed Central

Menon, Archita Venugopal; Chang, JuOae; Kim, Jonghan

2016-01-01

Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID:26551072

Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE.

PubMed

Sun, Qingxiang; Yong, Xin; Sun, Xiaodong; Yang, Fan; Dai, Zhonghua; Gong, Yanqiu; Zhou, Liming; Zhang, Xia; Niu, Dawen; Dai, Lunzhi; Liu, Jia-Jia; Jia, Da

2017-01-01

The endosomal trafficking pathways are essential for many cellular activities. They are also important targets by many intracellular pathogens. Key regulators of the endosomal trafficking include the retromer complex and sorting nexins (SNXs). Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport, but the exact mechanism has remained unclear. We present the crystal structure of the PX domain of SNX5 in complex with IncE, showing that IncE binds to a highly conserved hydrophobic groove of SNX5. The unique helical hairpin of SNX5/6 is essential for binding, explaining the specificity of SNX5/6 for IncE. The SNX5/6-IncE interaction is required for cellular localization of IncE and its inhibitory function. Mechanistically, IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains. Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking.

β-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli.

PubMed

Bramwell, Kenneth K C; Mock, Kelton; Ma, Ying; Weis, John H; Teuscher, Cory; Weis, Janis J

2015-08-15

The lysosomal enzyme β-glucuronidase (Gusb) is a key regulator of Lyme-associated and K/B×N-induced arthritis severity. The luminal enzymes present in lysosomes provide essential catabolic functions for the homeostatic degradation of a variety of macromolecules. In addition to this essential catabolic function, lysosomes play important roles in the inflammatory response following infection. Secretory lysosomes and related vesicles can participate in the inflammatory response through fusion with the plasma membrane and release of bioactive contents into the extracellular milieu. In this study, we show that GUSB hypomorphism potentiates lysosomal exocytosis following inflammatory stimulation. This leads to elevated secretion of lysosomal contents, including glycosaminoglycans, lysosomal hydrolases, and matrix metalloproteinase 9, a known modulator of Lyme arthritis severity. This mechanistic insight led us to test the efficacy of rapamycin, a drug known to suppress lysosomal exocytosis. Both Lyme and K/B×N-associated arthritis were suppressed by this treatment concurrent with reduced lysosomal release. Copyright © 2015 by The American Association of Immunologists, Inc.

The spectraplakin Short stop is an essential microtubule regulator involved in epithelial closure in Drosophila

PubMed Central

Takács, Zsanett; Vilmos, Péter; Lénárt, Péter; Röper, Katja; Erdélyi, Miklós

2017-01-01

ABSTRACT Dorsal closure of the Drosophila embryonic epithelium provides an excellent model system for the in vivo analysis of molecular mechanisms regulating cytoskeletal rearrangements. In this study, we investigated the function of the Drosophila spectraplakin Short stop (Shot), a conserved cytoskeletal structural protein, during closure of the dorsal embryonic epithelium. We show that Shot is essential for the efficient final zippering of the opposing epithelial margins. By using isoform-specific mutant alleles and genetic rescue experiments with truncated Shot variants, we demonstrate that Shot functions as an actin–microtubule cross-linker in mediating zippering. At the leading edge of epithelial cells, Shot regulates protrusion dynamics by promoting filopodia formation. Fluorescence recovery after photobleaching (FRAP) analysis and in vivo imaging of microtubule growth revealed that Shot stabilizes dynamic microtubules. The actin- and microtubule-binding activities of Shot are simultaneously required in the same molecule, indicating that Shot is engaged as a physical crosslinker in this process. We propose that Shot-mediated interactions between microtubules and actin filaments facilitate filopodia formation, which promotes zippering by initiating contact between opposing epithelial cells. PMID:28062848

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

Shiheido, Hirokazu, E-mail: shiheido@ak.med.kyoto-u.ac.jp; Shimizu, Jun

BEN domain-containing protein 3 (BEND3) has recently been reported to function as a heterochromatin-associated protein in transcriptional repression in the nucleus. BEND3 should have nuclear localization signals (NLSs) to localize to the nucleus in light of its molecular weight, which is higher than that allowed to pass through nuclear pore complexes. We here analyzed the subcellular localization of deletion/site-directed mutants of human BEND3 by an immunofluorescence assay in an attempt to identify the amino acids essential for its nuclear localization. We found that three basic amino acid residues located in the N-terminal region of BEND3 (BEND3{sub 56–58}, KRK) are essential,more » suggesting that these residues play a role as a functional NLS. These results provide valuable information for progressing research on BEND3. - Highlights: • BEND3 localizes to the nucleus. • The N-terminal 60 amino acids region of BEND3 contains NLS. • Amino acids located between 56 and 58 of BEND3 (KRK) are part of NLS. • KRK motif is highly conserved among BEND3 homologs.« less

Genetic Landscape of Auditory Dysfunction.

PubMed

Bowl, Michael R; Brown, S D M

2018-05-02

Over the past 25 years, human and mouse genetics research together has identified several hundred genes essential for mammalian hearing, leading to a greater understanding of the molecular mechanisms underlying auditory function. However, from the number of still as yet uncloned human deafness loci and the findings of large-scale mouse mutant screens, it is clear we are still far from identifying all of the genes critical for auditory function. In particular, while we have made great progress in understanding the genetic bases of congenital and early-onset hearing loss, we have only just begun to elaborate upon the genetic landscape of age-related hearing loss. With an aging population and a growing literature suggesting links between age-related hearing loss and neuropsychiatric conditions, such as dementia and depression, understanding the genetics and subsequently the molecular mechanisms underlying this very prevalent condition is of paramount importance. Increased knowledge of genes and molecular pathways required for hearing will ultimately provide the foundation upon which novel therapeutic approaches can be built. Here we discuss the current status of deafness genetics research and the ongoing efforts being undertaken for discovery of novel genes essential for hearing.

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

Tan, Kemin; Zhou, Qingxuan; Cheng, Bokun

Escherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain andmore » zinc ribbon-like domain bind ssDNA with primarily π -stacking interactions. Finally, this novel structure, in combination with new biochemical data, provides important insights into the mechanism of genome regulation by type IA topoisomerases that is essential for life, as well as the structures of homologous type IA TOP3α and TOP3β from higher eukaryotes that also have multiple 4-Cys zinc ribbon domains required for their physiological functions.« less

Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

PubMed

Yang, Laurence; Tan, Justin; O'Brien, Edward J; Monk, Jonathan M; Kim, Donghyuk; Li, Howard J; Charusanti, Pep; Ebrahim, Ali; Lloyd, Colton J; Yurkovich, James T; Du, Bin; Dräger, Andreas; Thomas, Alex; Sun, Yuekai; Saunders, Michael A; Palsson, Bernhard O

2015-08-25

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Structural Basis for Nucleotide Binding and Reaction Catalysis in Mevalonate Diphosphate Decarboxylase

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

Barta, Michael L.; McWhorter, William J.; Miziorko, Henry M.

2012-09-17

Mevalonate diphosphate decarboxylase (MDD) catalyzes the final step of the mevalonate pathway, the Mg{sup 2+}-ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP), producing isopentenyl diphosphate (IPP). Synthesis of IPP, an isoprenoid precursor molecule that is a critical intermediate in peptidoglycan and polyisoprenoid biosynthesis, is essential in Gram-positive bacteria (e.g., Staphylococcus, Streptococcus, and Enterococcus spp.), and thus the enzymes of the mevalonate pathway are ideal antimicrobial targets. MDD belongs to the GHMP superfamily of metabolite kinases that have been extensively studied for the past 50 years, yet the crystallization of GHMP kinase ternary complexes has proven to be difficult. To further ourmore » understanding of the catalytic mechanism of GHMP kinases with the purpose of developing broad spectrum antimicrobial agents that target the substrate and nucleotide binding sites, we report the crystal structures of wild-type and mutant (S192A and D283A) ternary complexes of Staphylococcus epidermidis MDD. Comparison of apo, MVAPP-bound, and ternary complex wild-type MDD provides structural information about the mode of substrate binding and the catalytic mechanism. Structural characterization of ternary complexes of catalytically deficient MDD S192A and D283A (k{sub cat} decreased 10{sup 3}- and 10{sup 5}-fold, respectively) provides insight into MDD function. The carboxylate side chain of invariant Asp{sup 283} functions as a catalytic base and is essential for the proper orientation of the MVAPP C3-hydroxyl group within the active site funnel. Several MDD amino acids within the conserved phosphate binding loop ('P-loop') provide key interactions, stabilizing the nucleotide triphosphoryl moiety. The crystal structures presented here provide a useful foundation for structure-based drug design.« less

Neuron-specific feeding RNAi in C. elegans and its use in a screen for essential genes required for GABA neuron function.

PubMed

Firnhaber, Christopher; Hammarlund, Marc

2013-11-01

Forward genetic screens are important tools for exploring the genetic requirements for neuronal function. However, conventional forward screens often have difficulty identifying genes whose relevant functions are masked by pleiotropy. In particular, if loss of gene function results in sterility, lethality, or other severe pleiotropy, neuronal-specific functions cannot be readily analyzed. Here we describe a method in C. elegans for generating cell-specific knockdown in neurons using feeding RNAi and its application in a screen for the role of essential genes in GABAergic neurons. We combine manipulations that increase the sensitivity of select neurons to RNAi with manipulations that block RNAi in other cells. We produce animal strains in which feeding RNAi results in restricted gene knockdown in either GABA-, acetylcholine-, dopamine-, or glutamate-releasing neurons. In these strains, we observe neuron cell-type specific behavioral changes when we knock down genes required for these neurons to function, including genes encoding the basal neurotransmission machinery. These reagents enable high-throughput, cell-specific knockdown in the nervous system, facilitating rapid dissection of the site of gene action and screening for neuronal functions of essential genes. Using the GABA-specific RNAi strain, we screened 1,320 RNAi clones targeting essential genes on chromosomes I, II, and III for their effect on GABA neuron function. We identified 48 genes whose GABA cell-specific knockdown resulted in reduced GABA motor output. This screen extends our understanding of the genetic requirements for continued neuronal function in a mature organism.

The role of assessment in enhancing the vocational success of people with multiple sclerosis.

PubMed

Roessler, R T

1996-01-01

The person/environment or ecological perspective on vocational evaluation provides a comprehensive assessment strategy for people with multiple sclerosis. The ecological model requires assessment of both personal variables such as rehabilitation outlook and MS symptoms and environmental variables such as barriers to workplace accessibility and performance of essential job functions. Measures of person and environment constructs are presented as are applications of the resulting information in vocational counseling and disability management services.

Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy.

PubMed

Rittmann, Bruce E; Krajmalnik-Brown, Rosa; Halden, Rolf U

2008-08-01

Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.

Space construction data base

NASA Technical Reports Server (NTRS)

1979-01-01

Construction of large systems in space is a technology requiring the development of construction methods to deploy, assemble, and fabricate the elements comprising such systems. A construction method is comprised of all essential functions and operations and related support equipment necessary to accomplish a specific construction task in a particular way. The data base objective is to provide to the designers of large space systems a compendium of the various space construction methods which could have application to their projects.

Towards the Synthesis of Dihydrooxepino[4,3-b]pyrrole-Containing Natural Products via Cope Rearrangement of Vinyl Pyrrole Epoxides.

PubMed

Cameron, Alex; Fisher, Brendan; Fisk, Nicholas; Hummel, Jessica; White, Jonathan M; Krenske, Elizabeth H; Rizzacasa, Mark A

2015-12-18

An approach to the dihydrooxepino[4,3-b]pyrrole core of diketopiperazine natural products which utilizes a vinyl pyrrole epoxide Cope rearrangement was investigated. It was found that an ester substituent on the epoxide was essential for the [3,3]-rearrangement to occur. Density functional calculations with M06-2X provided explanations for the effects of the pyrrole and ester groups on these rearrangements.

Three-Dimensional Mapping of Atmospheric Boundary Layer Structure and Winds with a High Performance Lidar

DTIC Science & Technology

1991-04-01

convective plumes which originate from the surface through solar heating. Unlike tower, sodar, and airplane measurements, lidar can provide essentially...average spacing between these bands is given by Xmax. The determination of Xma is complicated by the fact that the two-dimensional spectral power...eddy which results depends critically on the choice of the indicator function (Marht and Frank, 1988). This is due to the fact that the measurement

Rural Productivity Zones (RPZs) for microenterprises

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

Hansen, R.D.

1997-12-01

In this paper the authors discuss the concept of rural productivity zones (RPZs) which are defined as a business incubator to foster income-producing opportunities for the rural poor. The essential ingredients of such a program include: electric power; business development assistance; office services; and quality work space. The electric power source must be a good quality system, consisting of a diesel/wind/photovoltaic hybrid type system, providing reliable service, with a local maintenance program and a functional load management program.

Efficient Healing Takes Some Nerve: Electrical Stimulation Enhances Innervation in Cutaneous Human Wounds.

PubMed

Emmerson, Elaine

2017-03-01

Cutaneous nerves extend throughout the dermis and epidermis and control both the functional and reparative capacity of the skin. Denervation of the skin impairs cutaneous healing, presenting evidence that nerves provide cues essential for timely wound repair. Sebastian et al. demonstrate that electrical stimulation promotes reinnervation and neural differentiation in human acute wounds, thus accelerating wound repair. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Behavior-Based Language Generation for Believable Agents,

DTIC Science & Technology

1995-03-01

retaining only those aspects of the agent that are essential to express its personality and its role in the work of which it is part.1 While full realism is...must contain a type and a role feature. The type provides information about the expected elements of the group and the level of the group in the...linguistic hierarchy, for example morpheme, word, phrase, or clause. The role specifies the group’s function within its parent group. All subgroups

Insights into insect wing origin provided by functional analysis of vestigial in the red flour beetle, Tribolium castaneum.

PubMed

Clark-Hachtel, Courtney M; Linz, David M; Tomoyasu, Yoshinori

2013-10-15

Despite accumulating efforts to unveil the origin of insect wings, it remains one of the principal mysteries in evolution. Currently, there are two prominent models regarding insect wing origin: one connecting the origin to the paranotal lobe and the other to the proximodorsal leg branch (exite). However, neither hypothesis has been able to surpass the other. To approach this conundrum, we focused our analysis on vestigial (vg), a critical wing gene initially identified in Drosophila. Our investigation in Tribolium (Coleoptera) has revealed that, despite the well-accepted view of vg as an essential wing gene, there are two groups of vg-dependent tissues in the "wingless" first thoracic segment (T1). We show that one of these tissues, the carinated margin, also depends on other factors essential for wing development (such as Wingless signal and apterous), and has nubbin enhancer activity. In addition, our homeotic mutant analysis shows that wing transformation in T1 originates from both the carinated margin and the other vg-dependent tissue, the pleural structures (trochantin and epimeron). Intriguingly, these two tissues may actually be homologous to the two proposed wing origins (paranotal lobes and exite bearing proximal leg segments). Therefore, our findings suggest that the vg-dependent tissues in T1 could be wing serial homologs present in a more ancestral state, thus providing compelling functional evidence for the dual origin of insect wings.

Reconstruction and Validation of a Genome-Scale Metabolic Model for the Filamentous Fungus Neurospora crassa Using FARM

PubMed Central

Hood, Heather M.; Ocasio, Linda R.; Sachs, Matthew S.; Galagan, James E.

2013-01-01

The filamentous fungus Neurospora crassa played a central role in the development of twentieth-century genetics, biochemistry and molecular biology, and continues to serve as a model organism for eukaryotic biology. Here, we have reconstructed a genome-scale model of its metabolism. This model consists of 836 metabolic genes, 257 pathways, 6 cellular compartments, and is supported by extensive manual curation of 491 literature citations. To aid our reconstruction, we developed three optimization-based algorithms, which together comprise Fast Automated Reconstruction of Metabolism (FARM). These algorithms are: LInear MEtabolite Dilution Flux Balance Analysis (limed-FBA), which predicts flux while linearly accounting for metabolite dilution; One-step functional Pruning (OnePrune), which removes blocked reactions with a single compact linear program; and Consistent Reproduction Of growth/no-growth Phenotype (CROP), which reconciles differences between in silico and experimental gene essentiality faster than previous approaches. Against an independent test set of more than 300 essential/non-essential genes that were not used to train the model, the model displays 93% sensitivity and specificity. We also used the model to simulate the biochemical genetics experiments originally performed on Neurospora by comprehensively predicting nutrient rescue of essential genes and synthetic lethal interactions, and we provide detailed pathway-based mechanistic explanations of our predictions. Our model provides a reliable computational framework for the integration and interpretation of ongoing experimental efforts in Neurospora, and we anticipate that our methods will substantially reduce the manual effort required to develop high-quality genome-scale metabolic models for other organisms. PMID:23935467

Model-driven discovery of underground metabolic functions in Escherichia coli.

