Dutch Economic Textbooks in the 1970s: Raising the Status of a New Secondary School Type by Means of Mathematical Abstraction

ERIC Educational Resources Information Center

Gorter, Gerrit F.; Amsing, Hilda T. A.; Dekker, Jeroen J. H.

2016-01-01

Essential Economics, the influential economics education textbook written by Arnold Heertje for use in Dutch secondary schools in the 1970s, was characterized by a previously unknown and internationally exceptional degree of abstraction. Its users justified this degree of abstraction by arguing that it fulfilled the needs of mental schooling (in…

Phylogeography of Francisella tularensis from Tibet, China: Evidence for an asian origin and radiation of holarctica-type Tularemia.

PubMed

Lu, Yongfeng; Yu, Yonghui; Feng, Le; Li, Yanwei; He, Jun; Zhu, Hong; Duan, Qing; Song, Lihua

2016-07-01

The geographical origin and radiation of holarctica-type tularemia, which has spread across the northern hemisphere, is open to scientific debate. Here, through phylogenetics, we show that five Tibetan Francisella tularensis isolates subsp. holarctica cluster between basal-positioned Japanese isolates and all other subspecies strains in the world, providing evidence for a previously unknown intermediate lineage next to the Japanese isolates. Importantly, identification of this new intermediate lineage complements current knowledge of tularemia epidemiology, supporting a geographical origin and radiation of the subsp. holarctica in Asia. In addition, thirteen Tibetan isolates belonging to a clade previously found only in North America and Scandinavia, further increases the diversity of holarctica strains in Asia. In summary, this study provides evidence for an Asian origin and radiation of holarctica-type tularemia. Copyright © 2016 Elsevier GmbH. All rights reserved.

Molecular characterization of infants with type 2 Gaucher disease

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

Stubblefield, B.; Martin, B.M.; Ginns, E.I.

1994-09-01

Type 2 (acute neuronopathic) Gaucher disease was previously thought to be stereotypic in presentation with neurologic deterioration and death by age 2-3 years. However, the generation of a null allele knock-out Gaucher mouse led to the recognition of a subset of type 2 patients who die as neonates. To better understand this subgroup we studied DNA, RNA and residual enzyme activity in fibroblasts from neonatal type 2 Gaucher patients, {open_quotes}classic{close_quotes} type 2 patients, type 1 and type 3 patients and normal individuals. Mutational analysis revealed genotypic heterogeneity in each group. One patient with severe neonatal Gaucher disease and hydrops fetalismore » was homoallelic for a complex allele including mutations L44P, A456P and V460V, while others had different or unknown alleles. Northern blots demonstrated that transcription was intact even in the neonatal lethal patients. However, the more severe type 2 patients had virtually no protein on Western, indicating that the transcript is either not appropriately translated or results in an unstable protein. Thus type 2 Gaucher disease exhibits more phenotypic, genotypic and biochemical heterogeneity than previously appreciated.« less

Actinomyces cardiffensis sp. nov. from Human Clinical Sources

PubMed Central

Hall, Val; Collins, Mattew D.; Hutson, Roger; Falsen, Enevold; Duerden, Brian I.

2002-01-01

Eight strains of a previously undescribed catalase-negative Actinomyces-like bacterium were recovered from human clinical specimens. The morphological and biochemical characteristics of the isolates were consistent with their assignment to the genus Actinomyces, but they did not appear to correspond to any recognized species. 16S rRNA gene sequence analysis showed the organisms represent a hitherto unknown species within the genus Actinomyces related to, albeit distinct from, a group of species which includes Actinomyces turicensis and close relatives. Based on biochemical and molecular genetic evidence, it is proposed that the unknown isolates from human clinical sources be classified as a new species, Actinomyces cardiffensis sp. nov. The type strain of Actinomyces cardiffensis is CCUG 44997T. PMID:12202588

Approximate conditional teleportation of a Λ-type three-level atomic state based on cavity QED method beyond Bell-state measurement

NASA Astrophysics Data System (ADS)

Sehati, N.; Tavassoly, M. K.

2017-08-01

Inspiring from the scheme proposed in (Zheng in Phys Rev A 69:064,302 2004), our aim is to teleport an unknown qubit atomic state using the cavity QED method without using the explicit Bell-state measurement, and so the additional atom is not required. Two identical Λ-type three-level atoms are interacted separately and subsequently with a two-mode quantized cavity field where each mode is expressed with a single-photon field state. The interaction between atoms and field is well described via the Jaynes-Cummings model. It is then shown that how if the atomic detection results a particular state of atom 1, an unknown state can be appropriately teleported from atom 1 to atom 2. This teleportation procedure successfully leads to the high fidelity F (success probability P_g) in between 69%≲ F≲ 100% (0.14≲ P_g≲ 0.56). At last, we illustrated that our scheme considerably improves similar previous proposals.

The usage of fasting glucose and glycated hemoglobin for the identification of unknown type 2 diabetes in high risk patients with morbid obesity.

PubMed

Valderhaug, Tone G; Sharma, Archana; Kravdal, Gunnhild; Rønningen, Reidun; Nermoen, Ingrid

2017-11-01

In spite of increased vigilance of undiagnosed type 2 diabetes (DM2), the prevalence of unknown DM2 in subjects with morbid obesity is not known. To assess the prevalence of undiagnosed DM2 and compare the performance of glycated A1c (HbA1c) and fasting glucose (FG) for the diagnosis of DM2 and prediabetes (preDM) in patients with morbid obesity. We measured fasting glucose and HbA1c in 537 consecutive patients with morbid obesity without previously known DM2. A total of 49 (9%) patients with morbid obesity had unknown DM2 out of which 16 (33%) fulfilled both the criteria for HbA1c and FG. Out of 284 (53%) subjects with preDM, 133 (47%) fulfilled both the criteria for HbA1c and FG. Measurements of agreement for FG and HbA1c were moderate for DM2 (κ = 0.461, p < .001) and fair for preDM (κ = 0.317, p < .001). Areas under the curve for FG and HbA1c in predicting unknown DM2 were 0.970 (95% CI 0.942, 0.998) and 0.894 (95% CI 0.837, 0.951) respectively. The optimal thresholds to identify unknown DM2 were FG ≥6.6 mmol/L and HbA1c ≥ 6.1% (43 mmol/mol). The prevalence of DM2 remains high and both FG and HbA1c identify patients with unknown DM2. FG was slightly superior to HbA1c in predicting and separating patients with unknown DM2 from patients without DM2. We suggest that an FG ≥6.6 mmol/L or an HbA1c ≥6.1% (43 mmol/mol) may be used as primary cut points for the identification of unknown DM2 among patients with morbid obesity.

Twelve previously unknown phage genera are ubiquitous in global oceans

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

Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh B

Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in unknowns dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four wellknown viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria.more » Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage host systems for experimental hypothesis testing.« less

Twelve previously unknown phage genera are ubiquitous in global oceans.

PubMed

Holmfeldt, Karin; Solonenko, Natalie; Shah, Manesh; Corrier, Kristen; Riemann, Lasse; Verberkmoes, Nathan C; Sullivan, Matthew B

2013-07-30

Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in "unknowns" dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an underrepresented and environmentally abundant bacterial lineage. Comparative genomics delineated 12 phage groups that (i) each represent a new genus, and (ii) represent one novel and four well-known viral families. This diversity contrasts the few well-studied marine phage systems, but parallels the diversity of phages infecting human-associated bacteria. Although all 12 Cellulophaga phages represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages were exceptional, with genomes up to twice as large as those previously observed for each phage type. Structural novelty was also substantial, requiring experimental phage proteomics to identify 83% of the structural proteins. The presence of uncommon nucleotide metabolism genes in four genera likely underscores the importance of scavenging nutrient-rich molecules as previously seen for phages in marine environments. Metagenomic recruitment analyses suggest that these particular Cellulophaga phages are rare and may represent a first glimpse into the phage side of the rare biosphere. However, these analyses also revealed that these phage genera are widespread, occurring in 94% of 137 investigated metagenomes. Together, this diverse and novel collection of phages identifies a small but ubiquitous fraction of unknown marine viral diversity and provides numerous environmentally relevant phage-host systems for experimental hypothesis testing.

Role of MrkJ, a Phosphodiesterase, in Type 3 Fimbrial Expression and Biofilm Formation in Klebsiella pneumoniae▿

PubMed Central

Johnson, Jeremiah G.; Clegg, Steven

2010-01-01

Klebsiella pneumoniae is an opportunistic pathogen that has been shown to adhere to human extracellular matrices using the type 3 fimbriae. Introduction of plasmids carrying genes known to alter intracellular cyclic-di-GMP pools in Vibrio parahaemolyticus revealed that these genes also altered type 3 fimbrial surface expression in K. pneumoniae. Immediately adjacent to the type 3 fimbrial gene cluster is a gene, mrkJ, that is related to a family of bacterial genes encoding phosphodiesterases. We identify here a role for MrkJ, a functional phosphodiesterase exhibiting homology to EAL domain-containing proteins, in controlling type 3 fimbria production and biofilm formation in K. pneumoniae. Deletion of mrkJ resulted in an increase in type 3 fimbria production and biofilm formation as a result of the accumulation of intracellular cyclic-di-GMP. This gene was shown to encode a functional phosphodiesterase via restoration of motility in a V. parahaemolyticus strain previously shown to accumulate cyclic-di-GMP and in vitro using phosphodiesterase activity assays. The effect of the mrkJ mutation on type 3 fimbrial expression was shown to be at the level of mrkA gene transcription by using quantitative reverse transcription-PCR. These results reveal a previously unknown role for cyclic-di-GMP in type 3 fimbrial production. PMID:20511505

Optimal joint detection and estimation that maximizes ROC-type curves

PubMed Central

Wunderlich, Adam; Goossens, Bart; Abbey, Craig K.

2017-01-01

Combined detection-estimation tasks are frequently encountered in medical imaging. Optimal methods for joint detection and estimation are of interest because they provide upper bounds on observer performance, and can potentially be utilized for imaging system optimization, evaluation of observer efficiency, and development of image formation algorithms. We present a unified Bayesian framework for decision rules that maximize receiver operating characteristic (ROC)-type summary curves, including ROC, localization ROC (LROC), estimation ROC (EROC), free-response ROC (FROC), alternative free-response ROC (AFROC), and exponentially-transformed FROC (EFROC) curves, succinctly summarizing previous results. The approach relies on an interpretation of ROC-type summary curves as plots of an expected utility versus an expected disutility (or penalty) for signal-present decisions. We propose a general utility structure that is flexible enough to encompass many ROC variants and yet sufficiently constrained to allow derivation of a linear expected utility equation that is similar to that for simple binary detection. We illustrate our theory with an example comparing decision strategies for joint detection-estimation of a known signal with unknown amplitude. In addition, building on insights from our utility framework, we propose new ROC-type summary curves and associated optimal decision rules for joint detection-estimation tasks with an unknown, potentially-multiple, number of signals in each observation. PMID:27093544

Optimal Joint Detection and Estimation That Maximizes ROC-Type Curves.

PubMed

Wunderlich, Adam; Goossens, Bart; Abbey, Craig K

2016-09-01

Combined detection-estimation tasks are frequently encountered in medical imaging. Optimal methods for joint detection and estimation are of interest because they provide upper bounds on observer performance, and can potentially be utilized for imaging system optimization, evaluation of observer efficiency, and development of image formation algorithms. We present a unified Bayesian framework for decision rules that maximize receiver operating characteristic (ROC)-type summary curves, including ROC, localization ROC (LROC), estimation ROC (EROC), free-response ROC (FROC), alternative free-response ROC (AFROC), and exponentially-transformed FROC (EFROC) curves, succinctly summarizing previous results. The approach relies on an interpretation of ROC-type summary curves as plots of an expected utility versus an expected disutility (or penalty) for signal-present decisions. We propose a general utility structure that is flexible enough to encompass many ROC variants and yet sufficiently constrained to allow derivation of a linear expected utility equation that is similar to that for simple binary detection. We illustrate our theory with an example comparing decision strategies for joint detection-estimation of a known signal with unknown amplitude. In addition, building on insights from our utility framework, we propose new ROC-type summary curves and associated optimal decision rules for joint detection-estimation tasks with an unknown, potentially-multiple, number of signals in each observation.

Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka.

PubMed

Dharma-Wardana, M W C; Amarasiri, Sarath L; Dharmawardene, Nande; Panabokke, C R

2015-04-01

High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka is shown to correlate with the presence of irrigation works and rivers that bring-in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We review previous attempts to link CKDU with As, Cd and other standard toxins. Those studies (e.g. the WHO-sponsored study), while providing a wealth of data, are inconclusive in regard to aetiology. Here, we present new proposals based on increased ionicity of drinking water due to fertilizer runoff into the river system, redox processes in the soil and features of 'tank'-cascades and aquifers. The consequent chronic exposure to high ionicity in drinking water is proposed to debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism.

Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis A Virus.

PubMed

Anthony, S J; St Leger, J A; Liang, E; Hicks, A L; Sanchez-Leon, M D; Jain, K; Lefkowitch, J H; Navarrete-Macias, I; Knowles, N; Goldstein, T; Pugliares, K; Ip, H S; Rowles, T; Lipkin, W I

2015-08-25

Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV. Hepatitis A virus (HAV) is an important viral hepatitis in humans because of the substantial number of cases each year in regions with low socioeconomic status. The origin of HAV is unknown, and no nonprimate HAV-like viruses have been described. Here, we describe the discovery of an HAV-like virus in seals. This finding suggests that the diversity and evolutionary history of these viruses might be far greater than previously thought and may provide insight into the origin and pathogenicity of HAV. Copyright © 2015 Anthony et al.

Artesian Well Abandonment at Launch Complex 39A

NASA Technical Reports Server (NTRS)

Morgan, Lindsay; Johansen, Deda

2015-01-01

The artesian well tasked for abandonment was located on the LOX side (northwest area) of the launch complex. The exact date of well installation is unknown. The well was no longer in use at the time of the abandonment request, but was previously utilized under St. Johns River Water Management District (SJRWMD) consumptive use permit (No. 50054) for the Floridian Aquifer. The exact construction details of the LOX artesian well were also unknown; however, a similar-type artesian well was previously located on the LH2 side of the site, which was abandoned in 2012. Based on discussions with the NASA RPM and review of the LH2 artesian well abandonment completion report, the LH2 artesian well was reported to be an 8-inch diameter, 330-foot deep well. The NASA RPM communicated that the LOX artesian well was likely to be an 8-inch diameter, 380-foot deep well. This information was used for scoping, and was subsequently confirmed to be substantially accurate. No additional information could be found for the LOX artesian well using the NASA Remediation Information System (RIS).

Interpreting Medieval Inter-tidal Features at Weelie's Taing on Papa Westray, Orkney, NE Scotland

NASA Astrophysics Data System (ADS)

Pollard, Edward; Gibson, Julie; Littlewood, Mark

2016-12-01

Investigation of the inter-tidal heritage of the Orkney Islands is used to interpret a previously perplexing complex at Weelie's Taing on Papa Westray. The study revealed a previously unknown type of harbour since identified in several locations around Orkney. Situated in exposed environmental situations, shelter is formed by an `ayre', a type of spit that encloses a loch, and which has been used historically as a landing place or crossing of the inter-tidal zone. A complex landing area, pier, tower and ship-blockage suggest Weelie's Taing was used as a harbour. Important fishing grounds exploited since the Neolithic are nearby, and Papa Westray was the site of water-focussed religious communities. It is suggested that Weelie's Taing was in use in the medieval period when Papa Westray was less isolated than today with the presence of ecclesiastical communities and situation on the Orkney-Shetland route.

Proceedings of a workshop on Differences Between Antarctic and Non-Antarctic Meteorites

NASA Technical Reports Server (NTRS)

Koeberl, Christian (Editor); Cassidy, William A. (Editor)

1989-01-01

The known facts, together with new research results are reviewed, in order to examine apparent differences between the Antarctic and non-Antarctic populations. In view of the statistically significant number of Antarctic meteorites, and the existence of rare or previously unknown types of meteorites among the Antarctic meteorite collection, the question was really not so much whether there are differences, but to define which ones are significant and what their origin is. Two main causes for the possible differences have been suggested previously, namely differences in the meteorite parent populations and secondary effects (e.g., weathering). The workshop was structured to contain sessions on chemical, isotopic, petrological, and mineralogical studies of meteorites from the two collections; terrestrial age determinations; discussions on mass frequency distributions; relative abundances of meteorite types; and terrestrial meteorite flux rates and their possible changes with time.

Cell type transcriptome atlas for the planarian Schmidtea mediterranea.

PubMed

Fincher, Christopher T; Wurtzel, Omri; de Hoog, Thom; Kravarik, Kellie M; Reddien, Peter W

2018-05-25

The transcriptome of a cell dictates its unique cell type biology. We used single-cell RNA sequencing to determine the transcriptomes for essentially every cell type of a complete animal: the regenerative planarian Schmidtea mediterranea. Planarians contain a diverse array of cell types, possess lineage progenitors for differentiated cells (including pluripotent stem cells), and constitutively express positional information, making them ideal for this undertaking. We generated data for 66,783 cells, defining transcriptomes for known and many previously unknown planarian cell types and for putative transition states between stem and differentiated cells. We also uncovered regionally expressed genes in muscle, which harbors positional information. Identifying the transcriptomes for potentially all cell types for many organisms should be readily attainable and represents a powerful approach to metazoan biology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

On the Weyl anomaly of 4D conformal higher spins: a holographic approach

NASA Astrophysics Data System (ADS)

Acevedo, S.; Aros, R.; Bugini, F.; Diaz, D. E.

2017-11-01

We present a first attempt to derive the full (type-A and type-B) Weyl anomaly of four dimensional conformal higher spin (CHS) fields in a holographic way. We obtain the type-A and type-B Weyl anomaly coefficients for the whole family of 4D CHS fields from the one-loop effective action for massless higher spin (MHS) Fronsdal fields evaluated on a 5D bulk Poincaré-Einstein metric with an Einstein metric on its conformal boundary. To gain access to the type-B anomaly coefficient we assume, for practical reasons, a Lichnerowicz-type coupling of the bulk Fronsdal fields with the bulk background Weyl tensor. Remarkably enough, our holographic findings under this simplifying assumption are certainly not unknown: they match the results previously found on the boundary counterpart under the assumption of factorization of the CHS higher-derivative kinetic operator into Laplacians of "partially massless" higher spins on Einstein backgrounds.

Nuthatches eavesdrop on variations in heterospecific chickadee mobbing alarm calls

PubMed Central

Templeton, Christopher N.; Greene, Erick

2007-01-01

Many animals recognize the alarm calls produced by other species, but the amount of information they glean from these eavesdropped signals is unknown. We previously showed that black-capped chickadees (Poecile atricapillus) have a sophisticated alarm call system in which they encode complex information about the size and risk of potential predators in variations of a single type of mobbing alarm call. Here we show experimentally that red-breasted nuthatches (Sitta canadensis) respond appropriately to subtle variations of these heterospecific “chick-a-dee” alarm calls, thereby evidencing that they have gained important information about potential predators in their environment. This study demonstrates a previously unsuspected level of discrimination in intertaxon eavesdropping. PMID:17372225

Nuthatches eavesdrop on variations in heterospecific chickadee mobbing alarm calls.

PubMed

Templeton, Christopher N; Greene, Erick

2007-03-27

Many animals recognize the alarm calls produced by other species, but the amount of information they glean from these eavesdropped signals is unknown. We previously showed that black-capped chickadees (Poecile atricapillus) have a sophisticated alarm call system in which they encode complex information about the size and risk of potential predators in variations of a single type of mobbing alarm call. Here we show experimentally that red-breasted nuthatches (Sitta canadensis) respond appropriately to subtle variations of these heterospecific "chick-a-dee" alarm calls, thereby evidencing that they have gained important information about potential predators in their environment. This study demonstrates a previously unsuspected level of discrimination in intertaxon eavesdropping.

New Trichoptera records from Arkansas and Missouri

Treesearch

David A. Etnier

2010-01-01

Analysis of about 69,000 Trichoptera from Arkansas and Missouri resulted in identification of six species previously unknown from Arkansas (i.e., Agraylea costello, Neotrichia collata, Orthotrichia curta, Oxyethira glasa, O. pescadori, Neureclipsis piersoni) and three species previously unknown from Missouri (i.e., Cheumatopsyche mollala, Hydroptila broweri, H....

Algorithm comparison for schedule optimization in MR fingerprinting.

PubMed

Cohen, Ouri; Rosen, Matthew S

2017-09-01

In MR Fingerprinting, the flip angles and repetition times are chosen according to a pseudorandom schedule. In previous work, we have shown that maximizing the discrimination between different tissue types by optimizing the acquisition schedule allows reductions in the number of measurements required. The ideal optimization algorithm for this application remains unknown, however. In this work we examine several different optimization algorithms to determine the one best suited for optimizing MR Fingerprinting acquisition schedules. Copyright © 2017 Elsevier Inc. All rights reserved.

Previously unknown species of Aspergillus.

PubMed

Gautier, M; Normand, A-C; Ranque, S

2016-08-01

The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11.

PubMed

Kimberling, W J; Möller, C G; Davenport, S; Priluck, I A; Beighton, P H; Greenberg, J; Reardon, W; Weston, M D; Kenyon, J B; Grunkemeyer, J A

1992-12-01

Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.

New steroid 5alpha-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8.

PubMed

Eminović, I; Liović, M; Prezelj, J; Kocijancic, A; Rozman, D; Komel, R

2001-01-01

To date, two genes encoding 5alpha-reductase isoenzymes are known (type I, type II), and one type I pseudogene. The divergent localization of these genes and the still not fully understood function of the encoded enzymes as well as the perplexing results we obtained after sequencing PCR-amplified SRD5A1 gene fragments (out of genomic DNA), made us assume that, in addition to the known SRD5A1 gene, one or more different human 5alpha-reductase type I coding genes may exist. Our research provide the first evidence for the existence of two new SRD5A1 related, previously unidentified sequences in the human genome. These sequences which were localized to chromosomes 6 and 8 are highly homologous (> 99%) to SRD5A1, and also do not contain any deletions or insertions that are otherwise a characteristic of the SRD5API pseudogene. Our results imply that these sequences may be either coding parts of yet unknown, active SRD5A1 genes, and/or of previously unidentified pseudogenes. These findings additionally support data of Chen et al. who confirmed the existence of various SRD5A1 proteins in cultured human skin cells.

Genetics and Epigenetics of Mating Type Determination in Paramecium and Tetrahymena.

PubMed

Orias, Eduardo; Singh, Deepankar Pratap; Meyer, Eric

2017-09-08

While sex is an ancient and highly conserved eukaryotic invention, self-incompatibility systems such as mating types or sexes appear to be derived limitations that show considerable evolutionary plasticity. Within a single class of ciliates, Paramecium and Tetrahymena species have long been known to present a wide variety of mating type numbers and modes of inheritance, but only recently have the genes involved been identified. Although similar transmembrane proteins mediate self/nonself recognition in both ciliates, the mechanisms of mating type determination differ widely, ranging from Mendelian systems to developmental nuclear differentiation, either stochastic or maternally inherited. The non-Mendelian systems rely on programmed editing of the germline genome that occurs during differentiation of the somatic nucleus, and they have co-opted different DNA recombination mechanisms-some previously unknown. Here we review the recent molecular advances and some remaining unsolved questions and discuss the possible implications of these diverse mechanisms for inbreeding/outbreeding balance regulation.

PCSK9: From Basic Science Discoveries to Clinical Trials.

PubMed

Shapiro, Michael D; Tavori, Hagai; Fazio, Sergio

2018-05-11

Unknown 15 years ago, PCSK9 (proprotein convertase subtilisin/kexin type 9) is now common parlance among scientists and clinicians interested in prevention and treatment of atherosclerotic cardiovascular disease. What makes this story so special is not its recent discovery nor the fact that it uncovered previously unknown biology but rather that these important scientific insights have been translated into an effective medical therapy in record time. Indeed, the translation of this discovery to novel therapeutic serves as one of the best examples of how genetic insights can be leveraged into intelligent target drug discovery. The PCSK9 saga is unfolding quickly but is far from complete. Here, we review major scientific understandings as they relate to the role of PCSK9 in lipoprotein metabolism and atherosclerotic cardiovascular disease and the impact that therapies designed to inhibit its action are having in the clinical setting. © 2018 American Heart Association, Inc.

Statistical Physics Approaches to RNA Editing

NASA Astrophysics Data System (ADS)

Bundschuh, Ralf

2012-02-01

The central dogma of molecular Biology states that DNA is transcribed base by base into RNA which is in turn translated into proteins. However, some organisms edit their RNA before translation by inserting, deleting, or substituting individual or short stretches of bases. In many instances the mechanisms by which an organism recognizes the positions at which to edit or by which it performs the actual editing are unknown. One model system that stands out by its very high rate of on average one out of 25 bases being edited are the Myxomycetes, a class of slime molds. In this talk we will show how the computational methods and concepts from statistical Physics can be used to analyze DNA and protein sequence data to predict editing sites in these slime molds and to guide experiments that identified previously unknown types of editing as well as the complete set of editing events in the slime mold Physarum polycephalum.

Comparison of functional group selective ion-molecule reactions of trimethyl borate in different ion trap mass spectrometers

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

Habicht, S C; Vinueza, Nelson R; Amundson, Lucas M

2011-02-01

We report here a comparison of the use of diagnostic ion–molecule reactions for the identification of oxygen-containing functional groups in Fourier-transform ion cyclotron resonance (FTICR) and linear quadrupole ion trap (LQIT) mass spectrometers. The ultimate goal of this research is to be able to identify functionalities in previously unknown analytes by using many different types of mass spectrometers. Previous work has focused on the reactions of various boron reagents with protonated oxygen-containing analytes in FTICR mass spectrometers. By using a LQIT modified to allow the introduction of neutral reagents into the helium buffer gas, this methodology has been successfully implementedmore » to this type of an ion trap instrument. The products obtained from the reactions of trimethyl borate (TMB) with various protonated analytes are compared for the two instruments. Finally, the ability to integrate these reactions into LC-MS experiments on the LQIT is demonstrated.« less

Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

PubMed Central

Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

2013-01-01

Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

Taxonomic notes on the small resin bees Hypanthidioides subgenus Michanthidium (Hymenoptera, Megachilidae).

PubMed

Gonzalez, Victor H; Griswold, Terry L

2011-01-01

As part of ongoing investigations on anthidiine bees, the type of Anthidium albitarse Friese was found to be conspecific with one of the two species of the small resin bees Hypanthidioides subgenus Michanthidium. The new combination, Hypanthidioides (Michanthidium) albitarsis, is the oldest name, resulting in Gnathanthidium sakagamii Urban as a new junior synonym. The previously unknown male of the second species, Hypanthidioides ferrugineus, is described and figured, including the genitalic structure and associated sterna. Males and females of Hypanthidioides ferrugineus have been collected from flowers of Cuphea sp. (Lythraceae).

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

PubMed

Corradi, Nicolas; Sanders, Ian R

2006-03-10

The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Orbit Determination and Maneuver Detection Using Event Representation with Thrust-Fourier-Coefficients

NASA Astrophysics Data System (ADS)

Lubey, D.; Ko, H.; Scheeres, D.

The classical orbit determination (OD) method of dealing with unknown maneuvers is to restart the OD process with post-maneuver observations. However, it is also possible to continue the OD process through such unknown maneuvers by representing those unknown maneuvers with an appropriate event representation. It has been shown in previous work (Ko & Scheeres, JGCD 2014) that any maneuver performed by a satellite transitioning between two arbitrary orbital states can be represented as an equivalent maneuver connecting those two states using Thrust-Fourier-Coefficients (TFCs). Event representation using TFCs rigorously provides a unique control law that can generate the desired secular behavior for a given unknown maneuver. This paper presents applications of this representation approach to orbit prediction and maneuver detection problem across unknown maneuvers. The TFCs are appended to a sequential filter as an adjoint state to compensate unknown perturbing accelerations and the modified filter estimates the satellite state and thrust coefficients by processing OD across the time of an unknown maneuver. This modified sequential filter with TFCs is capable of fitting tracking data and maintaining an OD solution in the presence of unknown maneuvers. Also, the modified filter is found effective in detecting a sudden change in TFC values which indicates a maneuver. In order to illustrate that the event representation approach with TFCs is robust and sufficiently general to be easily adjustable, different types of measurement data are processed with the filter in a realistic LEO setting. Further, cases with mis-modeling of non-gravitational force are included in our study to verify the versatility and efficiency of our presented algorithm. Simulation results show that the modified sequential filter with TFCs can detect and estimate the orbit and thrust parameters in the presence of unknown maneuvers with or without measurement data during maneuvers. With no measurement data during maneuvers, the modified filter with TFCs uses an existing pre-maneuver orbit solution to compute a post-maneuver orbit solution by forcing TFCs to compensate for an unknown maneuver. With observation data available during maneuvers, maneuver start time and stop time is determined

Cryptic gentes revealed in pallid cuckoos Cuculus pallidus using reflectance spectrophotometry

PubMed Central

Starling, M; Heinsohn, R; Cockburn, A; Langmore, N.E

2006-01-01

Many cuckoo species lay eggs that match those of their hosts, which can significantly reduce rejection of their eggs by the host species. However, egg mimicry is problematic for generalist cuckoos that parasitize several host species with different egg types. Some generalist cuckoos have overcome this problem by evolving several host-specific races (gentes), each with its own, host-specific egg type. It is unknown how generalist cuckoos lacking gentes are able to avoid egg rejection by hosts. Here we use reflectance spectrophotometry (300–700 nm) on museum egg collections to test for host-specific egg types in an Australian generalist cuckoo reported to have a single egg type. We show that the colour of pallid cuckoo (Cuculus pallidus) eggs differed between four host species, and that their eggs closely mimicked the eggs of the host they parasitized. These results reveal that pallid cuckoos have host-specific egg types that have not been detected by human observation, and indicate that gentes could be more common than previously realized. PMID:16822754

Mycoplasma detection and isolation from one-humped camels (Camelus dromedarius).

PubMed

Mederos-Iriarte, Lidia E; Poveda, José B; Poveda, Carlos G; Vega-Orellana, Orestes M; Gutiérrez, Carlos; Corbera, Juan A; Ramírez, Ana S

2014-10-01

In scientific literature, a small amount of information is found concerning mycoplasmosis in camel species. Mycoplasma (M.) arginini, Acholeplasma (A.) laidlawii, and Acholeplasma oculi have been reported to be isolated from these host species. Serologically positive results have been reported for Mycoplasma mycoides subsp. mycoides SC type, Mycoplasma capricolum subsp. capripneumoniae, and M. mycoides subsp. capri. The aims of this study were to detect, isolate, and identify mycoplasmas from camels (Camelus dromedarius). Initially, saliva and ear smears plus conjunctival and vaginal secretions were taken from five female animals, but only conjunctival secretions in three male animals, all belonging to the same farm. An unknown mycoplasma was isolated from one of the vagina samples. Additionally, another unknown and uncultured mycoplasma was detected with molecular biology in the same sample. In the second stage, 23 vaginal secretions were taken from the same farm plus another secretion from a different one. Ten isolates of the same unknown and previously isolated mycoplasma were detected, nine of them recovered from the vagina of female camels. Some mycoplasmas have been related to reproductive disorders; however, there is no evidence that the isolated mycoplasmas are related to such disorders.

Structural and Mechanistic Roles of Novel Chemical Ligands on the SdiA Quorum-Sensing Transcription Regulator

DOE PAGES

Nguyen, Y.; Nguyen, Nam X.; Rogers, Jamie L.; ...

2015-05-19

Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However, some bacteria (such as Escherichia coli) do not produce AHLs. These LuxR orphans sense exogenous AHLs but also regulate transcription in the absence of AHLs. Importantly, this AHL-independent regulatory mechanism is still largely unknown. Here we present several structures of one such orphan LuxR-type protein, SdiA, from enterohemorrhagic E. coli (EHEC), in the presence and absence of AHL. SdiA is actually not inmore » an apo state without AHL but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL), which is ubiquitously found throughout the tree of life and serves as an energy source, signaling molecule, and substrate for membrane biogenesis. While exogenous AHL renders to SdiA higher stability and DNA binding affinity, OCL may function as a chemical chaperone placeholder that stabilizes SdiA, allowing for basal activity. Structural comparison between SdiA-AHL and SdiA-OCL complexes provides crucial mechanistic insights into the ligand regulation of AHL-dependent and -independent function of LuxR-type proteins. Importantly, in addition to its contribution to basic science, this work has implications for public health, inasmuch as the SdiA signaling system aids the deadly human pathogen EHEC to adapt to a commensal lifestyle in the gastrointestinal (GI) tract of cattle, its main reservoir. These studies open exciting and novel avenues to control shedding of this human pathogen in the environment. IMPORTANCE Quorum sensing refers to bacterial chemical signaling. The QS acyl homoserine lactone (AHL) signals are recognized by LuxR-type receptors that regulate gene transcription. However, some bacteria have orphan LuxR-type receptors and do not produce AHLs, sensing them from other bacteria. We solved three structures of the E. coli SdiA orphan, in the presence and absence of AHL. SdiA with no AHL is not in an apo state but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL). OCL is ubiquitously found in prokaryotes and eukaryotes and is a phospholipid precursor for membrane biogenesis and a signaling molecule. While AHL renders to SdiA higher stability and DNA-binding affinity, OCL functions as a chemical chaperone placeholder, stabilizing SdiA and allowing for basal activity. Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity.« less

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease

PubMed Central

Peters, James E.; Lyons, Paul A.; Lee, James C.; Richard, Arianne C.; Fortune, Mary D.; Newcombe, Paul J.; Richardson, Sylvia; Smith, Kenneth G. C.

2016-01-01

Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases. PMID:27015630

Streptococcus agalactiae Serotype IV in Humans and Cattle, Northern Europe1

PubMed Central

Lyhs, Ulrike; Kulkas, Laura; Katholm, Jørgen; Waller, Karin Persson; Saha, Kerttu; Tomusk, Richard J.

2016-01-01

Streptococcus agalactiae is an emerging pathogen of nonpregnant human adults worldwide and a reemerging pathogen of dairy cattle in parts of Europe. To learn more about interspecies transmission of this bacterium, we compared contemporaneously collected isolates from humans and cattle in Finland and Sweden. Multilocus sequence typing identified 5 sequence types (STs) (ST1, 8, 12, 23, and 196) shared across the 2 host species, suggesting possible interspecies transmission. More than 54% of the isolates belonged to those STs. Molecular serotyping and pilus island typing of those isolates did not differentiate between populations isolated from different host species. Isolates from humans and cattle differed in lactose fermentation, which is encoded on the accessory genome and represents an adaptation to the bovine mammary gland. Serotype IV-ST196 isolates were obtained from multiple dairy herds in both countries. Cattle may constitute a previously unknown reservoir of this strain. PMID:27869599

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

Hwang, Jai-chan; Noh, Hyerim

Special relativistic hydrodynamics with weak gravity has hitherto been unknown in the literature. Whether such an asymmetric combination is possible has been unclear. Here, the hydrodynamic equations with Poisson-type gravity, considering fully relativistic velocity and pressure under the weak gravity and the action-at-a-distance limit, are consistently derived from Einstein’s theory of general relativity. An analysis is made in the maximal slicing, where the Poisson’s equation becomes much simpler than our previous study in the zero-shear gauge. Also presented is the hydrodynamic equations in the first post-Newtonian approximation, now under the general hypersurface condition. Our formulation includes the anisotropic stress.

Taxonomic notes on the small resin bees Hypanthidioides subgenus Michanthidium (Hymenoptera, Megachilidae)

PubMed Central

Gonzalez, Victor H.; Griswold, Terry L.

2011-01-01

Abstract As part of ongoing investigations on anthidiine bees, the type of Anthidium albitarse Friese was found to be conspecific with one of the two species of the small resin bees Hypanthidioides subgenus Michanthidium. The new combination, Hypanthidioides (Michanthidium) albitarsis, is the oldest name, resulting in Gnathanthidium sakagamii Urban as a new junior synonym. The previously unknown male of the second species, Hypanthidioides ferrugineus, is described and figured, including the genitalic structure and associated sterna. Males and females of Hypanthidioides ferrugineus have been collected from flowers of Cuphea sp. (Lythraceae). PMID:21998505

Discovery of a novel hepatovirus (Phopivirus of seals) related to human Hepatitis A Virus

USGS Publications Warehouse

Anthony. S.J.,; St. Leger, J.A; Liang, E.; Hicks, A.L.; Sanchez-Leon, M.D; Ip, Hon S.; Jain, K.; Lefkowitch, J. H.; Navarrete-Macias, I.; Knowles, N.; Goldstein, T.; Pugliares, K.; Rowles, T.; Lipkin, W.I.

2015-01-01

Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV.

A new species of Rhadinella (Serpentes: Colubridae) from the Pacific versant of Oaxaca, Mexico.

PubMed

Campbell, Jonathan A

2015-02-12

I describe a new species of Rhadinella from the Pacific versant of Oaxaca, Mexico, a region where the genus was previously unknown. This diminutive snake is a member of a group of snakes that have dark dorsal coloration, which mostly or completely obfuscates a pattern of longitudinal striping characteristic of most species of Rhadinella. The closest relative of the new species, on the basis of morphological similarities, appears to be Rhadinella pilonaorum which occurs to the east of the Isthmus of Tehuantepec about 800 km from the type-locality of the new species.

Spontaneous trait inference and spontaneous trait transference are both unaffected by prior evaluations of informants.

PubMed

Zengel, Bettina; Ambler, James K; McCarthy, Randy J; Skowronski, John J

2017-01-01

This article reports results from a study in which participants encountered either (a) previously known informants who were positive (e.g. Abraham Lincoln), neutral (e.g., Jay Leno), or negative (e.g., Adolf Hitler), or (b) previously unknown informants. The informants ostensibly described either a trait-implicative positive behavior, a trait-implicative negative behavior, or a neutral behavior. These descriptions were framed as either the behavior of the informant or the behavior of another person. Results yielded evidence of informant-trait linkages for both self-informants and for informants who described another person. These effects were not moderated by informant type, behavior valence, or the congruency or incongruency between the prior knowledge of the informant and the behavior valence. Results are discussed in terms of theories of Spontaneous Trait Inference and Spontaneous Trait Transference.

Crystal structure of the toxin Msmeg_6760, the structural homolog of Mycobacterium tuberculosis Rv2035, a novel type II toxin involved in the hypoxic response

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

Bajaj, R. Alexandra; Arbing, Mark A.; Shin, Annie

The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin–antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate–latch mechanism. The function of the Msmeg_6760 toxin is unknown, but structure-based predictions revealed that Msmeg_6760 and Msmeg_6762 are homologous to Rv2034 and Rv2035, a predicted novelmore » TA system involved inMycobacterium tuberculosislatency during macrophage infection. The Msmeg_6760 toxin fold has not been previously described for bacterial toxins and its unique structural features suggest that toxin activation is likely to be mediated by a novel mechanism.« less

Myxococcus xanthus Developmental Cell Fate Production: Heterogeneous Accumulation of Developmental Regulatory Proteins and Reexamination of the Role of MazF in Developmental Lysis

PubMed Central

Lee, Bongsoo; Holkenbrink, Carina; Treuner-Lange, Anke

2012-01-01

Myxococcus xanthus undergoes a starvation-induced multicellular developmental program during which cells partition into three known fates: (i) aggregation into fruiting bodies followed by differentiation into spores, (ii) lysis, or (iii) differentiation into nonaggregating persister-like cells, termed peripheral rods. As a first step to characterize cell fate segregation, we enumerated total, aggregating, and nonaggregating cells throughout the developmental program. We demonstrate that both cell lysis and cell aggregation begin with similar timing at approximately 24 h after induction of development. Examination of several known regulatory proteins in the separated aggregated and nonaggregated cell fractions revealed previously unknown heterogeneity in the accumulation patterns of proteins involved in type IV pilus (T4P)-mediated motility (PilC and PilA) and regulation of development (MrpC, FruA, and C-signal). As part of our characterization of the cell lysis fate, we set out to investigate the unorthodox MazF-MrpC toxin-antitoxin system which was previously proposed to induce programmed cell death (PCD). We demonstrate that deletion of mazF in two different wild-type M. xanthus laboratory strains does not significantly reduce developmental cell lysis, suggesting that MazF's role in promoting PCD is an adaption to the mutant background strain used previously. PMID:22493014

A recurrent neural-network-based sensor and actuator fault detection and isolation for nonlinear systems with application to the satellite's attitude control subsystem.

PubMed

Talebi, H A; Khorasani, K; Tafazoli, S

2009-01-01

This paper presents a robust fault detection and isolation (FDI) scheme for a general class of nonlinear systems using a neural-network-based observer strategy. Both actuator and sensor faults are considered. The nonlinear system considered is subject to both state and sensor uncertainties and disturbances. Two recurrent neural networks are employed to identify general unknown actuator and sensor faults, respectively. The neural network weights are updated according to a modified backpropagation scheme. Unlike many previous methods developed in the literature, our proposed FDI scheme does not rely on availability of full state measurements. The stability of the overall FDI scheme in presence of unknown sensor and actuator faults as well as plant and sensor noise and uncertainties is shown by using the Lyapunov's direct method. The stability analysis developed requires no restrictive assumptions on the system and/or the FDI algorithm. Magnetorquer-type actuators and magnetometer-type sensors that are commonly employed in the attitude control subsystem (ACS) of low-Earth orbit (LEO) satellites for attitude determination and control are considered in our case studies. The effectiveness and capabilities of our proposed fault diagnosis strategy are demonstrated and validated through extensive simulation studies.

Does previous use affect litter box appeal in multi-cat households?

PubMed

Ellis, J J; McGowan, R T S; Martin, F

2017-08-01

It is commonly assumed that cats actively avoid eliminated materials (especially in multi-cat homes), suggesting regular litter box cleaning as the best defense against out-of-box elimination. The relationship between previous use and litter box appeal to familiar subsequent users is currently unknown. The purpose of this study was to investigate the relationship between previous litter box use and the identity of the previous user, type of elimination, odor, and presence of physical/visual obstructions in a multi-cat household scenario. Cats preferred a clean litter box to a dirty one, but the identity of the previous user had no impact on preferences. While the presence of odor from urine and/or feces did not impact litter box preferences, the presence of odorless faux-urine and/or feces did - with the presence of faux-feces being preferred over faux-urine. Results suggest neither malodor nor chemical communication play a role in litter box preferences, and instead emphasize the importance of regular removal of physical/visual obstructions as the key factor in promoting proper litter box use. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Map generation in unknown environments by AUKF-SLAM using line segment-type and point-type landmarks

NASA Astrophysics Data System (ADS)

Nishihta, Sho; Maeyama, Shoichi; Watanebe, Keigo

2018-02-01

Recently, autonomous mobile robots that collect information at disaster sites are being developed. Since it is difficult to obtain maps in advance in disaster sites, the robots being capable of autonomous movement under unknown environments are required. For this objective, the robots have to build maps, as well as the estimation of self-location. This is called a SLAM problem. In particular, AUKF-SLAM which uses corners in the environment as point-type landmarks has been developed as a solution method so far. However, when the robots move in an environment like a corridor consisting of few point-type features, the accuracy of self-location estimated by the landmark is decreased and it causes some distortions in the map. In this research, we propose AUKF-SLAM which uses walls in the environment as a line segment-type landmark. We demonstrate that the robot can generate maps in unknown environment by AUKF-SLAM, using line segment-type and point-type landmarks.

An expert system shell for inferring vegetation characteristics

NASA Technical Reports Server (NTRS)

Harrison, P. Ann; Harrison, Patrick R.

1993-01-01

The NASA VEGetation Workbench (VEG) is a knowledge based system that infers vegetation characteristics from reflectance data. VEG is described in detail in several references. The first generation version of VEG was extended. In the first year of this contract, an interface to a file of unknown cover type data was constructed. An interface that allowed the results of VEG to be written to a file was also implemented. A learning system that learned class descriptions from a data base of historical cover type data and then used the learned class descriptions to classify an unknown sample was built. This system had an interface that integrated it into the rest of VEG. The VEG subgoal PROPORTION.GROUND.COVER was completed and a number of additional techniques that inferred the proportion ground cover of a sample were implemented. This work was previously described. The work carried out in the second year of the contract is described. The historical cover type database was removed from VEG and stored as a series of flat files that are external to VEG. An interface to the files was provided. The framework and interface for two new VEG subgoals that estimate the atmospheric effect on reflectance data were built. A new interface that allows the scientist to add techniques to VEG without assistance from the developer was designed and implemented. A prototype Help System that allows the user to get more information about each screen in the VEG interface was also added to VEG.

42 CFR 493.1271 - Standard: Immunohematology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... must be tested with known A1 and B red cells. (3) The laboratory must determine the D(Rho) type by testing unknown red cells with anti-D (anti-Rho) blood typing reagent. (b) Immunohematological testing and...) through (e). (2) The laboratory must determine ABO group by concurrently testing unknown red cells with...

42 CFR 493.1271 - Standard: Immunohematology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... must be tested with known A1 and B red cells. (3) The laboratory must determine the D(Rho) type by testing unknown red cells with anti-D (anti-Rho) blood typing reagent. (b) Immunohematological testing and...) through (e). (2) The laboratory must determine ABO group by concurrently testing unknown red cells with...

42 CFR 493.1271 - Standard: Immunohematology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... must be tested with known A1 and B red cells. (3) The laboratory must determine the D(Rho) type by testing unknown red cells with anti-D (anti-Rho) blood typing reagent. (b) Immunohematological testing and...) through (e). (2) The laboratory must determine ABO group by concurrently testing unknown red cells with...

42 CFR 493.1271 - Standard: Immunohematology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... must be tested with known A1 and B red cells. (3) The laboratory must determine the D(Rho) type by testing unknown red cells with anti-D (anti-Rho) blood typing reagent. (b) Immunohematological testing and...) through (e). (2) The laboratory must determine ABO group by concurrently testing unknown red cells with...

Phylogenetic analysis of human immunodeficiency virus type 2 isolated from Cuban individuals.

PubMed

Machado, Liuber Y; Díaz, Héctor M; Noa, Enrique; Martín, Dayamí; Blanco, Madeline; Díaz, Dervel F; Sánchez, Yordank R; Nibot, Carmen; Sánchez, Lourdes; Dubed, Marta

2014-08-01

The presence of infection by human immunodeficiency virus type 2 (HIV-2) in Cuba has been previously documented. However, genetic information on the strains that circulate in the Cuban people is still unknown. The present work constitutes the first study concerning the phylogenetic relationship of HIV-2 Cuban isolates conducted on 13 Cuban patients who were diagnosed with HIV-2. The env sequences were analyzed for the construction of a phylogenetic tree with reference sequences of HIV-2. Phylogenetic analysis of the env gene showed that all the Cuban sequences clustered in group A of HIV-2. The analysis indicated several independent introductions of HIV-2 into Cuba. The results of the study will reinforce the program on the epidemiological surveillance of the infection in Cuba and make possible further molecular evolutionary studies.

GIS modeling of archaeological site locations: A low-tech approach

NASA Technical Reports Server (NTRS)

Futato, Eugene M.

1991-01-01

A Geographic Information System (GIS)-type analysis of archaeological site locations using a dBase III plus program and a desk top computer is presented. A previously developed model of site locations in the Sequatchie Valley of northeastern Alabama is tested against known site locations in another large survey area there. The model fails to account for site locations in the test area. A model is developed for the test area and indicates the site locations are indeed different. Whether this is due to differences in site locations on a sub-regional level, or to sample error in the original model is unknown.

Pregnenolone can protect the brain from cannabis intoxication.

PubMed

Vallée, Monique; Vitiello, Sergio; Bellocchio, Luigi; Hébert-Chatelain, Etienne; Monlezun, Stéphanie; Martin-Garcia, Elena; Kasanetz, Fernando; Baillie, Gemma L; Panin, Francesca; Cathala, Adeline; Roullot-Lacarrière, Valérie; Fabre, Sandy; Hurst, Dow P; Lynch, Diane L; Shore, Derek M; Deroche-Gamonet, Véronique; Spampinato, Umberto; Revest, Jean-Michel; Maldonado, Rafael; Reggio, Patricia H; Ross, Ruth A; Marsicano, Giovanni; Piazza, Pier Vincenzo

2014-01-03

Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.

In search of the elusive IrB 2: Can mechanochemistry help?

DOE PAGES

Xie, Zhilin; Blair, Richard G.; Orlovskaya, Nina; ...

2015-10-20

We produced hexagonal ReB 2-type IrB 2 diboride and orthorhombic IrB monoboride phases, that were previously unknown and saw them produced by mechanochemical syntheses. High energy ball milling of elemental Ir and B powder for 30 h, followed by annealing of the powder at 1050 °C for 48 h, resulted in the formation of the desired phases. Both traditional laboratory and high resolution synchrotron X-ray diffraction (XRD) analyses were used for phase identification of the synthesized powder. Additionally, scanning electron microscopy and transmission electron microscopy were employed, along with XRD, to further characterize the microstructure of the phases produced.

Albus 1: A Very Bright White Dwarf Candidate

NASA Astrophysics Data System (ADS)

Caballero, José Antonio; Solano, Enrique

2007-08-01

We have serendipitously discovered a previously unknown, bright source (BT=11.75+/-0.07 mag) with a very blue VT-Ks color, which we have named Albus 1. A photometric and astrometric study using Virtual Observatory tools has shown that it possesses an appreciable proper motion and magnitudes and colors very similar to those of the well-known white dwarf G191-B2B. We consider Albus 1 as a DA-type white dwarf located at about 40 pc. If its nature is confirmed, Albus 1 would be the sixth brightest isolated white dwarf in the sky, which would make it an excellent spectrophotometric standard.

In search of the elusive IrB 2: Can mechanochemistry help?

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

Xie, Zhilin; Blair, Richard G.; Orlovskaya, Nina

We produced hexagonal ReB 2-type IrB 2 diboride and orthorhombic IrB monoboride phases, that were previously unknown and saw them produced by mechanochemical syntheses. High energy ball milling of elemental Ir and B powder for 30 h, followed by annealing of the powder at 1050 °C for 48 h, resulted in the formation of the desired phases. Both traditional laboratory and high resolution synchrotron X-ray diffraction (XRD) analyses were used for phase identification of the synthesized powder. Additionally, scanning electron microscopy and transmission electron microscopy were employed, along with XRD, to further characterize the microstructure of the phases produced.

Reconstructed imaging of acoustic cloak using time-lapse reversal method

NASA Astrophysics Data System (ADS)

Zhou, Chen; Cheng, Ying; Xu, Jian-yi; Li, Bo; Liu, Xiao-jun

2014-08-01

We proposed and investigated a solution to the inverse acoustic cloak problem, an anti-stealth technology to make cloaks visible, using the time-lapse reversal (TLR) method. The TLR method reconstructs the image of an unknown acoustic cloak by utilizing scattered acoustic waves. Compared to previous anti-stealth methods, the TLR method can determine not only the existence of a cloak but also its exact geometric information like definite shape, size, and position. Here, we present the process for TLR reconstruction based on time reversal invariance. This technology may have potential applications in detecting various types of cloaks with different geometric parameters.

Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis A Virus

PubMed Central

St. Leger, J. A.; Liang, E.; Hicks, A. L.; Sanchez-Leon, M. D.; Jain, K.; Lefkowitch, J. H.; Navarrete-Macias, I.; Knowles, N.; Goldstein, T.; Pugliares, K.; Rowles, T.; Lipkin, W. I.

2015-01-01

ABSTRACT Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV. PMID:26307166

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

PubMed Central

Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

2013-01-01

Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH. PMID:22781098

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

PubMed

Beck, Bodo B; Baasner, Anne; Buescher, Anja; Habbig, Sandra; Reintjes, Nadine; Kemper, Markus J; Sikora, Przemyslaw; Mache, Christoph; Pohl, Martin; Stahl, Mirjam; Toenshoff, Burkhard; Pape, Lars; Fehrenbach, Henry; Jacob, Dorrit E; Grohe, Bernd; Wolf, Matthias T; Nürnberg, Gudrun; Yigit, Gökhan; Salido, Eduardo C; Hoppe, Bernd

2013-02-01

Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.

Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis.

PubMed

Cario, Holger; Schwarz, Klaus; Jorch, Norbert; Kyank, Ulrike; Petrides, Petro E; Schneider, Dominik T; Uhle, Renate; Debatin, Klaus-Michael; Kohne, Elisabeth

2005-01-01

Congenital erythrocytoses or polycythemias are rare and heterogeneous. A homozygous mutation (C598T->Arg200Trp) in the von Hippel-Lindau (VHL) gene was originally identified as the cause of the endemic Chuvash polycythemia. Subsequently this and other mutations in the VHL gene were also detected in several patients of different ethnic origin. Haplotype analyses of the VHL gene suggested a common origin for the Chuvash-type mutation. Thirty-four patients with presumable congenital erythrocytosis due to an unknown underlying disorder were examined for VHL gene mutations and VHL region haplotypes. Four patients were homozygous and one patient heterozygous for the Chuvash-type mutation. One additional patient presented a previously not described heterozygous mutation G311->T VHL in exon 1. The haplotype analyses were in agreement with recently published data for three of the four patients with homozygous mutations as well as for the patient with a heterozygous Chuvash-type mutation. One patient of Turkish origin with homozygous Chuvash-type mutation had a haplotype not previously found in individuals with Chuvash-type mutation. These results confirm that mutations in the VHL gene are responsible for a substantial proportion of patients with congenital erythrocytoses. Erythrocytoses due to a C598->T mutation of the VHL gene are not geographically restricted. The majority of patients with Chuvash polycythemia share a common VHL gene haplotype. The different haplotype in one of the patients with Chuvash-type mutation indicates that this mutation was not spread only from a single founder but developed independently in other individuals.

A new species of Rhadinella (Serpentes: Colubridae) from the Sierra Madre del Sur of Guerrero, Mexico.

PubMed

Campillo, Gustavo; Dávila-Galavíz, Luis Fernando; Flores-Villela, Oscar; Campbell, Jonathan A

2016-04-12

We describe a new species of Rhadinella from the Sierra Madre del Sur of Guerrero, Mexico, a region where the genus was previously unknown. This diminutive species is a member of a group of snakes previously allocated in the Rhadinaea godmani group, and more recently transferred to the genus Rhadinella. These snakes may have conspicuous dark longitudinal striping on a pale brown to orange background or may have dark brown to blackish dorsal ground coloration, which mostly or completely obfuscates a pattern of longitudinal striping. The new species is mostly dark with barely discernible slightly paler or darker striping (depending on how striping is interpreted). The closest relative of the new species, on the basis of morphological similarities and biogeography, appears to be Rhadinella donaji which occurs to the east in the Sierra Madre del Sur of Oaxaca about 275 km from the type-locality of the new species.

MUSIC-type imaging of small perfectly conducting cracks with an unknown frequency

NASA Astrophysics Data System (ADS)

Park, Won-Kwang

2015-09-01

MUltiple SIgnal Classification (MUSIC) is a famous non-iterative detection algorithm in inverse scattering problems. However, when the applied frequency is unknown, inaccurate locations are identified via MUSIC. This fact has been confirmed through numerical simulations. However, the reason behind this phenomenon has not been investigated theoretically. Motivated by this fact, we identify the structure of MUSIC-type imaging functionals with unknown frequency, by establishing a relationship with Bessel functions of order zero of the first kind. Through this, we can explain why inaccurate results appear.

Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.

PubMed

Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K

2016-07-01

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Opportunistic pathology-based screening for diabetes

PubMed Central

Simpson, Aaron J; Krowka, Renata; Kerrigan, Jennifer L; Southcott, Emma K; Wilson, J Dennis; Potter, Julia M; Nolan, Christopher J; Hickman, Peter E

2013-01-01

Objective To determine the potential of opportunistic glycated haemoglobin (HbA1c) testing of pathology samples to detect previously unknown diabetes. Design Pathology samples from participants collected for other reasons and suitable for HbA1c testing were utilised for opportunistic diabetes screening. HbA1c was measured with a Biorad Variant II turbo analyser and HbA1c levels of ≥6.5% (48 mmol/mol) were considered diagnostic for diabetes. Confirmation of previously unknown diabetes status was obtained by a review of hospital medical records and phone calls to general practitioners. Setting Hospital pathology laboratory receiving samples from hospital-based and community-based (CB) settings. Participants Participants were identified based on the blood sample collection location in the CB, emergency department (ED) and inpatient (IP) groups. Exclusions pretesting were made based on the electronic patient history of: age <18 years, previous diabetes diagnosis, query for diabetes status in the past 12 months, evidence of pregnancy and sample collected postsurgery or transfusion. Only one sample per individual participant was tested. Results Of the 22 396 blood samples collected, 4505 (1142 CB, 1113 ED, 2250 IP) were tested of which 327 (7.3%) had HbA1c levels ≥6.5% (48 mmol/mol). Of these 120 (2.7%) were determined to have previously unknown diabetes (11 (1%) CB, 21 (1.9%) ED, 88 (3.9%) IP). The prevalence of previously unknown diabetes was substantially higher (5.4%) in hospital-based (ED and IP) participants aged over 54 years. Conclusions Opportunistic testing of referred pathology samples can be an effective method of screening for diabetes, especially in hospital-based and older persons. PMID:24065696

HIV-negative and HIV-discordant Gay Male Couples’ Use of HIV Risk-Reduction Strategies: Differences by Partner Type and Couples’ HIV-status

PubMed Central

Mitchell, Jason W.

2014-01-01

Previous research has found that gay men and other men who have sex with men (MSM) have adopted a variety of HIV risk-reduction strategies to engage in unprotected anal intercourse (UAI). However, whether gay male couples’ use these strategies within and out of their relationships remains unknown. The present national cross-sectional study collected dyadic data from an online sample of 275 HIV-negative and 58 discordant gay male couples to assess their use of these strategies, and whether their use of these strategies had differed by partner type and couples’ HIV-status. The sample used a variety of risk-reduction strategies for UAI. Some differences and patterns by partner type and couples’ HIV status were detected about men’s use of these strategies. Findings indicate the need to bolster HIV prevention and education with gay male couples about their use of these strategies within and outside of their relationships. PMID:23247364

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

PubMed

Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

Type C botulism in pelicans and other fish-eating birds at the Salton Sea

USGS Publications Warehouse

Rocke, T.E.; Nol, P.; Pelizza, C.; Sturm, K.K.

2004-01-01

In 1996, type C avian botulism killed over 10,000 pelicans and nearly 10,000 other fish-eating birds at the Salton Sea in southern California. Although botulism had been previously documented in waterbirds at the Sea, this die-off was unusual in that it involved primarily fish-eating birds. The American White Pelican (Pelecanus erythrorynchos) was the species with the greatest mortality in 1996. Since 1996, mortality has recurred every year but losses have declined (<2,000 birds/year), with relatively more Brown Pelicans (P. occidentalis) than White Pelicans afflicted. In 2000, morbidity and mortality of Brown Pelicans with type C botulism (1311) approached the numbers afflicted in 1996 (2034). In recent years, mortality reached a peak earlier in the summer, July and August, in contrast to 1996 when mortality reached a peak in September. An exotic fish species, tilapia (Oreochromis mossambicus), has been implicated as the source of toxin for birds at Salton Sea, but the source of toxin for fish is unknown.

The developmental basis of an evolutionary diversification of female gametophyte structure in Piper and Piperaceae

PubMed Central

Madrid, Eric N.; Friedman, William E.

2009-01-01

Background and Aims Fritillaria-type female gametophyte development is a complex, yet homoplasious developmental pattern that is interesting from both evolutionary and developmental perspectives. Piper (Piperaceae) was chosen for this study of Fritillaria-type female gametophyte development because Piperales represent a ‘hotspot’ of female gametophyte developmental evolution and have been the subject of several recent molecular phylogenetic analyses. This wealth of phylogenetic and descriptive data make Piper an excellent candidate for inferring the evolutionary developmental basis for the origin of Fritillaria-type female gametophytes. Methods Developing ovules of Piper peltatum were taken from greenhouse collections, embedded in glycol methacrylate, and serially sectioned. Light microscopy and laser scanning confocal microscopy were combined to produce three-dimensional computer reconstructions of developing female gametophytes. The ploidies of the developing embryos and endosperms were calculated using microspectrofluorometry. Key Results The data describe female gametophyte development in Piper with highly detailed three-dimensional models, and document two previously unknown arrangements of megaspore nuclei during early development. Also collected were microspectrofluorometric data that indicate that Fritillaria-type female gametophyte development in Piper results in pentaploid endosperm. Conclusions The three-dimensional models resolve previous ambiguities in developmental interpretations of Fritillaria-type female gametophytes in Piper. The newly discovered arrangements of megaspore nuclei that are described allow for the construction of explicit hypotheses of female gametophyte developmental evolution within Piperaceae, and more broadly throughout Piperales. These detailed hypotheses indicate that the common ancestor of Piperaceae minus Verhuellia had a Drusa-type female gametophyte, and that evolutionary transitions to derived tetrasporic female gametophyte ontogenies in Piperaceae, including Fritillaria-type female gametophyte development, are the consequence of key nuclear migration and patterning events at the end of megasporogenesis. PMID:19202137

The first sexual associations in the genus Darditilla Casal, 1965 (Hymenoptera, Mutillidae)

PubMed Central

Luz, David R.; Williams, Kevin A.

2014-01-01

Abstract New sex associations are proposed for four species of Darditilla: Darditilla amabilis (Gerstaecker, 1874); Darditilla bejaranoi Casal, 1968; Darditilla debilis (Gerstaecker, 1874); and Darditilla felina (Burmeister, 1854). Darditilla botija Casal, 1965, syn. n. is the male of Darditilla amabilis; the other three males were previously unknown. Mutilla decorosa Kohl, 1882, syn. n. is conspecific with Darditilla felina. Descriptions and extended diagnoses are provided for previously unknown males and for females that were not adequately described. These represent the first sex associations for the genus Darditilla. PMID:25493066

TGFbeta type II receptor signaling controls Schwann cell death and proliferation in developing nerves.

PubMed

D'Antonio, Maurizio; Droggiti, Anna; Feltri, M Laura; Roes, Jürgen; Wrabetz, Lawrence; Mirsky, Rhona; Jessen, Kristján R

2006-08-16

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGFbeta signaling did not appear to affect other processes in which TGFbeta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.

Inhibition of membrane type-1 matrix metalloproteinase by cancer drugs interferes with the homing of diabetogenic T cells into the pancreas.

PubMed

Savinov, Alexei Y; Rozanov, Dmitri V; Golubkov, Vladislav S; Wong, F Susan; Strongin, Alex Y

2005-07-29

We have discovered that clinically tested inhibitors of matrix metalloproteinases can control the functional activity of T cell membrane type-1 matrix metalloproteinase (MT1-MMP) and the onset of disease in a rodent model of type 1 diabetes in non-obese diabetic mice. We determined that MT1-MMP proteolysis of the T cell surface CD44 adhesion receptor affects the homing of T cells into the pancreas. We also determined that both the induction of the intrinsic T cell MT1-MMP activity and the shedding of cellular CD44 follow the adhesion of insulin-specific, CD8-positive, Kd-restricted T cells to the matrix. Conversely, inhibition of these events by AG3340 (a potent hydroxamate inhibitor that was widely used in clinical trials in cancer patents) impedes the transmigration of diabetogenic T cells into the pancreas and protects non-obese diabetic mice from diabetes onset. Overall, our studies have divulged a previously unknown function of MT1-MMP and identified a promising novel drug target in type I diabetes.

Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1

PubMed Central

Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J. Preben; Andreasen, Peter A.; Jensen, Jan K.

2016-01-01

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). PMID:27189939

Tamoxifen treatment for pubertal gynecomastia in two siblings with partial androgen insensitivity syndrome.

PubMed

Saito, Reiko; Yamamoto, Yukiyo; Goto, Motohide; Araki, Shunsuke; Kubo, Kazuyasu; Kawagoe, Rinko; Kawada, Yasusada; Kusuhara, Koichi; Igarashi, Maki; Fukami, Maki

2014-01-01

Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.

Improving Hall Thruster Plume Simulation through Refined Characterization of Near-field Plasma Properties

NASA Astrophysics Data System (ADS)

Huismann, Tyler D.

Due to the rapidly expanding role of electric propulsion (EP) devices, it is important to evaluate their integration with other spacecraft systems. Specifically, EP device plumes can play a major role in spacecraft integration, and as such, accurate characterization of plume structure bears on mission success. This dissertation addresses issues related to accurate prediction of plume structure in a particular type of EP device, a Hall thruster. This is done in two ways: first, by coupling current plume simulation models with current models that simulate a Hall thruster's internal plasma behavior; second, by improving plume simulation models and thereby increasing physical fidelity. These methods are assessed by comparing simulated results to experimental measurements. Assessment indicates the two methods improve plume modeling capabilities significantly: using far-field ion current density as a metric, these approaches used in conjunction improve agreement with measurements by a factor of 2.5, as compared to previous methods. Based on comparison to experimental measurements, recent computational work on discharge chamber modeling has been largely successful in predicting properties of internal thruster plasmas. This model can provide detailed information on plasma properties at a variety of locations. Frequently, experimental data is not available at many locations that are of interest regarding computational models. Excepting the presence of experimental data, there are limited alternatives for scientifically determining plasma properties that are necessary as inputs into plume simulations. Therefore, this dissertation focuses on coupling current models that simulate internal thruster plasma behavior with plume simulation models. Further, recent experimental work on atom-ion interactions has provided a better understanding of particle collisions within plasmas. This experimental work is used to update collision models in a current plume simulation code. Previous versions of the code assume an unknown dependence between particles' pre-collision velocities and post-collision scattering angles. This dissertation focuses on updating several of these types of collisions by assuming a curve fit based on the measurements of atom-ion interactions, such that previously unknown angular dependences are well-characterized.

Rhodotorula bloemfonteinensis sp. nov., Rhodotorula eucalyptica sp. nov., Rhodotorula orientis sp. nov. and Rhodotorula pini sp. nov., yeasts isolated from monoterpene-rich environments.

PubMed

Pohl, Carolina H; Smit, Martha S; Albertyn, Jacobus

2011-09-01

Recent rDNA sequencing of 25 isolates from a previous study, during which limonene-utilizing yeasts were isolated from monoterpene-rich environments by using 1,4-disubstituted cyclohexanes as sole carbon sources, led to the identification of four hitherto unknown Rhodotorula species. Analyses of the 26S rDNA D1/D2 region as well as the internal transcribed spacer (ITS) domain indicated that two isolates (CBS 8499(T) and CBS 10736) were identical and were closely related to Rhodotorula cycloclastica, a previously described limonene-utilizing yeast. These novel isolates differed from known yeast species and could be distinguished from R. cycloclastica by standard physiological tests. The other three isolates represent three novel Rhodotorula species, closely related to Sporobolomyces magnisporus. These three species could also be distinguished from other Rhodotorula species by standard physiological tests. Based on these results, we suggest that the new isolates represent novel species, for which the names Rhodotorula eucalyptica sp. nov. (type strain CBS 8499(T)  = NRRL Y-48408(T)), Rhodotorula pini sp. nov. (type strain CBS 10735(T)  = NRRL Y-48410(T)), Rhodotorula bloemfonteinensis sp. nov. (type strain CBS 8598(T)  = NRRL Y-48407(T)) and Rhodotorula orientis sp. nov. (type strain CBS 8594(T)  = NRRL Y-48719(T)) are proposed. R. eucalyptica and R. pini can also utilize limonene.

Correlation of a Bipolar-Transistor-Based Neutron Displacement Damage Sensor Methodology with Proton Irradiations

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

Tonigan, Andrew M.; Arutt, Charles N.; Parma, Edward J.

For this research, a bipolar-transistor-based sensor technique has been used to compare silicon displacement damage from known and unknown neutron energy spectra generated in nuclear reactor and high-energy-density physics environments. The technique has been shown to yield 1-MeV(Si) equivalent neutron fluence measurements comparable to traditional neutron activation dosimetry. This study significantly extends previous results by evaluating three types of bipolar devices utilized as displacement damage sensors at a nuclear research reactor and at a Pelletron particle accelerator. Ionizing dose effects are compensated for via comparisons with 10-keV x-ray and/or cobalt-60 gamma ray irradiations. Non-ionizing energy loss calculations adequately approximate themore » correlations between particle-device responses and provide evidence for the use of one particle type to screen the sensitivity of the other.« less

Correlation of a Bipolar-Transistor-Based Neutron Displacement Damage Sensor Methodology with Proton Irradiations

DOE PAGES

Tonigan, Andrew M.; Arutt, Charles N.; Parma, Edward J.; ...

2017-11-16

For this research, a bipolar-transistor-based sensor technique has been used to compare silicon displacement damage from known and unknown neutron energy spectra generated in nuclear reactor and high-energy-density physics environments. The technique has been shown to yield 1-MeV(Si) equivalent neutron fluence measurements comparable to traditional neutron activation dosimetry. This study significantly extends previous results by evaluating three types of bipolar devices utilized as displacement damage sensors at a nuclear research reactor and at a Pelletron particle accelerator. Ionizing dose effects are compensated for via comparisons with 10-keV x-ray and/or cobalt-60 gamma ray irradiations. Non-ionizing energy loss calculations adequately approximate themore » correlations between particle-device responses and provide evidence for the use of one particle type to screen the sensitivity of the other.« less

Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man.

PubMed

Gillmore, J D; Booth, D R; Pepys, M B; Hawkins, P N

1999-09-01

An 83 year old white man with atrial fibrillation was admitted to hospital after a cerebral infarct. Echocardiography was characteristic of cardiac amyloid deposition and subsequent tests confirmed amyloidosis of transthyretin (TTR) type, in association with the Ile122 mutation of the TTR gene; this has only been reported previously in African Americans in whom it occurs with an allele frequency of 2%. Haplotype analysis did not suggest a different founder than for the African Ile122 mutation. Cardiac amyloidosis should be considered among elderly patients presenting with cardiac failure and/or arrhythmia, particularly if they are resistant to conventional treatment; if confirmed, it should be followed by precise characterisation of amyloid fibril type. The prevalence of autosomal dominant cardiac TTR amyloidosis in elderly white people is unknown but early diagnosis and supportive treatment may prevent complications among affected family members.

Community composition of known and uncultured archaeal lineages in anaerobic or anoxic wastewater treatment sludge.

PubMed

Kuroda, Kyohei; Hatamoto, Masashi; Nakahara, Nozomi; Abe, Kenichi; Takahashi, Masanobu; Araki, Nobuo; Yamaguchi, Takashi

2015-04-01

Microbial systems are widely used to treat different types of wastewater from domestic, agricultural, and industrial sources. Community composition is an important factor in determining the successful performance of microbial treatment systems; however, a variety of uncultured and unknown lineages exist in sludge that requires identification and characterization. The present study examined the archaeal community composition in methanogenic, denitrifying, and nitrogen-/phosphate-removing wastewater treatment sludge by Archaea-specific 16S rRNA gene sequencing analysis using Illumina sequencing technology. Phylotypes belonging to Euryarchaeota, including methanogens, were most abundant in all samples except for nitrogen-/phosphate-removing wastewater treatment sludge. High levels of Deep Sea Hydrothermal Vent Group 6 (DHVEG-6), WSA2, Terrestrial Miscellaneous Euryarchaeotal Group, and Miscellaneous Crenarchaeotic Group were also detected. Interestingly, DHVEG-6 was dominant in nitrogen-/phosphate-removing wastewater treatment sludge, indicating that unclear lineages of Archaea still exist in the anaerobic wastewater treatment sludges. These results reveal a previously unknown diversity of Archaea in sludge that can potentially be exploited for the development of more efficient wastewater treatment strategies.

Embryonic background risk promotes the survival of tadpoles facing surface predators

PubMed Central

Chivers, Douglas P.; Ferrari, Maud C. O.

2018-01-01

Exposure to intense predation risk can induce morphological and behavioural phenotypes that prepare prey, often at young ages, for surviving attacks from unknown predators. However, previous studies revealed that this survival advantage depended on the predator species. Here, we used alarm cues from injured conspecifics to simulate a period of high predation risk for embryonic wood frogs, Lithobates sylvaticus. Two weeks post-hatching, we tested whether the embryonic risk exposure influenced survival in encounters with two novel predators: (1) a spider (Dolomedes sp.) that ambushes prey exclusively on the surface of the water, and (2) the adult predacious diving beetle (Dytiscus sp.) which displays underwater sit-and-wait posture and pursuit tactics. Tadpoles exposed to embryonic high-risk survived longer when encountering spiders, whereas background risk had no influence on survival with adult beetles. These findings, coupled with survival studies involving other predator types, indicate that a high-risk environment promotes tadpole survival in future encounters with unknown sit-and-wait predators, but at the cost of increased vulnerability to novel predators capable of active pursuit. PMID:29561913

Experience improves feature extraction in Drosophila.

PubMed

Peng, Yueqing; Xi, Wang; Zhang, Wei; Zhang, Ke; Guo, Aike

2007-05-09

Previous exposure to a pattern in the visual scene can enhance subsequent recognition of that pattern in many species from honeybees to humans. However, whether previous experience with a visual feature of an object, such as color or shape, can also facilitate later recognition of that particular feature from multiple visual features is largely unknown. Visual feature extraction is the ability to select the key component from multiple visual features. Using a visual flight simulator, we designed a novel protocol for visual feature extraction to investigate the effects of previous experience on visual reinforcement learning in Drosophila. We found that, after conditioning with a visual feature of objects among combinatorial shape-color features, wild-type flies exhibited poor ability to extract the correct visual feature. However, the ability for visual feature extraction was greatly enhanced in flies trained previously with that visual feature alone. Moreover, we demonstrated that flies might possess the ability to extract the abstract category of "shape" but not a particular shape. Finally, this experience-dependent feature extraction is absent in flies with defective MBs, one of the central brain structures in Drosophila. Our results indicate that previous experience can enhance visual feature extraction in Drosophila and that MBs are required for this experience-dependent visual cognition.

Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae

PubMed Central

2011-01-01

Background The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in acyl-malonyl condensing enzyme proteins. In this paper, we present an evolutionary analysis of nucleotide sugar transporters in relation to the entire superfamily of drug/metabolite transporters that considers crucial intra-protein duplication events that have shaped the transporters. We use a method that combines the strengths of hidden Markov models and maximum likelihood to find relationships between drug/metabolite transporter families, and branches within families. Results We present evidence that the triose-phosphate transporters, domain unknown function 914, uracil-diphosphate glucose-N-acetylglucosamine, and nucleotide sugar transporter families have evolved from a domain duplication event before the radiation of Viridiplantae in the EamA family (previously called domain unknown function 6). We identify previously unknown branches in the solute carrier 30, 35 and 39 protein families that emerged simultaneously as key physiological developments after the radiation of Viridiplantae, including the "35C/E" branch of EamA, which formed in the lineage of T. adhaerens (Animalia). We identify a second cluster of DMTs, called the domain unknown function 1632 cluster, which has non-cytosolic N- and C-termini, and thus appears to have been formed from a different domain duplication event. We identify a previously uncharacterized motif, G-X(6)-G, which is overrepresented in the fifth transmembrane helix of C-terminal domains. We present evidence that the family called fatty acid elongases are homologous to transporters, not enzymes as had previously been thought. Conclusions The nucleotide sugar transporters families were formed through differentiation of the gene cluster EamA (domain unknown function 6) before Viridiplantae, showing for the first time the significance of EamA. PMID:21569384

Robot learning and error correction

NASA Technical Reports Server (NTRS)

Friedman, L.

1977-01-01

A model of robot learning is described that associates previously unknown perceptions with the sensed known consequences of robot actions. For these actions, both the categories of outcomes and the corresponding sensory patterns are incorporated in a knowledge base by the system designer. Thus the robot is able to predict the outcome of an action and compare the expectation with the experience. New knowledge about what to expect in the world may then be incorporated by the robot in a pre-existing structure whether it detects accordance or discrepancy between a predicted consequence and experience. Errors committed during plan execution are detected by the same type of comparison process and learning may be applied to avoiding the errors.

Modified human crania from Göbekli Tepe provide evidence for a new form of Neolithic skull cult

PubMed Central

Gresky, Julia; Haelm, Juliane; Clare, Lee

2017-01-01

Archaeological excavations at Göbekli Tepe, a transitional Neolithic site in southeast Turkey, have revealed the earliest megalithic ritual architecture with characteristic T-shaped pillars. Although human burials are still absent from the site, a number of fragmented human bones have been recovered from fill deposits of buildings and from adjacent areas. We focus on three partially preserved human skulls, all of which carry artificial modifications of a type so far unknown from contemporaneous sites and the ethnographic record. As such, modified skull fragments from Göbekli Tepe could indicate a new, previously undocumented variation of skull cult in the Early Neolithic of Anatolia and the Levant. PMID:28782013

A practical method for estimating maximum shear modulus of cemented sands using unconfined compressive strength

NASA Astrophysics Data System (ADS)

Choo, Hyunwook; Nam, Hongyeop; Lee, Woojin

2017-12-01

The composition of naturally cemented deposits is very complicated; thus, estimating the maximum shear modulus (Gmax, or shear modulus at very small strains) of cemented sands using the previous empirical formulas is very difficult. The purpose of this experimental investigation is to evaluate the effects of particle size and cement type on the Gmax and unconfined compressive strength (qucs) of cemented sands, with the ultimate goal of estimating Gmax of cemented sands using qucs. Two sands were artificially cemented using Portland cement or gypsum under varying cement contents (2%-9%) and relative densities (30%-80%). Unconfined compression tests and bender element tests were performed, and the results from previous studies of two cemented sands were incorporated in this study. The results of this study demonstrate that the effect of particle size on the qucs and Gmax of four cemented sands is insignificant, and the variation of qucs and Gmax can be captured by the ratio between volume of void and volume of cement. qucs and Gmax of sand cemented with Portland cement are greater than those of sand cemented with gypsum. However, the relationship between qucs and Gmax of the cemented sand is not affected by the void ratio, cement type and cement content, revealing that Gmax of the complex naturally cemented soils with unknown in-situ void ratio, cement type and cement content can be estimated using qucs.

Lod score curves for phase-unknown matings.

PubMed

Hulbert-Shearon, T; Boehnke, M; Lange, K

1996-01-01

For a phase-unknown nuclear family, we show that the likelihood and lod score are unimodal, and we describe conditions under which the maximum occurs at recombination fraction theta = 0, theta = 1/2, and 0 < theta < 1/2. These simply stated necessary and sufficient conditions seem to have escaped the notice of previous statistical geneticists.

Fatal Metacestode Infection in Bornean Orangutan Caused by Unknown Versteria Species

PubMed Central

Gendron-Fitzpatrick, Annette; Deering, Kathleen M.; Wallace, Roberta S.; Clyde, Victoria L.; Lauck, Michael; Rosen, Gail E.; Bennett, Andrew J.; Greiner, Ellis C.; O’Connor, David H.

2014-01-01

A captive juvenile Bornean orangutan (Pongo pygmaeus) died from an unknown disseminated parasitic infection. Deep sequencing of DNA from infected tissues, followed by gene-specific PCR and sequencing, revealed a divergent species within the newly proposed genus Versteria (Cestoda: Taeniidae). Versteria may represent a previously unrecognized risk to primate health. PMID:24377497

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

PubMed

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Evolution of mantis shrimps (Stomatopoda, Malacostraca) in the light of new Mesozoic fossils

PubMed Central

2010-01-01

Background We describe new specimens of Mesozoic mantis shrimps (Stomatopoda, Malacostraca) that exhibit morphological and developmental information previously unknown. Results Specimens assigned to the taxon Sculda exhibit preserved pleopods, thoracopods including all four raptorial limbs as well as details of antennae and antennulae. The pleopods and the antennulae resemble those of the modern mantis shrimps, but the raptorial limbs are not as differentiated as in the modern species. In some specimens, the first raptorial limb (second thoracopod) is not significantly larger than the similar-sized posterior three pairs (as in extant species), but instead these appendages become progressively smaller along the series. In this respect they resemble certain Palaeozoic stomatopods. Another specimen, most likely belonging to another species, has one pair of large anterior raptorial thoracopods, a median-sized pair and two more pairs of small-sized raptorial appendages and, thus, shows a new, previously unknown type of morphology. A single specimen of Pseudosculda laevis also exhibits the size of the raptorial limbs; they are differentiated as in modern species, one large pair and three small pairs. Furthermore, we report additional larval specimens and show also post-larval changes, e.g., of the tail fan. Conclusions These new data are used to reconsider the phylogeny of Stomatopoda. We still need a strict taxonomical revision of the Mesozoic mantis shrimps, but this first examination already demonstrates the importance of these fossils for understanding mantis shrimp evolution and the interpretation of evolutionary pathways of particular features. PMID:20858249

Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue

PubMed Central

Davidsson, Sabina; Carlsson, Jessica; Mölling, Paula; Gashi, Natyra; Andrén, Ove; Andersson, Swen-Olof; Brzuszkiewicz, Elzbieta; Poehlein, Anja; Al-Zeer, Munir A.; Brinkmann, Volker; Scavenius, Carsten; Nazipi, Seven; Söderquist, Bo; Brüggemann, Holger

2017-01-01

Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes. PMID:29201018

Contributions to the History of Astronomy, Vol. 3. (German Title: Beiträge zur Astronomiegeschichte, Band 3)

NASA Astrophysics Data System (ADS)

Dick, Wolfgang R.; Hamel, Jürgen

The main papers of this issue deal with previously unknown details of the foundation of the astronomical observatories in Gotha and in Königsberg (with numerous original documents by F.W. Bessel), with the Mecklenburg ordnance survey (1853-1873, with previously unknown letters by C.F. Gauss), with the merits of the Leipzig astronomer G.A. Jahn, with the internationality of the Astronomische Gesellschaft, and with early, previously little noted works on the expansion of the Universe. The issue contains a description of the important collection of sundials in the Kassel museum, discussions about the Medieval ``Phantom Period'', about Goethe's description of the zodiacal light, as well as obituaries and book reviews. Most papers in German, one in English.

"Physics is supposed to be spoken of with a bit of irony": unknown speech by L D Landau, 8 April 1960

NASA Astrophysics Data System (ADS)

Druzhinin, P. A.

2018-01-01

A previously unknown speech by Lev Landau dated 8 April 1960 has been published, as transcribed from a unique tape recording obtained from the Russian State Phonogram Archive (Moscow). This is Landau's only true public speech known to have been recorded.

Opsins in Limulus eyes: characterization of three visible light-sensitive opsins unique to and co-expressed in median eye photoreceptors and a peropsin/RGR that is expressed in all eyes

PubMed Central

Battelle, Barbara-Anne; Kempler, Karen E.; Saraf, Spencer R.; Marten, Catherine E.; Dugger, Donald R.; Speiser, Daniel I.; Oakley, Todd H.

2015-01-01

The eyes of the horseshoe crab Limulus polyphemus have long been used for studies of basic mechanisms of vision, and the structure and physiology of Limulus photoreceptors have been examined in detail. Less is known about the opsins Limulus photoreceptors express. We previously characterized a UV opsin (LpUVOps1) that is expressed in all three types of Limulus eyes (lateral compound eyes, median ocelli and larval eyes) and three visible light-sensitive rhabdomeric opsins (LpOps1, -2 and -5) that are expressed in Limulus lateral compound and larval eyes. Physiological studies showed that visible light-sensitive photoreceptors are also present in median ocelli, but the visible light-sensitive opsins they express were unknown. In the current study we characterize three newly identified, visible light-sensitive rhabdomeric opsins (LpOps6, -7 and -8) that are expressed in median ocelli. We show that they are ocellar specific and that all three are co-expressed in photoreceptors distinct from those expressing LpUVOps1. Our current findings show that the pattern of opsin expression in Limulus eyes is much more complex than previously thought and extend our previous observations of opsin co-expression in visible light-sensitive Limulus photoreceptors. We also characterize a Limulus peropsin/RGR (LpPerOps1). We examine the phylogenetic relationship of LpPerOps1 with other peropsins and RGRs, demonstrate that LpPerOps1 transcripts are expressed in each of the three types of Limulus eyes and show that the encoded protein is expressed in membranes of cells closely associated with photoreceptors in each eye type. These finding suggest that peropsin was in the opsin repertoire of euchelicerates. PMID:25524988

A comparison of infrared, radar, and geologic mapping of lunar craters

USGS Publications Warehouse

Thompson, T.W.; Masursky, H.; Shorthill, R.W.; Tyler, G.L.; Zisk, S.H.

1974-01-01

Between 1000 and 2000 infrared (eclipse) and radar anomalies have been mapped on the nearside hemisphere of the Moon. A study of 52 of these anomalies indicates that most are related to impact craters and that the nature of the infrared and radar responses is compatible with a previously developed geologic model of crater aging processes. The youngest craters are pronounced thermal and radar anomalies; that is, they have enhanced eclipse temperatures and are strong radar scatterers. With increasing crater age, the associated thermal and radar responses become progressively less noticeable until they assume values for the average lunar surface. The last type of anomaly to disappear is radar enhancement at longer wavelengths. A few craters, however, have infrared and radar behaviors not predicted by the aging model. One previously unknown feature - a field strewn with centimeter-sized rock fragments - has been identified by this technique of comparing maps at the infrared, radar, and visual wavelengths. ?? 1974 D. Reidel Publishing Company, Dordrecht-Holland.

Identification of a Golgi apparatus protein complex important for the asexual erythrocytic cycle of the malaria parasite Plasmodium falciparum.

PubMed

Hallée, Stéphanie; Thériault, Catherine; Gagnon, Dominic; Kehrer, Jessica; Frischknecht, Friedrich; Mair, Gunnar R; Richard, Dave

2018-03-26

Compared with other eukaryotic cell types, malaria parasites appear to possess a more rudimentary Golgi apparatus being composed of dispersed, unstacked cis and trans-cisternae. Despite playing a central role in the secretory pathway of the parasite, few Plasmodium Golgi resident proteins have been characterised. We had previously identified a new Golgi resident protein of unknown function, which we had named Golgi Protein 1, and now show that it forms a complex with a previously uncharacterised transmembrane protein (Golgi Protein 2, GP2). The Golgi Protein complex localises to the cis-Golgi throughout the erythrocytic cycle and potentially also during the mosquito stages. Analysis of parasite strains where GP1 expression is conditionally repressed and/or the GP2 gene is inactivated reveals that though the Golgi protein complex is not essential at any stage of the parasite life cycle, it is important for optimal asexual development in the blood stages. © 2018 John Wiley & Sons Ltd.

The Stellar Cusp in the Galactic Center: Three-Dimensional Orbits of Stars

NASA Astrophysics Data System (ADS)

Chappell, Samantha; Ghez, Andrea M.; Boehle, Anna; Yelda, Sylvana; Sitarski, Breann; Witzel, Gunther; Do, Tuan; Lu, Jessica R.; Morris, Mark; Becklin, Eric E.