PubMed

Guzmán, Gabriela I; Utrilla, José; Nurk, Sergey; Brunk, Elizabeth; Monk, Jonathan M; Ebrahim, Ali; Palsson, Bernhard O; Feist, Adam M

2015-01-20

Enzyme promiscuity toward substrates has been discussed in evolutionary terms as providing the flexibility to adapt to novel environments. In the present work, we describe an approach toward exploring such enzyme promiscuity in the space of a metabolic network. This approach leverages genome-scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence of unknown underground pathways stemming from enzymatic cross-reactivity. We demonstrate a workflow that couples constraint-based modeling and bioinformatic tools with KO strain analysis and adaptive laboratory evolution for the purpose of predicting promiscuity at the genome scale. Three cases of genes that are incorrectly predicted as essential in Escherichia coli--aspC, argD, and gltA--are examined, and isozyme functions are uncovered for each to a different extent. Seven isozyme functions based on genetic and transcriptional evidence are suggested between the genes aspC and tyrB, argD and astC, gabT and puuE, and gltA and prpC. This study demonstrates how a targeted model-driven approach to discovery can systematically fill knowledge gaps, characterize underground metabolism, and elucidate regulatory mechanisms of adaptation in response to gene KO perturbations.

The seaweed holobiont: understanding seaweed-bacteria interactions.

PubMed

Egan, Suhelen; Harder, Tilmann; Burke, Catherine; Steinberg, Peter; Kjelleberg, Staffan; Thomas, Torsten

2013-05-01

Seaweeds (macroalgae) form a diverse and ubiquitous group of photosynthetic organisms that play an essential role in aquatic ecosystems. These ecosystem engineers contribute significantly to global primary production and are the major habitat formers on rocky shores in temperate waters, providing food and shelter for aquatic life. Like other eukaryotic organisms, macroalgae harbor a rich diversity of associated microorganisms with functions related to host health and defense. In particular, epiphytic bacterial communities have been reported as essential for normal morphological development of the algal host, and bacteria with antifouling properties are thought to protect chemically undefended macroalgae from detrimental, secondary colonization by other microscopic and macroscopic epibiota. This tight relationship suggests that macroalgae and epiphytic bacteria interact as a unified functional entity or holobiont, analogous to the previously suggested relationship in corals. Moreover, given that the impact of diseases in marine ecosystems is apparently increasing, understanding the role of bacteria as saprophytes and pathogens in seaweed communities may have important implications for marine management strategies. This review reports on the recent advances in the understanding of macroalgal-bacterial interactions with reference to the diversity and functional role of epiphytic bacteria in maintaining algal health, highlighting the holobiont concept. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Integrative Identification of Arabidopsis Mitochondrial Proteome and Its Function Exploitation through Protein Interaction Network

PubMed Central

Cui, Jian; Liu, Jinghua; Li, Yuhua; Shi, Tieliu

2011-01-01

Mitochondria are major players on the production of energy, and host several key reactions involved in basic metabolism and biosynthesis of essential molecules. Currently, the majority of nucleus-encoded mitochondrial proteins are unknown even for model plant Arabidopsis. We reported a computational framework for predicting Arabidopsis mitochondrial proteins based on a probabilistic model, called Naive Bayesian Network, which integrates disparate genomic data generated from eight bioinformatics tools, multiple orthologous mappings, protein domain properties and co-expression patterns using 1,027 microarray profiles. Through this approach, we predicted 2,311 candidate mitochondrial proteins with 84.67% accuracy and 2.53% FPR performances. Together with those experimental confirmed proteins, 2,585 mitochondria proteins (named CoreMitoP) were identified, we explored those proteins with unknown functions based on protein-protein interaction network (PIN) and annotated novel functions for 26.65% CoreMitoP proteins. Moreover, we found newly predicted mitochondrial proteins embedded in particular subnetworks of the PIN, mainly functioning in response to diverse environmental stresses, like salt, draught, cold, and wound etc. Candidate mitochondrial proteins involved in those physiological acitivites provide useful targets for further investigation. Assigned functions also provide comprehensive information for Arabidopsis mitochondrial proteome. PMID:21297957

14 CFR 189.3 - Kinds of messages accepted or relayed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... essential to the safety or regulatory of aircraft operation; (ii) Essential to efficient functioning of... refers, containing information required for weight and balance computation and remarks essential to the... aircraft operating agencies or their representatives that directly bear on the efficient and economic...

Accurate mass and velocity functions of dark matter haloes

NASA Astrophysics Data System (ADS)

Comparat, Johan; Prada, Francisco; Yepes, Gustavo; Klypin, Anatoly

2017-08-01

N-body cosmological simulations are an essential tool to understand the observed distribution of galaxies. We use the MultiDark simulation suite, run with the Planck cosmological parameters, to revisit the mass and velocity functions. At redshift z = 0, the simulations cover four orders of magnitude in halo mass from ˜1011M⊙ with 8783 874 distinct haloes and 532 533 subhaloes. The total volume used is ˜515 Gpc3, more than eight times larger than in previous studies. We measure and model the halo mass function, its covariance matrix w.r.t halo mass and the large-scale halo bias. With the formalism of the excursion-set mass function, we explicit the tight interconnection between the covariance matrix, bias and halo mass function. We obtain a very accurate (<2 per cent level) model of the distinct halo mass function. We also model the subhalo mass function and its relation to the distinct halo mass function. The set of models obtained provides a complete and precise framework for the description of haloes in the concordance Planck cosmology. Finally, we provide precise analytical fits of the Vmax maximum velocity function up to redshift z < 2.3 to push for the development of halo occupation distribution using Vmax. The data and the analysis code are made publicly available in the Skies and Universes data base.

Is extreme learning machine feasible? A theoretical assessment (part II).

PubMed

Lin, Shaobo; Liu, Xia; Fang, Jian; Xu, Zongben

2015-01-01

An extreme learning machine (ELM) can be regarded as a two-stage feed-forward neural network (FNN) learning system that randomly assigns the connections with and within hidden neurons in the first stage and tunes the connections with output neurons in the second stage. Therefore, ELM training is essentially a linear learning problem, which significantly reduces the computational burden. Numerous applications show that such a computation burden reduction does not degrade the generalization capability. It has, however, been open that whether this is true in theory. The aim of this paper is to study the theoretical feasibility of ELM by analyzing the pros and cons of ELM. In the previous part of this topic, we pointed out that via appropriately selected activation functions, ELM does not degrade the generalization capability in the sense of expectation. In this paper, we launch the study in a different direction and show that the randomness of ELM also leads to certain negative consequences. On one hand, we find that the randomness causes an additional uncertainty problem of ELM, both in approximation and learning. On the other hand, we theoretically justify that there also exist activation functions such that the corresponding ELM degrades the generalization capability. In particular, we prove that the generalization capability of ELM with Gaussian kernel is essentially worse than that of FNN with Gaussian kernel. To facilitate the use of ELM, we also provide a remedy to such a degradation. We find that the well-developed coefficient regularization technique can essentially improve the generalization capability. The obtained results reveal the essential characteristic of ELM in a certain sense and give theoretical guidance concerning how to use ELM.

Novel Rhizosphere Soil Alleles for the Enzyme 1-Aminocyclopropane-1-Carboxylate Deaminase Queried for Function with an In Vivo Competition Assay

PubMed Central

Jin, Zhao; Di Rienzi, Sara C.; Janzon, Anders; Werner, Jeff J.; Angenent, Largus T.; Dangl, Jeffrey L.; Fowler, Douglas M.

2015-01-01

Metagenomes derived from environmental microbiota encode a vast diversity of protein homologs. How this diversity impacts protein function can be explored through selection assays aimed to optimize function. While artificially generated gene sequence pools are typically used in selection assays, their usage may be limited because of technical or ethical reasons. Here, we investigate an alternative strategy, the use of soil microbial DNA as a starting point. We demonstrate this approach by optimizing the function of a widely occurring soil bacterial enzyme, 1-aminocyclopropane-1-carboxylate (ACC) deaminase. We identified a specific ACC deaminase domain region (ACCD-DR) that, when PCR amplified from the soil, produced a variant pool that we could swap into functional plasmids carrying ACC deaminase-encoding genes. Functional clones of ACC deaminase were selected for in a competition assay based on their capacity to provide nitrogen to Escherichia coli in vitro. The most successful ACCD-DR variants were identified after multiple rounds of selection by sequence analysis. We observed that previously identified essential active-site residues were fixed in the original unselected library and that additional residues went to fixation after selection. We identified a divergent essential residue whose presence hints at the possible use of alternative substrates and a cluster of neutral residues that did not influence ACCD performance. Using an artificial ACCD-DR variant library generated by DNA oligomer synthesis, we validated the same fixation patterns. Our study demonstrates that soil metagenomes are useful starting pools of protein-coding-gene diversity that can be utilized for protein optimization and functional characterization when synthetic libraries are not appropriate. PMID:26637602

Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development.

PubMed

Das, Sujaan; Lemgruber, Leandro; Tay, Chwen L; Baum, Jake; Meissner, Markus

2017-08-15

The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo characterisation during invasion is lacking. Here we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum blood-stage development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion. This study provides important mechanistic insights into the definitive essential functions of PfACT1 in P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins, could also form the basis for the development of novel therapeutics against apicomplexans.

From Green to Blue: Site-Directed Mutagenesis of the Green Fluorescent Protein to Teach Protein Structure-Function Relationships

ERIC Educational Resources Information Center

Giron, Maria D.; Salto, Rafael

2011-01-01

Structure-function relationship studies in proteins are essential in modern Cell Biology. Laboratory exercises that allow students to familiarize themselves with basic mutagenesis techniques are essential in all Genetic Engineering courses to teach the relevance of protein structure. We have implemented a laboratory course based on the…

Marketing audit reveals holes and opportunities.

PubMed

Pearson, E

1990-07-01

The marketing department is an essential function of the hospital. But do you know if your marketing efforts are meeting your institution's objectives? An audit of the department is as essential as any other part of the marketing plan. The author tells you "how" and "why" you should seek the services of an auditor to examine your marketing function.

Current perspectives of CASA applications in diverse mammalian spermatozoa.

PubMed

van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

2018-03-26

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

Science of active galactic nuclei with the GTC and CanariCam

NASA Astrophysics Data System (ADS)

Levenson, Nancy A.; Packham, Christopher C.; Alonso-Herrero, Almudena; Aretxaga, Itziar; Colina, Luis; Díaz-Santos, Tanio; Elitzur, Moshe; Mason, Rachel E.; Perlman, Eric S.; Radomski, James T.; Roche, Patrick F.; Rodríguez Espinosa, José Miguel; Young, Stuart; Telesco, Charles M.

2008-07-01

CanariCam is the facility mid-infrared (MIR) instrument for the Gran Telescopio Canarias (GTC), a 10.4m telescope at the Observatorio del Roque de los Muchachos on La Palma. One of the science drivers for CanariCam is the study of active galactic nuclei (AGN). We will exploit the instrument's high sensitivity in imaging, spectroscopy, and polarimetry modes to answer fundamental questions of AGN and their host galaxies. Dust in the nucleus of an active galaxy reprocesses the intrinsic radiation of the central engine to emerge in the MIR. Current work demonstrates that the hot dust immediately associated with the AGN, which blocks direct views of the AGN from some lines of sight, is confined to small (parsec) scales. Thus, high spatial resolution is essential to probe the "torus" of unified AGN models separate from the host galaxy. CanariCam provides a 0.08" pixel scale for Nyquist sampling the diffraction-limited point spread function at 8μm, and narrow (0.2") spectroscopy slits (with R=120-1300). New observations with the GTC/CanariCam will provide key constraints on the physical conditions in the clumpy torus, and we will sensitively determine AGN obscuration as a function of nuclear activity. We will therefore address the fueling process and its relationship to the torus, the interaction with the host galaxy, and dust chemistry. These data will be essential preparation for the next generation of telescopes that will observe the distant universe directly to explore galaxy and black hole formation and evolution, and the GTC/CanariCam system uniquely provides multiple modes to probe AGN.

Functional analysis of UMOD gene and its effect on inflammatory cytokines in serum of essential hypertension patients.

PubMed

Jian, Liguo; Fa, Xian'en; Zhou, Zheng; Liu, Shichao

2015-01-01

The study aimed to investigate the function of uromodulin (UMOD) gene and its effect on inflammatory cytokines in serum of essential hypertension patients. The online database and software of computer were used for bioinformatics analysis on UMOD gene as well as the structure and function of its encoding proteins. Moreover, radioimmunoassay and enzyme linked immunosorbent assay was adopted to validate the content of urine UMOD protein of essential hypertension patients and their serum inflammatory cytokines. As an alkaline and hydrophilic protein, UMOD has no transmembrane region, but it does have a signal peptide sequence. It is mainly located extracellularly, belonging to a secreted protein, whose secondary structure was based mainly on Random coil which account for 58.44%. According to function prediction, it is found that the UMOD protein has stress response which may be participate in the inflammatory reaction. It has been observed from the experiment which was designed on the basis of the correlation between inflammation reaction and essential hypertension that the content of urine UMOD protein of essential hypertension patients who is in stage I was (28.71 ± 10.53) mg/24 h and when compared with the control group's content (30.15 ± 14.10 mg/24 h), the difference was not obviously; The content of urine UMOD protein of essential hypertension patients who's in stage II and III was (18.24 ± 6.12) mg/24 h and (9.43 ± 3.16) mg/24 h, respectively, which were obviously lower than that of the control group (P<0.01). Additionally, the serum inflammatory cytokines, such as TNF-α, IL-6 and IL1-α content of essential hypertension patients were all markedly higher than that of control group (P<0.05). For essential hypertension patients, there's a close relationship between the expression level of UMOD gene and inflammatory cytokines, which were manifested as the negative correlation between the level of the gene's expression and inflammatory cytokines. That has certain reference value to realize the targeted treatment for essential hypertension through regulated blood pressure conversely in the view of expression level of inflammatory cytokines.

Model systems: how chemical biologists study RNA

PubMed Central

Rios, Andro C.; Tor, Yitzhak

2009-01-01

Ribonucleic acids are structurally and functionally sophisticated biomolecules and the use of models, frequently truncated or modified sequences representing functional domains of the natural systems, is essential to their exploration. Functional non-coding RNAs such as miRNAs, riboswitches, and, in particular, ribozymes, have changed the view of RNA’s role in biology and its catalytic potential. The well-known truncated hammerhead model has recently been refined and new data provide a clearer molecular picture of the elements responsible for its catalytic power. A model for the spliceosome, a massive and highly intricate ribonucleoprotein, is also emerging, although its true utility is yet to be cemented. Such catalytic model systems could also serve as “chemo-paleontological” tools, further refining the RNA world hypothesis and its relevance to the origin and evolution of life. PMID:19879179

The role of TREX in gene expression and disease

PubMed Central

Heath, Catherine G.; Viphakone, Nicolas; Wilson, Stuart A.

2016-01-01

TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident. A complete elucidation of the composition, function and interactions of the complex will provide the framework for understanding the molecular basis for a variety of diseases. This review details the known composition of TREX, how it is regulated and its cellular functions with an emphasis on mammalian systems. PMID:27679854

Four Common Simplifications of Multi-Criteria Decision Analysis do not hold for River Rehabilitation

PubMed Central

2016-01-01

River rehabilitation aims at alleviating negative effects of human impacts such as loss of biodiversity and reduction of ecosystem services. Such interventions entail difficult trade-offs between different ecological and often socio-economic objectives. Multi-Criteria Decision Analysis (MCDA) is a very suitable approach that helps assessing the current ecological state and prioritizing river rehabilitation measures in a standardized way, based on stakeholder or expert preferences. Applications of MCDA in river rehabilitation projects are often simplified, i.e. using a limited number of objectives and indicators, assuming linear value functions, aggregating individual indicator assessments additively, and/or assuming risk neutrality of experts. Here, we demonstrate an implementation of MCDA expert preference assessments to river rehabilitation and provide ample material for other applications. To test whether the above simplifications reflect common expert opinion, we carried out very detailed interviews with five river ecologists and a hydraulic engineer. We defined essential objectives and measurable quality indicators (attributes), elicited the experts´ preferences for objectives on a standardized scale (value functions) and their risk attitude, and identified suitable aggregation methods. The experts recommended an extensive objectives hierarchy including between 54 and 93 essential objectives and between 37 to 61 essential attributes. For 81% of these, they defined non-linear value functions and in 76% recommended multiplicative aggregation. The experts were risk averse or risk prone (but never risk neutral), depending on the current ecological state of the river, and the experts´ personal importance of objectives. We conclude that the four commonly applied simplifications clearly do not reflect the opinion of river rehabilitation experts. The optimal level of model complexity, however, remains highly case-study specific depending on data and resource availability, the context, and the complexity of the decision problem. PMID:26954353

Functional Promoter Polymorphisms Govern Differential Expression of HMG-CoA Reductase Gene in Mouse Models of Essential Hypertension

PubMed Central

Sonawane, Parshuram J.; Sahu, Bhavani S.; Sasi, Binu K.; Geedi, Parimala; Lenka, Govinda; Mahapatra, Nitish R.