2015-01-01

We present new findings from our long term study of the nuclear star cluster around the Galaxy's central supermassive blackhole (SMBH). Measurements where made using speckle and laser guided adaptive optics imaging and integral field spectroscopy on the Keck telescopes. We report 13 new measurable accelerating sources around the SMBH, down to ~17 mag in K band, only 4 of which are known to be young stars, the rest are either known to be old stars or have yet to be spectral typed. Thus we more than double the number of measured accelerations for the known old stars and unknown spectral type population (increasing the number from 6 to 15). Previous observations suggest a flat density profile of late-type stars, contrary to the theorized Bahcall-Wolf cusp (Bahcall & Wolf 1976, 1977; Buchholz et al. 2009; Do et al. 2009; Bartko et al. 2010). With three-dimensional orbits of significantly accelerating sources, we will be able to better characterize the stellar cusp in the Galactic center, including the slope of the stellar density profile.

Identification of Yeast V-ATPase Mutants by Western Blots Analysis of Whole Cell Lysates

NASA Astrophysics Data System (ADS)

Parra-Belky, Karlett

2002-11-01

A biochemistry laboratory was designed for an undergraduate course to help students better understand the link between molecular engineering and biochemistry. Students identified unknown yeast strains with high specificity using SDS-PAGE and Western blot analysis of whole cell lysates. This problem-solving exercise is a common application of biochemistry in biotechnology research. Three different strains were used: a wild-type and two mutants for the proton pump vacuolar ATPase (V-ATPase). V-ATPases are multisubunit enzymes and the mutants used were deletion mutants; each lacked one structural gene of the complex. After three, three-hour labs, mutant strains were easily identified by the students and distinguished from wild-type cells analyzing the pattern of SDS-PAGE distribution of proteins. Identifying different subunits of one multimeric protein allowed for discussion of the structure and function of this metabolic enzyme, which captured the interest of the students. The experiment can be adapted to other multimeric protein complexes and shows improvement of the described methodology over previous reports, perhaps because the problem and its solution are representative of the type of techniques currently used in research labs.

GEM Building Taxonomy (Version 2.0)

USGS Publications Warehouse

Brzev, S.; Scawthorn, C.; Charleson, A.W.; Allen, L.; Greene, M.; Jaiswal, Kishor; Silva, V.

2013-01-01

/7/8/IRRE9/10/RSH3+RWO211/FW12/13/ which can be read as (1) Direction = [DX or DY] (the building has the same lateral load-resisting system in both directions); (2) Material = [Unreinforced Masonry + solid fired clay bricks + cement: lime mortar]; (3) Lateral Load-Resisting System = [Wall]; (4) Date of construction = [pre-1939]; (5) Heaight = [exactly 2 storeys]; (6) Occupancy = [residential, unknown type]; (7) Building Position = [unknown = no entry]; (8) Shape of building plan = [unknown = no entry]; (9) Structural irregularity = [regular]; (10) Exterior walls = [unknown = no entry]; (11) Roof = [Shape: pitched and hipped, Roof covering: clay tiles, Roof system material: wood, Roof system type: wood trusses]; (12) Floor = [Floor system: Wood, unknown]; (13) Foundation = [unknown = no entry]. Mapping of GEM Building Taxonomy to selected taxonomies is included in the report -- for example, the above building would be referenced by previous structural taxonomies as: PAGER-STR as UFB or UFB4, by the World Housing Encyclopedia as 7 or 8 and by the European Macroseismic Scale (98) as M5. The Building Taxonomy data model is highly flexible and has been incorporated within a relational database architecture. Due to its ability to represent building typologies using a shorthand form, it is also possible to use the taxonomy for non-database applications, and we discuss possible application of adaptation for Building Information Modelling (BIM) systems, and for the insurance industry. The GEM Building Taxonomy was independently evaluated and tested by the Earthquake Engineering Research Institute (EERI), which received 217 TaxT reports from 49 countries, representing a wide range of building typologies, including single and multi-storey buildings, reinforced and unreinforced masonry, confined masonry, concrete, steel, wood, and earthern buildings used for residential, commercial, industrial, and educational occupancy. Based on these submissions and other feedback, the EERI team validated that the GEM Building Taxonomy is highly functional, robust and able to describe different buildings around the world. The GEM Building Taxonomy is accompanied by supplementary resources. All terms have been explained in a companion online Glossary, which provides both text and graphic descriptions. The Taxonomy is accompanied by TaxT, a computer application that enables a user record information about a building or a building typology using the attributes of the GEM Building Taxonomy v2.0. TaxT can generate a taxonomy string and enable a user to generate a report in PDF format which summarizes the attribute values (s)he has chosen as representative of the building typology under consideration. The report concludes with recommendations for future development of the GEM Building Taxonomy. Appendices provide the detailed GEM Building Taxonomy tables and additional resource, as well as mappings to other taxonomies.

The role of ecological divergence in speciation between intertidal and subtidal Scoloplos armiger (Polychaeta, Orbiniidae)

NASA Astrophysics Data System (ADS)

Kruse, Inken; Strasser, Matthias; Thiermann, Frank

2004-02-01

The concept of ecological speciation implies that habitat differences may split a species by strong selection and rapid adaptation even under sympatric conditions. Studies on the polychaete Scoloplos armiger in the Wadden Sea (North Sea) indicate sibling species existing in sympatry: the intertidal 'Type I' with holobenthic development out of egg cocoons and the subtidal 'Type S' producing pelagic larvae. In the current study, Types I and S are compared in habitat-related traits of reproductive timing and physiological response to hypoxia and sulphide. Spawnings of Type I and Type S recorded over six years overlap in spring and both appear to be triggered by a rise in seawater temperature above 5 °C. Type S exhibits an additional autumn spawning (at seawater temperatures around 10 °C) which was previously unknown and is absent in Type I. The overall abundance of pelagic larvae in the Wadden Sea is higher in spring than in autumn. Tolerance of both sulphide and hypoxia was lower in Type S than in Type I. This correlates with a 5 to 10-fold lower sulphide concentration in the subtidal compared to the intertidal habitat. Physiological tolerance and divergence in developmental mode appear as traits which may have led to reproductive isolation between Type I and Type S. Their role in allopatric and sympatric speciation scenarios in S. armiger is discussed. Since the pelagic dispersal mode has been neglected so far, a reassessment of population dynamics models for S. armiger is suggested.

A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

DOE PAGES

Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

2014-11-06

Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components thatmore » form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.« less

[Pharmacovigilance in Portugal: Activity of the Central Pharmacovigilance Unit].

PubMed

Batel-Marques, Francisco; Mendes, Diogo; Alves, Carlos; Penedones, Ana; Dias, Patricia; Martins, Angelina; Santiago, Luiz Miguel; Fontes-Ribeiro, Carlos; Caramona, Margarida; Macedo, Tice

2015-01-01

The aim of this study was to characterize the spontaneous reports of adverse events that were received by the Central Portugal Regional Pharmacovigilance Unit. Spontaneous reports received between 01/2001 and 12/2013 were considered. The annual reporting ratios were estimated. The cases were characterized according to their seriousness, previous description, causality assessment, origin and professional group of the reporter, type of adverse event and pharmacotherapeutic groups of the suspected drugs most frequently reported. The Pharmacovigilance Unit received 2408 reports that contained 5749 adverse events. In 2013, the reporting rate was estimated at 171 reports per million inhabitants. Fifty-five percent of the reports were assessed as serious. Ninety percent of the cases were assessed as being at least possibly related with the suspected drug. The suspected drugs most frequently reported were anti-infectives for systemic use (n = 809, 33%). The most frequently reported adverse events were "Skin and subcutaneous tissue disorders" (n = 1139, 20%). There were 154 (6.4%) reports resulting in life-threatening situations and/or death, and 88 (3.6%) containing at least one adverse event assessed as serious, unknown and certain or probable. The present results are in line with those found in other studies, namely the seriousness and type of the adverse events and the pharmacotherapeutic groups of the most frequently reported suspected drugs. In the last years, the Central Portugal Regional Pharmacovigilance Unit has registered a growth in the reporting rate in general, as well as an increase in the reporting of unknown and serious adverse drug reactions.

Expression of the ADHD candidate gene Diras2 in the brain.

PubMed

Grünewald, Lena; Becker, Nils; Camphausen, Annika; O'Leary, Aet; Lesch, Klaus-Peter; Freudenberg, Florian; Reif, Andreas

2018-06-01

The distinct subgroup of the Ras family member 2 (DIRAS2) gene has been found to be associated with attention-deficit/hyperactivity disorder (ADHD) in one of our previous studies. This gene is coding for a small Ras GTPase with unknown function. DIRAS2 is highly expressed in the brain. However, the exact neural expression pattern of this gene was unknown so far. Therefore, we investigated the expressional profile of DIRAS2 in the human and murine brain. In the present study, qPCR analyses in the human and in the developing mouse brain, immunocytological double staining on murine hippocampal primary cells and RNA in situ hybridization (ISH) on brain sections of C57BL/6J wild-type mice, have been used to reveal the expression pattern of DIRAS2 in the brain. We could show that DIRAS2 expression in the human brain is the highest in the hippocampus and the cerebral cortex, which is in line with the ISH results in the mouse brain. During mouse brain development, Diras2 levels strongly increase from prenatal to late postnatal stages. Co-expression studies indicate Diras2 expression in glutamatergic and catecholaminergic neurons. Our findings support the idea of DIRAS2 as a candidate gene for ADHD as the timeline of its expression as well as the brain regions and cell types that show Diras2 expression correspond to those assumed to underlie the pathomechanisms of the disease.

Comparing the Effects of Unknown-Known Ratios on Word Reading Learning versus Learning Rates

ERIC Educational Resources Information Center

Joseph, Laurice M.; Nist, Lindsay M.

2006-01-01

An extension of G. L. Cates et al. (2003) investigation was conducted to determine if students' cumulative learning rates would be superior for words read under a traditional drill and practice condition (as they were for spelling in the previous study) than under interspersal conditions of varying ratios of unknown to known words. Participants…

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

PubMed Central

Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Richards, Kristy L.; Dunphy, Cherie H.; Choi, William W. L.; Yan Au, Wing; Srivastava, Gopesh; Czader, Magdalena B.; Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon; Naresh, Kikkeri N.; Evens, Andrew M.; Gordon, Leo I.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; Thompson, Michael A.; Gill, Javed I.; Liu, Qingquan; How, Tam; Grubor, Vladimir; Gao, Yuan; Patel, Amee; Wu, Han; Zhu, Jun; Blobe, Gerard C.; Lipsky, Peter E.; Chadburn, Amy

2010-01-01

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. PMID:20733160

Fragmentation pathways of O-alkyl methylphosphonothionocyanidates in the gas phase: toward unambiguous structural characterization of chemicals in the Chemical Weapons Convention framework.

PubMed

Saeidian, Hamid; Babri, Mehran; Ashrafi, Davood; Sarabadani, Mansour; Naseri, Mohammad Taghi

2013-08-01

The electron-impact (EI) mass spectra of a series of O-alkyl methylphosphonothionocyanidates were studied for Chemical Weapons Convention (CWC) purposes. General EI fragmentation pathways were constructed and discussed, and collision-induced dissociation studies of the major EI ions were performed to confirm proposed fragment structures by analyzing fragment ions of deuterated analogs and by use of density functional theory (DFT) calculations. Thiono-thiolo rearrangement, McLafferty-type rearrangement, and a previously unknown intramolecular electrophilic aromatic substitution reaction were observed and confirmed. The study also focused on differentiation of isomeric compounds. Retention indices for all compounds, and an electrophilicity index for several compounds, are reported and interpreted.

Use of satellite data in volcano monitoring

NASA Technical Reports Server (NTRS)

Mcclelland, Lindsay

1987-01-01

It is argued that Total Ozone Mapping Spectrometer (TOMS) data, especially data on sulfur dioxide detection in volcanic clouds, and weather satellite data complement each other. TOMS data is most useful for discovering previously unknown eruptions and indicating a minimum volume of SO sub 2 produced by a given eruption. Once an eruption has been reported, weather satellite data can be used to accurately monitor its progress. To be used effectively, these data need to be analyzed jointly and in real time. Toward this end, it is hoped that full and timely utilization can be made of existing TOMS data, a polar orbiting TOMS can be launched in the near future, and that TOMS type instruments can be included on future geostationary satellites.

Cytoplasmic vacuolization in cell death and survival

PubMed Central

Komissarov, Alexey A.; Rafieva, Lola M.; Kostrov, Sergey V.

2016-01-01

Cytoplasmic vacuolization (also called cytoplasmic vacuolation) is a well-known morphological phenomenon observed in mammalian cells after exposure to bacterial or viral pathogens as well as to various natural and artificial low-molecular-weight compounds. Vacuolization often accompanies cell death; however, its role in cell death processes remains unclear. This can be attributed to studying vacuolization at the level of morphology for many years. At the same time, new data on the molecular mechanisms of the vacuole formation and structure have become available. In addition, numerous examples of the association between vacuolization and previously unknown cell death types have been reported. Here, we review these data to make a deeper insight into the role of cytoplasmic vacuolization in cell death and survival. PMID:27331412

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

PubMed

Holman, Rury R; Bethel, M Angelyn; Mentz, Robert J; Thompson, Vivian P; Lokhnygina, Yuliya; Buse, John B; Chan, Juliana C; Choi, Jasmine; Gustavson, Stephanie M; Iqbal, Nayyar; Maggioni, Aldo P; Marso, Steven P; Öhman, Peter; Pagidipati, Neha J; Poulter, Neil; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F

2017-09-28

The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).

Morningness-eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus.

PubMed

Osonoi, Yusuke; Mita, Tomoya; Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Nakayama, Shiho; Someya, Yuki; Ishida, Hidenori; Kanazawa, Akio; Gosho, Masahiko; Fujitani, Yoshio; Watada, Hirotaka

2014-11-01

"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.

Injury trend analysis from the US Open Tennis Championships between 1994 and 2009.

PubMed

Sell, Katie; Hainline, Brian; Yorio, Michael; Kovacs, Mark

2014-04-01

Injuries can be a debilitating aspect of professional tennis. Injury rates and trends at the US Open Tennis Championships over multiple years are unknown. The purpose of this study was to examine injury trends in professional tennis players competing in a major professional tennis tournament between 1994 and 2009. From 1994 to 2009, injury data from the US Open Tennis Championships were recorded. Injuries were classified by location and type using terminology derived from a consensus statement developed specifically for tennis. Injury rates were determined based on the exposure of an athlete to a match event, and were calculated as the ratio of injuries per 1000 match exposures (MEs). There was a statistically significant fluctuation in injuries across the timeframe analysed (p<0.05). There were 76.2±19.6 total injuries and 43.8±11.8 acute injuries per year seeking medical assistance. Muscle or tendon injuries were the most common type of acute injury. The rate of lower limb injuries was significantly higher than upper limb and trunk injuries (p<0.01). The ankle, followed by the wrist, knee, foot/toe and shoulder/clavicle were the most common injury sites. Acute injuries occurred more frequently than gradual-onset injuries, and most common injury types were similar to previously examined populations. However, there were differences in injury location trends compared to previous research, suggesting that further research in this elite-level population is warranted.

HLA Type Inference via Haplotypes Identical by Descent

NASA Astrophysics Data System (ADS)

Setty, Manu N.; Gusev, Alexander; Pe'Er, Itsik

The Human Leukocyte Antigen (HLA) genes play a major role in adaptive immune response and are used to differentiate self antigens from non self ones. HLA genes are hyper variable with nearly every locus harboring over a dozen alleles. This variation plays an important role in susceptibility to multiple autoimmune diseases and needs to be matched on for organ transplantation. Unfortunately, HLA typing by serological methods is time consuming and expensive compared to high throughput Single Nucleotide Polymorphism (SNP) data. We present a new computational method to infer per-locus HLA types using shared segments Identical By Descent (IBD), inferred from SNP genotype data. IBD information is modeled as graph where shared haplotypes are explored among clusters of individuals with known and unknown HLA types to identify the latter. We analyze performance of the method in a previously typed subset of the HapMap population, achieving accuracy of 96% in HLA-A, 94% in HLA-B, 95% in HLA-C, 77% in HLA-DR1, 93% in HLA-DQA1 and 90% in HLA-DQB1 genes. We compare our method to a tag SNP based approach and demonstrate higher sensitivity and specificity. Our method demonstrates the power of using shared haplotype segments for large-scale imputation at the HLA locus.

[Antibodies and physiopathogeny of autoimmune hepatitis].

PubMed

García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

2003-01-01

Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

The relationship between semantic short-term memory and immediate serial recall of known and unknown words and nonwords: data from two Chinese individuals with aphasia.

PubMed

Wong, Winsy; Low, Sam-Po

2008-07-01

The present study investigated verbal recall of semantically preserved and degraded words and nonwords by taking into consideration the status of one's semantic short-term memory (STM). Two experiments were conducted on 2 Chinese individuals with aphasia. The first experiment showed that they had largely preserved phonological processing abilities accompanied by mild but comparable semantic processing deficits; however, their performance on STM tasks revealed a double dissociation. The second experiment found that the participant with more preserved semantic STM had better recall of known words and nonwords than of their unknown counterparts, whereas such effects were absent in the patient with severe semantic STM deficit. The results are compatible with models that assume separate phonological and semantic STM components, such as that of R. C. Martin, M. Lesch, and M. Bartha (1999). In addition, the distribution of error types was different from previous studies. This is discussed in terms of the methodology of the authors' experiments and current views regarding the nature of semantic STM and representations in the Chinese mental lexicon. (c) 2008 APA

Protein function prediction using neighbor relativity in protein-protein interaction network.

PubMed

Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

2013-04-01

There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vesuvius: Earthquakes from 1600 up to the 1631 eruption

NASA Astrophysics Data System (ADS)

Guidoboni, Emanuela; Mariotti, Dante

2011-03-01

This study examines the seismicity of Vesuvius in the decades leading up to the great eruption of 16th December 1631. The period 1600-1631 is analyzed with the aims to point out any long-term seismic precursor of the eruption. The historical research has focused on contemporary Neapolitan memoirs and a large screening of diplomatic correspondence from the main Italian courts of the age (Florence, Mantua, Parma, Venice and the Vatican). Information was gathered on 18 earthquakes that were felt in Naples between 1601 and 1630. These data were listed with the sequence of 34 shocks that took place in November and December 1631, that preceded the beginning of the eruption. The 52 seismic events that have been highlighted overall are unknown in the parametric catalogues of Italian historical seismicity and 17 are unknown even in the scientific literature. The authors' view is that it makes little sense to talk of one single previous seismic precursor in this case, given the frequent seismic sequences and tremors noted by contemporaries from January 1616 onwards. The present state of knowledge suggests that seismic activity is a strong, early and persistent warning sign of an eruption of Vesuvius, of the same type as that of December 1631.

Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.

PubMed

Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong

2018-04-01

Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.

Function-based Biosensor for Hazardous Waste Toxin Detection

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

James J Hickman

There is a need for new types of toxicity sensors in the DOE and other agencies that are based on biological function as the toxins encountered during decontamination or waste remediation may be previously unknown or their effects subtle. Many times the contents of the environmental waste, especially the minor components, have not been fully identified and characterized. New sensors of this type could target unknown toxins that cause death as well as intermediate levels of toxicity that impair function or cause long term impairment that may eventually lead to death. The primary question posed in this grant was tomore » create an electronically coupled neuronal cellular circuit to be used as sensor elements for a hybrid non-biological/biological toxin sensor system. A sensor based on the electrical signals transmitted between two mammalian neurons would allow the marriage of advances in solid state electronics with a functioning biological system to develop a new type of biosensor. Sensors of this type would be a unique addition to the field of sensor technology but would also be complementary to existing sensor technology that depends on knowledge of what is to be detected beforehand. We integrated physics, electronics, surface chemistry, biotechnology, and fundamental neuroscience in the development of this biosensor. Methods were developed to create artificial surfaces that enabled the patterning of discrete cells, and networks of cells, in culture; the networks were then aligned with transducers. The transducers were designed to measure electromagnetic fields (EMF) at low field strength. We have achieved all of the primary goals of the project. We can now pattern neurons routinely in our labs as well as align them with transducers. We have also shown the signals between neurons can be modulated by different biochemicals. In addition, we have made another significant advance where we have repeated the patterning results with adult hippocampal cells. Finally, we demonstrated that patterned cardiac cells on microelectrode arrays could act as sensors as well.« less

Correlating chemical sensitivity and basal gene expression reveals mechanism of action | Office of Cancer Genomics

Cancer.gov

Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown.

Chemical Analysis of the Chinese Liquor Luzhoulaojiao by Comprehensive Two-Dimensional Gas Chromatography/Time-of-Flight Mass Spectrometry

PubMed Central

Yao, Feng; Yi, Bin; Shen, Caihong; Tao, Fei; Liu, Yumin; Lin, Zhixin; Xu, Ping

2015-01-01

Luzhoulaojiao liquor is a type of Chinese liquor that dates back hundreds of years, but whose precise chemical composition remains unknown. This paper describes the screening of the liquor and the identification of its compounds using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC/TOF-MS). Samples were prepared by both liquid-liquid extraction and solid-phase microextraction, which facilitated the detection of thousands of compounds in the liquor, thus demonstrating the superior performance of the proposed method over those reported in previous studies. A total of 320 compounds were common to all 18 types of Luzhoulaojiao liquor studied here, and 13 abundant and potentially bioactive compounds were further quantified. The results indicated that the high-performance method presented here is well suited for the detection and identification of compounds in liquors. This study also contributes to enriching our knowledge of the contents of Chinese liquors. PMID:25857434

The impact of large-scale, long-term optical surveys on pulsating star research

NASA Astrophysics Data System (ADS)

Soszyński, Igor

2017-09-01

The era of large-scale photometric variability surveys began a quarter of a century ago, when three microlensing projects - EROS, MACHO, and OGLE - started their operation. These surveys initiated a revolution in the field of variable stars and in the next years they inspired many new observational projects. Large-scale optical surveys multiplied the number of variable stars known in the Universe. The huge, homogeneous and complete catalogs of pulsating stars, such as Cepheids, RR Lyrae stars, or long-period variables, offer an unprecedented opportunity to calibrate and test the accuracy of various distance indicators, to trace the three-dimensional structure of the Milky Way and other galaxies, to discover exotic types of intrinsically variable stars, or to study previously unknown features and behaviors of pulsators. We present historical and recent findings on various types of pulsating stars obtained from the optical large-scale surveys, with particular emphasis on the OGLE project which currently offers the largest photometric database among surveys for stellar variability.

The ultraviolet spectrum of noncoronal late-type stars - The Gamma Crucis (M3.4 III) reference spectrum

NASA Technical Reports Server (NTRS)

Carpenter, Kenneth G.; Pesce, Joseph E.; Stencel, Robert E.; Brown, Alexander; Johansson, Sveneric

1988-01-01

A guide is presented to the UV spectrum of M-type giants and supergiants whose outer atmospheres contain warm chromospheres but not coronae. The M3 giant Gamma Crucis is taken as the archetype of the cooler, oxygen-rich, noncoronal stars. Line identifications and integrated line flux measurements of the chromospheric emission features seen in the 1200-3200 A range of IUE high-resolution spectra are presented. The major fluorescence processes operating in the outer atmosphere of Gamma Crucis, including eight previously unknown pumping processes and 21 new fluorescent line products, are summarized, and the enhancements of selected line strengths by 'line leakage' is discussed. A set of absorption features toward the longer wavelength end of this range is identified which can be used to characterize the radial velocity of the stellar photospheres. The applicability of the results to the spectra of noncoronal stars with different effective temperatures and gravities is discussed.

Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence.

PubMed

Yang, Li; Teixeira, Paulo José Pereira Lima; Biswas, Surojit; Finkel, Omri M; He, Yijian; Salas-Gonzalez, Isai; English, Marie E; Epple, Petra; Mieczkowski, Piotr; Dangl, Jeffery L

2017-02-08

Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCF COI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement

PubMed Central

Louie, Gordon; Noel, Joseph P.; Baran, Phil S.; Palfey, Bruce; Moore, Bradley S.

2013-01-01

Flavoproteins catalyze a diversity of fundamental redox reactions and are one of the most studied enzyme families1,2. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate1,3,4. Here we report that the bacterial flavoenzyme EncM5,6 catalyzes the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics coupled with isotope labeling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unanticipated stable flavin oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization. PMID:24162851

The Young Solar Analogs Project

NASA Astrophysics Data System (ADS)

Lambert, Ryan; Gray, Richard, , Dr.

2014-03-01

The ultimate goal of the Young Solar Analogs Project is to give insight into the conditions in the early solar system when life was first forming on the earth and to assess the challenges the young, active sun presented to that early life. To achieve this, we have been monitoring since 2007 the stellar activity of 31 young solar-type stars with ages between 0.3 and 1.5 Gyrs. Many of these stars exhibit star spot cycles like the sun, but in a few cases we are seeing evidence for a previously unknown type of star spot cycle. Some vary chaotically. We have detected the presence of differential rotation in several stars. We have also detected a number of powerful flares both photometrically and spectroscopically. Optical irradiance changes in these stars can be as high as 10% in a single year; such solar variability would have led to catastropic climate change on the early earth. We would like to thank NSF for their generous donations to this project.

Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase

PubMed Central

Chang, Wei-chen; Layne, Andrew P; Miles, Linde A; Krebs, Carsten

2014-01-01

Iron-dependent halogenases employ cis-halo-Fe(IV)-oxo (haloferryl) complexes to functionalize unactivated aliphatic carbon centers, a capability elusive to synthetic chemists. Halogenation requires (1) coordination of a halide anion (Cl− or Br−) to the enzyme's Fe(II) cofactor; (2) coupled activation of O2 and decarboxylation of α-ketoglutarate to generate the haloferryl intermediate; (3) abstraction of hydrogen (H•) from the substrate by the ferryl oxo group; and (4) transfer of the cis halogen as Cl• or Br• to the substrate radical. This enzymatic solution to an unsolved chemical challenge is potentially generalizable to installation of other functional groups, provided that the corresponding anions can support the four requisite steps. We show here that the wild-type halogenase SyrB2 can indeed direct aliphatic nitration and azidation reactions by the same chemical logic. The discovery and enhancement by mutagenesis of these previously unknown reaction types suggests unrecognized or untapped versatility in ferryl-mediated enzymatic C–H-bond activation. PMID:24463698

Chemical Analysis of the Chinese Liquor Luzhoulaojiao by Comprehensive Two-Dimensional Gas Chromatography/Time-of-Flight Mass Spectrometry

NASA Astrophysics Data System (ADS)

Yao, Feng; Yi, Bin; Shen, Caihong; Tao, Fei; Liu, Yumin; Lin, Zhixin; Xu, Ping

2015-04-01

Luzhoulaojiao liquor is a type of Chinese liquor that dates back hundreds of years, but whose precise chemical composition remains unknown. This paper describes the screening of the liquor and the identification of its compounds using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC/TOF-MS). Samples were prepared by both liquid-liquid extraction and solid-phase microextraction, which facilitated the detection of thousands of compounds in the liquor, thus demonstrating the superior performance of the proposed method over those reported in previous studies. A total of 320 compounds were common to all 18 types of Luzhoulaojiao liquor studied here, and 13 abundant and potentially bioactive compounds were further quantified. The results indicated that the high-performance method presented here is well suited for the detection and identification of compounds in liquors. This study also contributes to enriching our knowledge of the contents of Chinese liquors.

Partner-Level Factors Associated with Insertive and Receptive Condomless Anal Intercourse Among Transgender Women in Lima, Peru.

PubMed

Satcher, Milan F; Segura, Eddy R; Silva-Santisteban, Alfonso; Sanchez, Jorge; Lama, Javier R; Clark, Jesse L

2017-08-01

Condomless anal intercourse among transgender women (TW) in Peru has been shown to vary by the type of partner involved (e.g. primary vs. casual vs. transactional sex partner), but no previous studies have explored variations in partner-level patterns of condom use according to type of anal intercourse. We evaluated the relationship between partnership characteristics and condom use during insertive (IAI) versus receptive anal intercourse (RAI) among TW with recent, non-female partners. Condomless IAI was more common with transactional and casual sex partners and by TW who self-reported HIV-uninfected serostatus (p < 0.05), alcohol use disorders, or substance use before sex. Condomless RAI was more common with primary partners and by TW who described their HIV serostatus as unknown (p < 0.05). Examining partner-level differences between condomless IAI and RAI reveals distinct patterns of HIV/STI risk among TW, suggesting a need for HIV prevention strategies tailored to the specific contexts of partners, practices, and networks.

Differential inputs to striatal cholinergic and parvalbumin interneurons imply functional distinctions

PubMed Central

Klug, Jason R; Engelhardt, Max D; Cadman, Cara N; Li, Hao; Smith, Jared B; Ayala, Sarah; Williams, Elora W; Hoffman, Hilary

2018-01-01

Striatal cholinergic (ChAT) and parvalbumin (PV) interneurons exert powerful influences on striatal function in health and disease, yet little is known about the organization of their inputs. Here using rabies tracing, electrophysiology and genetic tools, we compare the whole-brain inputs to these two types of striatal interneurons and dissect their functional connectivity in mice. ChAT interneurons receive a substantial cortical input from associative regions of cortex, such as the orbitofrontal cortex. Amongst subcortical inputs, a previously unknown inhibitory thalamic reticular nucleus input to striatal PV interneurons is identified. Additionally, the external segment of the globus pallidus targets striatal ChAT interneurons, which is sufficient to inhibit tonic ChAT interneuron firing. Finally, we describe a novel excitatory pathway from the pedunculopontine nucleus that innervates ChAT interneurons. These results establish the brain-wide direct inputs of two major types of striatal interneurons and allude to distinct roles in regulating striatal activity and controlling behavior. PMID:29714166

Use of traditional medicine among type 2 diabetic Libyans.

PubMed

Ashur, Sana Taher; Shah, Shamsul Azhar; Bosseri, Soad; Shamsuddin, Khadijah

2017-07-16

The use of traditional medicines is common among patients with chronic illnesses and this practice might pose health risks. The use among Libyan patients with diabetes is unknown. Therefore, this study aimed to estimate the prevalence of traditional medicine use in the previous year among Libyans with type 2 diabetes and to examine the association between its use and sociodemographic and clinical characteristics of the patients. A cross-sectional study was conducted at a large diabetes centre in Tripoli. A self-reported questionnaire was used for data collection. Of the 523 respondents, 28.9% used traditional remedies. Sex was the only variable significantly associated with traditional medicine use; more women used traditional medicines (P = 0.01). A total of 77 traditional medicine items were reported to be used, of which herbs were the most common. The use of traditional medicine for diabetes is prevalent and some of the reported items could pose health risks. Health education programmes are suggested to raise the awareness of the health risks of this practice.

Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations.

PubMed

Singanayagam, Aran; Glanville, Nicholas; Girkin, Jason L; Ching, Yee Man; Marcellini, Andrea; Porter, James D; Toussaint, Marie; Walton, Ross P; Finney, Lydia J; Aniscenko, Julia; Zhu, Jie; Trujillo-Torralbo, Maria-Belen; Calderazzo, Maria Adelaide; Grainge, Chris; Loo, Su-Ling; Veerati, Punnam Chander; Pathinayake, Prabuddha S; Nichol, Kristy S; Reid, Andrew T; James, Phillip L; Solari, Roberto; Wark, Peter A B; Knight, Darryl A; Moffatt, Miriam F; Cookson, William O; Edwards, Michael R; Mallia, Patrick; Bartlett, Nathan W; Johnston, Sebastian L

2018-06-08

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1 -/- ) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.

Evolution of planetary nebulae. III. Position-velocity images of butterfly-type nebulae

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

Icke, V.; Preston, H.L.; Balick, B.

1989-02-01

Observations of the motions of the shells of the planetary nebulae NGC 2346, NGC 2371-2, NGC 2440, NGC 6058, NGC 6210, IC 1747, IC 5217, J-320, and M2-9 are presented. These are all 'butterfly' type PNs, and show evidence for bipolar shocks. The observations are interpreted in terms of a fast spherical wind, driven by the central star into a quasi-toroidal envelope deposited earlier by the star, during its slow-wind phase on the asymptotic giant branch. It is shown that this model, which is a straightforward extension of a mechanism previously invoked to account for elliptical PNs, reproduces the essentialmore » kinematic features of butterfly PNs. It is inferred that the envelopes of butterflies must have a considerable equator-to-pole density gradient, and it is suggested that the origin of this asphericity must be sought in an as yet unknown mechanism during the AGB, Mira, or OH/IR phases of late stellar evolution. 28 references.« less

Music Training and Working Memory: An ERP Study

ERIC Educational Resources Information Center

George, Elyse M.; Coch, Donna

2011-01-01

While previous research has suggested that music training is associated with improvements in various cognitive and linguistic skills, the mechanisms mediating or underlying these associations are mostly unknown. Here, we addressed the hypothesis that previous music training is related to improved working memory. Using event-related potentials…

Assessment of source-specific health effects associated with an unknown number of major sources of multiple air pollutants: a unified Bayesian approach.

PubMed

Park, Eun Sug; Hopke, Philip K; Oh, Man-Suk; Symanski, Elaine; Han, Daikwon; Spiegelman, Clifford H

2014-07-01

There has been increasing interest in assessing health effects associated with multiple air pollutants emitted by specific sources. A major difficulty with achieving this goal is that the pollution source profiles are unknown and source-specific exposures cannot be measured directly; rather, they need to be estimated by decomposing ambient measurements of multiple air pollutants. This estimation process, called multivariate receptor modeling, is challenging because of the unknown number of sources and unknown identifiability conditions (model uncertainty). The uncertainty in source-specific exposures (source contributions) as well as uncertainty in the number of major pollution sources and identifiability conditions have been largely ignored in previous studies. A multipollutant approach that can deal with model uncertainty in multivariate receptor models while simultaneously accounting for parameter uncertainty in estimated source-specific exposures in assessment of source-specific health effects is presented in this paper. The methods are applied to daily ambient air measurements of the chemical composition of fine particulate matter ([Formula: see text]), weather data, and counts of cardiovascular deaths from 1995 to 1997 for Phoenix, AZ, USA. Our approach for evaluating source-specific health effects yields not only estimates of source contributions along with their uncertainties and associated health effects estimates but also estimates of model uncertainty (posterior model probabilities) that have been ignored in previous studies. The results from our methods agreed in general with those from the previously conducted workshop/studies on the source apportionment of PM health effects in terms of number of major contributing sources, estimated source profiles, and contributions. However, some of the adverse source-specific health effects identified in the previous studies were not statistically significant in our analysis, which probably resulted because we incorporated parameter uncertainty in estimated source contributions that has been ignored in the previous studies into the estimation of health effects parameters. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Decomposition of Multi-player Games

NASA Astrophysics Data System (ADS)

Zhao, Dengji; Schiffel, Stephan; Thielscher, Michael

Research in General Game Playing aims at building systems that learn to play unknown games without human intervention. We contribute to this endeavour by generalising the established technique of decomposition from AI Planning to multi-player games. To this end, we present a method for the automatic decomposition of previously unknown games into independent subgames, and we show how a general game player can exploit a successful decomposition for game tree search.

Nuclear and chloroplast DNA phylogeny reveals complex evolutionary history of Elymus pendulinus.

PubMed

Yan, Chi; Hu, Qianni; Sun, Genlou

2014-02-01

Evidence accumulated over the last decade has shown that allopolyploid genomes may undergo complex reticulate evolution. In this study, 13 accessions of tetraploid Elymus pendulinus were analyzed using two low-copy nuclear genes (RPB2 and PepC) and two regions of chloroplast genome (Rps16 and trnD-trnT). Previous studies suggested that Pseudoroegneria (St) and an unknown diploid (Y) were genome donors to E. pendulinus, and that Pseudoroegneria was the maternal donor. Our results revealed an extreme reticulate pattern, with at least four distinct gene lineages coexisting within this species that might be acquired through a possible combination of allotetraploidization and introgression from both within and outside the tribe Hordeeae. Chloroplast DNA data identified two potential maternal genome donors (Pseudoroegneria and an unknown species outside Hordeeae) to E. pendulinus. Nuclear gene data indicated that both Pseudoroegneria and an unknown Y diploid have contributed to the nuclear genome of E. pendulinus, in agreement with cytogenetic data. However, unexpected contributions from Hordeum and unknown aliens from within or outside Hordeeae to E. pendulinus without genome duplication were observed. Elymus pendulinus provides a remarkable instance of the previously unsuspected chimerical nature of some plant genomes and the resulting phylogenetic complexity produced by multiple historical reticulation events.

Investigation of taxa of the family Pasteurellaceae isolated from Syrian and European hamsters and proposal of Mesocricetibacter intestinalis gen. nov., sp. nov. and Cricetibacter osteomyelitidis gen. nov., sp. nov.

PubMed

Christensen, H; Nicklas, W; Bisgaard, M

2014-11-01

Eleven strains from hamster of Bisgaard taxa 23 and 24, also referred to as Krause's groups 2 and 1, respectively, were investigated by a polyphasic approach including data published previously. Strains showed small, regular and circular colonies with smooth and shiny appearance, typical of members of the family Pasteurellaceae. The strains formed two monophyletic groups based on 16S rRNA gene sequence comparison to other members of the family Pasteurellaceae. Partial rpoB sequencing as well as published data on DNA-DNA hybridization showed high genotypic relationships within both groups. Menaquinone 7 (MK7) was found in strains of both groups as well as an unknown ubiquinone with shorter chain length than previously reported for any other member of the family Pasteurellaceae. A new genus with one species, Mesocricetibacter intestinalis gen. nov., sp. nov., is proposed to accommodate members of taxon 24 of Bisgaard whereas members of taxon 23 of Bisgaard are proposed to represent Cricetibacter osteomyelitidis gen. nov., sp. nov. Major fatty acids of type strains of type species of both genera are C(14:0), C(14:0) 3-OH/iso-C(16:1) I, C(16:1)ω7c and C(16:0). The two genera are clearly separated by phenotype from each other and from existing genera of the family Pasteurellaceae. The type strain of Mesocricetibacter intestinalis is HIM 933/7(T) ( =Kunstyr 246/85(T) =CCUG 28030(T) =DSM 28403(T)) while the type strain of Cricetibacter osteomyelitidis is HIM943/7(T) ( =Kunstyr 507/85(T) =CCUG 36451(T) =DSM 28404(T)). © 2014 IUMS.

Modeling of load lifting process with unknown center of gravity position

NASA Astrophysics Data System (ADS)

Kamanin, Y. N.; Zhukov, M. I.; Panichkin, A. V.; Redelin, R. A.

2018-03-01

The article proposes a new type of lifting beams that allows one to lift loads where the position of the center of gravity is unknown beforehand. The benefit of implementing this type of traverse is confirmed by the high demand for this product from the industrial enterprises and lack of their availability on the market. In conducted studies, the main kinematic and dynamic dependencies of the load lifting process with an unknown position of the center of gravity were described allowing for design and verification calculations of the traverse with flexible slings and an adjustable bail to be carried out. The obtained results can be useful to engineers and employees of enterprises engaged in the design and manufacturing of the lifting equipment and scientists doing research in “Carrying and lifting machines”.

Identification of Unknown Contaminants in Water Samples from ISS Employing Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

NASA Technical Reports Server (NTRS)

Rutz, Jeffrey A.; Schultz, John R.

2008-01-01

Mass Spectrometry/Mass Spectrometry (MS/MS) is a powerful technique for identifying unknown organic compounds. For non-volatile or thermally unstable unknowns dissolved in liquids, liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) is often the variety of MS/MS used for the identification. One type of LC/MS/MS that is rapidly becoming popular is time-of-flight (TOF) mass spectrometry. This technique is now in use at the Johnson Space Center for identification of unknown nonvolatile organics in water samples from the space program. An example of the successful identification of one unknown is reviewed in detail in this paper. The advantages of time-of-flight instrumentation are demonstrated through this example as well as the strategy employed in using time-of-flight data to identify unknowns.

Phenotypic and genotypic properties of Microbacterium yannicii, a recently described multidrug resistant bacterium isolated from a lung transplanted patient with cystic fibrosis in France.

PubMed

Sharma, Poonam; Diene, Seydina M; Thibeaut, Sandrine; Bittar, Fadi; Roux, Véronique; Gomez, Carine; Reynaud-Gaubert, Martine; Rolain, Jean-Marc

2013-05-03

Cystic fibrosis (CF) lung microbiota consists of diverse species which are pathogens or opportunists or have unknown pathogenicity. Here we report the full characterization of a recently described multidrug resistant bacterium, Microbacterium yannicii, isolated from a CF patient who previously underwent lung transplantation. Our strain PS01 (CSUR-P191) is an aerobic, rod shaped, non-motile, yellow pigmented, gram positive, oxidase negative and catalase positive bacterial isolate. Full length 16S rRNA gene sequence showed 98.8% similarity with Microbacterium yannicii G72T type strain, which was previously isolated from Arabidopsis thaliana. The genome size is 3.95Mb, with an average G+C content of 69.5%. In silico DNA-DNA hybridization analysis between our Microbacterium yannicii PS01isolate in comparison with Microbacterium testaceum StLB037 and Microbacterium laevaniformans OR221 genomes revealed very weak relationship with only 28% and 25% genome coverage, respectively. Our strain, as compared to the type strain, was resistant to erythromycin because of the presence of a new erm 43 gene encoding a 23S rRNA N-6-methyltransferase in its genome which was not detected in the reference strain. Interestingly, our patient received azithromycin 250 mg daily for bronchiolitis obliterans syndrome for more than one year before the isolation of this bacterium. Although significance of isolating this bacterium remains uncertain in terms of clinical evolution, this bacterium could be considered as an opportunistic human pathogen as previously reported for other species in this genus, especially in immunocompromised patients.

Error analysis in inverse scatterometry. I. Modeling.

PubMed

Al-Assaad, Rayan M; Byrne, Dale M

2007-02-01

Scatterometry is an optical technique that has been studied and tested in recent years in semiconductor fabrication metrology for critical dimensions. Previous work presented an iterative linearized method to retrieve surface-relief profile parameters from reflectance measurements upon diffraction. With the iterative linear solution model in this work, rigorous models are developed to represent the random and deterministic or offset errors in scatterometric measurements. The propagation of different types of error from the measurement data to the profile parameter estimates is then presented. The improvement in solution accuracies is then demonstrated with theoretical and experimental data by adjusting for the offset errors. In a companion paper (in process) an improved optimization method is presented to account for unknown offset errors in the measurements based on the offset error model.

Schlieren Cinematography of Current Driven Plasma Jet Dynamics

NASA Astrophysics Data System (ADS)

Loebner, Keith; Underwood, Thomas; Cappelli, Mark

2016-10-01

Schlieren cinematography of a pulsed plasma deflagration jet is presented and analyzed. An ultra-high frame rate CMOS camera coupled to a Z-type laser Schlieren apparatus is used to obtain flow-field refractometry data for the continuous flow Z-pinch formed within the plasma deflagration jet. The 10 MHz frame rate for 256 consecutive frames provides high temporal resolution, enabling turbulent fluctuations and plasma instabilities to be visualized over the course of a single pulse (20 μs). The Schlieren signal is radiometrically calibrated to obtain a two dimensional mapping of the refraction angle of the axisymmetric pinch plasma, and this mapping is then Abel inverted to derive the plasma density distribution as a function radius, axial coordinate, and time. Analyses of previously unknown discharge characteristics and comparisons with prior work are discussed.

FATAL GASTRIC DILATION IN TWO ADULT BLACK-FOOTED FERRETS (MUSTELA NIGRIPES).

PubMed

Hinton, Jenna D; Aitken-Palmer, Copper; Joyner, Priscilla H; Ware, Lisa; Walsh, Timothy F

2016-03-01

Acute gastric dilation resulting in death was identified in two adult black-footed ferrets (Mustela nigripes) housed at the Smithsonian Conservation Biology Institute in Front Royal, Virginia. Both individuals were adult males (3 and 5 yr) and previously clinically healthy prior to the event. The etiology of gastric dilation in both cases could not be definitively determined, and necropsy revealed severe cardiovascular compromise secondary to bloat. Limited literature is available regarding a syndrome of this type in adult black-footed ferrets. Differential diagnoses considered included gastric dilatation volvulus (GDV), severe gastric distention of unknown origin, and gastric outflow obstruction. Given the severity of this syndrome and the findings in these two cases, acute gastric dilation should be considered in black-footed ferrets presenting with acute abdominal distention, respiratory distress, and cardiovascular compromise.

The interaction between water currents and salmon swimming behaviour in sea cages.

PubMed

Johansson, David; Laursen, Frida; Fernö, Anders; Fosseidengen, Jan Erik; Klebert, Pascal; Stien, Lars Helge; Vågseth, Tone; Oppedal, Frode

2014-01-01

Positioning of sea cages at sites with high water current velocities expose the fish to a largely unknown environmental challenge. In this study we observed the swimming behaviour of Atlantic salmon (Salmo salar L.) at a commercial farm with tidal currents altering between low, moderate and high velocities. At high current velocities the salmon switched from the traditional circular polarized group structure, seen at low and moderate current velocities, to a group structure where all fish kept stations at fixed positions swimming against the current. This type of group behaviour has not been described in sea cages previously. The structural changes could be explained by a preferred swimming speed of salmon spatially restricted in a cage in combination with a behavioural plasticity of the fish.

Hazardous-waste-characterization survey of unknown drums at the 21st Tactical Fighter Wing, Elmendorf and Shemya Air Force Bases, and Galena and King Salmon Airports, Alaska. Final report 2-13 Aug 91

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

Bishop, M.S.

1991-12-01

At the request of the USAF Regional Hospital Elmendorf/SGPB (PACAF), the Armstrong Laboratory, Occupational and Environmental Health Directorate, conducted a hazardous waste characterization survey of unknown drums at Elmendorf AFB from 2 Aug - 13 Aug 91. The scope of the survey was to sample and characterize drums of unknown material stored at Elmendorf AFB, Shemya AFB, and Galena and King Salmon Airports. Several waste streams were sampled at Elmendorf AFB to revalidate sample results from a previous survey.

Influence of multiple categories on the prediction of unknown properties

PubMed Central

Verde, Michael F.; Murphy, Gregory L.; Ross, Brian H.

2006-01-01

Knowing an item's category helps us predict its unknown properties. Previous studies suggest that when asked to evaluate the probability of an unknown property, people tend to consider only an item's most likely category, ignoring alternative categories. In the present study, property prediction took the form of either a probability rating or a speeded, binary-choice judgment. Consistent with past findings, subjects ignored alternative categories in their probability ratings. However, their binary-choice judgments were influenced by alternative categories. This novel finding suggests that the way category knowledge is used in prediction depends critically on the form of the prediction. PMID:16156183

Discriminatory Power and Reproducibility of Novel DNA Typing Methods for Mycobacterium tuberculosis Complex Strains

PubMed Central

Kremer, Kristin; Arnold, Catherine; Cataldi, Angel; Gutiérrez, M. Cristina; Haas, Walter H.; Panaiotov, Stefan; Skuce, Robin A.; Supply, Philip; van der Zanden, Adri G. M.; van Soolingen, Dick

2005-01-01

In recent years various novel DNA typing methods have been developed which are faster and easier to perform than the current internationally standardized IS6110 restriction fragment length polymorphism typing method. However, there has been no overview of the utility of these novel typing methods, and it is largely unknown how they compare to previously published methods. In this study, the discriminative power and reproducibility of nine recently described PCR-based typing methods for Mycobacterium tuberculosis were investigated using the strain collection of the interlaboratory study of Kremer et al. (J. Clin. Microbiol. 37:2607-2618, 1999). This strain collection contains 90 M. tuberculosis complex and 10 non-M. tuberculosis complex mycobacterial strains, as well as 31 duplicated DNA samples to assess reproducibility. The highest reproducibility was found with variable numbers of tandem repeat typing using mycobacterial interspersed repetitive units (MIRU VNTR) and fast ligation-mediated PCR (FLiP), followed by second-generation spoligotyping, ligation-mediated PCR (LM-PCR), VNTR typing using five repeat loci identified at the Queens University of Belfast (QUB VNTR), and the Amadio speciation PCR. Poor reproducibility was associated with fluorescent amplified fragment length polymorphism typing, which was performed in three different laboratories. The methods were ordered from highest discrimination to lowest by the Hunter-Gaston discriminative index as follows: QUB VNTR typing, MIRU VNTR typing, FLiP, LM-PCR, and spoligotyping. We conclude that both VNTR typing methods and FLiP typing are rapid, highly reliable, and discriminative epidemiological typing methods for M. tuberculosis and that VNTR typing is the epidemiological typing method of choice for the near future. PMID:16272496

Locus of control as a stress moderator and mediator in children of divorce.

PubMed

Kim, L S; Sandler, I N; Tein, J Y

1997-04-01

This paper examined the stress moderator and mediator effects of four dimensions of perceived control in children of divorce. The dimensions of locus of control included internal control for positive events, internal control for negative events, unknown control for positive events, and unknown control for negative events. The sample consisted of 222 children between the ages of 8 and 12 whose parents had divorced in the previous 2 years. Moderational analyses showed that unknown control for positive events interacted with negative events to predict total symptoms. Plots of the simple slopes indicated a stress buffering effect whereby the slope of negative events on symptoms was higher for high than for low levels of unknown control for positive events. Mediational analysis showed that the relations between negative events and symptoms were mediated by both unknown control for positive events and unknown control for negative events. In contrast, evidence was not found for either a stress mediational or a moderational model for perceived internal control for positive or negative events. These results suggest that unknown control beliefs may be a particularly important dimension of control for children of divorce.

Random sampling of the Central European bat fauna reveals the existence of numerous hitherto unknown adenoviruses.

PubMed

Vidovszky, Márton; Kohl, Claudia; Boldogh, Sándor; Görföl, Tamás; Wibbelt, Gudrun; Kurth, Andreas; Harrach, Balázs

2015-12-01

From over 1250 extant species of the order Chiroptera, 25 and 28 are known to occur in Germany and Hungary, respectively. Close to 350 samples originating from 28 bat species (17 from Germany, 27 from Hungary) were screened for the presence of adenoviruses (AdVs) using a nested PCR that targets the DNA polymerase gene of AdVs. An additional PCR was designed and applied to amplify a fragment from the gene encoding the IVa2 protein of mastadenoviruses. All German samples originated from organs of bats found moribund or dead. The Hungarian samples were excrements collected from colonies of known bat species, throat or rectal swab samples, taken from live individuals that had been captured for faunistic surveys and migration studies, as well as internal organs of dead specimens. Overall, 51 samples (14.73%) were found positive. We detected 28 seemingly novel and six previously described bat AdVs by sequencing the PCR products. The positivity rate was the highest among the guano samples of bat colonies. In phylogeny reconstructions, the AdVs detected in bats clustered roughly, but not perfectly, according to the hosts' families (Vespertilionidae, Rhinolophidae, Hipposideridae, Phyllostomidae and Pteropodidae). In a few cases, identical sequences were derived from animals of closely related species. On the other hand, some bat species proved to harbour more than one type of AdV. The high prevalence of infection and the large number of chiropteran species worldwide make us hypothesise that hundreds of different yet unknown AdV types might circulate in bats.

Blue large-amplitude pulsators as a new class of variable stars

NASA Astrophysics Data System (ADS)

Pietrukowicz, Paweł; Dziembowski, Wojciech A.; Latour, Marilyn; Angeloni, Rodolfo; Poleski, Radosław; di Mille, Francesco; Soszyński, Igor; Udalski, Andrzej; Szymański, Michał K.; Wyrzykowski, Łukasz; Kozłowski, Szymon; Skowron, Jan; Skowron, Dorota; Mróz, Przemek; Pawlak, Michał; Ulaczyk, Krzysztof

2017-08-01

Regular intrinsic brightness variations observed in many stars are caused by pulsations. These pulsations provide information on the global and structural parameters of the star. The pulsation periods range from seconds to years, depending on the compactness of the star and properties of the matter that forms its outer layers. Here, we report the discovery of more than a dozen previously unknown short-period variable stars: blue large-amplitude pulsators. These objects show very regular brightness variations with periods in the range of 20-40 min and amplitudes of 0.2-0.4 mag in the optical passbands. The phased light curves have a characteristic sawtooth shape, similar to the shape of classical Cepheids and RR Lyrae-type stars pulsating in the fundamental mode. The objects are significantly bluer than main-sequence stars observed in the same fields, which indicates that all of them are hot stars. Follow-up spectroscopy confirms a high surface temperature of about 30,000 K. Temperature and colour changes over the cycle prove the pulsational nature of the variables. However, large-amplitude pulsations at such short periods are not observed in any known type of stars, including hot objects. Long-term photometric observations show that the variable stars are very stable over time. Derived rates of period change are of the order of 10-7 per year and, in most cases, they are positive. According to pulsation theory, such large-amplitude oscillations may occur in evolved low-mass stars that have inflated helium-enriched envelopes. The evolutionary path that could lead to such stellar configurations remains unknown.

The Complex Biogeography of the Plant Pathogen Xylella fastidiosa: Genetic Evidence of Introductions and Subspecific Introgression in Central America

PubMed Central

Nunney, Leonard; Ortiz, Beatriz; Russell, Stephanie A.; Ruiz Sánchez, Rebeca; Stouthamer, Richard

2014-01-01

The bacterium Xylella fastidiosa is a plant pathogen with a history of economically damaging introductions of subspecies to regions where its other subspecies are native. Genetic evidence is presented demonstrating the introduction of two new taxa into Central America and their introgression into the native subspecies, X. fastidiosa subsp. fastidiosa. The data are from 10 genetic outliers detected by multilocus sequence typing (MLST) of isolates from Costa Rica. Six (five from oleander, one from coffee) defined a new sequence type (ST53) that carried alleles at six of the eight loci sequenced (five of the seven MLST loci) diagnostic of the South American subspecies Xylella fastidiosa subsp. pauca which causes two economically damaging plant diseases, citrus variegated chlorosis and coffee leaf scorch. The two remaining loci of ST53 carried alleles from what appears to be a new South American form of X. fastidiosa. Four isolates, classified as X. fastidiosa subsp. fastidiosa, showed a low level of introgression of non-native DNA. One grapevine isolate showed introgression of an allele from X. fastidiosa subsp. pauca while the other three (from citrus and coffee) showed introgression of an allele with similar ancestry to the alleles of unknown origin in ST53. The presence of X. fastidiosa subsp. pauca in Central America is troubling given its disease potential, and establishes another route for the introduction of this economically damaging subspecies into the US or elsewhere, a threat potentially compounded by the presence of a previously unknown form of X. fastidiosa. PMID:25379725

The complex biogeography of the plant pathogen Xylella fastidiosa: genetic evidence of introductions and Subspecific introgression in Central America.

PubMed

Nunney, Leonard; Ortiz, Beatriz; Russell, Stephanie A; Ruiz Sánchez, Rebeca; Stouthamer, Richard

2014-01-01

The bacterium Xylella fastidiosa is a plant pathogen with a history of economically damaging introductions of subspecies to regions where its other subspecies are native. Genetic evidence is presented demonstrating the introduction of two new taxa into Central America and their introgression into the native subspecies, X. fastidiosa subsp. fastidiosa. The data are from 10 genetic outliers detected by multilocus sequence typing (MLST) of isolates from Costa Rica. Six (five from oleander, one from coffee) defined a new sequence type (ST53) that carried alleles at six of the eight loci sequenced (five of the seven MLST loci) diagnostic of the South American subspecies Xylella fastidiosa subsp. pauca which causes two economically damaging plant diseases, citrus variegated chlorosis and coffee leaf scorch. The two remaining loci of ST53 carried alleles from what appears to be a new South American form of X. fastidiosa. Four isolates, classified as X. fastidiosa subsp. fastidiosa, showed a low level of introgression of non-native DNA. One grapevine isolate showed introgression of an allele from X. fastidiosa subsp. pauca while the other three (from citrus and coffee) showed introgression of an allele with similar ancestry to the alleles of unknown origin in ST53. The presence of X. fastidiosa subsp. pauca in Central America is troubling given its disease potential, and establishes another route for the introduction of this economically damaging subspecies into the US or elsewhere, a threat potentially compounded by the presence of a previously unknown form of X. fastidiosa.

The Prevalence and Characteristics of Metabolic Syndrome in Patients with Vertigo

PubMed Central

Yamanaka, Toshiaki; Fukuda, Takehiko; Shirota, Shiho; Sawai, Yachiyo; Murai, Takayuki; Fujita, Nobuya; Hosoi, Hiroshi

2013-01-01

Objectives/Hypothesis Metabolic syndrome (MetS) is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo. Study Design Case-control study Methods The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation definition, which is based on waist circumference, blood serum levels, and blood pressure. Results MetS was detected in 53 (15.9%) of 333 vertigo patients, including 24 males (22.4%) and 29 females (12.8%); i.e., the frequency of MetS was significantly higher among the male patients than the female patients. The overall prevalence of MetS (15.9%) among vertigo patients did not differ from that observed among general adults in previous Japanese surveillance studies; however, MetS was significantly more common among the vertigo patients in males than general adult males. The prevalence of MetS was also examined in five types of vertigo, Concomitant MetS was noted in many males with vertebrobasilar insufficiency (VBI) and isolated vertigo of unknown etiology. Conclusion It was suggested that MetS is involved in the development of vertigo in males. MetS might be a risk factor for vascular vertigo such as VBI in males. The high frequency of MetS among males with vertigo of unknown etiology suggested that the pathogenesis of metabolic syndrome is involved in this type of isolated vertigo. PMID:24312461

Sparse graph regularization for robust crop mapping using hyperspectral remotely sensed imagery with very few in situ data

NASA Astrophysics Data System (ADS)

Xue, Zhaohui; Du, Peijun; Li, Jun; Su, Hongjun

2017-02-01

The generally limited availability of training data relative to the usually high data dimension pose a great challenge to accurate classification of hyperspectral imagery, especially for identifying crops characterized with highly correlated spectra. However, traditional parametric classification models are problematic due to the need of non-singular class-specific covariance matrices. In this research, a novel sparse graph regularization (SGR) method is presented, aiming at robust crop mapping using hyperspectral imagery with very few in situ data. The core of SGR lies in propagating labels from known data to unknown, which is triggered by: (1) the fraction matrix generated for the large unknown data by using an effective sparse representation algorithm with respect to the few training data serving as the dictionary; (2) the prediction function estimated for the few training data by formulating a regularization model based on sparse graph. Then, the labels of large unknown data can be obtained by maximizing the posterior probability distribution based on the two ingredients. SGR is more discriminative, data-adaptive, robust to noise, and efficient, which is unique with regard to previously proposed approaches and has high potentials in discriminating crops, especially when facing insufficient training data and high-dimensional spectral space. The study area is located at Zhangye basin in the middle reaches of Heihe watershed, Gansu, China, where eight crop types were mapped with Compact Airborne Spectrographic Imager (CASI) and Shortwave Infrared Airborne Spectrogrpahic Imager (SASI) hyperspectral data. Experimental results demonstrate that the proposed method significantly outperforms other traditional and state-of-the-art methods.

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication.

PubMed

Kistler, Logan; Newsom, Lee A; Ryan, Timothy M; Clarke, Andrew C; Smith, Bruce D; Perry, George H

2015-12-08

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops' progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval.

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication

PubMed Central

Kistler, Logan; Newsom, Lee A.; Ryan, Timothy M.; Smith, Bruce D.; Perry, George H.

2015-01-01

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops’ progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval. PMID:26630007

Conformation Types of Ubiquitin [M+8H]8+ Ions from Water:Methanol Solutions: Evidence for the N and A States in Aqueous Solution

PubMed Central

Shi, Huilin; Pierson, Nicholas A.; Valentine, Stephen J.; Clemmer, David E.

2012-01-01

Ion mobility and mass spectrometry measurements are used to examine the gas-phase populations of [M+8H]8+ ubiquitin ions formed upon electrospraying 20 different solutions: from 100:0 to 5:95 water:methanol that are maintained at pH = 2.0. Over this range of solution conditions, mobility distributions for the +8 charge state show substantial variations. Here we develop a model that treats the combined measurements as one data set. By varying the relative abundances of a discrete set of conformation types, it is possible to represent distributions obtained from any solution. For solutions that favor the well-known A-state ubiquitin, it is possible to represent the gas-phase distributions with seven conformation types. Aqueous conditions that favor the native structure require four more structural types to represent the distribution. This analysis provides the first direct evidence for trace amounts of the A state under native conditions. The method of analysis presented here should help illuminate how solution populations evolve into new gas-phase structures as solvent is removed. Evidence for trace quantities of previously unknown states under native solution conditions may provide insight about the relationship of dynamics to protein function as well as misfolding and aggregation phenomena. PMID:22315998

Familial Hemiplegic Migraine Type 1 Associated with Parkinsonism: A Case Report

PubMed Central

Bruun, Marie; Hjermind, Lena Elisabeth; Thomsen, Carsten; Danielsen, Else; Thomsen, Lise Lykke; Pinborg, Lars Hageman; Khabbazbavani, Nastaran; Nielsen, Joergen Erik

2015-01-01

Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present with cerebellar signs, but parkinsonism has not previously been reported in FHM1 or EA2 even though parkinsonism has been described in SCA6. We report a 63-year-old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically presenting with migraine and permanent cerebellar ataxia. Since the age of 60 years, the patient also developed parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission computed tomography demonstrated a decreased DAT-binding potential in the putamen. We wish to draw attention to FHM1 associated with parkinsonism; however, whether the reported case is a consequence of FHM1 being allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or idiopathic Parkinson's disease remains unanswered. PMID:25969684

Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

PubMed Central

Skogman, Barbro H.; Hellberg, Sandra; Ekerfelt, Christina; Jenmalm, Maria C.; Forsberg, Pia; Ludvigsson, Johnny; Bergström, Sven; Ernerudh, Jan

2012-01-01

Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown. PMID:22190976

Development of a spreadsheet for SNPs typing using Microsoft EXCEL.

PubMed

Hashiyada, Masaki; Itakura, Yukio; Takahashi, Shirushi; Sakai, Jun; Funayama, Masato

2009-04-01

Single-nucleotide polymorphisms (SNPs) have some characteristics that make them very appropriate for forensic studies and applications. In our institute, SNPs typings were performed by the TaqMan SNP Genotyping Assays using the ABI PRISM 7500 FAST Real-Time PCR System (AppliedBiosystems) and Sequence Detection Software ver.1.4 (AppliedBiosystem). The TaqMan method was desired two positive control (Allele1 and 2) and one negative control to analyze each SNP locus. Therefore, it can be analyzed up to 24 loci of a person on a 96-well-plate at the same time. If SNPs analysis is expected to apply to biometrics authentication, 48 and over loci are required to identify a person. In this study, we designed a spreadsheet package using Microsoft EXCEL, and population data were used from our 120 SNPs population studies. On the spreadsheet, we defined SNP types using 'template files' instead of positive and negative controls. "Template files" consisted of the results of 94 unknown samples and two negative controls of each of 120 SNPs loci we had previously studied. By the use of the files, the spreadsheet could analyze 96 SNPs on a 96-wells-plate simultaneously.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

PubMed

Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

2014-01-01

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

PubMed

Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert; Liu, Xuhui

2014-07-01

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Tenebrio beetles use magnetic inclination compass

NASA Astrophysics Data System (ADS)

Vácha, Martin; Drštková, Dana; Půžová, Tereza

2008-08-01

Animals that guide directions of their locomotion or their migration routes by the lines of the geomagnetic field use either polarity or inclination compasses to determine the field polarity (the north or south direction). Distinguishing the two compass types is a guideline for estimation of the molecular principle of reception and has been achieved for a number of animal groups, with the exception of insects. A standard diagnostic method to distinguish a compass type is based on reversing the vertical component of the geomagnetic field, which leads to the opposite reactions of animals with two different compass types. In the present study, adults of the mealworm beetle Tenebrio molitor were tested by means of a two-step laboratory test of magnetoreception. Beetles that were initially trained to memorize the magnetic position of the light source preferred, during the subsequent test, this same direction, pursuant geomagnetic cues only. In the following step, the vertical component was reversed between the training and the test. The beetles significantly turned their preferred direction by 180°. Our results brought until then unknown original findings that insects, represented here by the T. molitor species, use—in contrast to another previously researched Arthropod, spiny lobster—the inclination compass.

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

Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org; Allen, Pamela K.; Wei, Xiong

Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followedmore » by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.« less

Intramembranous valine linked to schizophrenia is required for neuregulin 1 regulation of the morphological development of cortical neurons

PubMed Central

Chen, Yachi; Hancock, Melissa L.; Role, Lorna W.; Talmage, David A.

2010-01-01

Neuregulin 1 (NRG1) signaling is critical to various aspects of neuronal development and function. Among different NRG1 isoforms, the Type III isoforms of NRG1 are unique in their ability to signal via the intracellular domain following γ-secretase-dependent intramembranous processing. However, the functional consequences of Type III NRG1 signaling via its intracellular domain are largely unknown. In this study, we have identified mutations within Type III NRG1 that disrupt intramembranous proteolytic processing and abolish intracellular domain signaling. In particular, substitutions at valine 321, previously linked to schizophrenia risks, result in NRG1 proteins that fail to undergo γ-secretase-mediated nuclear localization and transcriptional activation. Using processing-defective mutants of Type III NRG1, we demonstrate that the intracellular domain signaling is specifically required for NRG1 regulation of the growth and branching of cortical dendrites but not axons. Consistent with the role of Type III NRG1 signaling via the intracellular domain in the initial patterning of cortical dendrites, our findings from pharmacological and genetic studies indicate that Type III NRG1 functions in dendritic development independent of ERBB kinase activity. Taken together, these results support the proposal that aberrant intracellular processing and defective signaling via the intracellular domain of Type III NRG1 impair a subset of NRG1 functions in cortical development and contribute to abnormal neuroconnectivity implicated in schizophrenia. PMID:20610754

Characterization of Marine Mammal Recordings from the Hawaii Range Complex

DTIC Science & Technology

2010-11-01

This was higher than known from a previous study at Palmyra Atoll (Baumann- Pickering, 2009), where the peak frequency was around 25-29 kHz. Recordings...cavirostris), signals known from an unknown species at Palmyra Atoll (possibly Mesoplodon hotaula, Baumann-Pickering et al., 2010), and an unknown...Measurement of Activity in Odontocete Species of Palmyra Atoll by Acoustic Monitoring,” Doctorate thesis, Eberhard-Karls-Universität Tübingen, Tübingen

Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel regulation of type 1 pili in uropathogenic Escherichia coli

PubMed Central

Zhang, Huibin; Susanto, Teodorus T.; Wan, Yue

2016-01-01

Type 1 pili (T1P) are major virulence factors for uropathogenic Escherichia coli (UPEC), which cause both acute and recurrent urinary tract infections. T1P expression therefore is of direct relevance for disease. T1P are phase variable (both piliated and nonpiliated bacteria exist in a clonal population) and are controlled by an invertible DNA switch (fimS), which contains the promoter for the fim operon encoding T1P. Inversion of fimS is stochastic but may be biased by environmental conditions and other signals that ultimately converge at fimS itself. Previous studies of fimS sequences important for T1P phase variation have focused on laboratory-adapted E. coli strains and have been limited in the number of mutations or by alteration of the fimS genomic context. We surmounted these limitations by using saturating genomic mutagenesis of fimS coupled with accurate sequencing to detect both mutations and phase status simultaneously. In addition to the sequences known to be important for biasing fimS inversion, our method also identifies a previously unknown pair of 5′ UTR inverted repeats that act by altering the relative fimA levels to control phase variation. Thus we have uncovered an additional layer of T1P regulation potentially impacting virulence and the coordinate expression of multiple pilus systems. PMID:27035967

Actinomyces gaoshouyii sp. nov., isolated from plateau pika (Ochotona curzoniae).

PubMed

Meng, Xiangli; Wang, Yiting; Lu, Shan; Lai, Xin-He; Jin, Dong; Yang, Jing; Xu, Jianguo

2017-09-01

Two strains (pika_113T and pika_114) of a previously undescribed Actinomyces-like bacterium were recovered from the intestinal contents of plateau pika (Ochotona curzoniae) on the Tibet-Qinghai Plateau, China. Results from biochemical characterization indicated that the two strains were phenotypically homogeneous and distinct from other previously described species of the genus Actinomyces. Based on the comparison of 16S rRNA gene sequences and genome analysis, the bacteria were determined to be a hitherto unknown subline within the genus Actinomyces, being most closely related to type strains of Actinomyces denticolens and Actinomyces timonensis with a respective 97.2 and 97.1 % similarity in their 16S rRNA gene sequences. Phylogenetic analyses confirmed that pika_113T was well separated from any other recognized species of the genus Actinomyces and within the cluster with A. denticolens and A. timonensis. The genome of strain pika_113T displayed less than 42 % relatedness in DNA-DNA hybridization with all the available genomes of existing species of the genus Actinomyces in the NCBI database. Collectively, based on the phenotypic characteristics and phylogenetic analyses results, we propose the novel isolates as representatives of Actinomyces gaoshouyii sp. nov. The type strain of Actinomyces gaoshouyii is pika_113T (=CGMCC 4.7372T=DSM 104049T), with a genomic DNA G+C content of 71 mol%.

Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel regulation of type 1 pili in uropathogenic Escherichia coli.

PubMed

Zhang, Huibin; Susanto, Teodorus T; Wan, Yue; Chen, Swaine L

2016-04-12

Type 1 pili (T1P) are major virulence factors for uropathogenic Escherichia coli (UPEC), which cause both acute and recurrent urinary tract infections. T1P expression therefore is of direct relevance for disease. T1P are phase variable (both piliated and nonpiliated bacteria exist in a clonal population) and are controlled by an invertible DNA switch (fimS), which contains the promoter for the fim operon encoding T1P. Inversion of fimS is stochastic but may be biased by environmental conditions and other signals that ultimately converge at fimS itself. Previous studies of fimS sequences important for T1P phase variation have focused on laboratory-adapted E coli strains and have been limited in the number of mutations or by alteration of the fimS genomic context. We surmounted these limitations by using saturating genomic mutagenesis of fimS coupled with accurate sequencing to detect both mutations and phase status simultaneously. In addition to the sequences known to be important for biasing fimS inversion, our method also identifies a previously unknown pair of 5' UTR inverted repeats that act by altering the relative fimA levels to control phase variation. Thus we have uncovered an additional layer of T1P regulation potentially impacting virulence and the coordinate expression of multiple pilus systems.

Bacterial phylogeny structures soil resistomes across habitats

PubMed Central

Forsberg, Kevin J.; Patel, Sanket; Gibson, Molly K.; Lauber, Christian L.; Knight, Rob; Fierer, Noah; Dantas, Gautam

2014-01-01

Summary Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil1–3, including genes identical to those in human pathogens4. Despite the apparent overlap between soil and clinical resistomes4–6, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown3. General metagenome functions often correlate with the underlying structure of bacterial communities7–12. However, ARGs are hypothesized to be highly mobile4,5,13, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions13,14. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2895 ARGs we discovered were predominantly novel, and represent all major resistance mechanisms15. We demonstrate that distinct soil types harbor distinct resistomes, and that nitrogen fertilizer amendments strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements syntenic with ARGs were rare in soil compared to sequenced pathogens, suggesting that ARGs in the soil may not transfer between bacteria as readily as is observed in the clinic. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny13,14. PMID:24847883

Bacterial phylogeny structures soil resistomes across habitats

NASA Astrophysics Data System (ADS)

Forsberg, Kevin J.; Patel, Sanket; Gibson, Molly K.; Lauber, Christian L.; Knight, Rob; Fierer, Noah; Dantas, Gautam

2014-05-01

Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil, including genes identical to those in human pathogens. Despite the apparent overlap between soil and clinical resistomes, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown. General metagenome functions often correlate with the underlying structure of bacterial communities. However, ARGs are proposed to be highly mobile, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2,895 ARGs we discovered were mostly new, and represent all major resistance mechanisms. We demonstrate that distinct soil types harbour distinct resistomes, and that the addition of nitrogen fertilizer strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements (genes responsible for horizontal gene transfer between bacteria such as transposases and integrases) syntenic with ARGs were rare in soil by comparison with sequenced pathogens, suggesting that ARGs may not transfer between soil bacteria as readily as is observed between human pathogens. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny.

On the Origin of Quasi-Periodic Temperature Variations in Kun-1 Well (Kunashir Island)

NASA Astrophysics Data System (ADS)

Demezhko, D. Yu.; Yurkov, A. K.

2017-12-01

The results of temperature monitoring in the 300-m kun-1 well (Kunashir Island) in 2011-2015 are considered. Quasi-periodic temperature variations with an amplitude of up to 0.3°C and a variation period of 14-26 h were added from November 2011 to the previously observed temperature variations caused by tidal deformations, free thermal convection, and deformation processes associated with the preparation and occurrence of tectonic earthquakes. Five cycles of such variations lasting from 2 to 6 months have been recorded. Each cycle was initiated by an earthquake with magnitude M > 2.5log( R), where R is the epicentral distance (km). According to their characteristics, the variations are unique and have not been described previously. Assumptions have been made about the possible connection of the registered variations with the inertial currents of the ocean or with hydrothermal processes in the Earth's subsurface. The phenomenon discovered requires further study not only as an object of fundamental science, but also as a feature of an earlier unknown type of geodynamic activity that can be a significant threat to the regional population.

[Role of biometric analysis in the retrospective assessment of exposure to asbestos].

PubMed

Pairon, J C; Dumortier, P

1999-12-01

Despite intrinsic limitations due to differences in the bio-persistence of the various asbestos types, in the definition of control populations and in analytical techniques used by the laboratories, mineralogical analysis of biological samples is useful in the assessment of past exposure to asbestos. It provides additional information to occupational and environmental questionnaires, particularly when exposure to asbestos is doubtful, unknown or forgotten by a subject. Results should be interpreted taking into account clinical information. A positive result does not mean existence of asbestos-related disease. A negative result does not exclude previous significant asbestos exposure, clearly identified by an occupational questionnaire (particularly for exposure to chrysotile). Threshold values indicative of a high probability of previous asbestos exposure have been established for bronchoalveolar lavage fluid (BALF) samples and lung tissue samples. Quantification of asbestos bodies by light microscopy is easy to perform. Sensitivity and specificity of this analysis towards the total pulmonary asbestos fiber burden is good. Therefore this analysis should be performed first. Mineralogical analysis in BALF or lung tissue should be considered only when sampling is supported by diagnostic or therapeutic implications.

A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

PubMed

Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

2015-06-01

Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

Modeling equine race surface vertical mechanical behaviors in a musculoskeletal modeling environment.

PubMed

Symons, Jennifer E; Fyhrie, David P; Hawkins, David A; Upadhyaya, Shrinivasa K; Stover, Susan M

2015-02-26

Race surfaces have been associated with the incidence of racehorse musculoskeletal injury, the leading cause of racehorse attrition. Optimal race surface mechanical behaviors that minimize injury risk are unknown. Computational models are an economical method to determine optimal mechanical behaviors. Previously developed equine musculoskeletal models utilized ground reaction floor models designed to simulate a stiff, smooth floor appropriate for a human gait laboratory. Our objective was to develop a computational race surface model (two force-displacement functions, one linear and one nonlinear) that reproduced experimental race surface mechanical behaviors for incorporation in equine musculoskeletal models. Soil impact tests were simulated in a musculoskeletal modeling environment and compared to experimental force and displacement data collected during initial and repeat impacts at two racetracks with differing race surfaces - (i) dirt and (ii) synthetic. Best-fit model coefficients (7 total) were compared between surface types and initial and repeat impacts using a mixed model ANCOVA. Model simulation results closely matched empirical force, displacement and velocity data (Mean R(2)=0.930-0.997). Many model coefficients were statistically different between surface types and impacts. Principal component analysis of model coefficients showed systematic differences based on surface type and impact. In the future, the race surface model may be used in conjunction with previously developed the equine musculoskeletal models to understand the effects of race surface mechanical behaviors on limb dynamics, and determine race surface mechanical behaviors that reduce the incidence of racehorse musculoskeletal injury through modulation of limb dynamics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sequence Elucidation of an Unknown Cyclic Peptide of High Doping Potential by ETD and CID Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Guan, Fuyu; Uboh, Cornelius E.; Soma, Lawrence R.; Rudy, Jeffrey

2011-04-01

Identification of an unknown substance without any information remains a daunting challenge despite advances in chemistry and mass spectrometry. However, an unknown cyclic peptide in a sample with very limited volume seized at a Pennsylvania racetrack has been successfully identified. The unknown sample was determined by accurate mass measurements to contain a small unknown peptide as the major component. Collision-induced dissociation (CID) of the unknown peptide revealed the presence of Lys (not Gln, by accurate mass), Phe, and Arg residues, and absence of any y-type product ion. The latter, together with the tryptic digestion results of the unusual deamidation and absence of any tryptic cleavage, suggests a cyclic structure for the peptide. Electron-transfer dissociation (ETD) of the unknown peptide indicated the presence of Gln (not Lys, by the unusual deamidation), Phe, and Arg residues and their connectivity. After all the results were pieced together, a cyclic tetrapeptide, cyclo[Arg-Lys-N(C6H9)Gln-Phe], is proposed for the unknown peptide. Observations of different amino acid residues from CID and ETD experiments for the peptide were interpreted by a fragmentation pathway proposed, as was preferential CID loss of a Lys residue from the peptide. ETD was used for the first time in sequencing of a cyclic peptide; product ions resulting from ETD of the peptide identified were categorized into two types and named pseudo-b and pseudo-z ions that are important for sequencing of cyclic peptides. The ETD product ions were interpreted by fragmentation pathways proposed. Additionally, multi-stage CID mass spectrometry cannot provide complete sequence information for cyclic peptides containing adjacent Arg and Lys residues. The identified cyclic peptide has not been documented in the literature, its pharmacological effects are unknown, but it might be a "designer" drug with athletic performance-enhancing effects.

Increased Kawasaki Disease Incidence Associated With Higher Precipitation and Lower Temperatures, Japan, 1991-2004.

PubMed

Abrams, Joseph Y; Blase, Jennifer L; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2018-06-01

Kawasaki disease (KD) is an acute febrile vasculitis, which primarily affects children. The etiology of KD is unknown; while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiologic surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5 and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. KD incidence was negatively associated with temperature in the previous 2, 3, 4 and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100 mm was associated with increased KD incidence (rate ratio [RR] 1.012, 95% confidence interval [CI]: 1.005-1.019), and an increase of monthly mean temperature by 1°C was associated with decreased KD incidence (RR 0.984, 95% CI: 0.978-0.990). KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted the variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway

PubMed Central

Movert, Elin; Lienard, Julia; Valfridsson, Christine; Johansson-Lindbom, Bengt

2018-01-01

From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and production of type I IFN occurred via M protein-dependent activation of the STING signaling pathway. Activation of STING was independent of the cytosolic double stranded DNA sensor cGAS, and infection did not induce detectable release into the cytosol of either mitochondrial, nuclear or bacterial DNA–indicating DNA-independent activation of the STING pathway in S. pyogenes infected macrophages. These findings provide mechanistic insight concerning how S. pyogenes induces the type I IFN response and identify a previously unrecognized macrophage-modulating role for the streptococcal M protein that may contribute to curb the inflammatory response to infection. PMID:29579113

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

PubMed

Seidman, Jeffrey D; Krishnan, Jayashree

2017-07-01

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.

Ternary chalcogenides C s 2 Z n 3 S e 4 and C s 2 Z n 3 T e 4 : Potential p -type transparent conducting materials

DOE PAGES

Shi, Hongliang; Saparov, Bayrammurad; Singh, David J.; ...

2014-11-11

Here we report prediction of two new ternary chalcogenides that can potentially be used as p-type transparent conductors along with experimental synthesis and initial characterization of these previously unknown compounds, Cs 2Zn 3Ch 4 (Ch = Se, Te). In particular, the structures are predicted based on density functional calculations and confirmed by experiments. Phase diagrams, electronic structure, optical properties, and defect properties of Cs 2Zn 3Se 4 and Cs 2Zn 3Te 4 are calculated to assess the viability of these materials as p-type TCMs. Cs 2Zn 3Se 4 and Cs 2Zn 3Te 4, which are stable under ambient air, displaymore » large optical band gaps (calculated to be 3.61 and 2.83 eV, respectively) and have small hole effective masses (0.5-0.77 m e) that compare favorably with other proposed p-type TCMs. Defect calculations show that undoped Cs2Zn3Se4 and Cs2Zn3Te4 are p-type materials. However, the free hole concentration may be limited by low-energy native donor defects, e.g., Zn interstitials. Lastly, non-equilibrium growth techniques should be useful for suppressing the formation of native donor defects, thereby increasing the hole concentration.« less

ATP-binding Cassette (ABC) Transport System Solute-binding Protein-guided Identification of Novel d-Altritol and Galactitol Catabolic Pathways in Agrobacterium tumefaciens C58*

PubMed Central

Wichelecki, Daniel J.; Vetting, Matthew W.; Chou, Liyushang; Al-Obaidi, Nawar; Bouvier, Jason T.; Almo, Steven C.; Gerlt, John A.

2015-01-01

Innovations in the discovery of the functions of uncharacterized proteins/enzymes have become increasingly important as advances in sequencing technology flood protein databases with an exponentially growing number of open reading frames. This study documents one such innovation developed by the Enzyme Function Initiative (EFI; U54GM093342), the use of solute-binding proteins for transport systems to identify novel metabolic pathways. In a previous study, this strategy was applied to the tripartite ATP-independent periplasmic transporters. Here, we apply this strategy to the ATP-binding cassette transporters and report the discovery of novel catabolic pathways for d-altritol and galactitol in Agrobacterium tumefaciens C58. These efforts resulted in the description of three novel enzymatic reactions as follows: 1) oxidation of d-altritol to d-tagatose via a dehydrogenase in Pfam family PF00107, a previously unknown reaction; 2) phosphorylation of d-tagatose to d-tagatose 6-phosphate via a kinase in Pfam family PF00294, a previously orphan EC number; and 3) epimerization of d-tagatose 6-phosphate C-4 to d-fructose 6-phosphate via a member of Pfam family PF08013, another previously unknown reaction. The epimerization reaction catalyzed by a member of PF08013 is especially noteworthy, because the functions of members of PF08013 have been unknown. These discoveries were assisted by the following two synergistic bioinformatics web tools made available by the Enzyme Function Initiative: the EFI-Enzyme Similarity Tool and the EFI-Genome Neighborhood Tool. PMID:26472925

Control of Complex Dynamic Systems by Neural Networks

NASA Technical Reports Server (NTRS)

Spall, James C.; Cristion, John A.

1993-01-01

This paper considers the use of neural networks (NN's) in controlling a nonlinear, stochastic system with unknown process equations. The NN is used to model the resulting unknown control law. The approach here is based on using the output error of the system to train the NN controller without the need to construct a separate model (NN or other type) for the unknown process dynamics. To implement such a direct adaptive control approach, it is required that connection weights in the NN be estimated while the system is being controlled. As a result of the feedback of the unknown process dynamics, however, it is not possible to determine the gradient of the loss function for use in standard (back-propagation-type) weight estimation algorithms. Therefore, this paper considers the use of a new stochastic approximation algorithm for this weight estimation, which is based on a 'simultaneous perturbation' gradient approximation that only requires the system output error. It is shown that this algorithm can greatly enhance the efficiency over more standard stochastic approximation algorithms based on finite-difference gradient approximations.

The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non‐syndromic mental retardation

PubMed Central

Basel‐Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

2006-01-01

Background The molecular basis of autosomal recessive non‐syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. Objective To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. Results The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I‐κB kinase/NFκB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. Conclusions A previously unknown signal transduction pathway is important in human cognitive development. PMID:16033914

The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation.

PubMed

Basel-Vanagaite, L; Attia, R; Yahav, M; Ferland, R J; Anteki, L; Walsh, C A; Olender, T; Straussberg, R; Magal, N; Taub, E; Drasinover, V; Alkelai, A; Bercovich, D; Rechavi, G; Simon, A J; Shohat, M

2006-03-01

The molecular basis of autosomal recessive non-syndromic mental retardation (NSMR) is poorly understood, mostly owing to heterogeneity and absence of clinical criteria for grouping families for linkage analysis. Only two autosomal genes, the PRSS12 gene on chromosome 4q26 and the CRBN on chromosome 3p26, have been shown to cause autosomal recessive NSMR, each gene in only one family. To identify the gene causing autosomal recessive NSMR on chromosome 19p13.12. The candidate region established by homozygosity mapping was narrowed down from 2.4 Mb to 0.9 Mb on chromosome 19p13.12. A protein truncating mutation was identified in the gene CC2D1A in nine consanguineous families with severe autosomal recessive NSMR. The absence of the wild type protein in the lymphoblastoid cells of the patients was confirmed. CC2D1A is a member of a previously uncharacterised gene family that carries two conserved motifs, a C2 domain and a DM14 domain. The C2 domain is found in proteins which function in calcium dependent phospholipid binding; the DM14 domain is unique to the CC2D1A protein family and its role is unknown. CC2D1A is a putative signal transducer participating in positive regulation of I-kappaB kinase/NFkappaB cascade. Expression of CC2D1A mRNA was shown in the embryonic ventricular zone and developing cortical plate in staged mouse embryos, persisting into adulthood, with highest expression in the cerebral cortex and hippocampus. A previously unknown signal transduction pathway is important in human cognitive development.

Bacterial Population Adherent to the Epithelium on the Roo of the Dorsal Rumen of Sheep †

PubMed Central

Dehority, Burk A.; Grubb, Jean A.

1981-01-01

By anaerobic procedures, the total number of adherent bacteria was determined on tissue samples obtained from the roof of the dorsal rumen of three sheep. After four washings, 1.91 × 107, 0.34 × 107, and 1.23 × 107 bacteria per cm2 were still attached to the rumen epithelium in sheep 1, 2, and 3, respectively. A total of 95 strains of bacteria were isolated from these three samples. Based on morphology, Gram stain, anaerobiosis, motility, and fermentation end products, they were presumptively identified as follows: Butyrivibrio fibrisolvens, 30 strains; atypical Butyrivibrio, 5 strains; Bacteroides ruminicola, 22 strains; Lactobacillus, 1 strain; and unknown Bacteroides species, 37 strains. For sheep 3, washing the rumen epithelium a total of 10 times reduced the adherent bacterial population by 93% (8.4 × 105 bacteria per cm2). Of 30 strains isolated from this sample, 22 were presumptively identified as Butyrivibrio and Bacteroides types. These results suggest that the epithelium on the roof of the dorsal rumen is primarily colonized by two genera of bacteria, Butyrivibrio and Bacteroides. Most Butyrivibrio and Bacteroides ruminicola strains appeared to be similar to previously isolated rumen strains. However, the unknown Bacteroides species differed considerably from the three species of this genus which are commonly isolated from rumen contents. PMID:16345797

New Ceratocystis species from Eucalyptus and Cunninghamia in South China.