2011-01-01

3-Hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase gene (Hmgcr) is a susceptibility gene for essential hypertension. Sequencing of the Hmgcr locus in genetically hypertensive BPH (blood pressure high), genetically hypotensive BPL (blood pressure low) and genetically normotensive BPN (blood pressure normal) mice yielded a number of single nucleotide polymorphisms (SNPs). BPH/BPL/BPN Hmgcr promoter-luciferase reporter constructs were generated and transfected into liver HepG2, ovarian CHO, kidney HEK-293 and neuronal N2A cells for functional characterization of the promoter SNPs. The BPH-Hmgcr promoter showed significantly less activity than the BPL-Hmgcr promoter under basal as well as nicotine/cholesterol-treated conditions. This finding was consistent with lower endogenous Hmgcr expression in liver and lower plasma cholesterol in BPH mice. Transfection experiments using 5′-promoter deletion constructs (strategically made to assess the functional significance of each promoter SNP) and computational analysis predicted lower binding affinities of transcription factors c-Fos, n-Myc and Max with the BPH-promoter as compared to the BPL-promoter. Corroboratively, the BPH promoter-luciferase reporter construct co-transfected with expression plasmids of these transcription factors displayed less pronounced augmentation of luciferase activity than the BPL construct, particularly at lower amounts of transcription factor plasmids. Electrophoretic mobility shift assays also showed diminished interactions of the BPH promoter with HepG2 nuclear proteins. Taken together, this study provides mechanistic basis for the differential Hmgcr expression in these mouse models of human essential hypertension and have implications for better understanding the role of this gene in regulation of blood pressure. PMID:21304971

Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology.

PubMed

Ishikawa, Yuichi; Maeda, Manami; Pasham, Mithun; Aguet, Francois; Tacheva-Grigorova, Silvia K; Masuda, Takeshi; Yi, Hai; Lee, Sung-Uk; Xu, Jian; Teruya-Feldstein, Julie; Ericsson, Maria; Mullally, Ann; Heuser, John; Kirchhausen, Tom; Maeda, Takahiro

2015-04-01

Clathrin-dependent endocytosis is an essential cellular process shared by all cell types. Despite this, precisely how endocytosis is regulated in a cell-type-specific manner and how this key pathway functions physiologically or pathophysiologically remain largely unknown. PICALM, which encodes the clathrin adaptor protein PICALM, was originally identified as a component of the CALM/AF10 leukemia oncogene. Here we show, by employing a series of conditional Picalm knockout mice, that PICALM critically regulates transferrin uptake in erythroid cells by functioning as a cell-type-specific regulator of transferrin receptor endocytosis. While transferrin receptor is essential for the development of all hematopoietic lineages, Picalm was dispensable for myeloid and B-lymphoid development. Furthermore, global Picalm inactivation in adult mice did not cause gross defects in mouse fitness, except for anemia and a coat color change. Freeze-etch electron microscopy of primary erythroblasts and live-cell imaging of murine embryonic fibroblasts revealed that Picalm function is required for efficient clathrin coat maturation. We showed that the PICALM PIP2 binding domain is necessary for transferrin receptor endocytosis in erythroblasts and absolutely essential for erythroid development from mouse hematopoietic stem/progenitor cells in an erythroid culture system. We further showed that Picalm deletion entirely abrogated the disease phenotype in a Jak2(V617F) knock-in murine model of polycythemia vera. Our findings provide new insights into the regulation of cell-type-specific transferrin receptor endocytosis in vivo. They also suggest a new strategy to block cellular uptake of transferrin-bound iron, with therapeutic potential for disorders characterized by inappropriate red blood cell production, such as polycythemia vera. Copyright© Ferrata Storti Foundation.

Smooth Muscle Cell Genome Browser: Enabling the Identification of Novel Serum Response Factor Target Genes

PubMed Central

Lee, Moon Young; Park, Chanjae; Berent, Robyn M.; Park, Paul J.; Fuchs, Robert; Syn, Hannah; Chin, Albert; Townsend, Jared; Benson, Craig C.; Redelman, Doug; Shen, Tsai-wei; Park, Jong Kun; Miano, Joseph M.; Sanders, Kenton M.; Ro, Seungil

2015-01-01

Genome-scale expression data on the absolute numbers of gene isoforms offers essential clues in cellular functions and biological processes. Smooth muscle cells (SMCs) perform a unique contractile function through expression of specific genes controlled by serum response factor (SRF), a transcription factor that binds to DNA sites known as the CArG boxes. To identify SRF-regulated genes specifically expressed in SMCs, we isolated SMC populations from mouse small intestine and colon, obtained their transcriptomes, and constructed an interactive SMC genome and CArGome browser. To our knowledge, this is the first online resource that provides a comprehensive library of all genetic transcripts expressed in primary SMCs. The browser also serves as the first genome-wide map of SRF binding sites. The browser analysis revealed novel SMC-specific transcriptional variants and SRF target genes, which provided new and unique insights into the cellular and biological functions of the cells in gastrointestinal (GI) physiology. The SRF target genes in SMCs, which were discovered in silico, were confirmed by proteomic analysis of SMC-specific Srf knockout mice. Our genome browser offers a new perspective into the alternative expression of genes in the context of SRF binding sites in SMCs and provides a valuable reference for future functional studies. PMID:26241044

Infrastructural challenges to better health in maternity facilities in rural Kenya: community and healthworker perceptions.

PubMed

Essendi, Hildah; Johnson, Fiifi Amoako; Madise, Nyovani; Matthews, Zoe; Falkingham, Jane; Bahaj, Abubakr S; James, Patrick; Blunden, Luke

2015-11-09

The efforts and commitments to accelerate progress towards the Millennium Development Goals for maternal and newborn health (MDGs 4 and 5) in low and middle income countries have focused primarily on providing key medical interventions at maternity facilities to save the lives of women at the time of childbirth, as well as their babies. However, in most rural communities in sub-Saharan, access to maternal and newborn care services is still limited and even where services are available they often lack the infrastructural prerequisites to function at the very basic level in providing essential routine health care services, let alone emergency care. Lists of essential interventions for normal and complicated childbirth, do not take into account these prerequisites, thus the needs of most health facilities in rural communities are ignored, although there is enough evidence that maternal and newborn deaths continue to remain unacceptably high in these areas. This study uses data gathered through qualitative interviews in Kitonyoni and Mwania sub-locations of Makueni County in Eastern Kenya to understand community and provider perceptions of the obstacles faced in providing and accessing maternal and newborn care at health facilities in their localities. The study finds that the community perceives various challenges, most of which are infrastructural, including lack of electricity, water and poor roads that adversely impact the provision and access to essential life-saving maternal and newborn care services in the two sub-locations. The findings and recommendations from this study are important for the attention of policy makers and programme managers in order to improve the state of lower-tier health facilities serving rural communities and to strengthen infrastructure with the aim of making basic routine and emergency obstetric and newborn care services more accessible.

DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

PubMed

Mistry, Divya; Wise, Roger P; Dickerson, Julie A

2017-01-01

Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be obtained from git.io/diffslcpy. The R implementation and code to reproduce the analysis is available via git.io/diffslc.

Molecular basis of essential amino acid transport from studies of insect nutrient amino acid transporters of the SLC6 family (NAT-SLC6)

PubMed Central

Boudko, Dmitri Y.

2012-01-01

Two protein families that represent major components of essential amino acid transport in insects have been identified. They are annotated as the SLC6 and SLC7 families of transporters according to phylogenetic proximity to characterized amino acid transporters (HUGO nomenclature). Members of these families have been identified as important apical and basolateral parts of transepithelial essential amino acid absorption in the metazoan alimentary canal. Synergistically, they play critical physiological roles as essential substrate providers to diverse metabolic processes, including generic protein synthesis. This review briefly clarifies the requirements for amino acid transport and a variety of amino acid transport mechanisms, including the aforementioned families. Further it focuses on the large group of Nutrient Amino acid Transporters (NATs), which comprise a recently identified subfamily of the Neurotransmitter Sodium Symporter family (NSS or SLC6). The first insect NAT, cloned from the caterpillar gut, has a broad substrate spectrum similar to mammalian B0 transporters. Several new NAT-SLC6 members have been characterized in an effort to explore mechanisms for the essential amino acid absorption in model dipteran insects. The identification and functional characterization of new B0-like and narrow specificity transporters of essential amino acids in fruit fly and mosquitoes leads to a fundamentally important insight: that NATs evolved and act together as the integrated active core of a transport network that mediates active alimentary absorption and systemic distribution of essential amino acids. This role of NATs is projected from the most primitive prokaryotes to the most complex metazoan organisms, and represents an interesting platform for unraveling the molecular evolution of amino acid transport and modeling amino acid transport disorders. The comparative study of NATs elucidates important adaptive differences between essential amino acid transportomes of invertebrate and vertebrate organisms, outlining a new possibility for selective targeting of essential amino acid absorption mechanisms to control medically and economically important arthropods and other invertebrate organisms. PMID:22230793

Combining functional and structural genomics to sample the essential Burkholderia structome.

PubMed

Baugh, Loren; Gallagher, Larry A; Patrapuvich, Rapatbhorn; Clifton, Matthew C; Gardberg, Anna S; Edwards, Thomas E; Armour, Brianna; Begley, Darren W; Dieterich, Shellie H; Dranow, David M; Abendroth, Jan; Fairman, James W; Fox, David; Staker, Bart L; Phan, Isabelle; Gillespie, Angela; Choi, Ryan; Nakazawa-Hewitt, Steve; Nguyen, Mary Trang; Napuli, Alberto; Barrett, Lynn; Buchko, Garry W; Stacy, Robin; Myler, Peter J; Stewart, Lance J; Manoil, Colin; Van Voorhis, Wesley C

2013-01-01

The genus Burkholderia includes pathogenic gram-negative bacteria that cause melioidosis, glanders, and pulmonary infections of patients with cancer and cystic fibrosis. Drug resistance has made development of new antimicrobials critical. Many approaches to discovering new antimicrobials, such as structure-based drug design and whole cell phenotypic screens followed by lead refinement, require high-resolution structures of proteins essential to the parasite. We experimentally identified 406 putative essential genes in B. thailandensis, a low-virulence species phylogenetically similar to B. pseudomallei, the causative agent of melioidosis, using saturation-level transposon mutagenesis and next-generation sequencing (Tn-seq). We selected 315 protein products of these genes based on structure-determination criteria, such as excluding very large and/or integral membrane proteins, and entered them into the Seattle Structural Genomics Center for Infection Disease (SSGCID) structure determination pipeline. To maximize structural coverage of these targets, we applied an "ortholog rescue" strategy for those producing insoluble or difficult to crystallize proteins, resulting in the addition of 387 orthologs (or paralogs) from seven other Burkholderia species into the SSGCID pipeline. This structural genomics approach yielded structures from 31 putative essential targets from B. thailandensis, and 25 orthologs from other Burkholderia species, yielding an overall structural coverage for 49 of the 406 essential gene families, with a total of 88 depositions into the Protein Data Bank. Of these, 25 proteins have properties of a potential antimicrobial drug target i.e., no close human homolog, part of an essential metabolic pathway, and a deep binding pocket. We describe the structures of several potential drug targets in detail. This collection of structures, solubility and experimental essentiality data provides a resource for development of drugs against infections and diseases caused by Burkholderia. All expression clones and proteins created in this study are freely available by request.

System control of an autonomous planetary mobile spacecraft

NASA Technical Reports Server (NTRS)

Dias, William C.; Zimmerman, Barbara A.

1990-01-01

The goal is to suggest the scheduling and control functions necessary for accomplishing mission objectives of a fairly autonomous interplanetary mobile spacecraft, while maximizing reliability. Goals are to provide an extensible, reliable system conservative in its use of on-board resources, while getting full value from subsystem autonomy, and avoiding the lure of ground micromanagement. A functional layout consisting of four basic elements is proposed: GROUND and SYSTEM EXECUTIVE system functions and RESOURCE CONTROL and ACTIVITY MANAGER subsystem functions. The system executive includes six subfunctions: SYSTEM MANAGER, SYSTEM FAULT PROTECTION, PLANNER, SCHEDULE ADAPTER, EVENT MONITOR and RESOURCE MONITOR. The full configuration is needed for autonomous operation on Moon or Mars, whereas a reduced version without the planning, schedule adaption and event monitoring functions could be appropriate for lower-autonomy use on the Moon. An implementation concept is suggested which is conservative in use of system resources and consists of modules combined with a network communications fabric. A language concept termed a scheduling calculus for rapidly performing essential on-board schedule adaption functions is introduced.

Decoupled form and function in disparate herbivorous dinosaur clades

NASA Astrophysics Data System (ADS)

Lautenschlager, Stephan; Brassey, Charlotte A.; Button, David J.; Barrett, Paul M.

2016-05-01

Convergent evolution, the acquisition of morphologically similar traits in unrelated taxa due to similar functional demands or environmental factors, is a common phenomenon in the animal kingdom. Consequently, the occurrence of similar form is used routinely to address fundamental questions in morphofunctional research and to infer function in fossils. However, such qualitative assessments can be misleading and it is essential to test form/function relationships quantitatively. The parallel occurrence of a suite of morphologically convergent craniodental characteristics in three herbivorous, phylogenetically disparate dinosaur clades (Sauropodomorpha, Ornithischia, Theropoda) provides an ideal test case. A combination of computational biomechanical models (Finite Element Analysis, Multibody Dynamics Analysis) demonstrate that despite a high degree of morphological similarity between representative taxa (Plateosaurus engelhardti, Stegosaurus stenops, Erlikosaurus andrewsi) from these clades, their biomechanical behaviours are notably different and difficult to predict on the basis of form alone. These functional differences likely reflect dietary specialisations, demonstrating the value of quantitative biomechanical approaches when evaluating form/function relationships in extinct taxa.

Decoupled form and function in disparate herbivorous dinosaur clades.

PubMed

Lautenschlager, Stephan; Brassey, Charlotte A; Button, David J; Barrett, Paul M

2016-05-20

Convergent evolution, the acquisition of morphologically similar traits in unrelated taxa due to similar functional demands or environmental factors, is a common phenomenon in the animal kingdom. Consequently, the occurrence of similar form is used routinely to address fundamental questions in morphofunctional research and to infer function in fossils. However, such qualitative assessments can be misleading and it is essential to test form/function relationships quantitatively. The parallel occurrence of a suite of morphologically convergent craniodental characteristics in three herbivorous, phylogenetically disparate dinosaur clades (Sauropodomorpha, Ornithischia, Theropoda) provides an ideal test case. A combination of computational biomechanical models (Finite Element Analysis, Multibody Dynamics Analysis) demonstrate that despite a high degree of morphological similarity between representative taxa (Plateosaurus engelhardti, Stegosaurus stenops, Erlikosaurus andrewsi) from these clades, their biomechanical behaviours are notably different and difficult to predict on the basis of form alone. These functional differences likely reflect dietary specialisations, demonstrating the value of quantitative biomechanical approaches when evaluating form/function relationships in extinct taxa.

Micronutrients in parenteral nutrition: boron, silicon, and fluoride.

PubMed

Nielsen, Forrest H

2009-11-01

Boron may be beneficial for bone growth and maintenance, central nervous system function, and the inflammatory response, and silicon may be beneficial for bone maintenance and wound healing. Fluoride is not an essential element but amounts provided by contamination may be beneficial for bone strength. Fluoride toxicity may be a concern in parenteral nutrition. Further studies are warranted to determine whether there are optimal amounts of boron and silicon that should be delivered to typical and special population patients receiving parenteral nutrition. In addition, further studies are needed to determine whether providing the dietary guideline of adequate intake amounts of fluoride parenterally would prevent or treat parenteral nutrition osteopenia.

Understanding the medical markers of elder abuse and neglect: physical examination findings.

PubMed

Gibbs, Lisa M

2014-11-01

A specific foundation of knowledge is important for evaluating potential abuse from physical findings in the older adult. The standard physical examination is a foundation for detecting many types of abuse. An understanding of traumatic injuries, including patterns of injury, is important for health care providers, and inclusion of elder abuse in the differential diagnosis of patient care is essential. One must possess the skills needed to piece the history, including functional capabilities, and physical findings together. Armed with this skill set, health care providers will develop the confidence needed to identify and intervene in cases of elder abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Adolescent substance involvement use and abuse.

PubMed

Monasterio, Erica B

2014-09-01

Substance use in adolescence is common, but not all use indicates a substance use disorder. The primary care provider has an essential role in screening for substance involvement, assessing the level of substance use and its impact on function, and engaging in a brief intervention to encourage and support behavioral change related to substance use. This article summarizes the literature on adolescent vulnerability to substance use disorders and their impact on adolescent health and well-being. Practical concrete suggestions for approaches to screening, brief interventions, and referral to treatment provide a stepwise approach to adolescent substance use assessment and intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Principles of management of growth plate fractures in the foot and ankle.

PubMed

Dayton, Paul; Feilmeier, Mindi; Coleman, Nathan

2013-10-01

Providers treating pediatric injuries must understand the properties of the pediatric skeleton and be sensitive to the psychological and social expectations of patients and their families. Immediate needs must be addressed, and the long-term prognosis must be explained. Detailed understanding of fracture mechanism and fracture patterns is essential for diagnosis and treatment. The provider must remain vigilant for changes in the osseous and soft tissue structures during treatment. Failure to recognize signs of growth interruption and changes in position may lead to functional abnormalities. This article presents an overview of pediatric growth plate injury management. Copyright © 2013 Elsevier Inc. All rights reserved.