PubMed

Liu, FeiFei; Mbenoun, Michael; Barnes, Irene; Roux, Jolanda; Wingfield, Michael J; Li, GuoQing; Li, JieQiong; Chen, ShuaiFei

2015-06-01

During routine surveys for possible fungal pathogens in the rapidly expanding plantations of Eucalyptus and Cunninghamia lanceolata in China, numerous isolates of unknown species in the genus Ceratocystis (Microascales) were obtained from tree wounds. In this study we identified the Ceratocystis isolates from Eucalyptus and Cunninghamia in the GuangDong, GuangXi, FuJian and HaiNan Provinces of South China based on morphology and through comparisons of DNA sequence data for the ITS, partial β-tubulin and TEF-1α gene regions. Morphological and DNA sequence comparisons revealed two previously unknown species residing in the Indo-Pacific Clade. These are described here as Ceratocystis cercfabiensis sp. nov. and Ceratocystis collisensis sp. nov. Isolates of Ceratocystis cercfabiensis showed intragenomic variation in their ITS sequences and four strains were selected for cloning of the ITS gene region. Twelve ITS haplotypes were obtained from 17 clones selected for sequencing, differing in up to seven base positions and representing two separate phylogenetic groups. This is the first evidence of multiple ITS types in isolates of Ceratocystis residing in the Indo-Pacific Clade. Caution should thus be exercised when using the ITS gene region as a barcoding marker for Ceratocystis species in this clade. This study also represents the first record of a species of Ceratocystis from Cunninghamia.

Invisible Colors of the Moon

NASA Image and Video Library

2009-09-24

Data from NASA Moon Mineralogy Mapper instrument on the Indian Space Research Organization Chandrayaan-1 spacecraft reveal subtle and previously unknown lunar diversity and features. Animation available at the Photojournal.

Neonatal blood transfusion as transmission route in chronic hepatitis C.

PubMed

Einberg, Afrodite Psaros; Lindh, Gudrun; Hökeberg, Ingegerd; Papadogiannakis, Nikos; Fischler, Björn

2014-05-01

The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown. Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied. Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response. Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992. © 2013 American Association of Blood Banks.

Teleporting an unknown quantum state with unit fidelity and unit probability via a non-maximally entangled channel and an auxiliary system

NASA Astrophysics Data System (ADS)

Rashvand, Taghi

2016-11-01

We present a new scheme for quantum teleportation that one can teleport an unknown state via a non-maximally entangled channel with certainly, using an auxiliary system. In this scheme depending on the state of the auxiliary system, one can find a class of orthogonal vectors set as a basis which by performing von Neumann measurement in each element of this class Alice can teleport an unknown state with unit fidelity and unit probability. A comparison of our scheme with some previous schemes is given and we will see that our scheme has advantages that the others do not.

Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa

PubMed Central

Aird, Steven D.; da Silva, Nelson Jorge; Qiu, Lijun; Villar-Briones, Alejandro; Saddi, Vera Aparecida; Pires de Campos Telles, Mariana; Grau, Miguel L.; Mikheyev, Alexander S.

2017-01-01

Venom gland transcriptomes and proteomes of six Micrurus taxa (M. corallinus, M. lemniscatus carvalhoi, M. lemniscatus lemniscatus, M. paraensis, M. spixii spixii, and M. surinamensis) were investigated, providing the most comprehensive, quantitative data on Micrurus venom composition to date, and more than tripling the number of Micrurus venom protein sequences previously available. The six venomes differ dramatically. All are dominated by 2–6 toxin classes that account for 91–99% of the toxin transcripts. The M. s. spixii venome is compositionally the simplest. In it, three-finger toxins (3FTxs) and phospholipases A2 (PLA2s) comprise >99% of the toxin transcripts, which include only four additional toxin families at levels ≥0.1%. Micrurus l. lemniscatus venom is the most complex, with at least 17 toxin families. However, in each venome, multiple structural subclasses of 3FTXs and PLA2s are present. These almost certainly differ in pharmacology as well. All venoms also contain phospholipase B and vascular endothelial growth factors. Minor components (0.1–2.0%) are found in all venoms except that of M. s. spixii. Other toxin families are present in all six venoms at trace levels (<0.005%). Minor and trace venom components differ in each venom. Numerous novel toxin chemistries include 3FTxs with previously unknown 8- and 10-cysteine arrangements, resulting in new 3D structures and target specificities. 9-cysteine toxins raise the possibility of covalent, homodimeric 3FTxs or heterodimeric toxins with unknown pharmacologies. Probable muscarinic sequences may be reptile-specific homologs that promote hypotension via vascular mAChRs. The first complete sequences are presented for 3FTxs putatively responsible for liberating glutamate from rat brain synaptosomes. Micrurus C-type lectin-like proteins may have 6–9 cysteine residues and may be monomers, or homo- or heterodimers of unknown pharmacology. Novel KSPIs, 3× longer than any seen previously, appear to have arisen in three species by gene duplication and fusion. Four species have transcripts homologous to the nociceptive toxin, (MitTx) α-subunit, but all six species had homologs to the β-subunit. The first non-neurotoxic, non-catalytic elapid phospholipase A2s are reported. All are probably myonecrotic. Phylogenetic analysis indicates that the six taxa diverged 15–35 million years ago and that they split from their last common ancestor with Old World elapines nearly 55 million years ago. Given their early diversification, many cryptic micrurine taxa are anticipated. PMID:28594382

Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization

NASA Astrophysics Data System (ADS)

Cabrera-Pardo, Jaime R.; Chai, David I.; Liu, Song; Mrksich, Milan; Kozmin, Sergey A.

2013-05-01

The identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We describe a highly effective and simple platform for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations, thereby revealing new chemical reactivity. Our strategy is based on labelling one of the reactants with a polyaromatic chemical tag, which selectively undergoes a photoionization/desorption process upon laser irradiation, without the assistance of an external matrix, and enables rapid mass spectrometric detection of any products originating from such labelled reactants in complex reaction mixtures without any chromatographic separation. This method was successfully used for high-throughput discovery and subsequent optimization of two previously unknown benzannulation reactions.

Prevalence of dyslalias in 8 to 16 year-old students with anterior open bite in the municipality of Envigado, Colombia.

PubMed

Ocampo-Parra, Andrea; Escobar-Toro, Bibiana; Sierra-Alzate, Valentina; Rueda, Zulma Vanessa; Lema, María Clara

2015-07-10

Anterior open bite AOB is the most common malocclusion associated with speech disorders and the literature has shown that problems of occlusion involve all oral functions. AOB not only produce aesthetic and occlusal problems for the patient and modifies the union of the lips, tongue, teeth, palate, palatal rugae and oropharynx, and thus affecting the ability to communicate well with their surroundings. The prevalence of AOB in children and adolescent in our population is unknown. Furthermore, the most frequent type of dyslalias in children with this malocclusion is also unknown. Therefore, the aim of the study was to describe the frequency and types of dyslalia in students between 8-16 years with AOB, as well as the difference in the types of dyslalia according to the magnitude of AOB. A cross-sectional study was conducted. Clinical assessment of AOB in students from the municipality of Envigado, Colombia, was performed. Students from 8 to 16 years of age were examined during the second semester of 2011 and first semester of 2012. Phonoaudiological assessment was carried out in students in the mixed or permanent dentition. Exclusion criteria included children with history of systemic disease, altered skeletal development, neurological and psychiatric disorders, and residents in other departments. In addition, students undergoing orthodontic treatment at the time of evaluation or with history of previous orthodontic treatment, as well as those who did not cooperate with the oral cavity evaluation, were excluded. Six thousand one hundred sixty five children were evaluated. One hundred sixty six presented AOB (prevalence: 2.7 %; 95 % CI: 2.28-3.10). Thirty four students were excluded. 26.5 % of the sample presented mild AOB, 66.7 % moderate, and 6.8 % severe. Some type of dyslalia was found in 77.4 % of the students, being distortion (75.8 %) the most common. The most frequently altered phonemes were: / d / t / s / ch / ñ /. No significant association between different types of dyslalia and AOB severity (p-value = 0.974) was found. Prevalence of AOB in Envigado is low (2.7 %). Phonation alterations are very common in children with AOB (77.8 %), and distortion is the most frequent type of dyslalia (75.8 %). In order to diagnose and treat occlusal and phonetic problems, and to avoid possible recurrence, interdisciplinary approach is recommended.

A new serotyping method for Klebsiella species: evaluation of the technique.

PubMed Central

Riser, E; Noone, P; Bonnet, M L

1976-01-01

A new indirect fluorescent typing method for Klebsiella species is compared with an established method, capsular swelling. The fluorescent antibody (FA) technique was tested with standards and unknowns, and the results were checked by capsular swelling. Several unknowns were sent away for confirmation of typing, by capsular swelling. The FA method was also tried by a technician in the routine department for blind identification of standards. Fluorescence typing gives close correlation with the established capsular swelling technique but has greater sensitivity; allows more econimical use of expensive antisera; possesses greater objectivity as it requires less operator skill in the reading of results; resolves most of the cross reactions observed with capsular swelling; and has a higher per cent success rate in identification. PMID:777043

Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

PubMed Central

Bhatty, Minny; Jan, Basit L; Tan, Wei; Pruett, Stephen B; Nanduri, Bindu

2011-01-01

Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild type and TLR4 hypo-responsive mice treated with ethanol and then challenged with a non pathogenic strain of Escherichia. coli (E. coli). Ethanol treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at two hours after challenge. Neither ethanol treatment nor a hypo-responsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 hours post infection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hypo-responsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on LIF (leukemia inhibitory factor) and eotaxin and provide the first evidence that IL-9 is induced through TLR4 in vivo. PMID:21872420

Description of Tersicoccus phoenicis gen. nov., sp. nov. isolated from spacecraft assembly clean room environments.

PubMed

Vaishampayan, Parag; Moissl-Eichinger, Christine; Pukall, Rüdiger; Schumann, Peter; Spröer, Cathrin; Augustus, Angela; Roberts, Anne Hayden; Namba, Greg; Cisneros, Jessica; Salmassi, Tina; Venkateswaran, Kasthuri

2013-07-01

Two strains of aerobic, non-motile, Gram-reaction-positive cocci were independently isolated from geographically distinct spacecraft assembly clean room facilities (Kennedy Space Center, Florida, USA and Centre Spatial Guyanais, Kourou, French Guiana). A polyphasic study was carried out to delineate the taxonomic identity of these two isolates (1P05MA(T) and KO_PS43). The 16S rRNA gene sequences exhibited a high similarity when compared to each other (100 %) and lower than 96.7 % relatedness with Arthrobacter crystallopoietes ATCC 15481(T), Arthrobacter luteolus ATCC BAA-272(T), Arthrobacter tumbae DSM 16406(T) and Arthrobacter subterraneus DSM 17585(T). In contrast with previously described Arthrobacter species, the novel isolates maintained their coccidal morphology throughout their growth and did not exhibit the rod-coccus life cycle typically observed in nearly all Arthrobacter species, except A. agilis. The distinct taxonomic identity of the novel isolates was confirmed based on their unique cell-wall peptidoglycan type (A.11.20; Lys-Ser-Ala2) and polar lipid profile (presence of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, an unknown phospholipid and two unknown glycolipids). The G+C content of the genomic DNA was 70.6 mol%. The novel strains revealed MK-9(H2) and MK-8(H2) as dominant menaquinones and exhibited fatty acid profiles consisting of major amounts of anteiso-C15 : 0 and anteiso-C17 : 0 and moderate amounts of iso-C15 : 0 discriminating them again from closely related Arthrobacter species. Based on these observations, the authors propose that strains 1P05MA(T) and KO_PS43 be assigned into a separate genus Tersicoccus gen. nov. For this new taxon, comprising strains 1P05MA(T) and KO_PS43, we propose the name Tersicoccus phoenicis gen. nov., sp. nov. (the type species of Tersicoccus), represented by the type strain Tersicoccus phoenicis 1P05MA(T) ( = NRRL B-59547(T) = DSM 30849(T)).

Streptomyces xylanilyticus sp. nov., isolated from soil.

PubMed

Moonmangmee, Duangtip; Kanchanasin, Pawina; Phongsopitanun, Wongsakorn; Tanasupawat, Somboon; Moonmangmee, Somporn

2017-10-01

A novel actinomycete, strain SR2-123 T , belonging to the genus Streptomyces, was isolated from a soil sample collected from the Sakaerat Environmental Research Station, Thailand Institute of Scientific and Technological Research, Nakhon Ratchasima Province, Thailand. The taxonomic position of the strain was characterized using a polyphasic study. Strain SR2-123 T contained ll-diaminopimelic acid, glucose, mannose and ribose in whole-cell hydrolysates. The N-acyl type of muramic acid was acetyl. Menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The predominant cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, anteiso-C17 : 0 and iso-C17 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, an unknown phospholipid, unknown glycolipids, an unknown aminophospholipid, unknown lipids and an unknown aminolipid. The DNA G+C content was 74.8 mol%. The strain was closely related to Streptomyces coeruleorubidus JCM 4359 T (98.5 %), Streptomyces flavofungini JCM 4753 T (98.5 %), Streptomyces coerulescens NBRC 12758 T (98. 5 %) and Streptomyces alboflavus JCM 4615 T (98.4 %), based on 16S rRNA gene sequence similarities. The novel strain exhibited low DNA-DNA relatedness values with the type strains (11.4-25.0 %) of closely related species. On the basis of phenotypic and genotypic characteristics, strain SR2-123 T could be distinguished from closely related species of the genus Streptomyces and represents a novel species of the genus Streptomyces for which the name Streptomyces xylanilyticus sp. nov. is proposed. The type strain is SR2-123 T (=TISTR 2493 T =KCTC 39909 T ).

[Riga-Fede disease].

PubMed

Marie, J; Fricain, J-C; Boralevi, F

2012-01-01

Riga-Fede disease is a benign affection of the oral mucosa which has been poorly described in the literature. This entity of unknown ethiopathogenicity is sometimes revealing of dysautonomic or neuropsychic disorders. We report a new case. A 10-month-old girl was referred to us for a unique deep ulceration of the lower lingual apex, in a context of right basal pneumopathy. Samples were negative for bacteriological, virological and mycological analysis. After successful treatment of the pneumopathy, the ulceration was unchanged and we diagnosed Riga-Fede disease. Our observation is representative of the Riga-Fede cases previously described in the literature, comparing the age of onset, the topography and the ulceration type. We did not diagnose any dysautonomic or neuropsychic disorder as reported in some cases. Suppression of the lingual trauma resulted in healing of the ulceration. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Animal pigment bilirubin discovered in plants.

PubMed

Pirone, Cary; Quirke, J Martin E; Priestap, Horacio A; Lee, David W

2009-03-04

The bile pigment bilirubin-IXalpha is the degradative product of heme, distributed among mammals and some other vertebrates. It can be recognized as the pigment responsible for the yellow color of jaundice and healing bruises. In this paper we present the first example of the isolation of bilirubin in plants. The compound was isolated from the brilliant orange-colored arils of Strelitzia nicolai, the white bird of paradise tree, and characterized by HPLC-ESMS, UV-visible, (1)H NMR, and (13)C NMR spectroscopy, as well as comparison with an authentic standard. This discovery indicates that plant cyclic tetrapyrroles may undergo degradation by a previously unknown pathway. Preliminary analyses of related plants, including S. reginae, the bird of paradise, also revealed bilirubin in the arils and flowers, indicating that the occurrence of bilirubin is not limited to a single species or tissue type.

Origin-based polyphenolic fingerprinting of Theobroma cacao in unfermented and fermented beans.

PubMed

D'Souza, Roy N; Grimbs, Sergio; Behrends, Britta; Bernaert, Herwig; Ullrich, Matthias S; Kuhnert, Nikolai

2017-09-01

A comprehensive analysis of cocoa polyphenols from unfermented and fermented cocoa beans from a wide range of geographic origins was carried out to catalogue systematic differences based on their origin as well as fermentation status. This study identifies previously unknown compounds with the goal to ascertain, which of these are responsible for the largest differences between bean types. UHPLC coupled with ultra-high resolution time-of-flight mass spectrometry was employed to identify and relatively quantify various oligomeric proanthocyanidins and their glycosides amongst several other unreported compounds. A series of biomarkers allowing a clear distinction between unfermented and fermented cocoa beans and for beans of different origins were identified. The large sample set employed allowed comparison of statistically significant variations of key cocoa constituents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adaptive control for a class of nonlinear complex dynamical systems with uncertain complex parameters and perturbations

PubMed Central

Liu, Jian; Liu, Kexin; Liu, Shutang

2017-01-01

In this paper, adaptive control is extended from real space to complex space, resulting in a new control scheme for a class of n-dimensional time-dependent strict-feedback complex-variable chaotic (hyperchaotic) systems (CVCSs) in the presence of uncertain complex parameters and perturbations, which has not been previously reported in the literature. In detail, we have developed a unified framework for designing the adaptive complex scalar controller to ensure this type of CVCSs asymptotically stable and for selecting complex update laws to estimate unknown complex parameters. In particular, combining Lyapunov functions dependent on complex-valued vectors and back-stepping technique, sufficient criteria on stabilization of CVCSs are derived in the sense of Wirtinger calculus in complex space. Finally, numerical simulation is presented to validate our theoretical results. PMID:28467431

The SARS algorithm: detrending CoRoT light curves with Sysrem using simultaneous external parameters

NASA Astrophysics Data System (ADS)

Ofir, Aviv; Alonso, Roi; Bonomo, Aldo Stefano; Carone, Ludmila; Carpano, Stefania; Samuel, Benjamin; Weingrill, Jörg; Aigrain, Suzanne; Auvergne, Michel; Baglin, Annie; Barge, Pierre; Borde, Pascal; Bouchy, Francois; Deeg, Hans J.; Deleuil, Magali; Dvorak, Rudolf; Erikson, Anders; Mello, Sylvio Ferraz; Fridlund, Malcolm; Gillon, Michel; Guillot, Tristan; Hatzes, Artie; Jorda, Laurent; Lammer, Helmut; Leger, Alain; Llebaria, Antoine; Moutou, Claire; Ollivier, Marc; Päetzold, Martin; Queloz, Didier; Rauer, Heike; Rouan, Daniel; Schneider, Jean; Wuchterl, Guenther

2010-05-01

Surveys for exoplanetary transits are usually limited not by photon noise but rather by the amount of red noise in their data. In particular, although the CoRoT space-based survey data are being carefully scrutinized, significant new sources of systematic noises are still being discovered. Recently, a magnitude-dependant systematic effect was discovered in the CoRoT data by Mazeh et al. and a phenomenological correction was proposed. Here we tie the observed effect to a particular type of effect, and in the process generalize the popular Sysrem algorithm to include external parameters in a simultaneous solution with the unknown effects. We show that a post-processing scheme based on this algorithm performs well and indeed allows for the detection of new transit-like signals that were not previously detected.

Adaptive control for a class of nonlinear complex dynamical systems with uncertain complex parameters and perturbations.

PubMed

Liu, Jian; Liu, Kexin; Liu, Shutang

2017-01-01

In this paper, adaptive control is extended from real space to complex space, resulting in a new control scheme for a class of n-dimensional time-dependent strict-feedback complex-variable chaotic (hyperchaotic) systems (CVCSs) in the presence of uncertain complex parameters and perturbations, which has not been previously reported in the literature. In detail, we have developed a unified framework for designing the adaptive complex scalar controller to ensure this type of CVCSs asymptotically stable and for selecting complex update laws to estimate unknown complex parameters. In particular, combining Lyapunov functions dependent on complex-valued vectors and back-stepping technique, sufficient criteria on stabilization of CVCSs are derived in the sense of Wirtinger calculus in complex space. Finally, numerical simulation is presented to validate our theoretical results.

Long-term infrared monitoring of stellar sources from earth orbit

NASA Technical Reports Server (NTRS)

Maran, S. P.; Heinsheimer, T. F.; Stocker, T. L.; Anand, S. P. S.; Chapman, R. D.; Hobbs, R. W.; Michalitsanos, A. G.; Wright, F. H.; Kipp, S. L.

1976-01-01

A program is discussed which involved monitoring the photometric activity of 18 bright variable IR stars at 2.7 microns with satellite- and rocket-borne instrumentation in the period from 1971 to 1975. The stellar sample includes 3 Lb variables, 8 semiregular variables, 5 Mira-type variables, and 2 previously unknown and unclassified IR variables. Detailed light curves of many of these stars were determined for intervals of 3 yr or more; spectra from 2.7 to 20 microns were constructed for nine of them using data obtained entirely with instruments above the atmosphere. Photometric IR light curves and other data are presented for SW Virginis, R Aquilae, S Scuti, IRC 00265, RT Hydrae, S Orionis, S Canis Minoris, Omicron Ceti, and R Leonis. Several hypotheses concerning the interpretation of the IR data are examined.

Quantum key distribution with an unknown and untrusted source

NASA Astrophysics Data System (ADS)

Zhao, Yi; Qi, Bing; Lo, Hoi-Kwong

2008-05-01

The security of a standard bidirectional “plug-and-play” quantum key distribution (QKD) system has been an open question for a long time. This is mainly because its source is equivalently controlled by an eavesdropper, which means the source is unknown and untrusted. Qualitative discussion on this subject has been made previously. In this paper, we solve this question directly by presenting the quantitative security analysis on a general class of QKD protocols whose sources are unknown and untrusted. The securities of standard Bennett-Brassard 1984 protocol, weak+vacuum decoy state protocol, and one-decoy state protocol, with unknown and untrusted sources are rigorously proved. We derive rigorous lower bounds to the secure key generation rates of the above three protocols. Our numerical simulation results show that QKD with an untrusted source gives a key generation rate that is close to that with a trusted source.

In Saturn Shadow

NASA Image and Video Library

2006-10-11

With giant Saturn hanging in the blackness and sheltering Cassini from the sun blinding glare, the spacecraft viewed the rings as never before, revealing previously unknown faint rings and even glimpsing its home world.

THE BERLIN EXOPLANET SEARCH TELESCOPE II CATALOG OF VARIABLE STARS. I. CHARACTERIZATION OF THREE SOUTHERN TARGET FIELDS

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

Fruth, T.; Cabrera, J.; Csizmadia, Sz.

2013-11-01

A photometric survey of three southern target fields with BEST II yielded the detection of 2406 previously unknown variable stars and an additional 617 stars with suspected variability. This study presents a catalog including their coordinates, magnitudes, light curves, ephemerides, amplitudes, and type of variability. In addition, the variability of 17 known objects is confirmed, thus validating the results. The catalog contains a number of known and new variables that are of interest for further astrophysical investigations, in order to, e.g., search for additional bodies in eclipsing binary systems, or to test stellar interior models. Altogether, 209,070 stars were monitoredmore » with BEST II during a total of 128 nights in 2009/2010. The overall variability fraction of 1.2%-1.5% in these target fields is well comparable to similar ground-based photometric surveys. Within the main magnitude range of R in [11, 17], we identify 0.67(3)% of all stars to be eclipsing binaries, which indicates a completeness of about one third for this particular type in comparison to space surveys.« less

Insights into substrate binding and catalysis in bacterial type I dehydroquinase.

PubMed

Maneiro, María; Peón, Antonio; Lence, Emilio; Otero, José M; Van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

2014-09-15

Structural, biochemical and computational studies to study substrate binding and the role of the conserved residues of the DHQ1 (type I dehydroquinase) enzyme active site are reported in the present paper. The crystal structure of DHQ1 from Salmonella typhi in complex with (2R)-2-methyl-3-dehydroquinic acid, a substrate analogue, was solved at 1.5 Å. The present study reveals a previously unknown key role for conserved Glu46, Phe145 and Met205 and Gln236, Pro234 and Ala233 residues, with the latter three being located in the flexible substrate-covering loop. Gln236 was shown to be responsible for the folding of this loop and for the dramatic reduction of its flexibility, which triggers active site closure. Glu46 was found to be key in bringing the substrate close to the lysine/histidine catalytic pocket to initiate catalysis. The present study could be useful in the rational design of inhibitors of this challenging and recognized target for the development of novel herbicides and antimicrobial agents.

Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

PubMed

Takeda, Hiroki; Hosoya, Makoto; Fujioka, Masato; Saegusa, Chika; Saeki, Tsubasa; Miwa, Toru; Okano, Hideyuki; Minoda, Ryosei

2018-01-31

There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

Hyperspectral signatures and WorldView-3 imagery of Indian River Lagoon and Banana River Estuarine water and bottom types

NASA Astrophysics Data System (ADS)

Bostater, Charles R.; Oney, Taylor S.; Rotkiske, Tyler; Aziz, Samin; Morrisette, Charles; Callahan, Kelby; Mcallister, Devin

2017-10-01

Hyperspectral signatures and imagery collected during the spring and summer of 2017 and 2016 are presented. Ground sampling distances (GSD) and pixel sizes were sampled from just over a meter to less than 4.0 mm. A pushbroom hyperspectral imager was used to calculate bidirectional reflectance factor (BRF) signatures. Hyperspectral signatures of different water types and bottom habitats such as submerged seagrasses, drift algae and algal bloom waters were scanned using a high spectral and digital resolution solid state spectrograph. WorldView-3 satellite imagery with minimal water wave sun glint effects was used to demonstrate the ability to detect bottom features using a derivative reflectance spectroscopy approach with the 1.3 m GSD multispectral satellite channels centered at the solar induced fluorescence band. The hyperspectral remote sensing data collected from the Banana River and Indian River Lagoon watersheds represents previously unknown signatures to be used in satellite and airborne remote sensing of water in turbid waters along the US Atlantic Ocean coastal region and the Florida littoral zone.

Retrospective Characterization of a Vaccine-Derived Poliovirus Type 1 Isolate from Sewage in Greece▿

PubMed Central

Dedepsidis, Evaggelos; Kyriakopoulou, Zaharoula; Pliaka, Vaia; Kottaridi, Christine; Bolanaki, Eugenia; Levidiotou-Stefanou, Stamatina; Komiotis, Dimitri; Markoulatos, Panayotis

2007-01-01

Retrospective molecular and phenotypic characterization of a vaccine-derived poliovirus (VDPV) type 1 isolate (7/b/97) isolated from sewage in Athens, Greece, in 1997 is reported. VP1 sequencing of this isolate revealed 1.87% divergence from the VP1 region of reference strain Sabin 1, while further genomic characterization of isolate 7/b/97 revealed a recombination event in the nonstructural part of the genome between a vaccine strain and a nonvaccine strain probably belonging to Enterovirus species C. Amino acid substitutions commonly found in previous studies were identified in the capsid coding region of the isolate, while most of the attenuation and temperature sensitivity determinants were reverted. The ultimate source of isolate 7/b/97 is unknown. The recovery of such a highly divergent derivative of a vaccine strain emphasizes the need for urgent implementation of environmental surveillance as a supportive procedure in the polio surveillance system even in countries with high rates of OPV coverage in order to prevent cases or even outbreaks of poliomyelitis that otherwise would be inevitable. PMID:17827314

MPS1 kinase as a potential therapeutic target in medulloblastoma

PubMed Central

Alimova, Irina; Ng, June; Harris, Peter; Birks, Diane; Donson, Andrew; Taylor, Michael D.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-01-01

Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma. PMID:27633003

MPS1 kinase as a potential therapeutic target in medulloblastoma.

PubMed

Alimova, Irina; Ng, June; Harris, Peter; Birks, Diane; Donson, Andrew; Taylor, Michael D; Foreman, Nicholas K; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-11-01

Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma.

Gene transfer strategies in animal transgenesis.

PubMed

Montoliu, Lluís

2002-01-01

Position effects in animal transgenesis have prevented the reproducible success and limited the initial expectations of this technique in many biotechnological projects. Historically, several strategies have been devised to overcome such position effects, including the progressive addition of regulatory elements belonging to the same or to a heterologous expression domain. An expression domain is thought to contain all regulatory elements that are needed to specifically control the expression of a given gene in time and space. The lack of profound knowledge on the chromatin structure of expression domains of biotechnological interest, such as mammary gland-specific genes, explains why most standard expression vectors have failed to drive high-level, position-independent, and copy-number-dependent expression of transgenes in a reproducible manner. In contrast, the application of artificial chromosome-type constructs to animal transgenesis usually ensures optimal expression levels. YACs, BACs, and PACs have become crucial tools in animal transgenesis, allowing the inclusion of distant key regulatory sequences, previously unknown, that are characteristic for each expression domain. These elements contribute to insulating the artificial chromosome-type constructs from chromosomal position effects and are fundamental in order to guarantee the correct expression of transgenes.

Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.

PubMed

Dudok, Barna; Barna, László; Ledri, Marco; Szabó, Szilárd I; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G; Henstridge, Christopher M; Balla, Gyula Y; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

2015-01-01

A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

Retrospective characterization of a vaccine-derived poliovirus type 1 isolate from sewage in Greece.

PubMed

Dedepsidis, Evaggelos; Kyriakopoulou, Zaharoula; Pliaka, Vaia; Kottaridi, Christine; Bolanaki, Eugenia; Levidiotou-Stefanou, Stamatina; Komiotis, Dimitri; Markoulatos, Panayotis

2007-11-01

Retrospective molecular and phenotypic characterization of a vaccine-derived poliovirus (VDPV) type 1 isolate (7/b/97) isolated from sewage in Athens, Greece, in 1997 is reported. VP1 sequencing of this isolate revealed 1.87% divergence from the VP1 region of reference strain Sabin 1, while further genomic characterization of isolate 7/b/97 revealed a recombination event in the nonstructural part of the genome between a vaccine strain and a nonvaccine strain probably belonging to Enterovirus species C. Amino acid substitutions commonly found in previous studies were identified in the capsid coding region of the isolate, while most of the attenuation and temperature sensitivity determinants were reverted. The ultimate source of isolate 7/b/97 is unknown. The recovery of such a highly divergent derivative of a vaccine strain emphasizes the need for urgent implementation of environmental surveillance as a supportive procedure in the polio surveillance system even in countries with high rates of OPV coverage in order to prevent cases or even outbreaks of poliomyelitis that otherwise would be inevitable.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

PubMed

Ishihara, Takeaki; Yamada, Kazunari; Harada, Aya; Yukiue, Haruhiro; Tanahashi, Masayuki; Niwa, Hiroshi; Matsui, Takashi; Yokomura, Koshi; Ejima, Yasuo; Sasaki, Ryohei

2018-05-03

The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

The quality of diagnosis and management of migraine and tension-type headache in three social groups in Russia.

PubMed

Lebedeva, Elena R; Kobzeva, Natalia R; Gilev, Denis V; Olesen, Jes

2017-03-01

Background Three successive editions of the International Classification of Headache Disorders and multiple guideline papers on headache care have described evidence based diagnosis and treatment of headache disorders. It remains unknown, however, to which extent this has improved the diagnosis and management of headache. That was the aim of our study in which we also analysed differences between three social groups in Russia. Methods We studied 1042 students (719 females, 323 males, mean age 20.6, age range 17-40), 1075 workers (146 females, 929 males, mean age 40.4, age range 21-67) and 1007 blood donors (484 females, 523 males, mean age 34.1, age range 18-64). We conducted a semi-structured, validated, face-to-face professional interview. Data on prevalence and associated factors have previously been published. A section of the interview focused on previous diagnosis and treatment, the topic of this paper. Results Only 496 of 2110 participants (23%) with headache in Russia had consulted because of headache. Students consulted more frequently (35%), workers and blood donors less often (13% and 14%). Only 12% of the patients with ICHD-3beta diagnosis of migraine and 11.7% with ICHD-3beta diagnosis of tension-type headache (TTH) had previously been correctly diagnosed. Triptans were used by only 6% of migraine patients. Only 0.4% of migraine patients and no TTH patients had received prophylactic treatment. Conclusion Despite existing guidelines about diagnosis and treatment, both remain poor in Russia. According to the literature this is only slightly better in Europe and America. Dissemination of existing knowledge should have higher priority in the future.

Treatment Option Overview (Carcinoma of Unknown Primary)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy are used to ...

Stellar cannibalism in fits and starts

NASA Astrophysics Data System (ADS)

Marsh, Thomas

2017-12-01

Dense stellar remnants called white dwarfs are often found in binary star systems. Satellite observations suggest a previously unknown way in which a white dwarf can draw material from its companion star.

PHENOTYPIC VARIABILITY IN INDIVIDUALS WITH TYPE V OSTEOGENESIS IMPERFECTA WITH IDENTICAL IFITM5 MUTATIONS

PubMed Central

Fitzgerald, Jamie; Holden, Paul; Wright, Hollis; Wilmot, Beth; Hata, Abigail; Steiner, Robert D.; Basel, Don

2016-01-01

Background Osteogenesis imperfecta (OI) type V is a dominantly inherited skeletal dysplasia characterized by fractures and progressive deformity of long bones. In addition, patients often present with radial head dislocation, hyperplastic callus, and calcification of the forearm interosseous membrane. Recently, a specific mutation in the IFITM5 gene was found to be responsible for OI type V. This mutation, a C to T transition 14 nucleotides upstream from the endogenous start codon, creates a new start methionine that appears to be preferentially used by the translational machinery. However, the mechanism by which the lengthened protein results in a dominant type of OI is unknown. Methods and Results We report 7 ethnically diverse (African-American, Caucasian, Hispanic, and African) individuals with OI type V from 2 families and 2 sporadic cases. Exome sequencing failed to identify a causative mutation. Using Sanger sequencing, we found that all affected individuals in our cohort possess the c.−14 IFITM5 variant, further supporting the notion that OI type V is caused by a single, discrete mutation. Our patient cohort demonstrated inter-and intrafamilial phenotypic variability, including a father with classic OI type V whose daughter had a phenotype similar to OI type I. This clinical variability suggests that modifier genes influence the OI type V phenotype. We also confirm that the mutation creates an aberrant IFITM5 protein containing an additional 5 amino acids at the N-terminus. Conclusions The variable clinical signs in these cases illustrate the significant variability of the OI type V phenotype caused by the c.−14 IFITM5 mutation. The affected individuals are more ethnically diverse than previously reported. PMID:28824928

Epistemic and aleatory uncertainty in the study of dynamic human-water systems

NASA Astrophysics Data System (ADS)

Di Baldassarre, Giuliano; Brandimarte, Luigia; Beven, Keith

2016-04-01

Here we discuss epistemic and aleatory uncertainty in the study of dynamic human-water systems (e.g. socio-hydrology), which is one of the main topics of Panta Rhei, the current scientific decade of the International Association of Hydrological Sciences (IAHS). In particular, we identify three types of lack of understanding: (i) known unknowns, which are things we know we don't know; (ii) unknown unknowns, which are things we don't know we don't know; and (iii) wrong assumptions, things we think we know, but we actually don't know. We posit that a better understanding of human-water interactions and feedbacks can help coping with wrong assumptions and known unknowns. Moreover, being aware of the existence of unknown unknowns, and their potential capability to generate surprises or black swans, suggest the need to rely more on bottom-up approaches, based on social vulnerabilities and possibilities of failures, and less on top-down approaches, based on optimization and quantitative predictions.

Typical ultraviolet spectra in combination with diagnostic mass fragmentation analysis for the rapid and comprehensive profiling of chlorogenic acids in the buds of Lonicera macranthoides.

PubMed

Zhang, Shui-Han; Hu, Xin; Shi, Shu-Yun; Huang, Lu-Qi; Chen, Wei; Chen, Lin; Cai, Ping

2016-05-01

A major challenge of profiling chlorogenic acids (CGA) in natural products is to effectively detect unknown or minor isomeric compounds. Here, we developed an effective strategy, typical ultraviolet (UV) spectra in combination with diagnostic mass fragmentation analysis based on HPLC-DAD-QTOF-MS/MS, to comprehensively profile CGA in the buds of Lonicera macranthoides. First, three CGA UV patterns were obtained by UV spectra screening. Second, 13 types of CGA classified by molecular weights were found by thorough analysis of CGA peaks using high-resolution MS. Third, selected ion monitoring (SIM) was carried out for each type of CGA to avoid overlooking of minor ones. Fourth, MS/MS spectra of each CGA were investigated. Then 70 CGA were identified by matching their UV spectra, accurate mass signals and fragmentation patterns with standards or previously reported compounds, including six caffeoylquinic acids (CQA), six diCQA, one triCQA, three caffeoylshikimic acids (CSA), six diCSA, one triCSA, three p-coumaroylquinic acids (pCoQA), four p-coumaroylcaffeoylquinic acids (pCoCQA), four feruloylquinic acids (FQA), five methyl caffeoylquinates (MCQ), three ethyl caffeoylquinates (ECQ), three dimethoxycinnamoylquinic acids (DQA), six caffeoylferuloylquinic acids (CFQA), six methyl dicaffeoylquinates (MdiCQ), four FQA glycosides (FQAG), six MCQ glycosides (MCQG), and three ethyl dicaffeoylquinates (EdiCQ). Forty-five of them were discovered from Lonicera species for the first time, and it is noted that CGA profiles were investigated for the first time in L. macranthoides. Results indicated that the developed method was a useful approach to explore unknown and minor isomeric compounds from complex natural products.

Mitochondrial DNA: An Endogenous Trigger for Immune Paralysis.

PubMed

Schäfer, Simon T; Franken, Lars; Adamzik, Michael; Schumak, Beatrix; Scherag, André; Engler, Andrea; Schönborn, Niels; Walden, Jennifer; Koch, Susanne; Baba, Hideo A; Steinmann, Jörg; Westendorf, Astrid M; Fandrey, Joachim; Bieber, Thomas; Kurts, Christian; Frede, Stilla; Peters, Jürgen; Limmer, Andreas

2016-04-01

Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown. Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector. Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3-dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality. The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients.

Analysis and functional annotation of expressed sequence tags from in vitro cell lines of elasmobranchs: spiny dogfish shark (Squalus acanthias) and little skate (Leucoraja erinacea)

PubMed Central

Parton, Angela; Bayne, Christopher J.; Barnes, David W.

2010-01-01

Elasmobranchs are the most commonly used experimental models among the jawed, cartilaginous fish (Chondrichthyes). Previously we developed cell lines from embryos of two elasmobranchs, Squalus acanthias the spiny dogfish shark (SAE line), and Leucoraja erinacea the little skate (LEE-1 line). From these lines cDNA libraries were derived and expressed sequence tags (ESTs) generated. From the SAE cell line 4303 unique transcripts were identified, with 1848 of these representing unknown sequences (showing no BLASTX identification). From the LEE-1 cell line, 3660 unique transcripts were identified, and unknown, unique sequences totaled 1333. Gene Ontology (GO) annotation showed that GO assignments for the two cell lines were in general similar. These results suggest that the procedures used to derive the cell lines led to isolation of cell types of the same general embryonic origin from both species. The LEE-1 transcripts included GO categories “envelope” and “oxidoreductase activity” but the SAE transcripts did not. GO analysis of SAE transcripts identified the category “anatomical structure formation” that was not present in LEE-1 cells. Increased organelle compartments may exist within LEE-1 cells compared to SAE cells, and the higher oxidoreductase activity in LEE-1 cells may indicate a role for these cells in responses associated with innate immunity or in steroidogenesis. These EST libraries from elasmobranch cell lines provide information for assembly of genomic sequences and are useful in revealing gene diversity, new genes and molecular markers, as well as in providing means for elucidation of full-length cDNAs and probes for gene array analyses. This is the first study of this type with members of the Chondrichthyes. PMID:20471924

Analysis and functional annotation of expressed sequence tags from in vitro cell lines of elasmobranchs: Spiny dogfish shark (Squalus acanthias) and little skate (Leucoraja erinacea).

PubMed

Parton, Angela; Bayne, Christopher J; Barnes, David W

2010-09-01

Elasmobranchs are the most commonly used experimental models among the jawed, cartilaginous fish (Chondrichthyes). Previously we developed cell lines from embryos of two elasmobranchs, Squalus acanthias the spiny dogfish shark (SAE line), and Leucoraja erinacea the little skate (LEE-1 line). From these lines cDNA libraries were derived and expressed sequence tags (ESTs) generated. From the SAE cell line 4303 unique transcripts were identified, with 1848 of these representing unknown sequences (showing no BLASTX identification). From the LEE-1 cell line, 3660 unique transcripts were identified, and unknown, unique sequences totaled 1333. Gene Ontology (GO) annotation showed that GO assignments for the two cell lines were in general similar. These results suggest that the procedures used to derive the cell lines led to isolation of cell types of the same general embryonic origin from both species. The LEE-1 transcripts included GO categories "envelope" and "oxidoreductase activity" but the SAE transcripts did not. GO analysis of SAE transcripts identified the category "anatomical structure formation" that was not present in LEE-1 cells. Increased organelle compartments may exist within LEE-1 cells compared to SAE cells, and the higher oxidoreductase activity in LEE-1 cells may indicate a role for these cells in responses associated with innate immunity or in steroidogenesis. These EST libraries from elasmobranch cell lines provide information for assembly of genomic sequences and are useful in revealing gene diversity, new genes and molecular markers, as well as in providing means for elucidation of full-length cDNAs and probes for gene array analyses. This is the first study of this type with members of the Chondrichthyes. Copyright 2010 Elsevier Inc. All rights reserved.

Estimates of the location of L-type Ca2+ channels in motoneurons of different sizes: a computational study.

PubMed

Grande, Giovanbattista; Bui, Tuan V; Rose, P Ken

2007-06-01

In the presence of monoamines, L-type Ca(2+) channels on the dendrites of motoneurons contribute to persistent inward currents (PICs) that can amplify synaptic inputs two- to sixfold. However, the exact location of the L-type Ca(2+) channels is controversial, and the importance of the location as a means of regulating the input-output properties of motoneurons is unknown. In this study, we used a computational strategy developed previously to estimate the dendritic location of the L-type Ca(2+) channels and test the hypothesis that the location of L-type Ca(2+) channels varies as a function of motoneuron size. Compartmental models were constructed based on dendritic trees of five motoneurons that ranged in size from small to large. These models were constrained by known differences in PIC activation reported for low- and high-conductance motoneurons and the relationship between somatic PIC threshold and the presence or absence of tonic excitatory or inhibitory synaptic activity. Our simulations suggest that L-type Ca(2+) channels are concentrated in hotspots whose distance from the soma increases with the size of the dendritic tree. Moving the hotspots away from these sites (e.g., using the hotspot locations from large motoneurons on intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold that occur experimentally during tonic excitatory or inhibitory synaptic activity. In models equipped with a size-dependent distribution of L-type Ca(2+) channels, the amplification of synaptic current by PICs depends on motoneuron size and the location of the synaptic input on the dendritic tree.

Unexpected Relationships and Inbreeding in HapMap Phase III Populations

PubMed Central

Stevens, Eric L.; Baugher, Joseph D.; Shirley, Matthew D.; Frelin, Laurence P.; Pevsner, Jonathan

2012-01-01

Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman's coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource. PMID:23185369

[Event-related synchronization/desynhronization during processing of target, no target and unknown visually presented words].

PubMed

Rebreikina, A B; Larionova, E B; Varlamov, A A

2015-01-01

The aim of this investigation is to study neurophysiologic mechanisms of processing of relevant words and unknown words. Event-related synchronization/desynchronization during categorization of three types of stimuli (known targets, known no targets and unknown words) was examined. The main difference between known targets and unknown stimuli was revealed in the thetal and theta2 bands at the early stage after stimuli onset (150-300 ms) and in the delta band (400-700 ms). In the late time window at about 800-1500 ms thetal ERS in response to the target stimuli was smaller than to other stimuli, but theta2 and alpha ERD in response to the target stimuli was larger than to known nontarget words.

Identification of "Known Unknowns" Utilizing Accurate Mass Data and ChemSpider

NASA Astrophysics Data System (ADS)

Little, James L.; Williams, Antony J.; Pshenichnov, Alexey; Tkachenko, Valery

2012-01-01

In many cases, an unknown to an investigator is actually known in the chemical literature, a reference database, or an internet resource. We refer to these types of compounds as "known unknowns." ChemSpider is a very valuable internet database of known compounds useful in the identification of these types of compounds in commercial, environmental, forensic, and natural product samples. The database contains over 26 million entries from hundreds of data sources and is provided as a free resource to the community. Accurate mass mass spectrometry data is used to query the database by either elemental composition or a monoisotopic mass. Searching by elemental composition is the preferred approach. However, it is often difficult to determine a unique elemental composition for compounds with molecular weights greater than 600 Da. In these cases, searching by the monoisotopic mass is advantageous. In either case, the search results are refined by sorting the number of references associated with each compound in descending order. This raises the most useful candidates to the top of the list for further evaluation. These approaches were shown to be successful in identifying "known unknowns" noted in our laboratory and for compounds of interest to others.