Soil Science and Global Issues

NASA Astrophysics Data System (ADS)

Lal, Rattan

2015-04-01

Sustainable management of soil is integral to any rational approach to addressing global issues of the 21st century. A high quality soil is essential to: i) advancing food and nutritional security, ii) mitigating and adapting to climate change, iii) improving quality and renewability of water, iv) enriching biodiversity, v) producing biofuel feedstocks for reducing dependence on fossil fuel, and vi) providing cultural, aesthetical and recreational opportunities. Being the essence of all terrestrial life, soil functions and ecosystem services are essential to wellbeing of all species of plants and animals. Yet, soil resources are finite, unequally distributed geographically, and vulnerable to degradation by natural and anthropogenic perturbations. Nonetheless, soil has inherent resilience, and its ecosystem functions and services can be restored over time. However, soil resilience depends on several key soil properties including soil organic carbon (SOC) concentration and pool, plant-available water capacity (PWAC), nutrient reserves, effective rooting depth, texture and clay mineralogy, pH, cation exchange capacity (CEC) etc. There is a close inter-dependence among these properties. For example, SOC concentration strongly affects, PWAC, nutrient reserve, activity and species diversity of soil flora and fauna, CEC etc. Thus, judicious management of SOC concentration to maintain it above the threshold level (~1.5-2%) in the root zone is critical to sustaining essential functions and ecosystem services. Yet, soils of some agroecosystems (e.g., those managed by resources-poor farmers and small landholders in the tropics and sub-tropics) are severely depleted of their SOC reserves. Consequently. Agronomic productivity and wellbeing of people dependent on degraded soils is jeopardized. The ecosystem C pool of the terrestrial biosphere has been mined by extractive practices, the nature demands recarbonization of its biosphere for maintenance of its functions and resilience. Commemorating 2015 IYS is timely to create awareness among policy makers and general public that soil should never be taken for granted.

Three friendly walkers

NASA Astrophysics Data System (ADS)

Jensen, Iwan

2017-01-01

More than 15 years ago Guttmann and Vöge (2002 J. Stat. Plan. Inference 101 107), introduced a model of friendly walkers. Since then it has remained unsolved. In this paper we provide the exact solution to a closely allied model which essentially only differs in the boundary conditions. The exact solution is expressed in terms of the reciprocal of the generating function for vicious walkers which is a D-finite function. However, ratios of D-finite functions are inherently not D-finite and in this case we prove that the friendly walkers generating function is the solution to a non-linear differential equation with polynomial coefficients, it is in other words D-algebraic. We find using numerically exact calculations a conjectured expression for the generating function of the original model as a ratio of a D-finite function and the generating function for vicious walkers. We obtain an expression for this D-finite function in terms of a {{}2}{{F}1} hypergeometric function with a rational pullback and its first and second derivatives. Dedicated to Tony Guttmann on the occasion of his 70th birthday.

An introduction to NMR-based approaches for measuring protein dynamics

PubMed Central

Kleckner, Ian R; Foster, Mark P

2010-01-01

Proteins are inherently flexible at ambient temperature. At equilibrium, they are characterized by a set of conformations that undergo continuous exchange within a hierarchy of spatial and temporal scales ranging from nanometers to micrometers and femtoseconds to hours. Dynamic properties of proteins are essential for describing the structural bases of their biological functions including catalysis, binding, regulation and cellular structure. Nuclear magnetic resonance (NMR) spectroscopy represents a powerful technique for measuring these essential features of proteins. Here we provide an introduction to NMR-based approaches for studying protein dynamics, highlighting eight distinct methods with recent examples, contextualized within a common experimental and analytical framework. The selected methods are (1) Real-time NMR, (2) Exchange spectroscopy, (3) Lineshape analysis, (4) CPMG relaxation dispersion, (5) Rotating frame relaxation dispersion, (6) Nuclear spin relaxation, (7) Residual dipolar coupling, (8) Paramagnetic relaxation enhancement. PMID:21059410

QUANTITATIVE MAGNETIC RESONANCE IMAGING OF ARTICULAR CARTILAGE AND ITS CLINICAL APPLICATIONS

PubMed Central

Li, Xiaojuan; Majumdar, Sharmila

2013-01-01

Cartilage is one of the most essential tissues for healthy joint function and is compromised in degenerative and traumatic joint diseases. There have been tremendous advances during the past decade using quantitative MRI techniques as a non-invasive tool for evaluating cartilage, with a focus on assessing cartilage degeneration during osteoarthritis (OA). In this review, after a brief overview of cartilage composition and degeneration, we discuss techniques that grade and quantify morphologic changes as well as the techniques that quantify changes in the extracellular matrix. The basic principles, in vivo applications, advantages and challenges for each technique are discussed. Recent studies using the OA Initiative (OAI) data are also summarized. Quantitative MRI provides non-invasive measures of cartilage degeneration at the earliest stages of joint degeneration, which is essential for efforts towards prevention and early intervention in OA. PMID:24115571

Construction of a minimal genome as a chassis for synthetic biology.

PubMed

Sung, Bong Hyun; Choe, Donghui; Kim, Sun Chang; Cho, Byung-Kwan

2016-11-30

Microbial diversity and complexity pose challenges in understanding the voluminous genetic information produced from whole-genome sequences, bioinformatics and high-throughput '-omics' research. These challenges can be overcome by a core blueprint of a genome drawn with a minimal gene set, which is essential for life. Systems biology and large-scale gene inactivation studies have estimated the number of essential genes to be ∼300-500 in many microbial genomes. On the basis of the essential gene set information, minimal-genome strains have been generated using sophisticated genome engineering techniques, such as genome reduction and chemical genome synthesis. Current size-reduced genomes are not perfect minimal genomes, but chemically synthesized genomes have just been constructed. Some minimal genomes provide various desirable functions for bioindustry, such as improved genome stability, increased transformation efficacy and improved production of biomaterials. The minimal genome as a chassis genome for synthetic biology can be used to construct custom-designed genomes for various practical and industrial applications. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures.

PubMed

Fekany, K; Yamanaka, Y; Leung, T; Sirotkin, H I; Topczewski, J; Gates, M A; Hibi, M; Renucci, A; Stemple, D; Radbill, A; Schier, A F; Driever, W; Hirano, T; Talbot, W S; Solnica-Krezel, L

1999-04-01

The dorsal gastrula organizer plays a fundamental role in establishment of the vertebrate axis. We demonstrate that the zebrafish bozozok (boz) locus is required at the blastula stages for formation of the embryonic shield, the equivalent of the gastrula organizer and expression of multiple organizer-specific genes. Furthermore, boz is essential for specification of dorsoanterior embryonic structures, including notochord, prechordal mesendoderm, floor plate and forebrain. We report that boz mutations disrupt the homeobox gene dharma. Overexpression of boz in the extraembryonic yolk syncytial layer of boz mutant embryos is sufficient for normal development of the overlying blastoderm, revealing an involvement of extraembryonic structures in anterior patterning in fish similarly to murine embryos. Epistatic analyses indicate that boz acts downstream of beta-catenin and upstream to TGF-beta signaling or in a parallel pathway. These studies provide genetic evidence for an essential function of a homeodomain protein in beta-catenin-mediated induction of the dorsal gastrula organizer and place boz at the top of a hierarchy of zygotic genes specifying the dorsal midline of a vertebrate embryo.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

PubMed

Bedell, Victoria M; Person, Anthony D; Larson, Jon D; McLoon, Anna; Balciunas, Darius; Clark, Karl J; Neff, Kevin I; Nelson, Katie E; Bill, Brent R; Schimmenti, Lisa A; Beiraghi, Soraya; Ekker, Stephen C

2012-02-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress–response pathway

PubMed Central

Skarie, Jonathan M.; Link, Brian A.

2008-01-01

Primary open-angle glaucoma (POAG) is a genetically complex neuropathy that affects retinal ganglion cells and is a leading cause of blindness worldwide. WDR36, a gene of unknown function, was recently identified as causative for POAG at locus GLC1G. Subsequent studies found disease-associated variants in control populations, leaving the role of WDR36 in this disease unclear. To address this issue, we determined the function of WDR36. We studied Wdr36 in zebrafish and found it is the functional homolog of yeast Utp21. Utp21 is cell essential and functions in the nucleolar processing of 18S rRNA, which is required for ribosome biogenesis. Evidence for functional homology comes from sequence alignment, ubiquitous expression, sub-cellular localization to the nucleolus and loss-of-function phenotypes that include defects in 18S rRNA processing and abnormal nucleolar morphology. Additionally, we show that loss of Wdr36 function leads to an activation of the p53 stress–response pathway, suggesting that co-inheritance of defects in p53 pathway genes may influence the impact of WDR36 variants on POAG. Although these results overall do not provide evidence for or against a role of WDR36 in POAG, they do provide important baseline information for future studies. PMID:18469340

Taurine in pediatric nutrition: review and update.

PubMed

Gaull, G E

1989-03-01

Taurine was long considered an end product of the metabolism of the sulfur-containing amino acids, methionine and cyst(e)ine. Its only clearly recognized biochemical role had been as a substrate in the conjugation of bile acids. Taurine is found free in millimolar concentrations in animal tissues, particularly those that are excitable, rich in membranes, and generate oxidants. Various lines of evidence suggest one major nutritional role as protecting cell membranes by attenuating toxic substances and/or by acting as an osmoregulator. The totality of evidence suggests that taurine is nonessential in the rodent, it is an essential amino acid in the cat, and it is conditionally essential in man and monkey. Absence from the diet of a conditionally essential nutrient does not produce immediate deficiency disease but, in the long term, can cause problems. Taurine is now added to many infant formulas as a measure of prudence to provide improved nourishment with the same margin of safety for its newly identified physiologic functions as that found in human milk. Such supplementation can be justified by the finding of improved fat absorption in preterm infants and in children with cystic fibrosis, as well as by salutary effects on auditory brainstem-evoked responses in preterm infants. Experimental findings in animal models and in human cell models provide further justification for taurine supplementation of infant formulas.

Placing a Disrupted Degradation Motif at the C Terminus of Proteasome Substrates Attenuates Degradation without Impairing Ubiquitylation*

PubMed Central

Alfassy, Omri S.; Cohen, Itamar; Reiss, Yuval; Tirosh, Boaz; Ravid, Tommer

2013-01-01

Protein elimination by the ubiquitin-proteasome system requires the presence of a cis-acting degradation signal. Efforts to discern degradation signals of misfolded proteasome substrates thus far revealed a general mechanism whereby the exposure of cryptic hydrophobic motifs provides a degradation determinant. We have previously characterized such a determinant, employing the yeast kinetochore protein Ndc10 as a model substrate. Ndc10 is essentially a stable protein that is rapidly degraded upon exposure of a hydrophobic motif located at the C-terminal region. The degradation motif comprises two distinct and essential elements: DegA, encompassing two amphipathic helices, and DegB, a hydrophobic sequence within the loosely structured C-terminal tail of Ndc10. Here we show that the hydrophobic nature of DegB is irrelevant for the ubiquitylation of substrates containing the Ndc10 degradation motif, but is essential for proteasomal degradation. Mutant DegB, in which the hydrophobic sequence was disrupted, acted as a dominant degradation inhibitory element when expressed at the C-terminal regions of ubiquitin-dependent and -independent substrates of the 26S proteasome. This mutant stabilized substrates in both yeast and mammalian cells, indicative of a modular recognition moiety. The dominant function of the mutant DegB provides a powerful experimental tool for evaluating the physiological implications of stabilization of specific proteasome substrates in intact cells and for studying the associated pathological effects. PMID:23519465

Validation of Essential Acoustic Parameters for Highly Urgent In-Vehicle Collision Warnings.

PubMed

Lewis, Bridget A; Eisert, Jesse L; Baldwin, Carryl L

2018-03-01

Objective The aim of this study was to validate the importance of key acoustic criteria for use as in-vehicle forward collision warning (FCW) systems. Background Despite recent advances in vehicle safety, automobile crashes remain one of the leading causes of death. As automation allows for more control of noncritical functions by the vehicle, the potential for disengagement and distraction from the driving task also increases. It is, therefore, as important as ever that in-vehicle safety-critical interfaces are intuitive and unambiguous, promoting effective collision avoidance responses upon first exposure even under divided-attention conditions. Method The current study used a driving simulator to assess the effectiveness of two warnings, one that met all essential acoustic parameters, one that met only some essential parameters, and a no-warning control in the context of a lead vehicle-following task in conjunction with a cognitive distractor task and collision event. Results Participants receiving an FCW comprising five essential acoustic components had improved collision avoidance responses relative to a no-warning condition and an FCW missing essential elements on their first exposure. Responses to a consistently good warning (GMU Prime) improved with subsequent exposures, whereas continued exposure to the less optimal FCW (GMU Sub-Prime) resulted in poorer performance even relative to receiving no warning at all. Conclusions This study provides support for previous warning design studies and for the validity of five key acoustic parameters essential for the design of effective in-vehicle FCWs. Application Results from this study have implications for the design of auditory FCWs and in-vehicle display design.

Essential oil variation in wild populations of Artemisia saharae (Asteraceae) from Tunisia: chemical composition, antibacterial and antioxidant properties.

PubMed

Zouari, Sami; Ayadi, Imen; Fakhfakh, Nahed; Jdir, Hamida; Aloui, Latifa; Kossentini, Mohamed; Rebai, Ahmed; Zouari, Nacim

2014-12-01

Artemisia saharae Pomel is a new taxon of Artemisia herba-alba Asso (Asteraceae) which is endemic to Tunisia and Algeria. This shrub, commonly known as white wormwood or desert wormwood, is largely used in folk medicine and as a culinary herb. The bulks aromatic plants come from wild populations whose essential oils compositions as well as their biological properties are severely affected by several factors such as geographic conditions. Therefore, the aim of the present work is to provide more information about the influence of altitude variation on the essential oil composition, antimicrobial and antioxidant properties of Artemisia saharae growing wild in the same geographical area. Essential oils were extracted by hydrodistillation of leaves and flowers of the plant collected from seven different altitudes of the Baten Zamour region (southwest of Tunisia). The highest essential oil yields (2.70-2.80%) were obtained for populations of high altitudes. Seventy-five compounds, representing 92.78 to 96.95% of the total essential oils, were separated and identified. Essential oils were characterized by very high percentage of oxygenated monoterpenes (52.1-72.6%) which constituted the predominant class. From the analyzed populations, the major compounds (>7%) were α-thujone, β-thujone, chrysanthenone, camphor, chrysanthenyl acetate, and sabinyl acetate. Sabinyl acetate which was detected in some populations at relatively high percentages (7.7-10.8%) seems to be characteristic to Southern Tunisian A. saharae. The studied essential oil showed a chemical diversity depending on the population altitude as revealed by linear discriminant and cluster analyses. Three population groups associated with altitudinal levels were distinguished. It is worthy to note that the most discriminating compounds of chemical groups were the minor ones. Despite the high variation of essential oil compositions, the high altitude population did not affect severely the antibacterial activity against the most tested strains. Altitude seems to be an important factor influencing the yield and the chemical profile of Artemisia saharae essential oils. Knowledge of the chemical composition of essential oils in relation to environmental factors is a very important quality criterion for their marketing and contributes to their valorization as functional ingredient in food technology.

Convergent functional genomics of psychiatric disorders.

PubMed

Niculescu, Alexander B

2013-10-01

Genetic and gene expression studies, in humans and animal models of psychiatric and other medical disorders, are becoming increasingly integrated. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit-to-disease way of extracting reproducible and biologically important signal, in contrast to the fit-to-cohort effect and limited reproducibility of human genetic analyses alone. With the advent of whole-genome sequencing and the realization that a major portion of the non-coding genome may contain regulatory variants, Convergent Functional Genomics (CFG) approaches are going to be essential to identify disease-relevant signal from the tremendous polymorphic variation present in the general population. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer, cardiovascular diseases, and diabetes. © 2013 Wiley Periodicals, Inc.

Nanoprocess and nanoscale surface functionalization on cathode materials for advanced lithium-ion batteries.

PubMed

Alaboina, Pankaj Kumar; Uddin, Md-Jamal; Cho, Sung-Jin

2017-10-26

Nanotechnology-driven development of cathode materials is an essential part to revolutionize the evolution of the next generation lithium ion batteries. With the progress of nanoprocess and nanoscale surface modification investigations on cathode materials in recent years, the advanced battery technology future seems very promising - Thanks to nanotechnology. In this review, an overview of promising nanoscale surface deposition methods and their significance in surface functionalization on cathodes is extensively summarized. Surface modified cathodes are provided with a protective layer to overcome the electrochemical performance limitations related to side reactions with electrolytes, reduce self-discharge reactions, improve thermal and structural stability, and further enhance the overall battery performance. The review addresses the importance of nanoscale surface modification on battery cathodes and concludes with a comparison of the different nanoprocess techniques discussed to provide a direction in the race to build advanced lithium-ion batteries.

Role of calcium permeable channels in dendritic cell migration.

PubMed

Sáez, Pablo J; Sáez, Juan C; Lennon-Duménil, Ana-María; Vargas, Pablo

2018-06-01

Calcium ion (Ca 2+ ) is an essential second messenger involved in multiple cellular and subcellular processes. Ca 2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca 2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca 2+ stores, channels and upstream signals involved in this process. Here, we focus on dendritic cells (DCs), because their immune sentinel function heavily relies on their capacity to migrate within tissues and later on between tissues and lymphoid organs. Deciphering the mechanisms by which cytoplasmic Ca 2+ regulate DC migration should shed light on their role in initiating and tuning immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Roles of insulin-like growth factors in metamorphic development of turbot (Scophthalmus maximus).