NIH Researchers Identify OCD Risk Gene

MedlinePlus

... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

Natural product biosynthesis: Tackling tunicamycin

NASA Astrophysics Data System (ADS)

Goddard-Borger, Ethan D.; Withers, Stephen G.

2012-07-01

The tunicamycins, secondary metabolites of various Streptomyces species, are invaluable tools in glycobiology. It has now been shown that their biosynthesis involves an unusual exo-glycal intermediate produced by previously unknown short-chain dehydrogenase/reductase activity.

Adaptive fuzzy prescribed performance control for MIMO nonlinear systems with unknown control direction and unknown dead-zone inputs.

PubMed

Shi, Wuxi; Luo, Rui; Li, Baoquan

2017-01-01

In this study, an adaptive fuzzy prescribed performance control approach is developed for a class of uncertain multi-input and multi-output (MIMO) nonlinear systems with unknown control direction and unknown dead-zone inputs. The properties of symmetric matrix are exploited to design adaptive fuzzy prescribed performance controller, and a Nussbaum-type function is incorporated in the controller to estimate the unknown control direction. This method has two prominent advantages: it does not require the priori knowledge of control direction and only three parameters need to be updated on-line for this MIMO systems. It is proved that all the signals in the resulting closed-loop system are bounded and that the tracking errors converge to a small residual set with the prescribed performance bounds. The effectiveness of the proposed approach is validated by simulation results. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Optofluidic Single-Cell Genome Amplification of Sub-micron Bacteria in the Ocean Subsurface

PubMed Central

Landry, Zachary C.; Vergin, Kevin; Mannenbach, Christopher; Block, Stephen; Yang, Qiao; Blainey, Paul; Carlson, Craig; Giovannoni, Stephen

2018-01-01

Optofluidic single-cell genome amplification was used to obtain genome sequences from sub-micron cells collected from the euphotic and mesopelagic zones of the northwestern Sargasso Sea. Plankton cells were visually selected and manually sorted with an optical trap, yielding 20 partial genome sequences representing seven bacterial phyla. Two organisms, E01-9C-26 (Gammaproteobacteria), represented by four single cell genomes, and Opi.OSU.00C, an uncharacterized Verrucomicrobia, were the first of their types retrieved by single cell genome sequencing and were studied in detail. Metagenomic data showed that E01-9C-26 is found throughout the dark ocean, while Opi.OSU.00C was observed to bloom transiently in the nutrient-depleted euphotic zone of the late spring and early summer. The E01-9C-26 genomes had an estimated size of 4.76–5.05 Mbps, and contained “O” and “W”-type monooxygenase genes related to methane and ammonium monooxygenases that were previously reported from ocean metagenomes. Metabolic reconstruction indicated E01-9C-26 are likely versatile methylotrophs capable of scavenging C1 compounds, methylated compounds, reduced sulfur compounds, and a wide range of amines, including D-amino acids. The genome sequences identified E01-9C-26 as a source of “O” and “W”-type monooxygenase genes related to methane and ammonium monooxygenases that were previously reported from ocean metagenomes, but are of unknown function. In contrast, Opi.OSU.00C genomes encode genes for catabolizing carbohydrate compounds normally associated with eukaryotic phytoplankton. This exploration of optofluidics showed that it was effective for retrieving diverse single-cell bacterioplankton genomes and has potential advantages in microbiology applications that require working with small sample volumes or targeting cells by their morphology.

Lab on a chip genotyping for Brucella spp. based on 15-loci multi locus VNTR analysis.

PubMed

De Santis, Riccardo; Ciammaruconi, Andrea; Faggioni, Giovanni; D'Amelio, Raffaele; Marianelli, Cinzia; Lista, Florigio

2009-04-07

Brucellosis is an important zoonosis caused by the genus Brucella. In addition Brucella represents potential biological warfare agents due to the high contagious rates for humans and animals. Therefore, the strain typing epidemiological tool may be crucial for tracing back source of infection in outbreaks and discriminating naturally occurring outbreaks versus bioterroristic event. A Multiple Locus Variable-number tandem repeats (VNTR) Analysis (MLVA) assay based on 15 polymorphic markers was previously described. The obtained MLVA band profiles may be resolved by techniques ranging from low cost manual agarose gels to the more expensive capillary electrophoresis sequencing. In this paper a rapid, accurate and reproducible system, based on the Lab on a chip technology was set up for Brucella spp. genotyping. Seventeen DNA samples of Brucella strains isolated in Sicily, previously genotyped, and twelve DNA samples, provided by MLVA Brucella VNTR ring trial, were analyzed by MLVA-15 on Agilent 2100. The DNA fragment sizes produced by Agilent, compared with those expected, showed discrepancies; therefore, in order to assign the correct alleles to the Agilent DNA fragment sizes, a conversion table was produced. In order to validate the system twelve unknown DNA samples were analyzed by this method obtaining a full concordance with the VNTR ring trial results. In this paper we described a rapid and specific detection method for the characterization of Brucella isolates. The comparison of the MLVA typing data produced by Agilent system with the data obtained by standard sequencing or ethidium bromide slab gel electrophoresis showed a general concordance of the results. Therefore this platform represents a fair compromise among costs, speed and specificity compared to any conventional molecular typing technique.

Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates.

PubMed

Wolsk, H M; Chawes, B L; Følsgaard, N V; Rasmussen, M A; Brix, S; Bisgaard, H

2016-06-01

Siblings have been shown to reduce the risk of childhood asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates, which could represent an underlying immune modulatory pathway. We measured 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosa of 571 one-month-old asymptomatic neonates from the Copenhagen Prospective Studies on Asthma in Childhood2010 birth cohort (COPSAC2010 ). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analysis (PCA). Neonates with siblings had an upregulated level of airway immune mediators, with predominance of Type 1- and Type 17-related mediators. This was supported by the PCA showing a highly significant difference between children with vs without siblings: P < 10(-10) , which persisted after adjustment for potential confounders including pathogenic airway bacteria and viruses: P < 0.0001. The immune priming effect was inversely associated with time since last childbirth: P = 0.0015. Siblings mediate a Type 1/Type 17-related immune-stimulatory effect in the airways of asymptomatic neonates, also after adjustment for pathogenic bacteria and viruses, indicating that siblings exert a transferable early immune modulatory effect. These findings may represent an in utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth, or it could relate to the presence of unidentified microbes, but further studies are needed to confirm our findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A new family of β-helix proteins with similarities to the polysaccharide lyases

DOE PAGES

Close, Devin W.; D'Angelo, Sara; Bradbury, Andrew R. M.

2014-09-27

Microorganisms that degrade biomass produce diverse assortments of carbohydrate-active enzymes and binding modules. Despite tremendous advances in the genomic sequencing of these organisms, many genes do not have an ascribed function owing to low sequence identity to genes that have been annotated. Consequently, biochemical and structural characterization of genes with unknown function is required to complement the rapidly growing pool of genomic sequencing data. A protein with previously unknown function (Cthe_2159) was recently isolated in a genome-wide screen using phage display to identify cellulose-binding protein domains from the biomass-degrading bacterium Clostridium thermocellum. Here, the crystal structure of Cthe_2159 is presentedmore » and it is shown that it is a unique right-handed parallel β-helix protein. Despite very low sequence identity to known β-helix or carbohydrate-active proteins, Cthe_2159 displays structural features that are very similar to those of polysaccharide lyase (PL) families 1, 3, 6 and 9. Cthe_2159 is conserved across bacteria and some archaea and is a member of the domain of unknown function family DUF4353. This suggests that Cthe_2159 is the first representative of a previously unknown family of cellulose and/or acid-sugar binding β-helix proteins that share structural similarities with PLs. More importantly, these results demonstrate how functional annotation by biochemical and structural analysis remains a critical tool in the characterization of new gene products.« less

A new family of β-helix proteins with similarities to the polysaccharide lyases

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

Close, Devin W.; D'Angelo, Sara; Bradbury, Andrew R. M.

Microorganisms that degrade biomass produce diverse assortments of carbohydrate-active enzymes and binding modules. Despite tremendous advances in the genomic sequencing of these organisms, many genes do not have an ascribed function owing to low sequence identity to genes that have been annotated. Consequently, biochemical and structural characterization of genes with unknown function is required to complement the rapidly growing pool of genomic sequencing data. A protein with previously unknown function (Cthe_2159) was recently isolated in a genome-wide screen using phage display to identify cellulose-binding protein domains from the biomass-degrading bacterium Clostridium thermocellum. Here, the crystal structure of Cthe_2159 is presentedmore » and it is shown that it is a unique right-handed parallel β-helix protein. Despite very low sequence identity to known β-helix or carbohydrate-active proteins, Cthe_2159 displays structural features that are very similar to those of polysaccharide lyase (PL) families 1, 3, 6 and 9. Cthe_2159 is conserved across bacteria and some archaea and is a member of the domain of unknown function family DUF4353. This suggests that Cthe_2159 is the first representative of a previously unknown family of cellulose and/or acid-sugar binding β-helix proteins that share structural similarities with PLs. More importantly, these results demonstrate how functional annotation by biochemical and structural analysis remains a critical tool in the characterization of new gene products.« less

Putative Monofunctional Type I Polyketide Synthase Units: A Dinoflagellate-Specific Feature?

PubMed Central

Eichholz, Karsten; Beszteri, Bánk; John, Uwe

2012-01-01

Marine dinoflagellates (alveolata) are microalgae of which some cause harmful algal blooms and produce a broad variety of most likely polyketide synthesis derived phycotoxins. Recently, novel polyketide synthesase (PKS) transcripts have been described from the Florida red tide dinoflagellate Karenia brevis (gymnodiniales) which are evolutionarily related to Type I PKS but were apparently expressed as monofunctional proteins, a feature typical of Type II PKS. Here, we investigated expression units of PKS I-like sequences in Alexandrium ostenfeldii (gonyaulacales) and Heterocapsa triquetra (peridiniales) at the transcript and protein level. The five full length transcripts we obtained were all characterized by polyadenylation, a 3′ UTR and the dinoflagellate specific spliced leader sequence at the 5′end. Each of the five transcripts encoded a single ketoacylsynthase (KS) domain showing high similarity to K. brevis KS sequences. The monofunctional structure was also confirmed using dinoflagellate specific KS antibodies in Western Blots. In a maximum likelihood phylogenetic analysis of KS domains from diverse PKSs, dinoflagellate KSs formed a clade placed well within the protist Type I PKS clade between apicomplexa, haptophytes and chlorophytes. These findings indicate that the atypical PKS I structure, i.e., expression as putative monofunctional units, might be a dinoflagellate specific feature. In addition, the sequenced transcripts harbored a previously unknown, apparently dinoflagellate specific conserved N-terminal domain. We discuss the implications of this novel region with regard to the putative monofunctional organization of Type I PKS in dinoflagellates. PMID:23139807

The Dental Fitness of Army War College Students, Class of 1985.

DTIC Science & Technology

1985-04-30

through April 1985) { TYPE OF TREATMENT RECEIVED # RECORDS N PT TX N OF APPTS EXAM PRO OPER C&B PROS PERIO OS ENDO 216 176 548 171 91 91 22 3 16 8 4 Notes...readiness. DEFINITIONS (3) DENTAL CONDITIONS are the oral or dental diseases, injuries , abnormalities, and situations which are regarded as pathologic...emerg 26 unknown 4 / E,O I Caries 62 unknown 4 / E,P,O I Caries 77 June 84 2 / E,O 2 Caries 82 July 77(84) 4 / EP,O I Caries 84 unknown 13 / E,O,C&B, Endo

Leading Process Branch Instability in Lis1+/− Nonradially Migrating Interneurons

PubMed Central

Gopal, Pallavi P.; Simonet, Jacqueline C.; Shapiro, William

2010-01-01

Mammalian forebrain development requires extensive migration, yet the mechanisms through which migrating neurons sense and respond to guidance cues are not well understood. Similar to the axon growth cone, the leading process and branches of neurons may guide migration, but the cytoskeletal events that regulate branching are unknown. We have previously shown that loss of microtubule-associated protein Lis1 reduces branching during migration compared with wild-type neurons. Using time-lapse imaging of Lis1+/− and Lis1+/+ cells migrating from medial ganglionic eminence explant cultures, we show that the branching defect is not due to a failure to initiate branches but a defect in the stabilization of new branches. The leading processes of Lis1+/− neurons have reduced expression of stabilized, acetylated microtubules compared with Lis1+/+ neurons. To determine whether Lis1 modulates branch stability through its role as the noncatalytic β regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b, exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type neurons phenocopies the branch instability observed in Lis1+/− neurons, and a PAF antagonist rescues leading process branching in Lis1+/− neurons. These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization. PMID:19861636

Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance.

PubMed

Ingram, Wendy Marie; Goodrich, Leeanne M; Robey, Ellen A; Eisen, Michael B

2013-01-01

Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.

In search of the elusive IrB{sub 2}: Can mechanochemistry help?

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

Xie, Zhilin; Blair, Richard G.; Department of Physics, University of Central Florida, Orlando, FL 32816

The previously unknown hexagonal ReB{sub 2}-type IrB{sub 2} diboride and orthorhombic IrB monoboride phases were produced by mechanochemical syntheses. High energy ball milling of elemental Ir and B powder for 30 h, followed by annealing of the powder at 1050 °C for 48 h, resulted in the formation of the desired phases. Both traditional laboratory and high resolution synchrotron X-ray diffraction (XRD) analyses were used for phase identification of the synthesized powder. In addition to XRD, scanning electron microscopy and transmission electron microscopy were employed to further characterize the microstructure of the phases produced. - Graphical abstract: ReB{sub 2}-type IrB{submore » 2} and a new IrB have been successfully synthesized for the first time using mechanochemical method. Crystal structures of IrB{sub 2} and IrB were studied by synchrotron X-ray diffraction. Microstructures of the new phases were characterized by SEM and TEM. - Highlights: • ReB{sub 2}-type IrB{sub 2} and a new IrB have been synthesized by mechanochemical method. • Crystal structures of IrB{sub 2} and IrB were studied by synchrotron XRD. • Microstructures of the new phases were characterized by SEM and TEM.« less

Heterogeneous nucleation of nitric acid trihydrate on clay minerals: relevance to type ia polar stratospheric clouds.

PubMed

Hatch, Courtney D; Gough, Raina V; Toon, Owen B; Tolbert, Margaret A

2008-01-17

Although critical to atmospheric modeling of stratospheric ozone depletion, selective heterogeneous nuclei that promote the formation of Type Ia polar stratospheric clouds (PSCs) are largely unknown. While mineral particles are known to be good ice nuclei, it is currently not clear whether they are also good nuclei for PSCs. In the present study, a high-vacuum chamber equipped with transmission Fourier transform infrared spectroscopy and a quadrupole mass spectrometer was used to study heterogeneous nucleation of nitric acid trihydrate (NAT) on two clay minerals-Na-montmorillonite and kaolinite-as analogs of atmospheric terrestrial and extraterrestrial minerals. The minerals are first coated with a 3:1 supercooled H2O/HNO3 solution prior to the observed nucleation of crystalline NAT. At 220 K, NAT formation was observed at low SNAT values of 12 and 7 on kaolinite and montmorillonite clays, respectively. These are the lowest SNAT values reported in the literature on any substrate. However, NAT nucleation exhibited significant temperature dependence. At lower temperatures, representative of typical polar stratospheric conditions, much higher supersaturations were required before nucleation was observed. Our results suggest that NAT nucleation on mineral particles, not previously treated with sulfuric acid, may not be an important nucleation platform for Type Ia PSCs under normal polar stratospheric conditions.

Epidemiology and pathogenesis of posttraumatic headache.

PubMed

Packard, R C

1999-02-01

This article presents an overview of the epidemiology and pathophysiology of posttraumatic headache. It reviews definitions of mild head injury (MHI), mild traumatic brain injury (MTBI), and concussion, and discusses the confusion that often occurs with these terms. Headache types and their pathophysiology are examined in detail. Just as the exact pathophysiology is unknown for migraine and other types of headache, the exact pathophysiology of headache after trauma is also still unknown in many cases. Possible connections between head or neck injuries and headache are reviewed, as well as hypothesized neurochemical changes that may occur in both migraine and traumatic brain injury (TBI). Psychological and legal factors are also considered.

Ichneumonidae (Hymenoptera) species new to the fauna of Norway

PubMed Central

2014-01-01

Abstract The present paper contains new distributional records for 61 species of ichneumon wasps (Hymenoptera, Ichneumonidae) previously unknown for Norway, six of them are reported from Scandinavia for the first time. PMID:24855440

Destination memory and familiarity: better memory for conversations with Elvis Presley than with unknown people.

PubMed

El Haj, Mohamad; Omigie, Diana; Samson, Séverine

2015-06-01

Familiarity is assumed to exert a beneficial effect on memory in older adults. Our paper investigated this issue specifically for destination memory, that is, memory of the destination of previously relayed information. Young and older adults were told familiar (Experiment 1) and unfamiliar (Experiment 2) proverbs associated with pictures depicting faces of celebrities (e.g., Elvis Presley) or unknown people, with a specific proverb assigned to each face. In a later recognition task, participants were presented with the previously exposed proverb-face pairs and for each pair had to decide whether they had previously relayed the given proverb to the given face. In general, destination performance was found to be higher for familiar than for unfamiliar faces. However while there was no difference between the two groups when the proverbs being relayed were unfamiliar, the advantage of face familiarity on destination memory was present only for older adults when the proverbs being relayed were familiar. Our results show that destination memory in older adults is sensitive to familiarity of both destination and output information.

Previously unknown apicomplexan species infecting Iceland scallop, Chlamys islandica (Müller, 1776), queen scallop, Aequipecten opercularis L., and king scallop, Pecten maximus L.

PubMed

Kristmundsson, Árni; Helgason, Sigurður; Bambir, Slavko Helgi; Eydal, Matthías; Freeman, Mark A

2011-11-01

Examination of three scallop species from three separate locations: Iceland scallop from Icelandic waters, king scallop from Scottish waters and queen scallop from Faroese and Scottish waters, revealed infections of a previously unknown apicomplexan parasite in all three scallop species. Developmental forms observed in the shells appeared to include both sexual and asexual stages of the parasite, i.e. merogony, gametogony and sporogony, which suggests a monoxenous life cycle. Meronts, gamonts, zygotes and mature oocysts were solely found in the muscular tissue. Zoites, which could be sporozoites and/or merozoites, were observed in great numbers, most frequently in muscles, both intracellular and free in the extracellular space. Zoites were also common inside haemocytes. Examination of the ultrastructure showed that the zoites contained all the major structures characterizing apicomplexans. This apicomplexan parasite is morphologically different from other apicomplexan species previously described from bivalves. Presently, its systematic position within the phylum Apicomplexa cannot be ascertained. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization of the Unusual Product from the Reaction between Cobalt(II) Chloride, Ethane-1,2-diamine, and Hydrochloric Acid: An Undergraduate Project Involving an Unknown Metal Complex.

ERIC Educational Resources Information Center

Curtis, Neil F.; And Others

1986-01-01

Discusses the need for student research-type chemistry projects based upon "unknown" metal complexes. Describes an experiment involving the product from the reaction between cobalt(II) chloride, ethane-1,2-diamine (en) and concentrated hydrochloric acid. Outlines the preparation of the cobalt complex, along with procedure, results and…

Assimilation efficiency and toxicokinetics of 14C-lindane in the terrestrial isopod Porcellionides pruinosus: the role of isopods in degradation of persistent soil pollutants.

PubMed

Loureiro, Susana; Sousa, J P; Nogueira, A J A; Soares, A M V M

2002-12-01

An achievable way to evaluate the bioavailability of a certain toxic in the environment is to measure the concentration inside soil organisms. Non-target saprotrophic organisms like isopods are often exposed to agrochemicals or other kind of persistent chemicals. In this study the isopod Porcellionides pruinosus was exposed to a constant concentration of Lindane (gamma-HCH) via food. Using toxicokinetic models the bioaccumulation and fate of the pesticide by isopods was assessed and compared with previous studies, where an unexpected decrease in gamma-HCH concentration was observed. Animal body burdens showed higher values, and a lower assimilation rate constant, although the elimination rate constant was twice the value previously observed. It was also observed that a significant amount of gamma-HCH had an unknown fate. To discover its possible destiny, a factorial experiment was carried out using two types of CO2 traps and contaminated leaves in the presence and absence of isopods. It was concluded that isopod activity might have been responsible for a more rapid biotransformation of gamma-HCH in leaves, since the amount of the pesticide is reduced in their presence.

Automobile tires--a potential source of highly carcinogenic dibenzopyrenes to the environment.

PubMed

Sadiktsis, Ioannis; Bergvall, Christoffer; Johansson, Christer; Westerholm, Roger

2012-03-20

Eight tires were analyzed for 15 high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAH), using pressurized fluid extraction. The variability of the PAH concentrations determined between different tires was large; a factor of 22.6 between the lowest and the highest. The relative abundance of the analytes was quite similar regardless of tire. Almost all (92.3%) of the total extractable PAH content was attributed to five PAHs: benzo[ghi]perylene, coronene, indeno[1,2,3-cd]pyrene, benzo[e]pyrene, and benzo[a]pyrene. The difference in the measured PAH content between summer and winter tires varied substantially across manufacturers, making estimates of total vehicle fleet emissions very uncertain. However, when comparing different types of tires from the same manufacturer they had significantly (p = 0.05) different PAH content. Previously, there have been no data available for carcinogenic dibenzopyrene isomers in automobile tires. In this study, the four dibenzopyrene isomers dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene, and dibenzo[a,h]pyrene constituted <2% of the sum of the 15 analyzed HMW PAHs. These findings show that automobile tires may be a potential previously unknown source of carcinogenic dibenzopyrenes to the environment.

Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages.

PubMed

Xia, Yin; Cortez-Retamozo, Virna; Niederkofler, Vera; Salie, Rishard; Chen, Shanzhuo; Samad, Tarek A; Hong, Charles C; Arber, Silvia; Vyas, Jatin M; Weissleder, Ralph; Pittet, Mikael J; Lin, Herbert Y

2011-02-01

Repulsive guidance molecule (RGM) family members RGMa, RGMb/Dragon, and RGMc/hemojuvelin were found recently to act as bone morphogenetic protein (BMP) coreceptors that enhance BMP signaling activity. Although our previous studies have shown that hemojuvelin regulates hepcidin expression and iron metabolism through the BMP pathway, the role of the BMP signaling mediated by Dragon remains largely unknown. We have shown previously that Dragon is expressed in neural cells, germ cells, and renal epithelial cells. In this study, we demonstrate that Dragon is highly expressed in macrophages. Studies with RAW264.7 and J774 macrophage cell lines reveal that Dragon negatively regulates IL-6 expression in a BMP ligand-dependent manner via the p38 MAPK and Erk1/2 pathways but not the Smad1/5/8 pathway. We also generated Dragon knockout mice and found that IL-6 is upregulated in macrophages and dendritic cells derived from whole lung tissue of these mice compared with that in respective cells derived from wild-type littermates. These results indicate that Dragon is an important negative regulator of IL-6 expression in immune cells and that Dragon-deficient mice may be a useful model for studying immune and inflammatory disorders.

Economics of infection control surveillance technology: cost-effective or just cost?

PubMed

Furuno, Jon P; Schweizer, Marin L; McGregor, Jessina C; Perencevich, Eli N

2008-04-01

Previous studies have suggested that informatics tools, such as automated alert and decision support systems, may increase the efficiency and quality of infection control surveillance. However, little is known about the cost-effectiveness of these tools. We focus on 2 types of economic analyses that have utility in assessing infection control interventions (cost-effectiveness analysis and business-case analysis) and review the available literature on the economics of computerized infection control surveillance systems. Previous studies on the effectiveness of computerized infection control surveillance have been limited to assessments of whether these tools increase the sensitivity and specificity of surveillance over traditional methods. Furthermore, we identified only 2 studies that assessed the costs associated with computerized infection control surveillance. Thus, it remains unknown whether computerized infection control surveillance systems are cost-effective and whether use of these systems improves patient outcomes. The existing data are insufficient to allow for a summary conclusion on the cost-effectiveness of infection control surveillance technology. All future studies of computerized infection control surveillance systems should aim to collect outcomes and economic data to inform decision making and assist hospitals with completing business-cases analyses.

The relationship of maternal characteristics and circulating progesterone concentrations with reproductive outcome in the bottlenose dolphin (Tursiops truncatus) after artificial insemination, with and without ovulation induction, and natural breeding.

PubMed

O'Brien, J K; Robeck, T R

2012-08-01

Bottlenose dolphins (Tursiops truncatus) undergoing natural breeding and artificial insemination (AI) were examined to characterize serum progesterone concentrations and determine relationships among age, parity, and reproductive outcome. Progesterone profiles of five cycle types (n = 119 total cycles from 54 animals) were characterized as follows: (i) conception and production of a live term calf (conceptive-term, n = 73); (ii) conception and abortion after Day 60 (conceptive-abortion, n = 12); (iii) unknown conception status with prolonged, elevated progesterone and absence of a fetus (conceptive-unknown, n = 14); (iv) conception failure with normal luteal phase progesterone concentrations (non-conceptive, n = 14, AI cycles only); and (v) conception failure with progesterone insufficiency occuring after spontaneous ovulation or owing to premature ovulation induction using GnRH (non-conceptive-PI, n = 6, AI cycles only). By Day 21 post-insemination (PI), progesterone concentrations were similar (P > 0.05) among conceptive-term, conceptive-abortion and conceptive-unknown, and higher (P < 0.05) for conceptive-term than non-conceptive and non-conceptive-PI cycles. Progesterone concentrations of known conceptive cycles peaked by Week 7 PI (P < 0.05) and remained elevated for the remainder of pregnancy (Weeks 8 up to 54, ≥ 5 days pre-partum). During midpregnancy (Days 121-240), conceptive-term cycles had higher (P > 0.05) progesterone concentrations than conceptive-abortion and unknown conception status cycles. Parity was not associated with reproductive outcome based on cycle type (P > 0.05). Age of females in conceptive-unknown (26.5 ± 10.1 yrs) and conceptive-abortion (22.1 ± 9.4 yrs) groups was higher (P < 0.05) than in conceptive-term (15.7 ± 7.2 yrs). The conceptive-unknown cycle type possibly represents undetected early embryonic loss occurring before Day 60 PI. Length of gestation using known conception dates was 376.1 ± 11.0 days and the range of this parameter (355-395 days) has implications for peri-parturient management procedures for the species. Copyright © 2012 Elsevier Inc. All rights reserved.

Distribution of small native plasmids in Streptococcus pyogenes in India.

PubMed

Bergmann, René; Nerlich, Andreas; Chhatwal, Gursharan S; Nitsche-Schmitz, D Patric

2014-05-01

Complete characterization of a Streptococcus pyogenes population from a defined geographic region comprises information on the plasmids that circulate in these bacteria. Therefore, we determined the distribution of small plasmids (<5kb) in a collection of 279 S. pyogenes isolates from India, where diversity of strains and incidence rates of S. pyogenes infections are high. The collection comprised 77 emm-types. For plasmid detection and discrimination, we developed PCRs for different plasmid replication initiation protein genes, the putative repressor gene copG and bacteriocin genes dysA and scnM57. Plasmid distribution was limited to 13 emm-types. Co-detection analysis using aforementioned PCRs revealed four distinct plasmid sub-types, two of which were previously unknown. Representative plasmids pA852 and pA996 of the two uncharacterized plasmid sub-types were sequenced. These two plasmids could be assigned to the pMV158 and the pC194/pUB110 family of rolling-circle plasmids, respectively. The majority of small plasmids found in India belonged to the two newly characterized sub-types, with pA852- and pA996-like plasmids amounting to 42% and 22% of all detected plasmids, respectively. None of the detected plasmids coded for a known antibiotic resistance gene. Instead, all of the four plasmid sub-types carried known or potential bacteriocin genes. These genes may have influence on the evolutionary success of certain S. pyogenes genotypes. Notably, pA852-like plasmids were found in all isolates of the most prevalent emm-type 11.0. Together, a priori fitness of this genotype and increased fitness due to the acquired plasmids may have rendered type emm11.0 successful and caused the prevalence of pA852-like plasmids in India. Copyright © 2013 Elsevier GmbH. All rights reserved.

Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.

PubMed

Graul-Neumann, Luitgard M; Hausser, Ingrid; Essayie, Maximilian; Rauch, Anita; Kraus, Cornelia

2008-04-15

Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. Only seven ADCL families with mutations in the elastin gene (ELN) have been described previously. We present morphological and molecular genetic studies in a cutis laxa kindred with a previously undescribed highly variable phenotype caused by a novel ELN mutation c.1621 C > T. The proband presented with severe cutis laxa, severe congenital lung disease previously undescribed in ADCL and pulmonary artery disease, which is often seen in ARCL but rare in ADCL. He also developed infantile spasms (OMIM 308350; West syndrome), which we consider a coincidental association although recessive cutis laxa or even digenic inheritance cannot be excluded. Electron microscopy of the proband's dermis revealed only mild rarefication of elastic fibers (in contrast to most recessive cutis laxa types). Apart from mild elastic fiber fragmentation, dermal morphology of the proband's father was within normal range. Molecular analysis of the ELN gene using genomic DNA from blood and RNA from cultured skin fibroblasts indicated a novel splice site mutation in the proband and his clinically healthy father. Analysis of ELN expression in fibroblasts provided evidence for a dominant-negative effect in the child, while due to an unknown mechanism, the father showed haploinsufficiency which might explain the significant clinical variability. Copyright 2008 Wiley-Liss, Inc.

Valyl-tRNA synthetase modification-dependent restriction of bacteriophage T4.

PubMed Central

Olson, N J; Marchin, G L

1984-01-01

A strain of Escherichia coli, CP 790302, severely restricts the growth of wild-type bacteriophage T4. In broth culture, most infections of single cells are abortive, although a few infected cells exhibit reduced burst sizes. In contrast, bacteriophage T4 mutants impaired in the ability to modify valyl-tRNA synthetase develop normally on this strain. Biochemical evidence indicates that the phage-modified valyl-tRNA synthetase in CP 790302 is different from that previously described. Although the enzyme is able to support normal protein synthesis, a disproportionate amount of phage structural protein (serum blocking power) fails to mature into particles of the appropriate density. The results with host strain CP 790302 are consistent with either a gratuitous inhibition of phage assembly by faulty modification or abrogation of an unknown role that valyl-tRNA synthetase might normally play in viral assembly. PMID:6374167

Patterns of call communication between group-housed zebra finches change during the breeding cycle.

PubMed

Gill, Lisa F; Goymann, Wolfgang; Ter Maat, Andries; Gahr, Manfred

2015-10-06

Vocal signals such as calls play a crucial role for survival and successful reproduction, especially in group-living animals. However, call interactions and call dynamics within groups remain largely unexplored because their relation to relevant contexts or life-history stages could not be studied with individual-level resolution. Using on-bird microphone transmitters, we recorded the vocalisations of individual zebra finches (Taeniopygia guttata) behaving freely in social groups, while females and males previously unknown to each other passed through different stages of the breeding cycle. As birds formed pairs and shifted their reproductive status, their call repertoire composition changed. The recordings revealed that calls occurred non-randomly in fine-tuned vocal interactions and decreased within groups while pair-specific patterns emerged. Call-type combinations of vocal interactions changed within pairs and were associated with successful egg-laying, highlighting a potential fitness relevance of calling dynamics in communication systems.

Topological relationships between brain and social networks.

PubMed

Sakata, Shuzo; Yamamori, Tetsuo

2007-01-01

Brains are complex networks. Previously, we revealed that specific connected structures are either significantly abundant or rare in cortical networks. However, it remains unknown whether systems from other disciplines have similar architectures to brains. By applying network-theoretical methods, here we show topological similarities between brain and social networks. We found that the statistical relevance of specific tied structures differs between social "friendship" and "disliking" networks, suggesting relation-type-specific topology of social networks. Surprisingly, overrepresented connected structures in brain networks are more similar to those in the friendship networks than to those in other networks. We found that balanced and imbalanced reciprocal connections between nodes are significantly abundant and rare, respectively, whereas these results are unpredictable by simply counting mutual connections. We interpret these results as evidence of positive selection of balanced mutuality between nodes. These results also imply the existence of underlying common principles behind the organization of brain and social networks.

Reorganization of corticospinal output during motor learning

PubMed Central

Peters, Andrew J.; Lee, Jun; Hedrick, Nathan G.; O’Neil, Keelin; Komiyama, Takaki

2017-01-01

Motor learning is accompanied by widespread changes within the motor cortex, but it is unknown whether these changes are ultimately funneled through a stable corticospinal output channel or if the corticospinal output itself is plastic. We investigated the consistency of the relationship between corticospinal neuron activity and movement through in vivo two-photon calcium imaging in mice learning a lever-press task. Corticospinal neurons exhibited heterogeneous correlations with movement, with the majority of movement-modulated neurons decreasing activity during movement. Individual cells changed their activity across days which led to novel associations between corticospinal activity and movement. Unlike previous observations in layer 2/3, activity accompanying learned movements did not become more consistent with learning, and instead the activity of dissimilar movements became more decorrelated. These results indicate that the relationship between corticospinal activity and movement is dynamic, and the types of activity and plasticity are different from and possibly complementary to layer 2/3. PMID:28671694

Variability search in M 31 using principal component analysis and the Hubble Source Catalogue

NASA Astrophysics Data System (ADS)

Moretti, M. I.; Hatzidimitriou, D.; Karampelas, A.; Sokolovsky, K. V.; Bonanos, A. Z.; Gavras, P.; Yang, M.

2018-06-01

Principal component analysis (PCA) is being extensively used in Astronomy but not yet exhaustively exploited for variability search. The aim of this work is to investigate the effectiveness of using the PCA as a method to search for variable stars in large photometric data sets. We apply PCA to variability indices computed for light curves of 18 152 stars in three fields in M 31 extracted from the Hubble Source Catalogue. The projection of the data into the principal components is used as a stellar variability detection and classification tool, capable of distinguishing between RR Lyrae stars, long-period variables (LPVs) and non-variables. This projection recovered more than 90 per cent of the known variables and revealed 38 previously unknown variable stars (about 30 per cent more), all LPVs except for one object of uncertain variability type. We conclude that this methodology can indeed successfully identify candidate variable stars.

In vitro study of cell differentiation by two type mouse embryo stem cells on mono- and multilayer nanocarbon tubes

NASA Astrophysics Data System (ADS)

Imai, Koichi; Akasaka, Tsukasa; Watari, Fumio; Tanoue, Akito; Nakamura, Kazuaki; Suese, Kazuhiko; Takashima, Hiromasa; Nishikawa, Tetsunari; Tanaka, Akio; Takeda, Shoji

2012-09-01

The effects of nanomaterials on human reproduction and development remain unknown. The risks of nanomaterials for future generations should be elucidated. Thus, it is important to establish an experimental method to accurately examine embryotoxicity. We previously investigated the myocardial cell differentiation of ES-D3 cells using monolayer (SWCNTs) and multilayer (MWCNTs) nanocarbon tubes. As a result, in spite of having the same carbon composition, the effects on the cell differentiation levels differed between the tubes. We investigated their cell differentiation and cytotoxic effects on EL M3 and ES-R1-EGFP B2/EGFP cells, which require feeder cells. As a result, myocardial pulse rates differed between the presence of SWCNTs and MWCNTs even when feeder cells existed between the samples and cells. The different surface structures of SWCNTs and MWCNTs may have influenced ES cell differentiation.

Postselection technique for quantum channels with applications to quantum cryptography.

PubMed

Christandl, Matthias; König, Robert; Renner, Renato

2009-01-16

We propose a general method for studying properties of quantum channels acting on an n-partite system, whose action is invariant under permutations of the subsystems. Our main result is that, in order to prove that a certain property holds for an arbitrary input, it is sufficient to consider the case where the input is a particular de Finetti-type state, i.e., a state which consists of n identical and independent copies of an (unknown) state on a single subsystem. Our technique can be applied to the analysis of information-theoretic problems. For example, in quantum cryptography, we get a simple proof for the fact that security of a discrete-variable quantum key distribution protocol against collective attacks implies security of the protocol against the most general attacks. The resulting security bounds are tighter than previously known bounds obtained with help of the exponential de Finetti theorem.

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound

NASA Astrophysics Data System (ADS)

Li, Lin; Wijaya, Hadhi; Samanta, Sanjay; Lam, Yulin; Yao, Shao Q.

2015-06-01

Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

PubMed Central

Bustamante, Jacinta; Arias, Andres A; Vogt, Guillaume; Picard, Capucine; Galicia, Lizbeth Blancas; Prando, Carolina; Grant, Audrey V; Marchal, Christophe C; Hubeau, Marjorie; Chapgier, Ariane; de Beaucoudrey, Ludovic; Puel, Anne; Feinberg, Jacqueline; Valinetz, Ethan; Jannière, Lucile; Besse, Céline; Boland, Anne; Brisseau, Jean-Marie; Blanche, Stéphane; Lortholary, Olivier; Fieschi, Claire; Emile, Jean-François; Boisson-Dupuis, Stéphanie; Al-Muhsen, Saleh; Woda, Bruce; Newburger, Peter E; Condino-Neto, Antonio; Dinauer, Mary C; Abel, Laurent; Casanova, Jean-Laurent

2011-01-01

Germline mutations in CYBB, the human gene encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This ‘experiment of nature’ indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria. PMID:21278736

Subcellular localization of celery mannitol dehydrogenase. A cytosolic metabolic enzyme in nuclei.

PubMed Central

Yamamoto, Y T; Zamski, E; Williamson, J D; Conkling, M A; Pharr, D M

1997-01-01

Mannitol dehydrogenase (MTD) is the first enzyme in mannitol catabolism in celery (Apium graveolens L. var dulce [Mill] Pers. cv Florida 638). Mannitol is an important photoassimilate, as well as providing plants with resistance to salt and osmotic stress. Previous work has shown that expression of the celery Mtd gene is regulated by many factors, such as hexose sugars, salt and osmotic stress, and salicylic acid. Furthermore, MTD is present in cells of sink organs, phloem cells, and mannitol-grown suspension cultures. Immunogold localization and biochemical analyses presented here demonstrate that celery MTD is localized in the cytosol and nuclei. Although the cellular density of MTD varies among different cell types, densities of nuclear and cytosolic MTD in a given cell are approximately equal. Biochemical analyses of nuclear extracts from mannitol-grown cultured cells confirmed that the nuclear-localized MTD is enzymatically active. The function(s) of nuclear-localized MTD is unknown. PMID:9414553

Blood type gene locus has no influence on ACE association with Alzheimer's disease.

PubMed

Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

2015-04-01

The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Parenclitic networks: uncovering new functions in biological data

PubMed Central

Zanin, Massimiliano; Alcazar, Joaquín Medina; Carbajosa, Jesus Vicente; Paez, Marcela Gomez; Papo, David; Sousa, Pedro; Menasalvas, Ernestina; Boccaletti, Stefano

2014-01-01

We introduce a novel method to represent time independent, scalar data sets as complex networks. We apply our method to investigate gene expression in the response to osmotic stress of Arabidopsis thaliana. In the proposed network representation, the most important genes for the plant response turn out to be the nodes with highest centrality in appropriately reconstructed networks. We also performed a target experiment, in which the predicted genes were artificially induced one by one, and the growth of the corresponding phenotypes compared to that of the wild-type. The joint application of the network reconstruction method and of the in vivo experiments allowed identifying 15 previously unknown key genes, and provided models of their mutual relationships. This novel representation extends the use of graph theory to data sets hitherto considered outside of the realm of its application, vastly simplifying the characterization of their underlying structure. PMID:24870931

A study of cell electrophoresis as a means of purifying growth hormone secreting cells

NASA Technical Reports Server (NTRS)

Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

1983-01-01

Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

A novel locus for dilated cardiomyopathy maps to canine chromosome 8.

PubMed

Werner, Petra; Raducha, Michael G; Prociuk, Ulana; Sleeper, Meg M; Van Winkle, Thomas J; Henthorn, Paula S

2008-06-01

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance.

PubMed

Wong, Connie H Y; Jenne, Craig N; Petri, Björn; Chrobok, Navina L; Kubes, Paul

2013-08-01

Through the use of intravital imaging of the liver, we demonstrate a collaborative role for platelets with Kupffer cells (KCs) in eradicating blood-borne bacterial infection. Under basal conditions, platelets, via the platelet-adhesion receptor GPIb, formed transient 'touch-and-go' interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria such as Bacillus cereus and methicillin-resistant Staphylococcus aureus (MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GPIbα-deficient mice had more endothelial and KC damage than did their wild-type counterparts, which led to more fluid leakage, substantial polycythemia and rapid mortality. Our study identifies a previously unknown surveillance mechanism by which platelets survey macrophages that rapidly converts to a critical host response to blood-borne bacteria.

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

T.Rex is used to explore tabular data sets containing up to ten million records to help rapidly understand a previously unknown data set. Analysis can quickly identify patterns of interest and the records and fields that capture those patterns. T.Rex contains a growing set of deep analytical tools and supports robust export capabilities that selected data can be incorporated into to other specialized tools for further analysis. T.Rex is flexible in ingesting different types and formats of data, allowing the user to interactively experiment and perform trial and error guesses on the structure of the data; and also has amore » variety of linked visual analytic tools that enable exploration of the data to find relevant content, relationships among content, trends within the content, and capture knowledge about the content. Finally, T.Rex has a rich export capability, to extract relevant subsets of a larger data source, to further analyze their data in other analytic tools.« less

Interdisciplinary applications and interpretations of ERTS data within the Susquehanna River Basin (resource inventory, land use, and pollution)

NASA Technical Reports Server (NTRS)

Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator)

1973-01-01

The author has identified the following significant results. An interdisciplinary group at Penn State University is analyzing ERTS-1 data. The geographical area of interest is that of the Susquehanna River Basin in Pennsylvania. The objectives of the work have been to ascertain the usefulness of ERTS-1 data in the areas of natural resources and land use inventory, geology and hydrology, and environmental quality. Specific results include a study of land use in the Harrisburg area, discrimination between types of forest resources and vegetation, detection of previously unknown geologic faults and correlation of these with known mineral deposits and ground water, mapping of mine spoils in the anthracite region of eastern Pennsylvania, and mapping of strip mines and acid mine drainage in central Pennsylvania. Both photointerpretive techniques and automatic computer processing methods have been developed and used, separately and in a combined approach.

Characterization of phenolic compounds in Brazilian pepper (Schinus terebinthifolius Raddi) exocarp.

PubMed

Feuereisen, Michelle M; Hoppe, Julia; Zimmermann, Benno F; Weber, Fabian; Schulze-Kaysers, Nadine; Schieber, Andreas

2014-07-02

The objective of this study was to characterize the phenolic composition of Brazilian pepper (Schinus terebinthifolius Raddi) exocarp extract. Using UHPLC-DAD-MS/MS analysis, four anthocyanins, three biflavonoids, gallic acid, and two types of hydrolyzable tannins (galloyl glucoses, galloyl shikimic acids) were tentatively identified. The structure of the so far unknown 7-O-methylpelargonidin 3-O-β-D-galactopyranoside was elucidated by 2D NMR. Within the group of gallotannins, galloyl shikimic acids with uncommon degrees of galloylation (tetra- to hexagalloyl shikimic acids) were detected. Among the biflavonoids, I3',II8-biapigenin (amentoflavone), I6,II8-biapigenin (agathisflavone), and II-2,3-dihydro-I3',II8-biapigenin were identified, which have already been described for Anacardiaceae. From the results of the present study together with previous findings on the phenolic profile of other Anacardiaceae plants, it is concluded that 7-methoxylated flavonoids are a chemotaxonomic trait frequently found in this family.

Autoantibody-mediated bowel and bladder dysfunction in a patient with chronic, nondiabetic neuropathy.

PubMed

Jackson, Michael W; Gordon, Thomas P; McCombe, Pamela A

2008-04-01

Physiological techniques can be used to detect novel autoantibodies causing alteration of autonomic function after passive transfer to mice. Previously, such antibodies have been detected in patients with type I diabetes mellitus, myasthenia gravis, and Sjogren's syndrome. We now describe a patient with an idiopathic nondiabetic neuropathy with prominent autonomic symptoms, including bladder and bowel dysfunction. Physiological assays of whole colon and bladder were used to determine the presence in the patient serum of functional autoantibodies capable of mediating autonomic dysfunction. Immunoglobulin G (IgG) from this patient was able to disrupt bladder and bowel function on passive transfer to mice. This is a new pattern of autoantibody-mediated abnormality. Although the target antigen is unknown, it is likely to be a cell-surface receptor or ion channel. This case highlights the usefulness of passive transfer studies in detecting functional antibodies in patients with autonomic neuropathy.

Number of discernible object colors is a conundrum.

PubMed

Masaoka, Kenichiro; Berns, Roy S; Fairchild, Mark D; Moghareh Abed, Farhad

2013-02-01

Widely varying estimates of the number of discernible object colors have been made by using various methods over the past 100 years. To clarify the source of the discrepancies in the previous, inconsistent estimates, the number of discernible object colors is estimated over a wide range of color temperatures and illuminance levels using several chromatic adaptation models, color spaces, and color difference limens. Efficient and accurate models are used to compute optimal-color solids and count the number of discernible colors. A comprehensive simulation reveals limitations in the ability of current color appearance models to estimate the number of discernible colors even if the color solid is smaller than the optimal-color solid. The estimates depend on the color appearance model, color space, and color difference limen used. The fundamental problem lies in the von Kries-type chromatic adaptation transforms, which have an unknown effect on the ranking of the number of discernible colors at different color temperatures.

Evaluation of (GTG)5-PCR for identification of Enterococcus spp.

PubMed

Svec, Pavel; Vancanneyt, Marc; Seman, Milan; Snauwaert, Cindy; Lefebvre, Karen; Sedlácek, Ivo; Swings, Jean

2005-06-01

A set of reference strains and a group of previously unidentified enterococci were analysed by rep-PCR with the (GTG)(5) primer to evaluate the discriminatory power and suitability of this method for typing and identification of enterococcal species. A total of 49 strains representing all validly described species were obtained from bacterial collections. For more extensive evaluation of this identification approach 112 well-defined and identified enterococci isolated from bryndza cheese were tested. The (GTG)(5)-PCR fingerprinting assigned all strains into well-differentiated clusters representing individual species. Subsequently, a group including 44 unidentified enterococci isolated from surface waters was analysed to evaluate this method for identification of unknown isolates. Obtained band patterns allowed us to identify all the strains clearly to the species level. This study proved that rep-PCR with (GTG)(5) primer is a reliable and fast method for species identification of enterococci.

T.Rex

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

2016-06-08

T.Rex is used to explore tabular data sets containing up to ten million records to help rapidly understand a previously unknown data set. Analysis can quickly identify patterns of interest and the records and fields that capture those patterns. T.Rex contains a growing set of deep analytical tools and supports robust export capabilities that selected data can be incorporated into to other specialized tools for further analysis. T.Rex is flexible in ingesting different types and formats of data, allowing the user to interactively experiment and perform trial and error guesses on the structure of the data; and also has amore » variety of linked visual analytic tools that enable exploration of the data to find relevant content, relationships among content, trends within the content, and capture knowledge about the content. Finally, T.Rex has a rich export capability, to extract relevant subsets of a larger data source, to further analyze their data in other analytic tools.« less

Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway.

PubMed

Islam, Rafique; Wei, Shu-Yi; Chiu, Wei-Hsin; Hortsch, Michael; Hsu, Jui-Chou

2003-05-01

echinoid (ed) encodes an cell-adhesion molecule (CAM) that contains immunoglobulin domains and regulates the EGFR signaling pathway during Drosophila eye development. Based on our previous genetic mosaic and epistatic analysis, we proposed that Ed, via homotypic interactions, activates a novel, as yet unknown pathway that antagonizes EGFR signaling. In this report, we demonstrate that Ed functions as a homophilic adhesion molecule and also engages in a heterophilic trans-interaction with Drosophila Neuroglian (Nrg), an L1-type CAM. Co-expression of ed and nrg in the eye exhibits a strong genetic synergy in inhibiting EGFR signaling. This synergistic effect requires the intracellular domain of Ed, but not that of Nrg. In addition, Ed and Nrg colocalize in the Drosophila eye and are efficiently co-immunoprecipitated. Together, our results suggest a model in which Nrg acts as a heterophilic ligand and activator of Ed, which in turn antagonizes EGFR signaling.

Resistance to human immunodeficiency virus type 1 (HIV-1) generated by lentivirus vector-mediated delivery of the CCR5Δ32 gene despite detectable expression of the HIV-1 co-receptors

PubMed Central

Jin, Qingwen; Marsh, Jon; Cornetta, Kenneth; Alkhatib, Ghalib

2009-01-01

It has previously been demonstrated that there are two distinct mechanisms for genetic resistance to human immunodeficiency virus type 1 (HIV-1) conferred by the CCR5Δ32 gene: the loss of wild-type CCR5 surface expression and the generation of CCR5Δ32 protein, which interacts with CXCR4. To analyse the protective effects of long-term expression of the CCR5Δ32 protein, recombinant lentiviral vectors were used to deliver the CCR5Δ32 gene into human cell lines and primary peripheral blood mononuclear cells that had been immortalized by human T-cell leukemia virus type 1. Blasticidin S-resistant cell lines expressing the lentivirus-encoded CCR5Δ32 showed a significant reduction in HIV-1 Env-mediated fusion assays. It was shown that CD4+ T lymphocytes expressing the lentivirus-encoded CCR5Δ32 gene were highly resistant to infection by a primary but not by a laboratory-adapted X4 strain, suggesting different infectivity requirements. In contrast to previous studies that analysed the CCR5Δ32 protective effects in a transient expression system, this study showed that long-term expression of CCR5Δ32 conferred resistance to HIV-1 despite cell-surface expression of the HIV co-receptors. The results suggest an additional unknown mechanism for generating the CCR5Δ32 resistance phenotype and support the hypothesis that the CCR5Δ32 protein acts as an HIV-suppressive factor by altering the stoichiometry of the molecules involved in HIV-1 entry. The lentiviral-CCR5Δ32 vectors offer a method of generating HIV-resistant cells by delivery of the CCR5Δ32 gene that may be useful for stem cell- or T-cell-based gene therapy for HIV-1 infection. PMID:18796731

Geological and hydrogeological investigations in west Malaysia

NASA Technical Reports Server (NTRS)

Ahmad, J. B. (Principal Investigator); Khoon, S. Y.

1977-01-01

The author has identified the following significant results. Large structures along the east coast of the peninsula were discovered. Of particular significance were the circular structures which were believed to be associated with mineralization and whose existence was unknown. The distribution of the younger sediments along the east coast appeared to be more widespread than previously indicated. Along the Pahang coast on the southern end, small traces of raised beach lines were noted up to six miles inland. The existence of these beach lines was unknown due to their isolation in large coastal swamps.

Irreversible temperature gating in trpv1 sheds light on channel activation

PubMed Central

Sánchez-Moreno, Ana; Guevara-Hernández, Eduardo; Contreras-Cervera, Ricardo; Rangel-Yescas, Gisela; Ladrón-de-Guevara, Ernesto; Rosenbaum, Tamara

2018-01-01

Temperature-activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening. PMID:29869983

Does modern high standard life style cause type 1 diabetes in children?

PubMed

Ludvigsson, Johnny; Holmqvist, Britt-Marie; Samuelsson, Ulf

2013-02-01

Type 1 diabetes is a serious disease which, in spite of intensive treatment, causes serious complications and increased mortality. The incidence is increasing, but the aetiology is unknown. As part of modern lifestyle, increased hygiene has been suspected as one contributing cause but so far there is no evidence. Several large epidemiological studies, mainly restricted to children with increased genetic risk for type 1 diabetes, have so far given no clue. All Babies in Southeast Sweden is unique in its design as it has followed an unselected group of children from birth 1997-1999 and onwards with regular follow-ups. This report is based on questionnaires from initially 16 051 children of whom 80 have later on developed type 1 diabetes. The parents answered questionnaires at the birth of their child and then after 1, 2-3, 5-6 and 8 years. A number of parameters possibly related to hygiene were analysed with several statistical methods, both with univariate and in regression models. Our study cannot identify any crucial environmental factor. This indicates that hygiene-related parameters traditionally regarded as part of 'modern life style' do not play any important role for the aetiology of type 1 diabetes. There is no reason to recommend a change of that part of our lifestyle. We find weak associations to previous gastrointestinal infections, which gives a hint that development of type 1 diabetes may be related to problems in the gut and maybe one should look closer into the microbes living in the gut. Copyright © 2012 John Wiley & Sons, Ltd.

Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions

PubMed Central

Katz, Matthew L.; Viney, Tim J.; Nikolic, Konstantin

2016-01-01

Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information (“Quadratic Mutual Information”). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells’ response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types. PMID:26845435

Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise.

PubMed

Nishimune, Hiroshi; Numata, Tomohiro; Chen, Jie; Aoki, Yudai; Wang, Yonghong; Starr, Miranda P; Mori, Yasuo; Stanford, John A

2012-01-01

The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca(2+) influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise.

Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens.

PubMed

Medina Escobar, Pedro; Moser, Michel; Risch, Lorenz; Risch, Martin; Nydegger, Urs Ernst; Stanga, Zeno

2015-01-01

To estimate the prevalence of unknown impaired glucose metabolism, also referred to as prediabetes (PreD), and unknown type 2 diabetes mellitus (T2DM) among subjectively healthy Swiss senior citizens. The fasting plasma glucose (FPG) and glycated haemoglobin A(1c) (HbA(1c)) levels were used for screening. A total of 1 362 subjects were included (613 men and 749 women; age range 60-99 years). Subjects with known T2DM were excluded. The FPG was processed immediately for analysis under standardised preanalytical conditions in a cross-sectional cohort study; plasma glucose levels were measured by means of the hexokinase procedure, and HbA(1c) was measured chromatographically and classified using the current American Diabetes Association (ADA) criteria. The crude prevalence of individuals unaware of having prediabetic FPG or HbA(1c) levels, was 64.5% (n = 878). Analogously, unknown T2DM was found in 8.4% (n = 114) On the basis of HbA(1c) criteria alone, significantly more subjects with unknown fasting glucose impairment and laboratory T2DM could be identified than with the FPG. The prevalence of PreD as well as of T2DM increased with age. The mean HOMA indices (homeostasis model assessment) for the different age groups, between 2.12 and 2.59, are consistent with clinically hidden disease and are in agreement with the largely orderly Body Mass Indices found in the normal range. Laboratory evidence of impaired glucose metabolism and, to a lesser extent, unknown T2DM, has a high prevalence among subjectively healthy older Swiss individuals. Laboratory identification of people with unknown out-of-range glucose values and overt diabetic hyperglycaemia might improve the prognosis by delaying the emergence of overt disease.

The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor

PubMed Central

Mayer, François L.; Wilson, Duncan; Jacobsen, Ilse D.; Miramón, Pedro; Große, Katharina; Hube, Bernhard

2012-01-01

Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31) elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine. PMID:22438810

Amlodipine Inhibits Vascular Cell Senescence and Protects Against Atherogenesis Through the Mechanism Independent of Calcium Channel Blockade.

PubMed

Kayamori, Hiromi; Shimizu, Ippei; Yoshida, Yohko; Hayashi, Yuka; Suda, Masayoshi; Ikegami, Ryutaro; Katsuumi, Goro; Wakasugi, Takayuki; Minamino, Tohru

2018-05-30

Vascular cells have a finite lifespan and eventually enter irreversible growth arrest called cellular senescence. We have previously suggested that vascular cell senescence contributes to the pathogenesis of human atherosclerosis. Amlodipine is a mixture of two enantiomers, one of which (S- enantiomer) has L-type channel blocking activity, while the other (R+ enantiomer) shows ~1000-fold weaker channel blocking activity than S- enantiomer and has other unknown effects. It has been reported that amlodipine inhibits the progression of atherosclerosis in humans, but the molecular mechanism of this beneficial effect remains unknown. Apolipoprotein E-deficient mice on a high-fat diet were treated with amlodipine, its R+ enantiomer or vehicle for eight weeks. Compared with vehicle treatment, both amlodipine and the R+ enantiomer significantly reduced the number of senescent vascular cells and inhibited plaque formation to a similar extent. Expression of the pro-inflammatory molecule interleukin-1β was markedly upregulated in vehicle-treated mice, but was inhibited to a similar extent by treatment with amlodipine or the R+ enantiomer. Likewise, activation of p53 (a critical inducer of senescence) was markedly suppressed by treatment with amlodipine or the R+ enantiomer. These results suggest that amlodipine inhibits vascular cell senescence and protects against atherogenesis at least partly by a mechanism that is independent of calcium channel blockade.

Porphyrins and pheomelanins contribute to the reddish juvenal plumage of black-shouldered kites.

PubMed

Negro, Juan J; Bortolotti, Gary R; Mateo, Rafael; García, Isabel M

2009-07-01

Porphyrins are a widespread group of pigments in nature, but, contrary to melanins and carotenoids, their occurrence as plumage colorants seems to be anecdotal and their function, if any, is unknown. Using thin-layer chromatography and high pressure liquid chromatography, we have found coproporphyrin III, the same porphyrin type previously reported in owls, in the plumage of nestling black-shouldered kites (Elanus caeruleus). The first plumage grown at the nest in this species includes reddish-brown contour feathers in the upperparts, and particularly in the breast area, which fade during the weeks-long post-fledging period to become either gray or white consistent with the definitive adult plumage. In these reddish feathers, we have also found small amounts of pheomelanins and traces of eumelanin. The contribution of each pigment to the final colour perceived by birds or other animals is unknown. In white and grey feathers of the same species no porphyrin was found, and only traces of eumelanin were detected in the grey ones. The fact that the reddish feathers are only found in the juvenal plumage, when individuals are vulnerable in an open nest, leads us to hypothesize a camouflage role for this ephemeral plumage. As porphyrins are involved, although not exclusively, we can for the first time ascribe them a function in the plumage of birds.

Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?

PubMed Central

Hertz, Laura; Huisjes, Rick; Llaudet-Planas, Esther; Petkova-Kirova, Polina; Makhro, Asya; Danielczok, Jens G.; Egee, Stephane; del Mar Mañú-Pereira, Maria; van Wijk, Richard; Vives Corrons, Joan-Lluis; Bogdanova, Anna; Kaestner, Lars

2017-01-01

For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca2+ in red blood cells (RBCs) from patients with sickle cell disease, thalassemia, or Gardos channelopathy. Therefore we analyzed RBCs' Ca2+ content from 35 patients with different types of anemia (16 patients with hereditary spherocytosis, 11 patients with hereditary xerocytosis, 5 patients with enzymopathies, and 3 patients with hemolytic anemia of unknown cause). Intracellular Ca2+ in RBCs was measured by fluorescence microscopy using the fluorescent Ca2+ indicator Fluo-4 and subsequent single cell analysis. We found that in RBCs from patients with hereditary spherocytosis and hereditary xerocytosis the intracellular Ca2+ levels were significantly increased compared to healthy control samples. For enzymopathies and hemolytic anemia of unknown cause the intracellular Ca2+ levels in RBCs were not significantly different. These results lead us to the hypothesis that increased Ca2+ levels in RBCs are a shared component in the mechanism causing an accelerated clearance of RBCs from the blood stream in channelopathies such as hereditary xerocytosis and in diseases involving defects of cytoskeletal components like hereditary spherocytosis. Future drug developments should benefit from targeting Ca2+ entry mediating molecular players leading to better therapies for patients. PMID:28932200

Quantum key distribution with an unknown and untrusted source

NASA Astrophysics Data System (ADS)

Zhao, Yi; Qi, Bing; Lo, Hoi-Kwong

2009-03-01

The security of a standard bi-directional ``plug & play'' quantum key distribution (QKD) system has been an open question for a long time. This is mainly because its source is equivalently controlled by an eavesdropper, which means the source is unknown and untrusted. Qualitative discussion on this subject has been made previously. In this paper, we present the first quantitative security analysis on a general class of QKD protocols whose sources are unknown and untrusted. The securities of standard BB84 protocol, weak+vacuum decoy state protocol, and one-decoy decoy state protocol, with unknown and untrusted sources are rigorously proved. We derive rigorous lower bounds to the secure key generation rates of the above three protocols. Our numerical simulation results show that QKD with an untrusted source gives a key generation rate that is close to that with a trusted source. Our work is published in [1]. [4pt] [1] Y. Zhao, B. Qi, and H.-K. Lo, Phys. Rev. A, 77:052327 (2008).

Botulism mortality in the USA, 1975–2009

PubMed Central

Jackson, Kelly A.; Mahon, Barbara E.; Copeland, John; Fagan, Ryan P.

2017-01-01

Botulism had mortality rates >60% before the 1950s. We reviewed confirmed botulism cases in the USA during 1975–2009 including infant, foodborne, wound, and other/unknown acquisition categories, and calculated mortality ratios. We created a multivariate logistic regression model for non-infant cases (foodborne, wound, and other/unknown). Overall mortality was 3.0% with 109 botulism-related deaths among 3,618 botulism cases [18 (<1%) deaths among 2,352 infant botulism cases, 61 (7.1%) deaths among 854 foodborne botulism cases, 18 (5.0%) deaths among 359 wound botulism cases, and 12 (22.6%) deaths among 53 other/unknown botulism cases]. Mortality among all cases increased with age; it was lowest among infants (0.8%) and highest among persons ≥80 years old (34.4%). Toxin type F had higher mortality (13.8%) than types A, B, or E (range, 1.4% to 4.1%). Efforts to reduce botulism mortality should target non-infant transmission categories and older adults. PMID:28603554

Adaptive neural control for a class of nonlinear time-varying delay systems with unknown hysteresis.

PubMed

Liu, Zhi; Lai, Guanyu; Zhang, Yun; Chen, Xin; Chen, Chun Lung Philip

2014-12-01

This paper investigates the fusion of unknown direction hysteresis model with adaptive neural control techniques in face of time-delayed continuous time nonlinear systems without strict-feedback form. Compared with previous works on the hysteresis phenomenon, the direction of the modified Bouc-Wen hysteresis model investigated in the literature is unknown. To reduce the computation burden in adaptation mechanism, an optimized adaptation method is successfully applied to the control design. Based on the Lyapunov-Krasovskii method, two neural-network-based adaptive control algorithms are constructed to guarantee that all the system states and adaptive parameters remain bounded, and the tracking error converges to an adjustable neighborhood of the origin. In final, some numerical examples are provided to validate the effectiveness of the proposed control methods.

Active learning for ontological event extraction incorporating named entity recognition and unknown word handling.

PubMed

Han, Xu; Kim, Jung-jae; Kwoh, Chee Keong

2016-01-01

Biomedical text mining may target various kinds of valuable information embedded in the literature, but a critical obstacle to the extension of the mining targets is the cost of manual construction of labeled data, which are required for state-of-the-art supervised learning systems. Active learning is to choose the most informative documents for the supervised learning in order to reduce the amount of required manual annotations. Previous works of active learning, however, focused on the tasks of entity recognition and protein-protein interactions, but not on event extraction tasks for multiple event types. They also did not consider the evidence of event participants, which might be a clue for the presence of events in unlabeled documents. Moreover, the confidence scores of events produced by event extraction systems are not reliable for ranking documents in terms of informativity for supervised learning. We here propose a novel committee-based active learning method that supports multi-event extraction tasks and employs a new statistical method for informativity estimation instead of using the confidence scores from event extraction systems. Our method is based on a committee of two systems as follows: We first employ an event extraction system to filter potential false negatives among unlabeled documents, from which the system does not extract any event. We then develop a statistical method to rank the potential false negatives of unlabeled documents 1) by using a language model that measures the probabilities of the expression of multiple events in documents and 2) by using a named entity recognition system that locates the named entities that can be event arguments (e.g. proteins). The proposed method further deals with unknown words in test data by using word similarity measures. We also apply our active learning method for the task of named entity recognition. We evaluate the proposed method against the BioNLP Shared Tasks datasets, and show that our method can achieve better performance than such previous methods as entropy and Gibbs error based methods and a conventional committee-based method. We also show that the incorporation of named entity recognition into the active learning for event extraction and the unknown word handling further improve the active learning method. In addition, the adaptation of the active learning method into named entity recognition tasks also improves the document selection for manual annotation of named entities.

Thalamic amplification of cortical connectivity sustains attentional control

PubMed Central

Schmitt, L. Ian; Wimmer, Ralf D.; Nakajima, Miho; Happ, Michael; Mofakham, Sima; Halassa, Michael M.

2017-01-01

While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought. PMID:28467827

Lupus erythematosus cells in bone marrow: the only clue to a previously unsuspected diagnosis of systemic lupus erythematosus.

PubMed

Pujani, Mukta; Kushwaha, Shivani; Sethi, Neha; Beniwal, Anu; Shukla, Shailaja

2013-01-01

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease characterized by the development of antinuclear antibodies. Nowadays considered outdated, lupus erythematosus (LE) cell preparation served as a screening test for SLE for decades. However, the importance of discovering LE cells on routine cytology cannot be overemphasized. We report the case of a 30-year-old female in whom bone marrow aspiration (BMA) was performed during an investigative workup for pyrexia of unknown origin. The observation of LE cells in direct bone marrow smears (without the use of an anticoagulant) raised the suspicion of SLE, which was later confirmed by antinuclear antibody testing. In the present case, LE cells were observed on BMA performed for the investigation of fever of unknown origin. The unexpected observation of LE cells in BMA smears emphasizes the fact that good morphological observation of marrow aspirates can provide crucial clues to a previously unsuspected diagnosis.

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala.

PubMed

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M; Cocas, Laura A; Huntsman, Molly M; Corbin, Joshua G

2009-02-01

The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.

Spatial Distribution of Small Water Body Types across Indiana Ecoregions

EPA Science Inventory

Due to their large numbers and biogeochemical activity, small water bodies (SWB), such as ponds and wetlands, can have substantial cumulative effects on hydrologic, biogeochemical, and biological processes; yet the spatial distributions of various SWB types are often unknown. Usi...

Polymerase recognition of 2-thio-iso-guanine·5-methyl-4-pyrimidinone (iGs·P)--A new DD/AA base pair.

PubMed

Lee, Dong-Kye; Switzer, Christopher

2016-02-15

Polymerase specificity is reported for a previously unknown base pair with a non-standard DD/AA hydrogen bonding pattern: 2-thio-iso-guanine·5-methyl-4-pyrimidinone. Our findings suggest that atomic substitution may provide a solution for low fidelity previously associated with enzymatic copying of iso-guanine. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new genus of long-legged flies displaying remarkable wing directional asymmetry

Treesearch

Justin B. Runyon; Richard L. Hurley

2004-01-01

A previously unknown group of flies is described whose males exhibit directional asymmetry, in that the left wing is larger than, and of a different shape from, the right wing. To our knowledge, wing asymmetry of this degree has not previously been reported in an animal capable of flight. Such consistent asymmetry must result from a left­right axis during development...

Primary Adenocarcinoma of Intestinal Type Arising From a Vaginal Mass: A Case Report.

PubMed

Morrell, Lindsay H; Matthews, Kirk J; Chafe, Weldon E

2015-07-01

A patient with a history of a severe vaginal laceration during vaginal birth, unknown degree, presented with recurrent vaginal discharge and was found to have a vaginal mass. Pathologic analysis showed squamous mucosa transitioning into colonic type of mucosa with adenocarcinoma developed from colonic type of mucosa, reminiscent of anorectal junction.

The Efficacy of Dictionary Use while Reading for Learning New Words

ERIC Educational Resources Information Center

Hamilton, Harley

2012-01-01

This paper describes a study investigating the use of three types of dictionaries by deaf (i.e., with severe to profound hearing loss) high school students while reading to determine the effectiveness of each type for acquiring the meanings of unknown vocabulary in text. The dictionary types used include an online bilingual multimedia English-ASL…

The Efficacy of Dictionary Use while Reading for Learning New Words

ERIC Educational Resources Information Center

Hamilton, Harley

2012-01-01

The researcher investigated the use of three types of dictionaries while reading by high school students with severe to profound hearing loss. The objective of the study was to determine the effectiveness of each type of dictionary for acquiring the meanings of unknown vocabulary in text. The three types of dictionaries were (a) an online…

North Qinling Terrain as a provenance of Kuanping Group: LA-ICP-MS U-Pb Geochronology of detrital zircons

NASA Astrophysics Data System (ADS)

Hu, B.; Li, S.; Zhai, M.; Wu, J.; Jia, X.

2017-12-01

Though some Neoproterozoic S-type granites in the North Qinling Terrain (NQT), China indicate the collision between the NQT and an unknown block, there are still controversial. The LA-ICP-MS U-Pb ages of detrital zircons of meta-sandstones from the Kuanping Group in Luonan area, NQT, provide sedimentology evidence to prove that the NQT and an unknown block from Rodinia supercontinent have been collided during Meso-Neoproterozoic. The U-Pb ages of detrital zircons from the Kuanping Group show that the main age peaks are at 2.58 Ga, 2.46 Ga, 2.0 Ga, 1.78 Ga, 1.6 Ga, 1.45 Ga and 1.27 Ga. The youngest age of 880 Ma indicates that the sedimentary age of the Kuanping Group is less than 880 Ma. The provenances, which provide 1.45 - 0.88 Ga sediments may come from NQT, which magmatic and metamorphic rocks during this period outcropped. Whereas provenances providing 2.6- 1.6 Ga sediments may come from an unknown block. This indicates that the Kuangping Group received both NQT and the unknown block materials. Therefore, the NQT and the unknown block may have collided before 880 Ma. 889 - 848 Ma A-type granites distributing the NQT was considered forming under a post-collisional tectonics. According the youngest detrital zircon ages of 880 Ma, it is inferred that the Kuanping Basin may also form in the same tectonic environments. Neoproterozoic Kuanping basin and 889 - 848 Ma A-type granites may be a result which NQT broken off a block of Rodinia supercontinent. Acknowledgments: This research is supported by National Key Research and Development Plan of China (2016YFC0601002), Special Fund for Basic Scientific Research of Central Colleges, Chang'an University (310827172201, 0009-2014G1271067) and National Nature Science Foundation of China (41402042).

Functional Genome Mining for Metabolites Encoded by Large Gene Clusters through Heterologous Expression of a Whole-Genome Bacterial Artificial Chromosome Library in Streptomyces spp.

PubMed Central

Xu, Min; Wang, Yemin; Zhao, Zhilong; Gao, Guixi; Huang, Sheng-Xiong; Kang, Qianjin; He, Xinyi; Lin, Shuangjun; Pang, Xiuhua; Deng, Zixin

2016-01-01

ABSTRACT Genome sequencing projects in the last decade revealed numerous cryptic biosynthetic pathways for unknown secondary metabolites in microbes, revitalizing drug discovery from microbial metabolites by approaches called genome mining. In this work, we developed a heterologous expression and functional screening approach for genome mining from genomic bacterial artificial chromosome (BAC) libraries in Streptomyces spp. We demonstrate mining from a strain of Streptomyces rochei, which is known to produce streptothricins and borrelidin, by expressing its BAC library in the surrogate host Streptomyces lividans SBT5, and screening for antimicrobial activity. In addition to the successful capture of the streptothricin and borrelidin biosynthetic gene clusters, we discovered two novel linear lipopeptides and their corresponding biosynthetic gene cluster, as well as a novel cryptic gene cluster for an unknown antibiotic from S. rochei. This high-throughput functional genome mining approach can be easily applied to other streptomycetes, and it is very suitable for the large-scale screening of genomic BAC libraries for bioactive natural products and the corresponding biosynthetic pathways. IMPORTANCE Microbial genomes encode numerous cryptic biosynthetic gene clusters for unknown small metabolites with potential biological activities. Several genome mining approaches have been developed to activate and bring these cryptic metabolites to biological tests for future drug discovery. Previous sequence-guided procedures relied on bioinformatic analysis to predict potentially interesting biosynthetic gene clusters. In this study, we describe an efficient approach based on heterologous expression and functional screening of a whole-genome library for the mining of bioactive metabolites from Streptomyces. The usefulness of this function-driven approach was demonstrated by the capture of four large biosynthetic gene clusters for metabolites of various chemical types, including streptothricins, borrelidin, two novel lipopeptides, and one unknown antibiotic from Streptomyces rochei Sal35. The transfer, expression, and screening of the library were all performed in a high-throughput way, so that this approach is scalable and adaptable to industrial automation for next-generation antibiotic discovery. PMID:27451447

GLRT-based array receivers for the detection of a known signal with unknown parameters corrupted by noncircular interferences

NASA Astrophysics Data System (ADS)

Chevalier, Pascal; Oukaci, Abdelkader; Delmas, Jean-Pierre

2011-12-01

The detection of a known signal with unknown parameters in the presence of noise plus interferences (called total noise) whose covariance matrix is unknown is an important problem which has received much attention these last decades for applications such as radar, satellite localization or time acquisition in radio communications. However, most of the available receivers assume a second order (SO) circular (or proper) total noise and become suboptimal in the presence of SO noncircular (or improper) interferences, potentially present in the previous applications. The scarce available receivers which take the potential SO noncircularity of the total noise into account have been developed under the restrictive condition of a known signal with known parameters or under the assumption of a random signal. For this reason, following a generalized likelihood ratio test (GLRT) approach, the purpose of this paper is to introduce and to analyze the performance of different array receivers for the detection of a known signal, with different sets of unknown parameters, corrupted by an unknown noncircular total noise. To simplify the study, we limit the analysis to rectilinear known useful signals for which the baseband signal is real, which concerns many applications.

Partial autolysis of μ/m-calpain during post mortem aging of chicken muscle.

PubMed

Zhao, Liang; Jiang, Nanqi; Li, Miaozhen; Huang, Ming; Zhou, Guanghong

2016-12-01

The objective of this study was to investigate changes occurring in μ/m-calpain in post mortem chicken muscles and to determine the origin of the unknown bands found in calpain casein zymography. The unknown bands were reported with slightly greater mobility compared to conventional μ/m-calpain bands in casein zymography. Identification of these bands was accomplished using native polyacrylamide gel electrophoresis, liquid chromatography tandem mass spectrometry and with protein phosphatase treatment. Results showed that the unknown bands were corresponding to μ/m-calpain, and dephosphorylation by protein phosphatase did not change their appearance. The calpain samples were then incubated with various concentrations of Ca 2+ to determine the relationship between changes in μ/m-calpain and the appearance of the unknown bands. The products of μ/m-calpain partial autolysis were found to be consistent with the appearance of the unknown bands. Therefore, the appearance of these bands did not result from phosphorylation of μ/m-calpain as previously hypothesized, but from partial autolysis of μ/m-calpain. Also their presence suggests that μ/m-calpain undergoes partial autolysis during aging which may play certain roles in meat quality improvement. © 2016 Japanese Society of Animal Science.

Grasshoppers, Crickets and Katydids (Insecta: Orthoptera) of Cuba: an annotated checklist.

PubMed

Yong, Sheyla; Perez-Gelabert, Daniel E

2014-07-07

An annotated list of the Cuban fauna of Orthoptera is presented. For each species we include details of valid names, synonyms, type specimens (type category, sex, locality and depository), geographic distribution and bibliographic references. Clarifying notes are added, as well as comments on the species considered doubtful. A total of 140 species included in 62 genera, 31 subfamilies and 12 families make up the known Cuban fauna of Orthoptera. The family Episactidae, the acridid subfamily Ommatolampidinae with 3 unknown genera, 3 unknown genera of Tettigoniidae (Conocephalinae) and 1 undescribed new genus of Tetrigidae (Cladonotinae) are here recorded for the first time from Cuba. Syntypes are designated for Hygronemobius histrionicus Zayas.

Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck.

PubMed

Patel, Sapna A; Parvathaneni, Aarthi; Parvathaneni, Upendra; Houlton, Jeffrey J; Karni, Ron J; Liao, Jay J; Futran, Neal D; Méndez, Eduardo

2017-09-01

Our primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). We conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. The tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. Surgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability. Published by Elsevier Ltd.

Human skeletal muscle: transition between fast and slow fibre types.

PubMed

Neunhäuserer, Daniel; Zebedin, Michaela; Obermoser, Magdalena; Moser, Gerhard; Tauber, Mark; Niebauer, Josef; Resch, Herbert; Galler, Stefan

2011-05-01

Human skeletal muscles consist of different fibre types: slow fibres (slow twitch or type I) containing the myosin heavy chain isoform (MHC)-I and fast fibres (fast twitch or type II) containing MHC-IIa (type IIA) or MHC-IId (type IID). The following order of decreasing kinetics is known: type IID > type IIA > type I. This order is especially based on the kinetics of stretch activation, which is the most discriminative property among fibre types. In this study we tested if hybrid fibres containing both MHC-IIa and MHC-I (type C fibres) provide a transition in kinetics between fast (type IIA) and slow fibres (type I). Our data of stretch activation kinetics suggest that type C fibres, with different ratios of MHC-IIa and MHC-I, do not provide a continuous transition. Instead, a specialized group of slow fibres, which we called "transition fibres", seems to provide a transition. Apart of their kinetics of stretch activation, which is most close to that of type IIA, the transition fibres are characterized by large cross-sectional areas and low maximal tensions. The molecular cause for the mechanical properties of the transition fibres is unknown. It is possible that the transition fibres contain an unknown slow MHC isoform, which cannot be separated by biochemical methods. Alternatively, or in addition, isoforms of myofibrillar proteins, other than MHC, and posttranslational modifications of myofibrillar proteins could play a role regarding the characteristics of the transition fibres.

Genome Study Yields Clues to Head and Neck Cancers

Cancer.gov

Researchers have surveyed the genetic changes in nearly 300 head and neck cancers, revealing some previously unknown alterations that may play a role in the disease, including in patients whose cancer is associated with the human papillomavirus (HPV).

First Stars or Stray Stars? A Cosmic Infrared Mystery

NASA Image and Video Library

2014-11-06

Our sky is filled with a diffuse background glow, known as the cosmic infrared background. Much of the light is from galaxies we know about, but previous Spitzer measurements have shown an extra component of unknown origin.

Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

PubMed Central

Chakrabarti, Kausik; Pearson, Michael; Grate, Leslie; Sterne-Weiler, Timothy; Deans, Jonathan; Donohue, John Paul; Ares, Manuel

2007-01-01

As the genomes of more eukaryotic pathogens are sequenced, understanding how molecular differences between parasite and host might be exploited to provide new therapies has become a major focus. Central to cell function are RNA-containing complexes involved in gene expression, such as the ribosome, the spliceosome, snoRNAs, RNase P, and telomerase, among others. In this article we identify by comparative genomics and validate by RNA analysis numerous previously unknown structural RNAs encoded by the Plasmodium falciparum genome, including the telomerase RNA, U3, 31 snoRNAs, as well as previously predicted spliceosomal snRNAs, SRP RNA, MRP RNA, and RNAse P RNA. Furthermore, we identify six new RNA coding genes of unknown function. To investigate the relationships of the RNA coding genes to other genomic features in related parasites, we developed a genome browser for P. falciparum (http://areslab.ucsc.edu/cgi-bin/hgGateway). Additional experiments provide evidence supporting the prediction that snoRNAs guide methylation of a specific position on U4 snRNA, as well as predicting an snRNA promoter element particular to Plasmodium sp. These findings should allow detailed structural comparisons between the RNA components of the gene expression machinery of the parasite and its vertebrate hosts. PMID:17901154

Classification of longitudinal data through a semiparametric mixed-effects model based on lasso-type estimators.

PubMed

Arribas-Gil, Ana; De la Cruz, Rolando; Lebarbier, Emilie; Meza, Cristian

2015-06-01

We propose a classification method for longitudinal data. The Bayes classifier is classically used to determine a classification rule where the underlying density in each class needs to be well modeled and estimated. This work is motivated by a real dataset of hormone levels measured at the early stages of pregnancy that can be used to predict normal versus abnormal pregnancy outcomes. The proposed model, which is a semiparametric linear mixed-effects model (SLMM), is a particular case of the semiparametric nonlinear mixed-effects class of models (SNMM) in which finite dimensional (fixed effects and variance components) and infinite dimensional (an unknown function) parameters have to be estimated. In SNMM's maximum likelihood estimation is performed iteratively alternating parametric and nonparametric procedures. However, if one can make the assumption that the random effects and the unknown function interact in a linear way, more efficient estimation methods can be used. Our contribution is the proposal of a unified estimation procedure based on a penalized EM-type algorithm. The Expectation and Maximization steps are explicit. In this latter step, the unknown function is estimated in a nonparametric fashion using a lasso-type procedure. A simulation study and an application on real data are performed. © 2015, The International Biometric Society.

The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes

PubMed Central

Weitman, Efraim; Bachar, Etty; Suissa, Yaron; Cohen, Guy; Schyr, Rachel Ben-Haroush; Sabanay, Helena; Horwitz, Elad; Glaser, Benjamin; Dor, Yuval; Pribluda, Ariel; Hanna, Jacob H.

2013-01-01

NK cells rapidly kill tumor cells, virus infected cells and even self cells. This is mediated via killer receptors, among which NKp46 (NCR1 in mice) is prominent. We have recently demonstrated that in type 1 diabetes (T1D) NK cells accumulate in the diseased pancreas and that they manifest a hyporesponsive phenotype. In addition, we found that NKp46 recognizes an unknown ligand expressed by beta cells derived from humans and mice and that blocking of NKp46 activity prevented diabetes development. Here we investigated the properties of the unknown NKp46 ligand. We show that the NKp46 ligand is mainly located in insulin granules and that it is constitutively secreted. Following glucose stimulation the NKp46 ligand translocates to the cell membrane and its secretion decreases. We further demonstrate by using several modalities that the unknown NKp46 ligand is not insulin. Finally, we studied the expression of the NKp46 ligand in type 2 diabetes (T2D) using 3 different in vivo models and 2 species; mice and gerbils. We demonstrate that the expression of the NKp46 ligand is decreased in all models of T2D studied, suggesting that NKp46 is not involved in T2D. PMID:24009765

Simulation of free energies of bicontinuous morphologies formed through block copolymer/homopolymer self-assembly

NASA Astrophysics Data System (ADS)

Padmanabhan, Poornima; Martinez-Veracoechea, Francisco; Escobedo, Fernando

Different types of bicontinuous phases can be formed from A-B diblock copolymers by the addition of A-type homopolymers over a range of compositions and relative chain lengths. Particle-based molecular simulations were used to study three bicontinuous phases - double gyroid (G), double diamond (D) and plumber's nightmare (P) - near their triple point of coexistence. For 3-D ordered phases, the stability of the morphology formed in simulation is highly sensitive to box size whose exact size is unknown a-priori. Accurate free energy estimates are required to ascertain the stable phase, particularly when multiple competing phases spontaneously form at the conditions of interest. A variant of thermodynamic integration was implemented to obtain free energies and hence identify the stable phases and their optimal box sizes by tracing a reversible path that connects the ordered and disordered phases. Clear evidence was found of D-G and D-P phase coexistence, consistent with previous predictions for the same blend using Self-consistent field theory. Our simulations also allowed us to examine the microscopic details of these coexisting bicontinuous phases and detect key differences between the microstructure of their nodes and struts.

Inositol Depletion Restores Vesicle Transport in Yeast Phospholipid Flippase Mutants

PubMed Central

Yamagami, Kanako; Yamamoto, Takaharu; Sakai, Shota; Mioka, Tetsuo; Sano, Takamitsu; Igarashi, Yasuyuki; Tanaka, Kazuma

2015-01-01

In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipid bilayer. Flippases function in the formation of transport vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic recycling defects of flippase mutants in budding yeast. Consistent with a previous report that Art5p downregulates the inositol transporter Itr1p by endocytosis, we found that flippase mutations were also suppressed by the disruption of ITR1, as well as by depletion of inositol from the culture medium. Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositol depletion also partially restored the formation of secretory vesicles in a flippase mutant. Inositol depletion caused changes in lipid composition, including a decrease in phosphatidylinositol and an increase in phosphatidylserine. A reduction in phosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthase Pis1p also suppressed a flippase mutation. These results suggest that inositol depletion changes the lipid composition of the endosomal/TGN membranes, which results in vesicle formation from these membranes in the absence of flippases. PMID:25781026

Developmentally programmed DNA splicing in Paramecium reveals short-distance crosstalk between DNA cleavage sites

PubMed Central

Gratias, Ariane; Lepère, Gersende; Garnier, Olivier; Rosa, Sarah; Duharcourt, Sandra; Malinsky, Sophie; Meyer, Eric; Bétermier, Mireille

2008-01-01

Somatic genome assembly in the ciliate Paramecium involves the precise excision of thousands of short internal eliminated sequences (IESs) that are scattered throughout the germline genome and often interrupt open reading frames. Excision is initiated by double-strand breaks centered on the TA dinucleotides that are conserved at each IES boundary, but the factors that drive cleavage site recognition remain unknown. A degenerate consensus was identified previously at IES ends and genetic analyses confirmed the participation of their nucleotide sequence in efficient excision. Even for wild-type IESs, however, variant excision patterns (excised or nonexcised) may be inherited maternally through sexual events, in a homology-dependent manner. We show here that this maternal epigenetic control interferes with the targeting of DNA breaks at IES ends. Furthermore, we demonstrate that a mutation in the TA at one end of an IES impairs DNA cleavage not only at the mutant end but also at the wild-type end. We conclude that crosstalk between both ends takes place prior to their cleavage and propose that the ability of an IES to adopt an excision-prone conformation depends on the combination of its nucleotide sequence and of additional determinants. PMID:18420657

Long-term differences in extinction risk among the seven forms of rarity

PubMed Central

Harnik, Paul G.; Simpson, Carl; Payne, Jonathan L.

2012-01-01

Rarity is widely used to predict the vulnerability of species to extinction. Species can be rare in markedly different ways, but the relative impacts of these different forms of rarity on extinction risk are poorly known and cannot be determined through observations of species that are not yet extinct. The fossil record provides a valuable archive with which we can directly determine which aspects of rarity lead to the greatest risk. Previous palaeontological analyses confirm that rarity is associated with extinction risk, but the relative contributions of different types of rarity to extinction risk remain unknown because their impacts have never been examined simultaneously. Here, we analyse a global database of fossil marine animals spanning the past 500 million years, examining differential extinction with respect to multiple rarity types within each geological stage. We observe systematic differences in extinction risk over time among marine genera classified according to their rarity. Geographic range played a primary role in determining extinction, and habitat breadth a secondary role, whereas local abundance had little effect. These results suggest that current reductions in geographic range size will lead to pronounced increases in long-term extinction risk even if local populations are relatively large at present. PMID:23097507

Long-term differences in extinction risk among the seven forms of rarity.

PubMed

Harnik, Paul G; Simpson, Carl; Payne, Jonathan L

2012-12-22

Rarity is widely used to predict the vulnerability of species to extinction. Species can be rare in markedly different ways, but the relative impacts of these different forms of rarity on extinction risk are poorly known and cannot be determined through observations of species that are not yet extinct. The fossil record provides a valuable archive with which we can directly determine which aspects of rarity lead to the greatest risk. Previous palaeontological analyses confirm that rarity is associated with extinction risk, but the relative contributions of different types of rarity to extinction risk remain unknown because their impacts have never been examined simultaneously. Here, we analyse a global database of fossil marine animals spanning the past 500 million years, examining differential extinction with respect to multiple rarity types within each geological stage. We observe systematic differences in extinction risk over time among marine genera classified according to their rarity. Geographic range played a primary role in determining extinction, and habitat breadth a secondary role, whereas local abundance had little effect. These results suggest that current reductions in geographic range size will lead to pronounced increases in long-term extinction risk even if local populations are relatively large at present.