PubMed

Jia, Yudong

2018-01-31

Larval turbot (Scophthalmus maximus) undergo metamorphosis, a late post-embryonic developmental event that precedes juvenile transition. Insulin-like growth factors (IGFs) are important endocrine/autocrine/paracrine factors that provide essential signals to control of the embryonic and postnatal development of vertebrate species, including fish. Accumulating evidence suggests that IGFs are involved in regulating the metamorphic development of flatfish. This mini review focus on the functions of all known IGFs (IGF-I and IGF-II) during the metamorphic development of turbot. Information about IGFs and insulin-like growth factors binding proteins (IGFBPs) from other teleosts is also included in this review to provide an overview of IGFs functions in the metamorphic development of turbot. These findings may enhance our understanding of the potential roles of the IGFs system in controlling of flatfish metamorphosis and contributing to the improvement of broodstock management strategies for larval turbot. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

PubMed

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Bacteria-bacteria interactions within the microbiota of the ancestral metazoan Hydra contribute to fungal resistance.

PubMed

Fraune, Sebastian; Anton-Erxleben, Friederike; Augustin, René; Franzenburg, Sören; Knop, Mirjam; Schröder, Katja; Willoweit-Ohl, Doris; Bosch, Thomas C G

2015-07-01

Epithelial surfaces of most animals are colonized by diverse microbial communities. Although it is generally agreed that commensal bacteria can serve beneficial functions, the processes involved are poorly understood. Here we report that in the basal metazoan Hydra, ectodermal epithelial cells are covered with a multilayered glycocalyx that provides a habitat for a distinctive microbial community. Removing this epithelial microbiota results in lethal infection by the filamentous fungus Fusarium sp. Restoring the complex microbiota in gnotobiotic polyps prevents pathogen infection. Although mono-associations with distinct members of the microbiota fail to provide full protection, additive and synergistic interactions of commensal bacteria are contributing to full fungal resistance. Our results highlight the importance of resident microbiota diversity as a protective factor against pathogen infections. Besides revealing insights into the in vivo function of commensal microbes in Hydra, our findings indicate that interactions among commensal bacteria are essential to inhibit pathogen infection.

Bacteria–bacteria interactions within the microbiota of the ancestral metazoan Hydra contribute to fungal resistance

PubMed Central

Fraune, Sebastian; Anton-Erxleben, Friederike; Augustin, René; Franzenburg, Sören; Knop, Mirjam; Schröder, Katja; Willoweit-Ohl, Doris; Bosch, Thomas CG

2015-01-01

Epithelial surfaces of most animals are colonized by diverse microbial communities. Although it is generally agreed that commensal bacteria can serve beneficial functions, the processes involved are poorly understood. Here we report that in the basal metazoan Hydra, ectodermal epithelial cells are covered with a multilayered glycocalyx that provides a habitat for a distinctive microbial community. Removing this epithelial microbiota results in lethal infection by the filamentous fungus Fusarium sp. Restoring the complex microbiota in gnotobiotic polyps prevents pathogen infection. Although mono-associations with distinct members of the microbiota fail to provide full protection, additive and synergistic interactions of commensal bacteria are contributing to full fungal resistance. Our results highlight the importance of resident microbiota diversity as a protective factor against pathogen infections. Besides revealing insights into the in vivo function of commensal microbes in Hydra, our findings indicate that interactions among commensal bacteria are essential to inhibit pathogen infection. PMID:25514534

HIV/AIDS case management tasks and activities: the results of a functional analysis study.

PubMed

Grube, B; Chernesky, R H

2001-01-01

Functional analysis, a variation of the time study technique, was used to examine how HIV/AIDS case managers in the tri-county region of New York State spend their time-the actual tasks and activities they choose to perform relative to the total universe of activities and tasks subsumed in the general category of case management. The picture developed was of a system operating primarily in a crisis mode, spending relatively brief amounts of time completing a range of activities and providing an extensive scope of services for or on behalf of clients. The bulk of the work was client centered, not administrative, and involved providing disease management and essential services (e.g., family and mental health). The implications of these findings are discussed, with particular attention paid to the potential influence of client profiles and worker demographics.

Cognitive impairment and pragmatics.

PubMed

Gutiérrez-Rexach, Javier; Schatz, Sara

2016-01-01

One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

Determination of the protease cleavage site repertoire—The RNase H but not the RT domain is essential for foamy viral protease activity

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

Spannaus, Ralf; Bodem, Jochen, E-mail: Jochen.Bodem@vim.uni-wuerzburg.de

2014-04-15

In contrast to orthoretroviruses, the foamy virus protease is only active as a protease-reverse transcriptase fusion protein and requires viral RNA for activation. Maturation of foamy viral proteins seems to be restricted to a single cleavage site in Gag and Pol. We provide evidence that unprocessed Gag is required for optimal infectivity, which is unique among retroviruses. Analyses of the cleavage site sequences of the Gag and Pol cleavage sites revealed a high similarity compared to those of Lentiviruses. We show that positions P2' and P2 are invariant and that Gag and Pol cleavage sites are processed with similar efficiencies.more » The RNase H domain is essential for protease activity, but can functionally be substituted by RNase H domains of other retroviruses. Thus, the RNase H domain might be involved in the stabilization of the protease dimer, while the RT domain is essential for RNA dependent protease activation. - Highlights: • Unprocessed Gag is required for optimal infectivity of foamy viruses. • Positions P2 and P2' are invariant in the foamy viral cleavage sites. • The RNaseH domain is essential for protease activity. • The RNaseH domains of other retroviruses support foamy viral protease activity.« less

Response variance in functional maps: neural darwinism revisited.

PubMed

Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

2013-01-01

The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

Response Variance in Functional Maps: Neural Darwinism Revisited

PubMed Central

Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

2013-01-01

The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population. PMID:23874733

Collaboration among eldercare workers: barriers, facilitators and supporting processes.

PubMed

Jakobsen, Louise M; Albertsen, Karen; Jorgensen, Anette F B; Greiner, Birgit A; Rugulies, Reiner

2018-05-03

To retain qualified care workers and to ensure high-quality care for residents in eldercare homes, well-functioning collaboration among care workers is pivotal. This study aims to identify barriers and facilitators of collaboration among eldercare workers and to describe the processes leading to well-functioning collaboration. We collected focus group data from 33 eldercare workers from seven Danish eldercare homes. We found that collaboration was hampered by a number of formal and informal divisions among care workers. To ensure well-functioning collaboration, social and professional relations among care workers needed to be dealt with actively by care workers and by managers. The analysis showed that managers are essential for creating a well-functioning framework around the collaboration between care workers by providing guidelines and procedures for working across various divisions, by being attentive to care workers and taking decisive action when needed and by dealing with conflicts in the workgroups. © 2018 Nordic College of Caring Science.

Functional Foods and Nutraceuticals as Dietary Intervention in Chronic Diseases; Novel Perspectives for Health Promotion and Disease Prevention.

PubMed

Adefegha, Stephen Adeniyi

2017-12-27

Functional foods describe the importance of foods in promoting health and preventing diseases aside their primary role of providing the body with the required amount of essential nutrients such as proteins, carbohydrates, vitamins, fats, and oils needed for its healthy survival. This review explains the interaction of functional food bioactive compounds including polyphenols (phenolic acids [hydroxybenzoic acids and hydroxycinnamic acids], flavonoids [flavonols, flavones, flavanols, flavanones, isoflavones, proanthocyanidins], stilbenes, and lignans), terpenoids, carotenoids, alkaloids, omega-3 and polyunsaturated fatty acids, among others with critical enzymes (α- amylase, α- glucosidase, angiotensin-I converting enzyme [ACE], acetylcholinesterase [AChE], and arginase) linked to some degenerative diseases (type-2 diabetes, cardiovascular diseases [hypertension], neurodegenerative diseases [Alzheimer's disease] and erectile dysfunction). Different functional food bioactive compounds may synergistically/additively confer an overwhelming protection against these degenerative diseases by modulating/altering the activities of these critical enzymes of physiological importance.

A Study of Shared-Memory Mutual Exclusion Protocols Using CADP

NASA Astrophysics Data System (ADS)

Mateescu, Radu; Serwe, Wendelin

Mutual exclusion protocols are an essential building block of concurrent systems: indeed, such a protocol is required whenever a shared resource has to be protected against concurrent non-atomic accesses. Hence, many variants of mutual exclusion protocols exist in the shared-memory setting, such as Peterson's or Dekker's well-known protocols. Although the functional correctness of these protocols has been studied extensively, relatively little attention has been paid to their non-functional aspects, such as their performance in the long run. In this paper, we report on experiments with the performance evaluation of mutual exclusion protocols using Interactive Markov Chains. Steady-state analysis provides an additional criterion for comparing protocols, which complements the verification of their functional properties. We also carefully re-examined the functional properties, whose accurate formulation as temporal logic formulas in the action-based setting turns out to be quite involved.

Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros

PubMed Central

Uckun, Fatih M.; Ma, Hong; Zhang, Jian; Ozer, Zahide; Dovat, Sinisa; Mao, Cheney; Ishkhanian, Rita; Goodman, Patricia; Qazi, Sanjive

2012-01-01

Ikaros is a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis through transcriptional regulation of the earliest stages of lymphocyte ontogeny and differentiation. Functional deficiency of Ikaros has been implicated in the pathogenesis of acute lymphoblastic leukemia, the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros activity is considered of paramount importance, but the operative molecular mechanisms responsible for its regulation remain largely unknown. Here we provide multifaceted genetic and biochemical evidence for a previously unknown function of spleen tyrosine kinase (SYK) as a partner and posttranslational regulator of Ikaros. We demonstrate that SYK phoshorylates Ikaros at unique C-terminal serine phosphorylation sites S358 and S361, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Mechanistically, we establish that SYK-induced Ikaros activation is essential for its nuclear localization and optimal transcription factor function. PMID:23071339

The Role of Echocardiography in Coronary Artery Disease and Acute Myocardial Infarction

PubMed Central

Esmaeilzadeh, Maryam; Parsaee, Mozhgan; Maleki, Majid

2013-01-01

Echocardiography is a non-invasive diagnostic technique which provides information regarding cardiac function and hemodynamics. It is the most frequently used cardiovascular diagnostic test after electrocardiography and chest X-ray. However, in a patient with acute chest pain, Transthoracic Echocardiography is essential both for diagnosing acute coronary syndrome, zeroing on the evaluation of ventricular function and the presence of regional wall motion abnormalities, and for ruling out other etiologies of acute chest pain or dyspnea, including aortic dissection and pericardial effusion. Echocardiography is a versatile imaging modality for the management of patients with chest pain and assessment of left ventricular systolic function, diastolic function, and even myocardial and coronary perfusion and is, therefore, useful in the diagnosis and triage of patients with acute chest pain or dyspnea. This review has focused on the current applications of echocardiography in patients with coronary artery disease and myocardial infarction. PMID:23646042

Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules

NASA Astrophysics Data System (ADS)

Sun, Xixi; Lee, Hyelee; Lee, Sunggi; Tan, Kian L.

2013-09-01

Carbohydrates and natural products serve essential roles in nature, and also provide core scaffolds for pharmaceutical agents and vaccines. However, the inherent complexity of these molecules imposes significant synthetic hurdles for their selective functionalization and derivatization. Nature has, in part, addressed these issues by employing enzymes that are able to orient and activate substrates within a chiral pocket, which increases dramatically both the rate and selectivity of organic transformations. In this article we show that similar proximity effects can be utilized in the context of synthetic catalysts to achieve general and predictable site-selective functionalization of complex molecules. Unlike enzymes, our catalysts apply a single reversible covalent bond to recognize and bind to specific functional group displays within substrates. By combining this unique binding selectivity and asymmetric catalysis, we are able to modify the less reactive axial positions within monosaccharides and natural products.

A computational prediction of structure and function of novel homologue of Arabidopsis thaliana Vps51/Vps67 subunit in Corchorus olitorius.

PubMed

Zaman, Aubhishek; Fancy, Nurun Nahar

2012-12-01

Vps mediated vesicular transport is important for transferring macromolecules trapped inside a vesicle. Although highly abundant, Vps shows tremendous sequence variation among diverse array of species. However, this difference in sequence, which seems to also translate into substantial functional variation, is hardly characterized in Corchorus spp. Here, our computational study investigates structural and functional features of one of the Vps subunit namely Vps51/Vps67 in C. olitorius. Broad scale structural characterization revealed novel information about the overall Vps structure and binding sites. Moreover, functional analyses indicate interaction partners which were unexplored to date. Since membrane trafficking is essentially associated with nutrient uptake and chemical de-toxification, characterization of the Vps subunit can well provide us with better insight into important agronomic traits such as stress response, immune response and phytoremediation capacity.

Stem cells and bone diseases: new tools, new perspective

PubMed Central

Riminucci, Mara; Remoli, Cristina; Robey, Pamela G.; Bianco, Paolo

2017-01-01

Postnatal skeletal stem cells are a unique class of progenitors with biological properties that extend well beyond the limits of stemness as commonly defined. Skeletal stem cells sustain skeletal tissue homeostasis, organize and maintain the complex architectural structure of the bone marrow microenvironment and provide a niche for hematopoietic progenitor cells. The identification of stem cells in the human post-natal skeleton has profoundly changed our approach to the physiology and pathology of this system. Skeletal diseases have been long interpreted essentially in terms of defective function of differentiated cells and/or abnormal turnover of the matrix they produce. The notion of a skeletal stem cell has brought forth multiple, novel concepts in skeletal biology that provide potential alternative concepts. At the same time, the recognition of the complex functions played by skeletal progenitors, such as the structural and functional organization of the bone marrow, has provided an innovative, unifying perspective for understanding bone and bone marrow changes simultaneously occurring in many disorders. Finally, the possibility to isolate and highly enrich for skeletal progenitors, enables us to reproduce perfectly normal or pathological organ miniatures. These, in turn, provide suitable models to investigate and manipulate the pathogenetic mechanisms of many genetic and non-genetic skeletal diseases. PMID:25240458

Microbial avirulence determinants: guided missiles or antigenic flak?

PubMed

Skamnioti, Paraskevi; Ridout, Christopher J

2005-09-01

SUMMARY Avirulence (avr) determinants are incompatibility factors which elicit host plant defence responses in a gene-for-gene manner. They are produced by fungi, bacteria and viruses, and their recognition by resistance genes has been extensively studied for decades. But why should a microbe keep a molecule that allows it to be recognized? One argument is that avr genes perform some essential function and must be kept despite giving the pathogen away. Many bacterial avr determinants have been shown to be effectors, which contribute to virulence and aggressiveness. If this were always the case, mutants lacking these essential molecules would be at a serious disadvantage. Some disadvantage has been shown for a small number, but for the majority there is no effect on virulence. This has been explained by functional redundancy for bacterial and fungal avr determinants, with other molecules compensating for the deletion of these essential genes. However, this argument is counter-intuitive because by definition these individual genes are no longer essential; so why keep them? With increasing numbers of avr genes being identified, efforts to elucidate their function are increasing. In this review, we take stock of the accumulating literature, and consider what the real function of avr determinants might be.

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

PubMed Central

Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.

2017-01-01

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719

Development of the Digestive System-Experimental Challenges and Approaches of Infant Lipid Digestion.

PubMed

Abrahamse, Evan; Minekus, Mans; van Aken, George A; van de Heijning, Bert; Knol, Jan; Bartke, Nana; Oozeer, Raish; van der Beek, Eline M; Ludwig, Thomas

2012-12-01

At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the nervous and digestive systems, depends fundamentally on these. Epidemiological data suggest that human milk provides unique health benefits during early infancy that extend to long-lasting benefits. Preclinical findings show that qualitative changes in dietary lipids, i.e., lipid structure and FA composition, during early life may contribute to the reported long-term effects. Little is known in this respect about the development of digestive function and the digestion and absorption of lipids by the newborn. This review gives a detailed overview of the distinct functionalities that dietary lipids from human milk and infant formula provide and the profound differences in the physiology and biochemistry of lipid digestion between infants and adults. Fundamental mechanisms of infant lipid digestion can, however, almost exclusively be elucidated in vitro. Experimental approaches and their challenges are reviewed in depth.

Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions.

PubMed

Delaforge, Elise; Milles, Sigrid; Huang, Jie-Rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J; Blackledge, Martin

2016-01-01

Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales.

Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions

PubMed Central

Delaforge, Elise; Milles, Sigrid; Huang, Jie-rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J.; Blackledge, Martin

2016-01-01

Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales. PMID:27679800

FOXP3 and GARP (LRRC32): the master and its minion.

PubMed

Probst-Kepper, Michael; Buer, Jan

2010-02-05

The transcription factor FOXP3 is essential for the development and function of CD4+CD25hiFOXP3+ regulatory T (T(reg)) cells, but also expressed in activated human helper T cells without acquisition of a regulatory phenotype. This comment focuses on glycoprotein-A repetitions predominant (GARP or LRRC32) recently identified as specific marker of activated human T(reg) cells, which may provide the missing link toward a better molecular definition of the regulatory phenotype.

Dual Causality and the Autonomy of Biology.

PubMed

Bock, Walter J

2017-03-01

Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

Pondering the Pulvinar.

PubMed

Lakatos, Peter; O'Connell, Monica N; Barczak, Annamaria

2016-01-06

While the function of the pulvinar remains one of the least explored among the thalamic nuclei despite occupying the most thalamic volume in primates, it has long been suspected to play a crucial role in attentive stimulus processing. In this issue of Neuron, Zhou et al. (2016) use simultaneous pulvinar-visual cortex recordings and pulvinar inactivation to provide evidence that the pulvinar is essential for intact stimulus processing, maintenance of neuronal oscillatory dynamics, and mediating the effects of attention. Copyright © 2016 Elsevier Inc. All rights reserved.

Boron in plants: deficiency and toxicity.

PubMed

Camacho-Cristóbal, Juan J; Rexach, Jesús; González-Fontes, Agustín

2008-10-01

Boron (B) is an essential nutrient for normal growth of higher plants, and B availability in soil and irrigation water is an important determinant of agricultural production. To date, a primordial function of B is undoubtedly its structural role in the cell wall; however, there is increasing evidence for a possible role of B in other processes such as the maintenance of plasma membrane function and several metabolic pathways. In recent years, the knowledge of the molecular basis of B deficiency and toxicity responses in plants has advanced greatly. The aim of this review is to provide an update on recent findings related to these topics, which can contribute to a better understanding of the role of B in plants.

The Age-ility Project (Phase 1): Structural and functional imaging and electrophysiological data repository.

PubMed

Karayanidis, Frini; Keuken, Max C; Wong, Aaron; Rennie, Jaime L; de Hollander, Gilles; Cooper, Patrick S; Ross Fulham, W; Lenroot, Rhoshel; Parsons, Mark; Phillips, Natalie; Michie, Patricia T; Forstmann, Birte U

2016-01-01

Our understanding of the complex interplay between structural and functional organisation of brain networks is being advanced by the development of novel multi-modal analyses approaches. The Age-ility Project (Phase 1) data repository offers open access to structural MRI, diffusion MRI, and resting-state fMRI scans, as well as resting-state EEG recorded from the same community participants (n=131, 15-35 y, 66 male). Raw imaging and electrophysiological data as well as essential demographics are made available via the NITRC website. All data have been reviewed for artifacts using a rigorous quality control protocol and detailed case notes are provided. Copyright © 2015. Published by Elsevier Inc.

A sarcoidosis clinician's perspective of MHC functional elements outside the antigen binding site.

PubMed

Judson, Marc A

2018-05-30

Sarcoidosis is a multisystem granulomatous disease of unknown cause. Evidence supports an integral role for interactions at the MHC binding site in the development of sarcoidosis. However, despite this evidence, there are clinical data that suggest that additional mechanisms are involved in the immunopathogenesis of this disease. This manuscript provides a brief clinical description of sarcoidosis, and a clinician's perspective of the immunopathogenesis of sarcoidosis in terms of the MHC binding site, MHC functional elements beyond the binding site, and other possible alternative mechanisms. Input from clinicians will be essential in establishing the immunologic cause of sarcoidosis as a detailed phenotypic characterization of disease will be required. Copyright © 2018. Published by Elsevier Inc.

Designing Biomimetic Materials from Marine Organisms.

PubMed

Nichols, William T

2015-01-01

Two biomimetic design approaches that apply biological solutions to engineering problems are discussed. In the first case, motivation comes from an engineering problem and the key challenge is to find analogous biological functions and map them into engineering materials. We illustrate with an example of water pollution remediation through appropriate design of a biomimetic sponge. In the second case, a biological function is already known and the challenge is to identify the appropriate engineering problem. We demonstrate the biological approach with marine diatoms that control energy and materials at their surface providing inspiration for a number of engineering applications. In both cases, it is essential to select materials and structures at the nanoscale to control energy and materials flows at interfaces.

The business management preceptorship within the nurse practitioner program.

PubMed

Wing, D M

1998-01-01

Changes in health care reimbursement practices have affected the way in which primary health care is provided. To be successful, nurse practitioners must have a proficient understanding of basic business functions, including accounting, finance, economics, marketing, and reimbursement practices. Yet, many graduates of nurse practitioner programs are not adequately prepared to make fundamental business decisions. Therefore, it is essential that nurse practitioner faculty provide learning experiences on primary practice business. Because the preceptor experience is an integral aspect of nurse practitioner education, a business preceptorship provides students with pragmatic knowledge of the clinical practice within a business framework. The University of Indianapolis School of Nursing offers a nurse practitioner business preceptorship. The implementation, challenges, and positive outcomes of the course are discussed in this article.

Delay effects in the human sensory system during balancing.

PubMed

Stepan, Gabor

2009-03-28

Mechanical models of human self-balancing often use the Newtonian equations of inverted pendula. While these mathematical models are precise enough on the mechanical side, the ways humans balance themselves are still quite unexplored on the control side. Time delays in the sensory and motoric neural pathways give essential limitations to the stabilization of the human body as a multiple inverted pendulum. The sensory systems supporting each other provide the necessary signals for these control tasks; but the more complicated the system is, the larger delay is introduced. Human ageing as well as our actual physical and mental state affects the time delays in the neural system, and the mechanical structure of the human body also changes in a large range during our lives. The human balancing organ, the labyrinth, and the vision system essentially adapted to these relatively large time delays and parameter regions occurring during balancing. The analytical study of the simplified large-scale time-delayed models of balancing provides a Newtonian insight into the functioning of these organs that may also serve as a basis to support theories and hypotheses on balancing and vision.

Measuring nursing essential contributions to quality patient care outcomes.

PubMed

Wolgast, Kelly A; Taylor, Katherine; Garcia, Dawn; Watkins, Miko

2011-01-01

Workload Management System for Nursing (WMSN) is a core Army Medical Department business system that has provided near real-time, comprehensive nursing workload and manpower data for decision making at all levels for over 25 years. The Army Manpower Requirements and Documentation Agency populates data from WMSN into the Manpower Staffing Standards System (Inpatient module within Automated Staffing Assessment Model). The current system, Workload Management System for Nursing Internet (WMSNi), is an interim solution that requires additional functionalities for modernization and integration at the enterprise level. The expanding missions and approved requirements for WMSNi support strategic initiatives on the Army Medical Command balanced scorecard and require continued sustainment for multiple personnel and manpower business processes for both inpatient and outpatient nursing care. This system is currently being leveraged by the TRICARE Management Activity as an interim multiservice solution, and is being used at 24 Army medical treatment facilities. The evidenced-based information provided to Army decision makers through the methods used in the WMSNi will be essential across the Army Medical Command throughout the system's life cycle.

Guidelines for reporting and using prediction tools for genetic variation analysis.

PubMed

Vihinen, Mauno

2013-02-01

Computational prediction methods are widely used for the analysis of human genome sequence variants and their effects on gene/protein function, splice site aberration, pathogenicity, and disease risk. New methods are frequently developed. We believe that guidelines are essential for those writing articles about new prediction methods, as well as for those applying these tools in their research, so that the necessary details are reported. This will enable readers to gain the full picture of technical information, performance, and interpretation of results, and to facilitate comparisons of related methods. Here, we provide instructions on how to describe new methods, report datasets, and assess the performance of predictive tools. We also discuss what details of predictor implementation are essential for authors to understand. Similarly, these guidelines for the use of predictors provide instructions on what needs to be delineated in the text, as well as how researchers can avoid unwarranted conclusions. They are applicable to most prediction methods currently utilized. By applying these guidelines, authors will help reviewers, editors, and readers to more fully comprehend prediction methods and their use. © 2012 Wiley Periodicals, Inc.

Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.

PubMed

Wang, Hao; Mann, Paul A; Xiao, Li; Gill, Charles; Galgoci, Andrew M; Howe, John A; Villafania, Artjohn; Barbieri, Christopher M; Malinverni, Juliana C; Sher, Xinwei; Mayhood, Todd; McCurry, Megan D; Murgolo, Nicholas; Flattery, Amy; Mack, Matthias; Roemer, Terry

2017-05-18

Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. We provide genetic, biophysical, computational, biochemical, and pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is specifically required to develop broad-spectrum Gram-positive antibacterial agents targeting RF metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comprehensively molecular haplotype-resolved genome of a European individual

PubMed Central

Suk, Eun-Kyung; McEwen, Gayle K.; Duitama, Jorge; Nowick, Katja; Schulz, Sabrina; Palczewski, Stefanie; Schreiber, Stefan; Holloway, Dustin T.; McLaughlin, Stephen; Peckham, Heather; Lee, Clarence; Huebsch, Thomas; Hoehe, Margret R.

2011-01-01

Independent determination of both haplotype sequences of an individual genome is essential to relate genetic variation to genome function, phenotype, and disease. To address the importance of phase, we have generated the most complete haplotype-resolved genome to date, “Max Planck One” (MP1), by fosmid pool-based next generation sequencing. Virtually all SNPs (>99%) and 80,000 indels were phased into haploid sequences of up to 6.3 Mb (N50 ∼1 Mb). The completeness of phasing allowed determination of the concrete molecular haplotype pairs for the vast majority of genes (81%) including potential regulatory sequences, of which >90% were found to be constituted by two different molecular forms. A subset of 159 genes with potentially severe mutations in either cis or trans configurations exemplified in particular the role of phase for gene function, disease, and clinical interpretation of personal genomes (e.g., BRCA1). Extended genomic regions harboring manifold combinations of physically and/or functionally related genes and regulatory elements were resolved into their underlying “haploid landscapes,” which may define the functional genome. Moreover, the majority of genes and functional sequences were found to contain individual or rare SNPs, which cannot be phased from population data alone, emphasizing the importance of molecular phasing for characterizing a genome in its molecular individuality. Our work provides the foundation to understand that the distinction of molecular haplotypes is essential to resolve the (inherently individual) biology of genes, genomes, and disease, establishing a reference point for “phase-sensitive” personal genomics. MP1's annotated haploid genomes are available as a public resource. PMID:21813624

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

PubMed

Buijink, A W G; Broersma, M; van der Stouwe, A M M; van Wingen, G A; Groot, P F C; Speelman, J D; Maurits, N M; van Rootselaar, A F

2015-04-01

Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. Copyright © 2015 Elsevier Ltd. 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

Small molecule analysis and imaging of fatty acids in the zebra finch song system using time-of-flight-secondary ion mass spectrometry.

PubMed

Amaya, Kensey R; Sweedler, Jonathan V; Clayton, David F

2011-08-01

Fatty acids are central to brain metabolism and signaling, but their distributions within complex brain circuits have been difficult to study. Here we applied an emerging technique, time-of-flight secondary ion mass spectrometry (ToF-SIMS), to image specific fatty acids in a favorable model system for chemical analyses of brain circuits, the zebra finch (Taeniopygia guttata). The zebra finch, a songbird, produces complex learned vocalizations under the control of an interconnected set of discrete, dedicated brain nuclei 'song nuclei'. Using ToF-SIMS, the major song nuclei were visualized by virtue of differences in their content of essential and non-essential fatty acids. Essential fatty acids (arachidonic acid and docosahexaenoic acid) showed distinctive distributions across the song nuclei, and the 18-carbon fatty acids stearate and oleate discriminated the different core and shell subregions of the lateral magnocellular nucleus of the anterior nidopallium. Principal component analysis of the spectral data set provided further evidence of chemical distinctions between the song nuclei. By analyzing the robust nucleus of the arcopallium at three different ages during juvenile song learning, we obtain the first direct evidence of changes in lipid content that correlate with progression of song learning. The results demonstrate the value of ToF-SIMS to study lipids in a favorable model system for probing the function of lipids in brain organization, development and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

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

In Vivo Studies in Rhodospirillum rubrum Indicate That Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) Catalyzes Two Obligatorily Required and Physiologically Significant Reactions for Distinct Carbon and Sulfur Metabolic Pathways*♦

PubMed Central

Dey, Swati; North, Justin A.; Sriram, Jaya; Evans, Bradley S.; Tabita, F. Robert

2015-01-01

All organisms possess fundamental metabolic pathways to ensure that needed carbon and sulfur compounds are provided to the cell in the proper chemical form and oxidation state. For most organisms capable of using CO2 as sole source of carbon, ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) catalyzes primary carbon dioxide assimilation. In addition, sulfur salvage pathways are necessary to ensure that key sulfur-containing compounds are both available and, where necessary, detoxified in the cell. Using knock-out mutations and metabolomics in the bacterium Rhodospirillum rubrum, we show here that Rubisco concurrently catalyzes key and essential reactions for seemingly unrelated but physiologically essential central carbon and sulfur salvage metabolic pathways of the cell. In this study, complementation and mutagenesis studies indicated that representatives of all known extant functional Rubisco forms found in nature are capable of simultaneously catalyzing reactions required for both CO2-dependent growth as well as growth using 5-methylthioadenosine as sole sulfur source under anaerobic photosynthetic conditions. Moreover, specific inactivation of the CO2 fixation reaction did not affect the ability of Rubisco to support anaerobic 5-methylthioadenosine metabolism, suggesting that the active site of Rubisco has evolved to ensure that this enzyme maintains both key functions. Thus, despite the coevolution of both functions, the active site of this protein may be differentially modified to affect only one of its key functions. PMID:26511314

Are civil-law notaries rent-seeking monopolists or essential market intermediaries? Endogenous development of a property rights institution in Mexico.

PubMed

Monkkonen, Paavo

2016-01-01

As the fourth contribution in the 'Land' section, this paper forms a research 'diptych' with the next paper by Levy. Whereas she focuses on the notarial institution in mid-nineteenth century Mexico, this contribution examines it in a contemporary context. The notary is one of the chief components of property rights protection in civil-law systems, performing various public functions such as writing deeds for real estate property. Yet notaries are considered an 'inefficient' institution by many, due to the perception of rent-seeking behavior enabled by their near-monopoly over validating property rights claims. This study examines notaries in Mexico to unpack the apparent contradiction in the role of notaries in economic development. I use a combination of interviews with notaries and clients, and data on notarial practice and bureaucratic outcomes across the country, to examine notaries' social function. The theoretical lens of endogenous development and institutional functionalism reveals an alternate explanation for their seemingly high-cost services, as well as their role in economic development. Mexican notaries have a dual social function: public representative and private service provider. They perform diverse and essential activities, which in other countries are performed by multiple actors such as real estate agents, escrow offices and title insurance companies. Thus, what is perceived as inefficiency by some can be interpreted as an efficient response to the context in which they operate, and their semi-privatized nature can overcome problems found in other bureaucratic arrangements.

Remote sensing of Essential Biodiversity Variables: new measurements linking ecosystem structure, function and composition

NASA Astrophysics Data System (ADS)

Schimel, D.; Pavlick, R.; Stavros, E. N.; Townsend, P. A.; Ustin, S.; Thompson, D. R.

2017-12-01

Remote sensing can inform a wide variety of essential biodiversity variables, including measurements that define primary productivity, forest structure, biome distribution, plant communities, land use-land cover change and climate drivers of change. Emerging remote sensing technologies can add significantly to remote sensing of EBVs, providing new, large scale insights on plant and habitat diversity itself, as well as causes and consequences of biodiversity change. All current biodiversity assessments identify major data gaps, with insufficient coverage in critical regions, limited observations to monitor change over time, with very limited revisit of sample locations, as well as taxon-specific biased biases. Remote sensing cannot fill many of the gaps in global biodiversity observations, but spectroscopic measurements in terrestrial and marine environments can aid in assessing plant/phytoplankton functional diversity and efficiently reveal patterns in space, as well as changes over time, and, by making use of chlorophyll fluorescence, reveal associated patterns in photosynthesis. LIDAR and RADAR measurements quantify ecosystem structure, and can precisely define changes due to growth, disturbance and land use. Current satellite-based EBVs have taken advantage of the extraordinary time series from LANDSAT and MODIS, but new measurements more directly reveal ecosystem structure, function and composition. We will present results from pre-space airborne studies showing the synergistic ability of a suite of new remote observation techniques to quantify biodiversity and ecosystem function and show how it changes during major disturbance events.

Characterization of motor units in behaving adult mice shows a wide primary range

PubMed Central

Ritter, Laura K.; Tresch, Matthew C.; Heckman, C. J.; Manuel, Marin

2014-01-01

The mouse is essential for genetic studies of motor function in both normal and pathological states. Thus it is important to consider whether the structure of motor output from the mouse is in fact analogous to that recorded in other animals. There is a striking difference in the basic electrical properties of mouse motoneurons compared with those in rats, cats, and humans. The firing evoked by injected currents produces a unique frequency-current (F-I) function that emphasizes recruitment of motor units at their maximum force. These F-I functions, however, were measured in anesthetized preparations that lacked two key components of normal synaptic input: high levels of synaptic noise and neuromodulatory inputs. Recent studies suggest that the alterations in the F-I function due to these two components are essential for recreating firing behavior of motor units in human subjects. In this study we provide the first data on firing patterns of motor units in the awake mouse, focusing on steady output in quiet stance. The resulting firing patterns did not match the predictions from the mouse F-I behaviors but instead revealed rate modulation across a remarkably wide range (10–60 Hz). The low end of the firing range may be due to changes in the F-I relation induced by synaptic noise and neuromodulatory inputs. The high end of the range may indicate that, unlike other species, quiet standing in the mouse involves recruitment of relatively fast-twitch motor units. PMID:24805075

Plants: An International Scientific Open Access Journal to Publish All Facets of Plants, Their Functions and Interactions with the Environment and Other Living Organisms.

PubMed

Fernando, W G Dilantha

2012-02-06

Plants are one of the two major groups of living organisms that are an essential entity to the function of the biosphere. Plants can be found in all known parts of the earth, in all shapes and sizes. They include the green algae, mosses, ferns, vines, grasses, bushes, herbs, flowering plants and trees. Although some plants are parasitic, most produce their own food through photosynthesis. Most plants initiate from a seed. The importance of plants in the food chain dates back to ancient times. The first humans gathered wild plants for food. As settlements developed, food crops were cultivated, leading to selection of high-yielding cultivated varieties to feed the growing populations. Unlike plants, humans and other animals are unable to manufacture their own food. Therefore, they are dependent, directly or indirectly, on plants. Plants are found in natural ecosystems such as rain forests, and also in agricultural areas and urbanized settings. They are an essential part of our daily lives providing food, clean air, and important ecosystem functions. The study of plants and their function could be considered the most complex of interactions. From the time a seed germinates, it goes through a myriad of physiological processes that can be closely studied using modern tools and molecular biological methods. An open access journal such as Plants will give millions of readers access to that information around the world.

Plants: An International Scientific Open Access Journal to Publish All Facets of Plants, Their Functions and Interactions with the Environment and Other Living Organisms

PubMed Central

Fernando, W.G. Dilantha

2012-01-01

Plants are one of the two major groups of living organisms that are an essential entity to the function of the biosphere. Plants can be found in all known parts of the earth, in all shapes and sizes. They include the green algae, mosses, ferns, vines, grasses, bushes, herbs, flowering plants and trees. Although some plants are parasitic, most produce their own food through photosynthesis. Most plants initiate from a seed. The importance of plants in the food chain dates back to ancient times. The first humans gathered wild plants for food. As settlements developed, food crops were cultivated, leading to selection of high-yielding cultivated varieties to feed the growing populations. Unlike plants, humans and other animals are unable to manufacture their own food. Therefore, they are dependent, directly or indirectly, on plants. Plants are found in natural ecosystems such as rain forests, and also in agricultural areas and urbanized settings. They are an essential part of our daily lives providing food, clean air, and important ecosystem functions. The study of plants and their function could be considered the most complex of interactions. From the time a seed germinates, it goes through a myriad of physiological processes that can be closely studied using modern tools and molecular biological methods. An open access journal such as Plants will give millions of readers access to that information around the world. PMID:27137635

Characterization of motor units in behaving adult mice shows a wide primary range.

PubMed

Ritter, Laura K; Tresch, Matthew C; Heckman, C J; Manuel, Marin; Tysseling, Vicki M

2014-08-01

The mouse is essential for genetic studies of motor function in both normal and pathological states. Thus it is important to consider whether the structure of motor output from the mouse is in fact analogous to that recorded in other animals. There is a striking difference in the basic electrical properties of mouse motoneurons compared with those in rats, cats, and humans. The firing evoked by injected currents produces a unique frequency-current (F-I) function that emphasizes recruitment of motor units at their maximum force. These F-I functions, however, were measured in anesthetized preparations that lacked two key components of normal synaptic input: high levels of synaptic noise and neuromodulatory inputs. Recent studies suggest that the alterations in the F-I function due to these two components are essential for recreating firing behavior of motor units in human subjects. In this study we provide the first data on firing patterns of motor units in the awake mouse, focusing on steady output in quiet stance. The resulting firing patterns did not match the predictions from the mouse F-I behaviors but instead revealed rate modulation across a remarkably wide range (10-60 Hz). The low end of the firing range may be due to changes in the F-I relation induced by synaptic noise and neuromodulatory inputs. The high end of the range may indicate that, unlike other species, quiet standing in the mouse involves recruitment of relatively fast-twitch motor units. Copyright © 2014 the American Physiological Society.

Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis

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

Ansong, Charles; Ortega, Corrie; Payne, Samuel H.

The annotation of protein function is almost completely performed by in silico approaches. However, computational prediction of protein function is frequently incomplete and error prone. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins. This lack of functional information severely limits our understanding of Mtb pathogenicity. Current tools for experimental functional annotation are limited and often do not scale to entire protein families. Here, we report a generally applicable chemical biology platform to functionally annotate bacterial proteins by combining activity-based protein profiling (ABPP) and quantitative LC-MS-based proteomics. As an example ofmore » this approach for high-throughput protein functional validation and discovery, we experimentally annotate the families of ATP-binding proteins in Mtb. Our data experimentally validate prior in silico predictions of >250 ATPases and adenosine nucleotide-binding proteins, and reveal 73 hypothetical proteins as novel ATP-binding proteins. We identify adenosine cofactor interactions with many hypothetical proteins containing a diversity of unrelated sequences, providing a new and expanded view of adenosine nucleotide binding in Mtb. Furthermore, many of these hypothetical proteins are both unique to Mycobacteria and essential for infection, suggesting specialized functions in mycobacterial physiology and pathogenicity. Thus, we provide a generally applicable approach for high throughput protein function discovery and validation, and highlight several ways in which application of activity-based proteomics data can improve the quality of functional annotations to facilitate novel biological insights.« less

A dorsolateral prefrontal cortex semi-automatic segmenter

NASA Astrophysics Data System (ADS)

Al-Hakim, Ramsey; Fallon, James; Nain, Delphine; Melonakos, John; Tannenbaum, Allen

2006-03-01

Structural, functional, and clinical studies in schizophrenia have, for several decades, consistently implicated dysfunction of the prefrontal cortex in the etiology of the disease. Functional and structural imaging studies, combined with clinical, psychometric, and genetic analyses in schizophrenia have confirmed the key roles played by the prefrontal cortex and closely linked "prefrontal system" structures such as the striatum, amygdala, mediodorsal thalamus, substantia nigra-ventral tegmental area, and anterior cingulate cortices. The nodal structure of the prefrontal system circuit is the dorsal lateral prefrontal cortex (DLPFC), or Brodmann area 46, which also appears to be the most commonly studied and cited brain area with respect to schizophrenia. 1, 2, 3, 4 In 1986, Weinberger et. al. tied cerebral blood flow in the DLPFC to schizophrenia.1 In 2001, Perlstein et. al. demonstrated that DLPFC activation is essential for working memory tasks commonly deficient in schizophrenia. 2 More recently, groups have linked morphological changes due to gene deletion and increased DLPFC glutamate concentration to schizophrenia. 3, 4 Despite the experimental and clinical focus on the DLPFC in structural and functional imaging, the variability of the location of this area, differences in opinion on exactly what constitutes DLPFC, and inherent difficulties in segmenting this highly convoluted cortical region have contributed to a lack of widely used standards for manual or semi-automated segmentation programs. Given these implications, we developed a semi-automatic tool to segment the DLPFC from brain MRI scans in a reproducible way to conduct further morphological and statistical studies. The segmenter is based on expert neuroanatomist rules (Fallon-Kindermann rules), inspired by cytoarchitectonic data and reconstructions presented by Rajkowska and Goldman-Rakic. 5 It is semi-automated to provide essential user interactivity. We present our results and provide details on our DLPFC open-source tool.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

PubMed

Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

2016-08-01

The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. Copyright © 2016 Herod et al.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

PubMed Central

Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

2016-01-01

ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. PMID:27194768

Debris buster is a Drosophila scavenger receptor essential for airway physiology.

PubMed

Wingen, Almut; Carrera, Pilar; Ekaterini Psathaki, Olympia; Voelzmann, André; Paululat, Achim; Hoch, Michael

2017-10-01

Scavenger receptors class B (SR-B) are multifunctional transmembrane proteins, which in vertebrates participate in lipid transport, pathogen clearance, lysosomal delivery and intracellular sorting. Drosophila has 14 SR-B members whose functions are still largely unknown. Here, we reveal a novel role for the SR-B family member Debris buster (Dsb) in Drosophila airway physiology. Larvae lacking dsb show yeast avoidance behavior, hypoxia, and severe growth defects associated with impaired elongation and integrity along the airways. Furthermore, in dsb mutant embryos, the barrier function of the posterior spiracles, which are critical for gas exchange, is not properly established and liquid clearance is locally impaired at the spiracular lumen. We found that Dsb is specifically expressed in a group of distal epithelial cells of the posterior spiracle organ and not throughout the entire airways. Furthermore, tissue-specific knockdown and rescue experiments demonstrate that Dsb function in the airways is only required in the posterior spiracles. Dsb localizes in intracellular vesicles, and a subset of these associate with lysosomes. However, we found that depletion of proteins involved in vesicular transport to the apical membrane, but not in lysosomal function, causes dsb-like airway elongation defects. We propose a model in which Dsb sorts components of the apical extracellular matrix which are essential for airway physiology. Since SR-B LIMP2-deficient mice show reduced expression of several apical plasma membrane proteins, sorting of proteins to the apical membrane is likely an evolutionary conserved function of Dsb and LIMP2. Our data provide insights into a spatially confined function of the SR-B Dsb in intracellular trafficking critical for the physiology of the whole tubular airway network. Copyright © 2017 Elsevier Inc. All rights reserved.

Physiological roles of taurine in heart and muscle

PubMed Central

2010-01-01

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals. PMID:20804594

Physiological roles of taurine in heart and muscle.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

2010-08-24

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.

Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells.

PubMed

Jaiswal, Alok; Peddinti, Gopal; Akimov, Yevhen; Wennerberg, Krister; Kuznetsov, Sergey; Tang, Jing; Aittokallio, Tero

2017-06-01

Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity. We performed a systematic, quantitative analysis of the consistency between two genome-wide shRNA screens conducted on a compendium of cancer cell lines, and also compared several gene summarization methods for inferring gene essentiality from shRNA level data. We then devised novel concepts of seed essentiality and shRNA family, based on seed region sequences of shRNAs, to study in-depth the contribution of seed-mediated off-target effects to the consistency of the two screens. We further investigated two seed-sequence properties, seed pairing stability, and target abundance in terms of their capability to minimize the off-target effects in post-screening data analysis. Finally, we applied this novel methodology to identify genetic interactions and synthetic lethal partners of cancer drivers, and confirmed differential essentiality phenotypes by detailed CRISPR/Cas9 experiments. Using the novel concepts of seed essentiality and shRNA family, we demonstrate how genome-wide loss-of-function profiling of a common set of cancer cell lines can be actually made fairly reproducible when considering seed-mediated off-target effects. Importantly, by excluding shRNAs having higher propensity for off-target effects, based on their seed-sequence properties, one can remove noise from the genome-wide shRNA datasets. As a translational application case, we demonstrate enhanced reproducibility of genetic interaction partners of common cancer drivers, as well as identify novel synthetic lethal partners of a major oncogenic driver, PIK3CA, supported by a complementary CRISPR/Cas9 experiment. We provide practical guidelines for improved design and analysis of genome-wide loss-of-function profiling and demonstrate how this novel strategy can be applied towards improved mapping of genetic dependencies of cancer cells to aid development of targeted anticancer treatments.

Analysis of essential gene dynamics under antibiotic stress in Streptococcus sanguinis

PubMed Central

El-Rami, Fadi; Kong, Xiangzhen; Parikh, Hardik; Zhu, Bin; Stone, Victoria; Kitten, Todd; Xu, Ping

2018-01-01

The paradoxical response of Streptococcus sanguinis to drugs prescribed for dental and clinical practices has complicated treatment guidelines and raised the need for further investigation. We conducted a high throughput study on concomitant transcriptome and proteome dynamics in a time course to assess S. sanguinis behaviour under a sub-inhibitory concentration of ampicillin. Temporal changes at the transcriptome and proteome level were monitored to cover essential genes and proteins over a physiological map of intricate pathways. Our findings revealed that translation was the functional category in S. sanguinis that was most enriched in essential proteins. Moreover, essential proteins in this category demonstrated the greatest conservation across 2774 bacterial proteomes, in comparison to other essential functional categories like cell wall biosynthesis and energy production. In comparison to non-essential proteins, essential proteins were less likely to contain ‘degradation-prone’ amino acids at their N-terminal position, suggesting a longer half-life. Despite the ampicillin-induced stress, the transcriptional up-regulation of amino acid-tRNA synthetases and proteomic elevation of amino acid biosynthesis enzymes favoured the enriched components of essential proteins revealing ‘proteomic signatures’ that can be used to bridge the genotype–phenotype gap of S. sanguinis under ampicillin stress. Furthermore, we identified a significant correlation between the levels of mRNA and protein for essential genes and detected essential protein-enriched pathways differentially regulated through a persistent stress response pattern at late time points. We propose that the current findings will help characterize a bacterial model to study the dynamics of essential genes and proteins under clinically relevant stress conditions. PMID:29393020

Integrating the Functions of Institutional Research, Institutional Effectiveness, and Information Management. Professional File. Number 126, Summer 2012

ERIC Educational Resources Information Center

Posey, James T.; Pitter, Gita Wijesinghe

2012-01-01

The objective of this paper is to identify common essential information and data needs of colleges and universities and to suggest a model to integrate these data needs into one office or department. The paper suggests there are five major data and information foundations that are essential to the effective functioning of an institution: (a)…

Effects of Functional Oils on Coccidiosis and Apparent Metabolizable Energy in Broiler Chickens

PubMed Central

Murakami, A. E.; Eyng, C.; Torrent, J.

2014-01-01

The objective of the present study was to investigate the effects of a mixture of functional oils (Essential, Oligo Basics Agroind. Ltda) on performance response of chickens challenged with coccidiosis and the determination of apparent metabolizable energy (AME), nitrogen-corrected apparent metabolizable energy (AMEn), the coefficients of protein and ether extract digestibility and intestinal morphology of broilers fed with diets containing Essential. In Exp. 1, a completely randomized design (CRD) was used, with one control diet without Essential inclusion with coccidiosis (Eimeria acervulina, Eimeria maxima, and Eimeria tenella) challenged birds and two different inclusion rates of Essential (1.5 kg/ton and 2 kg/ton) with coccidiosis-challenged and non-challenged birds for each inclusion rate, using 10 replicates and 50 birds per experimental unit. After 7 d of coccidiosis challenge, the livability was approximately 10% lower (p<0.05) for the control group. Intestinal lesion scores were lower (p<0.05) in the anterior intestine and the cecum for the chickens supplemented. Feed efficiency and growth rate were improved in birds supplemented with Essential (p<0.05) before the coccidiosis challenge and during the first 7 d post infection. In Exp. 2, a CRD was used, with one control diet without Essential inclusion and one diet with inclusion of Essential (1.5 kg/ton), using nine replications and 33 chicks per pen. The diets with Essential yielded approximately 4% higher AME (p = 0.003) and AMEn (p = 0.001). Essential supplementation increased villus height in the jejunum on d 14 (p<0.05). Villus height:crypt depth ratio for the supplemented birds was larger (p<0.05) in the jejunum on d 7, larger (p<0.05) in the jejunum and ileum on d 14. In conclusion, these functional oils improved the energy utilization and the livability and decreased lesions caused by coccidiosis in supplemented birds. PMID:25050040

Interactions between late acting proteins required for peptidoglycan synthesis during sporulation

PubMed Central

Fay, Allison; Meyer, Pablo; Dworkin, Jonathan

2010-01-01

The requirement of peptidoglycan synthesis for growth complicates the analysis of interactions between proteins involved in this pathway. In particular, the later steps that involve membrane-linked substrates have proven largely recalcitrant to in vivo analysis. Here we have taken advantage of the peptidoglycan synthesis that occurs during sporulation in Bacillus subtilis to examine the interactions between SpoVE, a non-essential, sporulation-specific homolog of the well-conserved and essential SEDS proteins, and SpoVD, a non-essential class B penicillin binding protein (PBP). We found that localization of SpoVD is dependent on SpoVE and that SpoVD protects SpoVE from in vivo proteolysis. Co-immunoprecipitations and Fluorescence Resonance Energy Transfer experiments indicated that SpoVE and SpoVD interact and co-affinity purification in E. coli demonstrated that this interaction is direct. Finally, we generated a functional protein consisting of a SpoVE-SpoVD fusion and found that a loss-of-function point mutation in either part of the fusion resulted in a loss of function of the entire fusion that was not complemented by a wild type protein. Thus, SpoVE has a direct and functional interaction with SpoVD and this conclusion will facilitate understanding the essential function SpoVE and related SEDS proteins such as FtsW and RodA play in bacterial growth and division. PMID:20417640

On the Singularity Structure of WKB Solution of the Boosted Whittaker Equation: its Relevance to Resurgent Functions with Essential Singularities

NASA Astrophysics Data System (ADS)

Kamimoto, Shingo; Kawai, Takahiro; Koike, Tatsuya

2016-12-01

Inspired by the symbol calculus of linear differential operators of infinite order applied to the Borel transformed WKB solutions of simple-pole type equation [Kamimoto et al. (RIMS Kôkyûroku Bessatsu B 52:127-146, 2014)], which is summarized in Section 1, we introduce in Section 2 the space of simple resurgent functions depending on a parameter with an infra-exponential type growth order, and then we define the assigning operator A which acts on the space and produces resurgent functions with essential singularities. In Section 3, we apply the operator A to the Borel transforms of the Voros coefficient and its exponentiation for the Whittaker equation with a large parameter so that we may find the Borel transforms of the Voros coefficient and its exponentiation for the boosted Whittaker equation with a large parameter. In Section 4, we use these results to find the explicit form of the alien derivatives of the Borel transformed WKB solutions of the boosted Whittaker equation with a large parameter. The results in this paper manifest the importance of resurgent functions with essential singularities in developing the exact WKB analysis, the WKB analysis based on the resurgent function theory. It is also worth emphasizing that the concrete form of essential singularities we encounter is expressed by the linear differential operators of infinite order.

Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

PubMed Central

Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

2014-01-01

Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

Lower bound for LCD image quality

NASA Astrophysics Data System (ADS)

Olson, William P.; Balram, Nikhil

1996-03-01

The paper presents an objective lower bound for the discrimination of patterns and fine detail in images on a monochrome LCD. In applications such as medical imaging and military avionics the information of interest is often at the highest frequencies in the image. Since LCDs are sampled data systems, their output modulation is dependent on the phase between the input signal and the sampling points. This phase dependence becomes particularly significant at high spatial frequencies. In order to use an LCD for applications such as those mentioned above it is essential to have a lower (worst case) bound on the performance of the display. We address this problem by providing a mathematical model for the worst case output modulation of an LCD in response to a sine wave input. This function can be interpreted as a worst case modulation transfer function (MTF). The intersection of the worst case MTF with the contrast threshold function (CTF) of the human visual system defines the highest spatial frequency that will always be detectable. In addition to providing the worst case limiting resolution, this MTF is combined with the CTF to produce objective worst case image quality values using the modulation transfer function area (MTFA) metric.

New Perspectives on the Essential Trace Elements.

ERIC Educational Resources Information Center

Frieden, Earl

1985-01-01

Provides a comprehensive overview of the 19 essential trace elements, examining: the concept of essentiality; evolution of these elements; possible future essential elements; the lanthanides and actinides; how essential trace elements work; the metalloenzymes; the nonmetals; iodine and the thyroid hormones; and antagonism among these elements. (JN)

Hematopoietic tissue repair under chronic low daily dose irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.

The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). In our laboratory we have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d^-1). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific (three major responding subgroups identified) and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup 1), the failure to augment basic repair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments (particularly marked within erythroid compartments) that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccommodated and either prone- or not prone to ML, subgroup 2 & 3) appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high-tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity. The kinetics of these repair-mediated, regenerative hematopoietic responses within the major subgroups are under study and should provide useful insights into the nature of hematopoietic accommodation (or its failure) under greatly extended periods of chronic, low-daily-dose ionizing radiation exposure.

Vav family exchange factors: an integrated regulatory and functional view

PubMed Central

Bustelo, Xosé R

2014-01-01

The Vav family is a group of tyrosine phosphorylation-regulated signal transduction molecules hierarchically located downstream of protein tyrosine kinases. The main function of these proteins is to work as guanosine nucleotide exchange factors (GEFs) for members of the Rho GTPase family. In addition, they can exhibit a variety of catalysis-independent roles in specific signaling contexts. Vav proteins play essential signaling roles for both the development and/or effector functions of a large variety of cell lineages, including those belonging to the immune, nervous, and cardiovascular systems. They also contribute to pathological states such as cancer, immune-related dysfunctions, and atherosclerosis. Here, I will provide an integrated view about the evolution, regulation, and effector properties of these signaling molecules. In addition, I will discuss the pros and cons for their potential consideration as therapeutic targets. PMID:25483299

Epigenetic dysregulation in cognitive disorders.

PubMed

Gräff, Johannes; Mansuy, Isabelle M

2009-07-01

Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.

Dietary Sodium and Health: More Than Just Blood Pressure

PubMed Central

Farquhar, William B.; Edwards, David G.; Jurkovitz, Claudine T.; Weintraub, William S.

2016-01-01

Sodium is essential for cellular homeostasis and physiological function. Excess dietary sodium has been linked to elevations in blood pressure (BP). Salt-sensitivity of BP varies widely, but certain subgroups tend to be more salt-sensitive. The mechanisms underlying sodium-induced increases in BP are not completely understood, but may involve alterations in renal function, fluid volume, fluid regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. Recent pre-clinical and clinical data support that even in the absence of an increase in BP, excess dietary sodium can adversely affect target organs, including the blood vessels, heart, kidneys, and brain. In this review, we address these issues and the epidemiological literature relating dietary sodium to BP and cardiovascular health outcomes, addressing recent controversies. We also provide information and strategies for reducing dietary sodium. PMID:25766952

Non-localization of eigenfunctions for Sturm-Liouville operators and applications

NASA Astrophysics Data System (ADS)

Liard, Thibault; Lissy, Pierre; Privat, Yannick

2018-02-01

In this article, we investigate a non-localization property of the eigenfunctions of Sturm-Liouville operators Aa = -∂xx + a (ṡ) Id with Dirichlet boundary conditions, where a (ṡ) runs over the bounded nonnegative potential functions on the interval (0 , L) with L > 0. More precisely, we address the extremal spectral problem of minimizing the L2-norm of a function e (ṡ) on a measurable subset ω of (0 , L), where e (ṡ) runs over all eigenfunctions of Aa, at the same time with respect to all subsets ω having a prescribed measure and all L∞ potential functions a (ṡ) having a prescribed essentially upper bound. We provide some existence and qualitative properties of the minimizers, as well as precise lower and upper estimates on the optimal value. Several consequences in control and stabilization theory are then highlighted.

EOL-1, the Homolog of the Mammalian Dom3Z, Regulates Olfactory Learning in C. elegans

PubMed Central

Shen, Yu; Zhang, Jiangwen; Calarco, John A.

2014-01-01

Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. PMID:25274815

Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.

PubMed

Chi, Congwu; Zhu, Huanhu; Han, Min; Zhuang, Yuan; Wu, Xiaohui; Xu, Tian

2010-07-09

Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the Ras(V12) cells. Knocking down either of the two other components of the Class C VPS complex, carnation (car) and vps16A, also renders Ras(V12) cells capable for uncontrolled growth and metastatic behavior. Finally, chemical disruption of the lysosomal function by feeding animals with antimalarial drugs, chloroquine or monensin, leads to malignant tumor growth of the Ras(V12) cells. Taken together, our data provide evidence for a causative role of lysosome dysfunction in tumor growth and invasion and indicate that members of the Class C VPS complex behave as tumor suppressors.

Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome.

PubMed

Febo, Marcelo; Blum, Kenneth; Badgaiyan, Rajendra D; Baron, David; Thanos, Panayotis K; Colon-Perez, Luis M; Demortrovics, Zsolt; Gold, Mark S

2017-01-01

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

Charge requirements of lipid II flippase activity in Escherichia coli.

PubMed

Butler, Emily K; Tan, Wee Boon; Joseph, Hildy; Ruiz, Natividad

2014-12-01

Peptidoglycan (PG) is an extracytoplasmic glycopeptide matrix essential for the integrity of the envelope of most bacteria. The PG building block is a disaccharide-pentapeptide that is synthesized as a lipid-linked precursor called lipid II. The translocation of the amphipathic lipid II across the cytoplasmic membrane is required for subsequent incorporation of the disaccharide-pentapeptide into PG. In Escherichia coli, the essential inner membrane protein MurJ is the lipid II flippase. Previous studies showed that 8 charged residues in the central cavity region of MurJ are crucial for function. Here, we completed the functional analysis of all 57 charged residues in MurJ and demonstrated that the respective positive or negative charge of the 8 aforementioned residues is required for proper MurJ function. Loss of the negative charge in one of these residues, D39, causes a severe defect in MurJ biogenesis; by engineering an intragenic suppressor mutation that restores MurJ biogenesis, we found that this charge is also essential for MurJ function. Because of the low level of homology between MurJ and putative orthologs from Gram-positive bacteria, we explored the conservation of these 8 charged residues in YtgP, a homolog from Streptococcus pyogenes. We found that only 3 positive charges are similarly positioned and essential in YtgP; YtgP possesses additional charged residues within its predicted cavity that are essential for function and conserved among Gram-positive bacteria. From these data, we hypothesize that some charged residues in the cavity region of MurJ homologs are required for interaction with lipid II and/or energy coupling during transport. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

[Aromatherapy in nursing practice].

PubMed

Tseng, Yueh-Hsia

2005-08-01

Aromatherapy is the use of essential oils which are distilled from aromatic plants to obtain holistic effects on the mind, body, and spirit. Among nurses, aromatherapy is the second most commonly used complementary therapy. The chemical components of essential oils, such as ketones, aldehydes, and esters, determine the specific effects of the essential oils. Essential oils may be administered by inhalation, bathing, or massage to decrease anxiety, pain, and fatigue, and improve wound healing. As neuronal, liver, and kidney toxicity, as well as skin allergies may occur, it is recommended not to use essential oils on a regular basis. Research has provided evidence on the effects of essential oils, but further research is needed to identify the effects of their interaction with medications, and whether there are any side effects or contraindications. Consequently, it will provide a scientific base on the use of essential oils and enhance the possibilities for the use of essential oils in health care.

Essential equivalence of the general equation for the nonequilibrium reversible-irreversible coupling (GENERIC) and steepest-entropy-ascent models of dissipation for nonequilibrium thermodynamics.

PubMed

Montefusco, Alberto; Consonni, Francesco; Beretta, Gian Paolo

2015-04-01

By reformulating the steepest-entropy-ascent (SEA) dynamical model for nonequilibrium thermodynamics in the mathematical language of differential geometry, we compare it with the primitive formulation of the general equation for the nonequilibrium reversible-irreversible coupling (GENERIC) model and discuss the main technical differences of the two approaches. In both dynamical models the description of dissipation is of the "entropy-gradient" type. SEA focuses only on the dissipative, i.e., entropy generating, component of the time evolution, chooses a sub-Riemannian metric tensor as dissipative structure, and uses the local entropy density field as potential. GENERIC emphasizes the coupling between the dissipative and nondissipative components of the time evolution, chooses two compatible degenerate structures (Poisson and degenerate co-Riemannian), and uses the global energy and entropy functionals as potentials. As an illustration, we rewrite the known GENERIC formulation of the Boltzmann equation in terms of the square root of the distribution function adopted by the SEA formulation. We then provide a formal proof that in more general frameworks, whenever all degeneracies in the GENERIC framework are related to conservation laws, the SEA and GENERIC models of the dissipative component of the dynamics are essentially interchangeable, provided of course they assume the same kinematics. As part of the discussion, we note that equipping the dissipative structure of GENERIC with the Leibniz identity makes it automatically SEA on metric leaves.

Insights into insect wing origin provided by functional analysis of vestigial in the red flour beetle, Tribolium castaneum

PubMed Central

Clark-Hachtel, Courtney M.; Linz, David M.; Tomoyasu, Yoshinori

2013-01-01

Despite accumulating efforts to unveil the origin of insect wings, it remains one of the principal mysteries in evolution. Currently, there are two prominent models regarding insect wing origin: one connecting the origin to the paranotal lobe and the other to the proximodorsal leg branch (exite). However, neither hypothesis has been able to surpass the other. To approach this conundrum, we focused our analysis on vestigial (vg), a critical wing gene initially identified in Drosophila. Our investigation in Tribolium (Coleoptera) has revealed that, despite the well-accepted view of vg as an essential wing gene, there are two groups of vg-dependent tissues in the “wingless” first thoracic segment (T1). We show that one of these tissues, the carinated margin, also depends on other factors essential for wing development (such as Wingless signal and apterous), and has nubbin enhancer activity. In addition, our homeotic mutant analysis shows that wing transformation in T1 originates from both the carinated margin and the other vg-dependent tissue, the pleural structures (trochantin and epimeron). Intriguingly, these two tissues may actually be homologous to the two proposed wing origins (paranotal lobes and exite bearing proximal leg segments). Therefore, our findings suggest that the vg-dependent tissues in T1 could be wing serial homologs present in a more ancestral state, thus providing compelling functional evidence for the dual origin of insect wings. PMID:24085843

A dominant conformational role for amino acid diversity in minimalist protein–protein interfaces

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

Gilbreth, Ryan N.; Esaki, Kaori; Koide, Akiko

Recent studies have shown that highly simplified interaction surfaces consisting of combinations of just two amino acids, Tyr and Ser, exhibit high affinity and specificity. The high functional levels of such minimalist interfaces might thus indicate small contributions of greater amino acid diversity seen in natural interfaces. Toward addressing this issue, we have produced a pair of binding proteins built on the fibronectin type III scaffold, termed “monobodies.” One monobody contains the Tyr/Ser binary-code interface (termed YS) and the other contains an expanded amino acid diversity interface (YSX), but both bind to an identical target, maltose-binding protein. The YSX monobodymore » bound with higher affinity, a slower off rate and a more favorable enthalpic contribution than the YS monobody. High-resolution X-ray crystal structures revealed that both proteins bound to an essentially identical epitope, providing a unique opportunity to directly investigate the role of amino acid diversity in a protein interaction interface. Surprisingly, Tyr still dominates the YSX paratope and the additional amino acid types are primarily used to conformationally optimize contacts made by tyrosines. Scanning mutagenesis showed that while all contacting Tyr side chains are essential in the YS monobody, the YSX interface was more tolerant to mutations. These results suggest that the conformational, not chemical, diversity of additional types of amino acids provided higher functionality and evolutionary robustness, supporting the dominant role of Tyr and the importance of conformational diversity in forming protein interaction interfaces.« less

A Dominant Conformational Role for Amino Acid Diversity in Minimalist Protein-Protein Interfaces

PubMed Central

Gilbreth, Ryan N.; Esaki, Kaori; Koide, Akiko; Sidhu, Sachdev S.; Koide, Shohei

2008-01-01

Recent studies have shown that highly simplified interaction surfaces consisting of combinations of just two amino acids, Tyr and Ser, exhibit high affinity and specificity. The high functional levels of such minimalist interfaces might thus indicate small contributions of greater amino acid diversity seen in natural interfaces. Toward addressing this issue, we have produced a pair of binding proteins built on the fibronectin type III scaffold, termed “monobodies”. One monobody contains the Tyr/Ser binary-code interface (termed YS) and the other contains an expanded amino acid diversity interface (YSX), but both bind to an identical target, maltose binding protein (MBP). The YSX monobody bound with higher affinity, a slower off rate and a more favorable enthalpic contribution than the YS monobody. High-resolution x-ray crystal structures revealed that both proteins bound to an essentially identical epitope, providing a unique opportunity to directly investigate the role of amino acid diversity in a protein interaction interface. Surprisingly, Tyr still dominates the YSX paratope and the additional amino acid types are primarily used to conformationally optimize contacts made by tyrosines. Scanning mutagenesis showed that while all contacting Tyr side-chains are essential in the YS monobody, the YSX interface was more tolerant to mutations. These results suggest that the conformational, not chemical, diversity of additional types of amino acids provided higher functionality and evolutionary robustness, supporting the dominant role of Tyr and the importance of conformational diversity in forming protein interaction interfaces. PMID:18602117

Experiences From Developing and Upgrading a Web-Based Surveillance System for Malaria Elimination in Cambodia

PubMed Central

Mellor, Steve; Aryal, Siddhi; Sovannaroth, Siv; Roca-Feltrer, Arantxa

2017-01-01

Strengthening the surveillance component is key toward achieving country-wide malaria elimination in Cambodia. A Web-based upgraded malaria information system (MIS) was deemed to essentially act as the central component for surveillance strengthening. New functionality (eg, data visualization) and operational (eg, data quality) attributes of the system received particular attention. However, building from the lessons learned in previous systems’ developments, other aspects unique to Cambodia were considered to be equally important; for instance, feasibility issues, particularly at the field level (eg, user acceptability at various health levels), and sustainability needs (eg, long-term system flexibility). The Cambodian process of identifying the essential changes and critical attributes for this new information system can provide a model for other countries at various stages of the disease control and elimination continuum. Sharing these experiences not only facilitates the establishment of “best practices” but also accelerates global and regional malaria elimination efforts. In this article, Cambodia’s experience in developing and upgrading its MIS to remain responsive to country-specific needs demonstrates the necessity for considering functionality, operationalization, feasibility, and sustainability of an information system in the context of malaria elimination. PMID:28615155

Operationalising emergency care delivery in sub-Saharan Africa: consensus-based recommendations for healthcare facilities.

PubMed

Calvello, Emilie J B; Tenner, Andrea G; Broccoli, Morgan C; Skog, Alexander P; Muck, Andrew E; Tupesis, Janis P; Brysiewicz, Petra; Teklu, Sisay; Wallis, Lee; Reynolds, Teri

2016-08-01

A major barrier to successful integration of acute care into health systems is the lack of consensus on the essential components of emergency care within resource-limited environments. The 2013 African Federation of Emergency Medicine Consensus Conference was convened to address the growing need for practical solutions to further implementation of emergency care in sub-Saharan Africa. Over 40 participants from 15 countries participated in the working group that focused on emergency care delivery at health facilities. Using the well-established approach developed in the WHO's Monitoring Emergency Obstetric Care, the workgroup identified the essential services delivered-signal functions-associated with each emergency care sentinel condition. Levels of emergency care were assigned based on the expected capacity of the facility to perform signal functions, and the necessary human, equipment and infrastructure resources identified. These consensus-based recommendations provide the foundation for objective facility capacity assessment in developing emergency health systems that can bolster strategic planning as well as facilitate monitoring and evaluation of service delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/