On the Invariant Cantor Sets of Period Doubling Type of Infinitely Renormalizable Area-Preserving Maps

NASA Astrophysics Data System (ADS)

Lilja, Dan

2018-03-01

Since its inception in the 1970s at the hands of Feigenbaum and, independently, Coullet and Tresser the study of renormalization operators in dynamics has been very successful at explaining universality phenomena observed in certain families of dynamical systems. The first proof of existence of a hyperbolic fixed point for renormalization of area-preserving maps was given by Eckmann et al. (Mem Am Math Soc 47(289):vi+122, 1984). However, there are still many things that are unknown in this setting, in particular regarding the invariant Cantor sets of infinitely renormalizable maps. In this paper we show that the invariant Cantor set of period doubling type of any infinitely renormalizable area-preserving map in the universality class of the Eckmann-Koch-Wittwer renormalization fixed point is always contained in a Lipschitz curve but never contained in a smooth curve. This extends previous results by de Carvalho, Lyubich and Martens about strongly dissipative maps of the plane close to unimodal maps to the area-preserving setting. The method used for constructing the Lipschitz curve is very similar to the method used in the dissipative case but proving the nonexistence of smooth curves requires new techniques.

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

Mack, Hildegard I.D.; Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu

Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in knownmore » LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer.« less

[Learning and Repetive Reproduction of Memorized Sequences by the Right and the Left Hand].

PubMed

Bobrova, E V; Lyakhovetskii, V A; Bogacheva, I N

2015-01-01

An important stage of learning a new skill is repetitive reproduction of one and the same sequence of movements, which plays a significant role in forming of the movement stereotypes. Two groups of right-handers repeatedly memorized (6-10 repetitions) the sequences of their hand transitions by experimenter in 6 positions, firstly by the right hand (RH), and then--by the left hand (LH) or vice versa. Random sequences previously unknown to the volunteers were reproduced in the 11 series. Modified sequences were tested in the 2nd and 3rd series, where the same elements' positions were presented in different order. The processes of repetitive sequence reproduction were similar for RH and LH. However, the learning of the modified sequences differed: Information about elements' position disregarding the reproduction order was used only when LH initiated task performing. This information was not used when LH followed RH and when RH performed the task. Consequently, the type of information coding activated by LH helped learn the positions of sequence elements, while the type of information coding activated by RH prevented learning. It is supposedly connected with the predominant role of right hemisphere in the processes of positional coding and motor learning.

The impact of early behavior disturbances on academic achievement in high school.

PubMed

Breslau, Joshua; Miller, Elizabeth; Breslau, Naomi; Bohnert, Kipling; Lucia, Victoria; Schweitzer, Julie

2009-06-01

Previous research has indicated that childhood behavioral disturbances predict lower scores on academic tests and curtail educational attainment. It is unknown which types of childhood behavioral problems are most likely to predict these outcomes. An ethnically diverse cohort was assessed at 6 years of age for behavioral problems and IQ and at 17 years of age for academic achievement in math and reading. Of the original cohort of 823 children, 693 (84%) had complete data. Multiple regressions were used to estimate associations of attention and internalizing and externalizing problems at age 6 and with math and reading achievement at age 17, adjusting for IQ and indicators of family socioeconomic status. Adjusting for IQ, inner-city community, and maternal education and marital status, teacher ratings of attention, internalizing behavior, and externalizing problems at age 6 significantly predict math and reading achievement at age 17. When types of problems are examined simultaneously, attention problems predict math and reading achievement with little attenuation, whereas the influence of externalizing and internalizing problems is materially reduced and not significant. Interventions that target attention problems at school entry should be tested as a potential avenue for improving educational achievement.

JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation

PubMed Central

Lu, Ben; Antoine, Daniel J.; Kwan, Kevin; Lundbäck, Peter; Wähämaa, Heidi; Schierbeck, Hanna; Robinson, Melissa; Van Zoelen, Marieke A. D.; Yang, Huan; Li, Jianhua; Erlandsson-Harris, Helena; Chavan, Sangeeta S.; Wang, Haichao; Andersson, Ulf; Tracey, Kevin J.

2014-01-01

Extracellular high-mobility group box (HMGB)1 mediates inflammation during sterile and infectious injury and contributes importantly to disease pathogenesis. The first critical step in the release of HMGB1 from activated immune cells is mobilization from the nucleus to the cytoplasm, a process dependent upon hyperacetylation within two HMGB1 nuclear localization sequence (NLS) sites. The inflammasomes mediate the release of cytoplasmic HMGB1 in activated immune cells, but the mechanism of HMGB1 translocation from nucleus to cytoplasm was previously unknown. Here, we show that pharmacological inhibition of JAK/STAT1 inhibits LPS-induced HMGB1 nuclear translocation. Conversely, activation of JAK/STAT1 by type 1 interferon (IFN) stimulation induces HMGB1 translocation from nucleus to cytoplasm. Mass spectrometric analysis unequivocally revealed that pharmacological inhibition of the JAK/STAT1 pathway or genetic deletion of STAT1 abrogated LPS- or type 1 IFN-induced HMGB1 acetylation within the NLS sites. Together, these results identify a critical role of the JAK/STAT1 pathway in mediating HMGB1 cytoplasmic accumulation for subsequent release, suggesting that the JAK/STAT1 pathway is a potential drug target for inhibiting HMGB1 release. PMID:24469805

Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2.

PubMed

Sitkiewicz, Izabela; Nagiec, Michal J; Sumby, Paul; Butler, Stephanie D; Cywes-Bentley, Colette; Musser, James M

2006-10-24

The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic DeltaslaA mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.

RNAi and heterochromatin repress centromeric meiotic recombination

PubMed Central

Ellermeier, Chad; Higuchi, Emily C.; Phadnis, Naina; Holm, Laerke; Geelhood, Jennifer L.; Thon, Genevieve; Smith, Gerald R.

2010-01-01

During meiosis, the formation of viable haploid gametes from diploid precursors requires that each homologous chromosome pair be properly segregated to produce an exact haploid set of chromosomes. Genetic recombination, which provides a physical connection between homologous chromosomes, is essential in most species for proper homologue segregation. Nevertheless, recombination is repressed specifically in and around the centromeres of chromosomes, apparently because rare centromeric (or pericentromeric) recombination events, when they do occur, can disrupt proper segregation and lead to genetic disabilities, including birth defects. The basis by which centromeric meiotic recombination is repressed has been largely unknown. We report here that, in fission yeast, RNAi functions and Clr4-Rik1 (histone H3 lysine 9 methyltransferase) are required for repression of centromeric recombination. Surprisingly, one mutant derepressed for recombination in the heterochromatic mating-type region during meiosis and several mutants derepressed for centromeric gene expression during mitotic growth are not derepressed for centromeric recombination during meiosis. These results reveal a complex relation between types of repression by heterochromatin. Our results also reveal a previously undemonstrated role for RNAi and heterochromatin in the repression of meiotic centromeric recombination and, potentially, in the prevention of birth defects by maintenance of proper chromosome segregation during meiosis. PMID:20421495

PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine.

PubMed

Xu, Guanlong; Zhang, Xuxiao; Liu, Qinfang; Bing, Guoxia; Hu, Zhe; Sun, Honglei; Xiong, Xin; Jiang, Ming; He, Qiming; Wang, Yu; Pu, Juan; Guo, Xin; Yang, Hanchun; Liu, Jinhua; Sun, Yipeng

2017-08-01

Previous studies have identified a functional role of PA-X for influenza viruses in mice and avian species; however, its role in swine remains unknown. Toward this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple-reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral replication and host protein synthesis shutoff, and inhibited the mRNA levels of type I IFNs and proinflammatory cytokines in porcine cells. A delay of proinflammatory responses was observed in lungs of pigs infected by wild type SIV (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted more efficiently than Sw-FS in pigs. These results highlight the importance of PA-X in the moderation of virulence and immune responses of TR SIV in swine, which indicated that PA-X is a pro-virulence factor in TR SIV in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

Diverse styles of submarine venting on the ultraslow spreading Mid-Cayman Rise

PubMed Central

German, C. R.; Bowen, A.; Coleman, M. L.; Honig, D. L.; Huber, J. A.; Jakuba, M. V.; Kinsey, J. C.; Kurz, M. D.; Leroy, S.; McDermott, J. M.; de Lépinay, B. Mercier; Nakamura, K.; Seewald, J. S.; Smith, J. L.; Sylva, S. P.; Van Dover, C. L.; Whitcomb, L. L.; Yoerger, D. R.

2010-01-01

Thirty years after the first discovery of high-temperature submarine venting, the vast majority of the global mid-ocean ridge remains unexplored for hydrothermal activity. Of particular interest are the world’s ultraslow spreading ridges that were the last to be demonstrated to host high-temperature venting but may host systems particularly relevant to prebiotic chemistry and the origins of life. Here we report evidence for previously unknown, diverse, and very deep hydrothermal vents along the ∼110 km long, ultraslow spreading Mid-Cayman Rise (MCR). Our data indicate that the MCR hosts at least three discrete hydrothermal sites, each representing a different type of water-rock interaction, including both mafic and ultramafic systems and, at ∼5,000 m, the deepest known hydrothermal vent. Although submarine hydrothermal circulation, in which seawater percolates through and reacts with host lithologies, occurs on all mid-ocean ridges, the diversity of vent types identified here and their relative geographic isolation make the MCR unique in the oceans. These new sites offer prospects for an expanded range of vent-fluid compositions, varieties of abiotic organic chemical synthesis and extremophile microorganisms, and unparalleled faunal biodiversity—all in close proximity. PMID:20660317

TMPRSS4 induces cancer cell invasion through pro-uPA processing.

PubMed

Min, Hye-Jin; Lee, Myung Kyu; Lee, Jung Weon; Kim, Semi

2014-03-28

TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates cancer cell invasion, epithelial-mesenchymal transition, and metastasis and that increased TMPRSS4 expression correlates with colorectal cancer progression. We also demonstrated that TMPRSS4 upregulates urokinase-type plasminogen activator (uPA) gene expression to induce cancer cell invasion. However, it remains unknown how proteolytic activity of TMPRSS4 contributes to invasion. In this study, we report that TMPRSS4 directly converted inactive pro-uPA into the active form through its proteolytic activity. Analysis of conditioned medium from cells overexpressing TMPRSS4 demonstrated that the active TMPRSS4 protease domain is released from the cells and is associated with the plasma membrane. Furthermore, TMPRSS4 could increase pro-uPA-mediated invasion in a serine proteolytic activity-dependent manner. These observations suggest that TMPRSS4 is an upstream regulator of pro-uPA activation. This study provides valuable insights into the proteolytic function of TMPRSS4 as well as mechanisms for the control of invasion. Copyright © 2014 Elsevier Inc. All rights reserved.

Phenylalanine derived cyanogenic diglucosides from Eucalyptus camphora and their abundances in relation to ontogeny and tissue type.

PubMed

Neilson, Elizabeth H; Goodger, Jason Q D; Motawia, Mohammed Saddik; Bjarnholt, Nanna; Frisch, Tina; Olsen, Carl Erik; Møller, Birger Lindberg; Woodrow, Ian E

2011-12-01

The cyanogenic glucoside profile of Eucalyptus camphora was investigated in the course of plant ontogeny. In addition to amygdalin, three phenylalanine-derived cyanogenic diglucosides characterized by unique linkage positions between the two glucose moieties were identified in E. camphora tissues. This is the first time that multiple cyanogenic diglucosides have been shown to co-occur in any plant species. Two of these cyanogenic glucosides have not previously been reported and are named eucalyptosin B and eucalyptosin C. Quantitative and qualitative differences in total cyanogenic glucoside content were observed across different stages of whole plant and tissue ontogeny, as well as within different tissue types. Seedlings of E. camphora produce only the cyanogenic monoglucoside prunasin, and genetically based variation was observed in the age at which seedlings initiate prunasin biosynthesis. Once initiated, total cyanogenic glucoside concentration increased throughout plant ontogeny with cyanogenic diglucoside production initiated in saplings and reaching a maximum in flower buds of adult trees. The role of multiple cyanogenic glucosides in E. camphora is unknown, but may include enhanced plant defense and/or a primary role in nitrogen storage and transport. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genomic study of the Type IVC secretion system in Clostridium difficile: understanding C. difficile evolution via horizontal gene transfer.

PubMed

Zhang, Wen; Cheng, Ying; Du, Pengcheng; Zhang, Yuanyuan; Jia, Hongbing; Li, Xianping; Wang, Jing; Han, Na; Qiang, Yujun; Chen, Chen; Lu, Jinxing

2017-01-01

Clostridium difficile, the etiological agent of Clostridium difficile infection (CDI), is a gram-positive, spore-forming bacillus that is responsible for ∼20% of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. Previous data have shown that a substantial proportion (11%) of the C. difficile genome consists of mobile genetic elements, including seven conjugative transposons. However, the mechanism underlying the formation of a mosaic genome in C. difficile is unknown. The type-IV secretion system (T4SS) is the only secretion system known to transfer DNA segments among bacteria. We searched genome databases to identify a candidate T4SS in C. difficile that could transfer DNA among different C. difficile strains. All T4SS gene clusters in C. difficile are located within genomic islands (GIs), which have variable lengths and structures and are all conjugative transposons. During the horizontal-transfer process of T4SS GIs within the C. difficile population, the excision sites were altered, resulting in different short-tandem repeat sequences among the T4SS GIs, as well as different chromosomal insertion sites and additional regions in the GIs.

Cocoon formation in patients with midgut neuroendocrine tumors: a rare and unrecognized final pathway.

PubMed

Wang, Yi-Zarn; King, Heather; Diebold, Anne

2013-08-01

Neuroendocrine tumors (NETs) are relatively rare with an indolent nature. As a result, treatment is often delayed and passive. The most commonly recognized disease progression leading to death is from the sequelae of bowel obstruction, ischemia, or liver failure secondary to liver metastasis. We recently recognized a rare cocoon-like formation in patients with metastatic gastroenteropancreatic NETs and hypothesize that this may be a distinct, final pathway for these patients. Ten patients with stage IV gastroenteropancreatic NETs, seen at our center between October 2008 and November 2011, who developed a cocoon were identified. Patient's charts, operative reports, pathology, and tumor markers were reviewed. No discernable predictors were identified as precursors to this condition. One patient survived 13 months after cocoon diagnosis, and the remaining 9 patients were all deceased within 5 months. Surgical treatment was attempted in 6 patients and was only partially successful in 1 patient who had the earliest stage of cocoon formation (type 1). Cocoon-like formations in patients with stage IV gastroenteropancreatic NETs is rare and may be a terminal disease progression that has not been previously recognized. The best treatment option remains unknown. Surgical treatment is not advisable, with the exception of type 1 abdominal cocoons.

75 FR 66009 - Airworthiness Directives; Cessna Aircraft Company (Type Certificate Previously Held by Columbia...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... Company (Type Certificate Previously Held by Columbia Aircraft Manufacturing (Previously the Lancair... Company (Type Certificate Previously Held by Columbia Aircraft Manufacturing (Previously The Lancair...-15895. Applicability (c) This AD applies to the following Cessna Aircraft Company (type certificate...

Urothelial melanosis of the bladder.

PubMed

Valente, Sara L; Bieniek, Jared M; Kesler, Stuart S

2017-10-01

Urothelial melanosis is a rare finding characterized by abnormal pigmentation noted on cystoscopic evaluation and histologically defined by melanin deposition in the urothelium. Although generally considered benign, few cases of urothelial melanosis have been reported in the literature and the risk of recurrence or progression remains largely unknown. Four cases associated with urothelial cell carcinoma have been previously described. Here, we report a case of urothelial melanosis and review previously published cases in the literature.

Global tracking for a class of uncertain nonlinear systems with unknown sign-switching control direction by output feedback

NASA Astrophysics Data System (ADS)

Roux Oliveira, Tiago; Jacoud Peixoto, Alessandro; Hsu, Liu

2015-09-01

This paper addresses the design of a sliding mode controller for a class of high-order uncertain nonlinear plants with unmatched state-dependent nonlinearities and unknown sign of the high frequency gain, i.e., the control direction is assumed unknown. Differently from most previous studies, the control direction is allowed to switch its sign. We show that it is possible to obtain global exact tracking using only output-feedback by coupling a relay periodic switching function with a norm state observer. One significant advantage of the new scheme is its robustness and improved transient response under arbitrary changes of the control direction which have been theoretically demonstrated for jump variations and successfully tested by simulations. The proposed controller is also evaluated with a DC motor control experiment.

Fluorogenic kinetic assay for high-throughput discovery of stereoselective ketoreductases relevant to pharmaceutical synthesis.

PubMed

Thai, Yen-Chi; Szekrenyi, Anna; Qi, Yuyin; Black, Gary W; Charnock, Simon J; Fessner, Wolf-Dieter

2018-04-01

Enantiomerically pure 1-(6-methoxynaphth-2-yl) and 1-(6-(dimethylamino)naphth-2-yl) carbinols are fluorogenic substrates for aldo/keto reductase (KRED) enzymes, which allow the highly sensitive and reliable determination of activity and kinetic constants of known and unknown enzymes, as well as an immediate enantioselectivity typing. Because of its simplicity in microtiter plate format, the assay qualifies for the discovery of novel KREDs of yet unknown specificity among this vast enzyme superfamily. The suitability of this approach for enzyme typing is illustrated by an exemplary screening of a large collection of short-chain dehydrogenase/reductase (SDR) enzymes arrayed from a metagenomic approach. We believe that this assay format should match well the pharmaceutical industry's demand for acetophenone-type substrates and the continuing interest in new enzymes with broad substrate promiscuity for the synthesis of chiral, non-racemic carbinols. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.

PubMed

Suzuki, Masako; Maekawa, Ryo; Patterson, Nicole E; Reynolds, David M; Calder, Brent R; Reznik, Sandra E; Heo, Hye J; Einstein, Francine Hughes; Greally, John M

2016-01-01

Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8 % of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, using purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of the placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to proteinuria or hypertension and fetuses from normal pregnancies. We performed a genome-wide DNA methylation analysis, HpaII tiny fragment Enrichment by Ligation-mediated PCR (HELP)-tagging, on 62 amnion samples from the placentas of uncomplicated, normal pregnancies and from those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85, and 99 loci with high-confidence hypertension-associated, proteinuria-associated, and hypertension- and proteinuria-associated DNA methylation changes, respectively. A gene ontology analysis showed DNA methylation changes to be selecting genes with different biological processes in exposure status. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amniotic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions.

Regulation of adiponectin in adipocytes upon exposure to HIV-1

USDA-ARS?s Scientific Manuscript database

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

Exploring the Unknown: International Service and Individual Transformation

ERIC Educational Resources Information Center

Chang, Wei-Wen; Chen, Cheng-Hui Lucy; Huang, Yu-Fu; Yuan, Yu-Hsi

2012-01-01

Empirical studies have found that participation in international service increases learners' intercultural competence, language skills, appreciation of cultural differences, and tolerance for ambiguity. While previous studies suggest that international service experience is potentially transformative in nature, the present study examined…

Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies

PubMed Central

Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

2016-01-01

Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab′)2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool. PMID:27484487

A Caenorhabditis elegans Wild Type Defies the Temperature–Size Rule Owing to a Single Nucleotide Polymorphism in tra-3

PubMed Central

Kammenga, Jan E; Doroszuk, Agnieszka; Riksen, Joost A. G; Hazendonk, Esther; Spiridon, Laurentiu; Petrescu, Andrei-Jose; Tijsterman, Marcel; Plasterk, Ronald H. A; Bakker, Jaap

2007-01-01

Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature–size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature–size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature–size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 × CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature–size rule, which has puzzled biologists for decades. PMID:17335351

Differential Sox10 Genomic Occupancy in Myelinating Glia

PubMed Central

Lopez-Anido, Camila; Sun, Guannan; Koenning, Matthias; Srinivasan, Rajini; Hung, Holly A.; Emery, Ben; Keles, Sunduz; Svaren, John

2015-01-01

Myelin is formed by specialized myelinating glia: oligodendrocytes and Schwann cells in the central and peripheral nervous systems, respectively. While there are distinct developmental aspects and regulatory pathways in these two cell types, myelination in both systems requires the transcriptional activator Sox10. Sox10 interacts with cell type-specific transcription factors at some loci to induce myelin gene expression, but it is largely unknown how Sox10 transcriptional networks globally compare between oligodendrocytes and Schwann cells. We used in vivo ChIP-Seq analysis of spinal cord and peripheral nerve (sciatic nerve) to identify unique and shared Sox10 binding sites and assess their correlation with active enhancers and transcriptional profiles in oligodendrocytes and Schwann cells. Sox10 binding sites overlap with active enhancers and critical cell type-specific regulators of myelination, such as Olig2 and Myrf in oligodendrocytes, and Egr2/Krox20 in Schwann cells. Sox10 sites also associate with genes critical for myelination in both oligodendrocytes and Schwann cells, and are found within super-enhancers previously defined in brain. In Schwann cells, Sox10 sites contain binding motifs of putative partners in the Sp/Klf, Tead, and nuclear receptor protein families. Specifically, siRNA analysis of nuclear receptors Nr2f1 and Nr2f2 revealed downregulation of myelin genes Mbp and Ndrg1 in primary Schwann cells. Our analysis highlights different mechanisms that establish cell type-specific genomic occupancy of Sox10, which reflects the unique characteristics of oligodendrocyte and Schwann cell differentiation. PMID:25974668

A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation

PubMed Central

Pearson, Jaclyn S; Riedmaier, Patrice; Marchès, Olivier; Frankel, Gad; Hartland, Elizabeth L

2011-01-01

Many bacterial pathogens utilize a type III secretion system (T3SS) to inject virulence effector proteins into host cells during infection. Previously, we found that enteropathogenic Escherichia coli (EPEC) uses the type III effector, NleE, to block the inflammatory response by inhibiting IκB degradation and nuclear translocation of the p65 subunit of NF-κB. Here we screened further effectors with unknown function for their capacity to prevent p65 nuclear translocation. We observed that ectopic expression of GFP–NleC in HeLa cells led to the degradation of p65. Delivery of NleC by the T3SS of EPEC also induced degradation of p65 in infected cells as well as other NF-κB components, c-Rel and p50. Recombinant His6-NleC induced p65 and p50 cleavage in HeLa cell lysates and mutation of a consensus zinc metalloprotease motif, HEIIH, abrogated NleC proteolytic activity. NleC inhibited IL-8 production during prolonged EPEC infection of HeLa cells in a protease activity-dependent manner. A double nleE/nleC mutant was further impaired for its ability to inhibit IL-8 secretion than either a single nleE or a single nleC mutant. We conclude that NleC is a type III effector protease that degrades NF-κB thereby contributing the arsenal of bacterial effectors that inhibit innate immune activation. PMID:21306441

Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

PubMed

Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

2015-02-19

Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Irreversible temperature gating in trpv1 sheds light on channel activation.

PubMed

Sánchez-Moreno, Ana; Guevara-Hernández, Eduardo; Contreras-Cervera, Ricardo; Rangel-Yescas, Gisela; Ladrón-de-Guevara, Ernesto; Rosenbaum, Tamara; Islas, León D

2018-06-05

Temperature-activated TRP channels or thermoTRPs are among the only proteins that can directly convert temperature changes into changes in channel open probability. In spite of a wealth of functional and structural information, the mechanism of temperature activation remains unknown. We have carefully characterized the repeated activation of TRPV1 by thermal stimuli and discovered a previously unknown inactivation process, which is irreversible. We propose that this form of gating in TRPV1 channels is a consequence of the heat absorption process that leads to channel opening. © 2018, Sánchez-Moreno et al.

National Dam Inspection Program. Jennings Pond Dam (NDI I.D. PA-0891 DER I.D. 066-012) Susquehanna River Basin, Little Mehoopany Creek, Wyoming County, Pennsylvania. Phase I Inspection Report,

DTIC Science & Technology

1981-03-19

Area 7.9 square miles(1) b. Discharge at Dam Site ( cfs ) Maximum known flood at dam site Unknown Outlet conduit at maximum pool Unknown Gated spillway...700 cfs , based on the available 2.4-foot freeboard relative to the low spot on the left abutment. b. Experience Data. As previously stated, Jennings...in Appendix D. The inflow hydrograph for one-half PMF was found to have a peak flow of 6835 cfs . Computer input and summary of computer output are

Unknown beaked whale echolocation signals recorded off eastern New Zealand.

PubMed

Giorli, Giacomo; Goetz, Kimberly T; Delarue, Julien; Maxner, Emily; Kowarski, Katie A; Bruce Martin, Steven; McPherson, Craig

2018-04-01

The echolocation signals of most beaked whale species are still unknown. In fact, out of the 22 species comprising the family Ziphiidae, only the echolocation pulses for 7 species have been clearly described. This study describes two distinct beaked whale echolocation signals recorded in the Cook Strait region using passive acoustic technology. These signals differ from previously described Ziphiid species clicks. A description of the time-frequency characteristics of the two signals is provided. Understanding the characteristics of these signals is necessary to correctly identify species from their echolocation signals and enables future monitoring of beaked whales using passive acoustics techniques.

Proteomics and transcriptomics analyses of Arabidopsis floral buds uncover important functions of ARABIDOPSIS SKP1-LIKE1

DOE PAGES

Lu, Dihong; Ni, Weimin; Stanley, Bruce A.; ...

2016-03-03

The ARABIDOPSIS SKP1-LIKE1 (ASK1) protein functions as a subunit of SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases. Previous genetic studies showed that ASK1 plays important roles in Arabidopsis flower development and male meiosis. However, the molecular impact of ASK1-containing SCF E3 ubiquitin ligases (ASK1-E3s) on the floral proteome and transcriptome is unknown. Here we identified proteins that are potentially regulated by ASK1-E3s by comparing floral bud proteomes of wild-type and the ask1 mutant plants. More than 200 proteins were detected in the ask1 mutant but not in wild-type and >300 were detected at higher levels in the ask1 mutant than in wild-type,more » but their RNA levels were not significantly different between wild-type and ask1 floral buds as shown by transcriptomics analysis, suggesting that they are likely regulated at the protein level by ASK1-E3s. Integrated analyses of floral proteomics and transcriptomics of ask1 and wild-type uncovered several potential aspects of ASK1-E3 functions, including regulation of transcription regulators, kinases, peptidases, and ribosomal proteins, with implications on possible mechanisms of ASK1-E3 functions in floral development. In conclusion, our results suggested that ASK1-E3s play important roles in Arabidopsis protein degradation during flower development. This study opens up new possibilities for further functional studies of these candidate E3 substrates.« less

The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation.

PubMed

Holmes, Amie L; Joyce, Kellie; Xie, Hong; Falank, Carolyne; Hinz, John M; Wise, John Pierce

2014-04-01

Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation. Copyright © 2014 Elsevier B.V. All rights reserved.

Proteomics and transcriptomics analyses of Arabidopsis floral buds uncover important functions of ARABIDOPSIS SKP1-LIKE1

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

Lu, Dihong; Ni, Weimin; Stanley, Bruce A.

The ARABIDOPSIS SKP1-LIKE1 (ASK1) protein functions as a subunit of SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases. Previous genetic studies showed that ASK1 plays important roles in Arabidopsis flower development and male meiosis. However, the molecular impact of ASK1-containing SCF E3 ubiquitin ligases (ASK1-E3s) on the floral proteome and transcriptome is unknown. Here we identified proteins that are potentially regulated by ASK1-E3s by comparing floral bud proteomes of wild-type and the ask1 mutant plants. More than 200 proteins were detected in the ask1 mutant but not in wild-type and >300 were detected at higher levels in the ask1 mutant than in wild-type,more » but their RNA levels were not significantly different between wild-type and ask1 floral buds as shown by transcriptomics analysis, suggesting that they are likely regulated at the protein level by ASK1-E3s. Integrated analyses of floral proteomics and transcriptomics of ask1 and wild-type uncovered several potential aspects of ASK1-E3 functions, including regulation of transcription regulators, kinases, peptidases, and ribosomal proteins, with implications on possible mechanisms of ASK1-E3 functions in floral development. In conclusion, our results suggested that ASK1-E3s play important roles in Arabidopsis protein degradation during flower development. This study opens up new possibilities for further functional studies of these candidate E3 substrates.« less

The Usher Syndrome Type IIIB Histidyl-tRNA Synthetase Mutation Confers Temperature Sensitivity.

PubMed

Abbott, Jamie A; Guth, Ethan; Kim, Cindy; Regan, Cathy; Siu, Victoria M; Rupar, C Anthony; Demeler, Borries; Francklyn, Christopher S; Robey-Bond, Susan M

2017-07-18

Histidyl-tRNA synthetase (HARS) is a highly conserved translation factor that plays an essential role in protein synthesis. HARS has been implicated in the human syndromes Charcot-Marie-Tooth (CMT) Type 2W and Type IIIB Usher (USH3B). The USH3B mutation, which encodes a Y454S substitution in HARS, is inherited in an autosomal recessive fashion and associated with childhood deafness, blindness, and episodic hallucinations during acute illness. The biochemical basis of the pathophysiologies linked to USH3B is currently unknown. Here, we present a detailed functional comparison of wild-type (WT) and Y454S HARS enzymes. Kinetic parameters for enzymes and canonical substrates were determined using both steady state and rapid kinetics. Enzyme stability was examined using differential scanning fluorimetry. Finally, enzyme functionality in a primary cell culture was assessed. Our results demonstrate that the Y454S substitution leaves HARS amino acid activation, aminoacylation, and tRNA His binding functions largely intact compared with those of WT HARS, and the mutant enzyme dimerizes like the wild type does. Interestingly, during our investigation, it was revealed that the kinetics of amino acid activation differs from that of the previously characterized bacterial HisRS. Despite the similar kinetics, differential scanning fluorimetry revealed that Y454S is less thermally stable than WT HARS, and cells from Y454S patients grown at elevated temperatures demonstrate diminished levels of protein synthesis compared to those of WT cells. The thermal sensitivity associated with the Y454S mutation represents a biochemical basis for understanding USH3B.

Risk factors for death from canine parvoviral-related disease in Australia.

PubMed

Ling, Monika; Norris, Jacqueline M; Kelman, Mark; Ward, Michael P

2012-08-17

Canine parvovirus (CPV) is a highly contagious cause of serious and often fatal disease in dogs worldwide despite the availability of safe and efficacious vaccines. Although a number of studies have focussed on identifying risk factors in disease development, risk factors associated with death from CPV are largely unknown. In this study we analysed a total of 1451 CPV cases reported from an Australian surveillance system - using univariate and multivariate techniques - to determine significant risk factors associated with death and euthanasia. A crude case fatality rate of 42.3% was estimated - higher than has been reported previously. We found that 3.3% of CPV cases had a history of vaccination in the previous 12 months, despite having completed the primary puppy vaccination course. The majority (89.5%) of these cases occurred in dogs <12 months of age, indicating failure of the primary vaccination course to provide protective immunity (most likely due to interference of the vaccine antigen with maternal antibodies but other reasons are discussed). Extending the age at which the final puppy vaccination is administered might be one of several strategies to consider. The final multivariate model showed that in non-litter CPV cases, risk of death was significantly associated with season of diagnosis (summer) and pedigree type (hounds and non-sporting dogs). Euthanasia in non-litter CPV cases was significantly associated with season of diagnosis (summer), state of residence (Northern Territory/South Australia/Tasmania combined), age (

The predominant circular form of avocado sunblotch viroid accumulates in planta as a free RNA adopting a rod-shaped secondary structure unprotected by tightly bound host proteins.

PubMed

López-Carrasco, Amparo; Flores, Ricardo

2017-07-01

Avocado sunblotch viroid (ASBVd), the type member of the family Avsunviroidae, replicates and accumulates in chloroplasts. Whether this minimal non-protein-coding circular RNA of 246-250 nt exists in vivo as a free nucleic acid or closely associated with host proteins remains unknown. To tackle this issue, the secondary structures of the monomeric circular (mc) (+) and (-) strands of ASBVd have been examined in silico by searching those of minimal free energy, and in vitro at single-nucleotide resolution by selective 2'-hydroxyl acylation analysed by primer extension (SHAPE). Both approaches resulted in predominant rod-like secondary structures without tertiary interactions, with the mc (+) RNA being more compact than its (-) counterpart as revealed by non-denaturing polyacryamide gel electrophoresis. Moreover, in vivo SHAPE showed that the mc ASBVd (+) form accumulates in avocado leaves as a free RNA adopting a similar rod-shaped conformation unprotected by tightly bound host proteins. Hence, the mc ASBVd (+) RNA behaves in planta like the previously studied mc (+) RNA of potato spindle tuber viroid, the type member of nuclear viroids (family Pospiviroidae), indicating that two different viroids replicating and accumulating in distinct subcellular compartments, have converged into a common structural solution. Circularity and compact secondary structures confer to these RNAs, and probably to all viroids, the intrinsic stability needed to survive in their natural habitats. However, in vivo SHAPE has not revealed the (possibly transient or loose) interactions of the mc ASBVd (+) RNA with two host proteins observed previously by UV irradiation of infected avocado leaves.

A Sequence-Independent Strategy for Detection and Cloning of Circular DNA Virus Genomes by Using Multiply Primed Rolling-Circle Amplification

PubMed Central

Rector, Annabel; Tachezy, Ruth; Van Ranst, Marc

2004-01-01

The discovery of novel viruses has often been accomplished by using hybridization-based methods that necessitate the availability of a previously characterized virus genome probe or knowledge of the viral nucleotide sequence to construct consensus or degenerate PCR primers. In their natural replication cycle, certain viruses employ a rolling-circle mechanism to propagate their circular genomes, and multiply primed rolling-circle amplification (RCA) with φ29 DNA polymerase has recently been applied in the amplification of circular plasmid vectors used in cloning. We employed an isothermal RCA protocol that uses random hexamer primers to amplify the complete genomes of papillomaviruses without the need for prior knowledge of their DNA sequences. We optimized this RCA technique with extracted human papillomavirus type 16 (HPV-16) DNA from W12 cells, using a real-time quantitative PCR assay to determine amplification efficiency, and obtained a 2.4 × 104-fold increase in HPV-16 DNA concentration. We were able to clone the complete HPV-16 genome from this multiply primed RCA product. The optimized protocol was subsequently applied to a bovine fibropapillomatous wart tissue sample. Whereas no papillomavirus DNA could be detected by restriction enzyme digestion of the original sample, multiply primed RCA enabled us to obtain a sufficient amount of papillomavirus DNA for restriction enzyme analysis, cloning, and subsequent sequencing of a novel variant of bovine papillomavirus type 1. The multiply primed RCA method allows the discovery of previously unknown papillomaviruses, and possibly also other circular DNA viruses, without a priori sequence information. PMID:15113879

Rainforest understory beetles of the Neotropics, Mizotrechus Bates 1872, a generic synopsis with descriptions of new species from Central America and northern South America (Coleoptera, Carabidae, Perigonini).

PubMed

Erwin, Terry L

2011-01-01

Information on the single previously described species, Mizotrechus novemstriatus Bates 1872 (type locality: Brazil - Amazonas, Tefé), is updated and 17 new species for the genus from Nicaragua, Costa Rica, Panamá, Colombia, Venezuela, and Guyane are described. The species records in the literature and on determined specimens in some collections of Mizotrechus novemstriatus Bates from Central America are not that species; currently, Mizotrechus novemstriatus is known only from its type locality in Amazonian Brazil. For the new species described, their known general distributions are as follows: Mizotrechus batesisp. n. (Guyane), Mizotrechus bellorumsp. n. (Guyane), Mizotrechus bruleisp. n. (Guyane), Mizotrechus belevederesp. n. (Guyane), Mizotrechus costaricensissp. n. (Costa Rica), Mizotrechus dalensisp. n. (Guyane), Mizotrechus edithpiafaesp. n. (provenance unknown), Mizotrechus fortunensissp. n. (Panamá), Mizotrechus gorgona. sp. n. (Colombia), Mizotrechus grossussp. n. (Guyane), Mizotrechus jefesp. n. (Panamá), Mizotrechus marielaforetaesp. n. (Guyane), Mizotrechus minutussp. n. (Guyane), Mizotrechus neblinensissp. n. (Guyane, Venezuela), Mizotrechus poirierisp. n. (Guyane), and Mizotrechus woldaisp. n. (Panamá). Long-term use of flight intercept traps in Guyane provided so many new species that apparently the use of FITs is the way to collect adults of this taxon, previously known from very few specimens. Many more species of this genus can be expected to be discovered throughout the Neotropics; the present contribution is a preliminary synopsis with identification key and adult images of all known species. Likely numerous species are yet to be discovered throughout tropical climes.

Jumping to conclusions and persecutory delusions.

PubMed

Startup, Helen; Freeman, Daniel; Garety, Philippa A

2008-09-01

It is unknown whether a 'jumping to conclusions' (JTC) data-gathering bias is apparent in specific delusion sub-types. A group with persecutory delusions is compared with a sample of non-clinical controls on a probabilistic reasoning task. Results suggest JTC is apparent in individuals with the persecutory sub-type of delusions.

Titres and cross reactions of commercial antisera for the capsular typing of Klebsiella species.

PubMed Central

Casewell, M W

1975-01-01

Ninety commercially supplied sera for the capsular typing of Klebsiella species were tested in a full chequerboard against 72 type strains. Only four of 144 homologous reactions could not be detected. Of the 6336 possible heterologous reactions, 91 actual cross reactions were found. All positive reactions were titrated and working dilutions deduced. This provides essential information for the successful typing of unknown strains with these sera. PMID:1091662

Non-predictor control of a class of feedforward nonlinear systems with unknown time-varying delays

NASA Astrophysics Data System (ADS)

Koo, Min-Sung; Choi, Ho-Lim

2016-08-01

This paper generalises the several recent results on the control of feedforward time-delay nonlinear systems. First, in view of system formulation, there are unknown time-varying delays in both states and main control input. Also, the considered nonlinear system has extended feedforward nonlinearities. Second, in view of control solution, our proposed controller is a non-predictor feedback controller whereas smith-predictor type controllers are used in the several existing results. Moreover, our controller does not need any information on the unknown delays except their upper bounds. Thus, our result has certain merits in both system formulation and control solution perspective. The analysis and example are given for clear illustration.

Two antibacterial C-type lectins from crustacean, Eriocheir sinensis, stimulated cellular encapsulation in vitro.

PubMed

Jin, Xing-Kun; Li, Shuang; Guo, Xiao-Nv; Cheng, Lin; Wu, Min-Hao; Tan, Shang-Jian; Zhu, You-Ting; Yu, Ai-Qing; Li, Wei-Wei; Wang, Qun

2013-12-01

The first step of host fighting against pathogens is that pattern recognition receptors recognized pathogen-associated molecular patterns. However, the specificity of recognition within the innate immune molecular of invertebrates remains largely unknown. In the present study, we investigated how invertebrate pattern recognition receptor (PRR) C-type lectins might be involved in the antimicrobial response in crustacean. Based on our previously obtained completed coding regions of EsLecA and EsLecG in Eriocheir sinensis, the recombinant EsLectin proteins were produced via prokaryotic expression system and affinity chromatography. Subsequently, both rEsLecA and rEsLecG were discovered to have wide spectrum binding activities towards microorganisms, and their microbial-binding was calcium-independent. Moreover, the binding activities of both rEsLecA and rEsLecG induced the aggregation against microbial pathogens. Both microorganism growth inhibitory activities assays and antibacterial activities assays revealed their capabilities of suppressing microorganisms growth and directly killing microorganisms respectively. Furthermore, the encapsulation assays signified that both rEsLecA and rEsLecG could stimulate the cellular encapsulation in vitro. Collectively, data presented here demonstrated the successful expression and purification of two C-type lectins proteins in the Chinese mitten crab, and their critical role in the innate immune system of an invertebrate. Copyright © 2013 Elsevier Ltd. All rights reserved.

WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.

PubMed

Domfeh, Akosua B; Carley, AnnaMarie L; Striebel, Joan M; Karabakhtsian, Rouzan G; Florea, Anca V; McManus, Kim; Beriwal, Sushil; Bhargava, Rohit

2008-10-01

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Cutaneous Nod2 Expression Regulates the Skin Microbiome and Wound Healing in a Murine Model.

PubMed

Williams, Helen; Crompton, Rachel A; Thomason, Helen A; Campbell, Laura; Singh, Gurdeep; McBain, Andrew J; Cruickshank, Sheena M; Hardman, Matthew J

2017-11-01

The skin microbiome exists in dynamic equilibrium with the host, but when the skin is compromised, bacteria can colonize the wound and impair wound healing. Thus, the interplay between normal skin microbial interactions versus pathogenic microbial interactions in wound repair is important. Bacteria are recognized by innate host pattern recognition receptors, and we previously showed an important role for the pattern recognition receptor NOD2 in skin wound repair. NOD2 is implicated in changes in the composition of the intestinal microbiota in Crohn's disease, but its role on skin microbiota is unknown. Nod2-deficient (Nod2 -/- ) mice had an inherently altered skin microbiome compared with wild-type controls. Furthermore, we found that Nod2 -/- skin microbiome dominated and caused impaired healing, shown in cross-fostering experiments of wild-type pups with Nod2 -/- pups, which then acquired altered cutaneous bacteria and delayed healing. High-throughput sequencing and quantitative real-time PCR showed a significant compositional shift, specifically in the genus Pseudomonas in Nod2 -/- mice. To confirm whether Pseudomonas species directly impair wound healing, wild-type mice were infected with Pseudomonas aeruginosa biofilms and, akin to Nod2 -/- mice, were found to exhibit a significant delay in wound repair. Collectively, these studies show the importance of the microbial communities in skin wound healing outcome. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.

PubMed

Xu, Jijun; Zhang, Lingjun; Xie, Mian; Li, Yan; Huang, Ping; Saunders, Thomas L; Fox, David A; Rosenquist, Richard; Lin, Feng

2018-06-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease. Copyright © 2018 by The American Association of Immunologists, Inc.

Two subpopulations of Crocosphaera watsonii have distinct distributions in the North and South Pacific.

PubMed

Bench, Shellie R; Frank, Ildiko; Robidart, Julie; Zehr, Jonathan P

2016-02-01

Crocosphaera watsonii is a unicellular nitrogen (N2)-fixing cyanobacterium with ecological importance in oligotrophic oceans. In cultivated strains there are two phenotypes of C. watsonii (large and small cells) with differences that could differentially impact biogeochemical processes. Recent work has shown the phenotypes diverged through loss or addition of type-specific genes in a fraction of their genomes, whereas the rest of the genomes were maintained at 99-100% DNA identity. Previous molecular assays for C. watsonii abundances targeted the conserved regions and therefore could not differentiate between phenotypes, so their relative distributions in natural communities were unknown. To determine phenotype distributions, this study developed and applied type-specific quantitative polymerase chain reaction assays to samples from the North and South Pacific. Abundances of both Crocosphaera types declined sharply with depth between 45 and 75 m in both sites. In surface water small cells were 10-100 times more abundant than large cells in the N. Pacific, whereas in the S. Pacific the two phenotypes were nearly equal. Evidence for large cell aggregation was only found in N. Pacific samples. The differences in C. watsonii sub-populations in the North and South Pacific have direct implications for biogeochemistry and carbon export in oligotrophic gyres. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

PubMed

Kotteas, E A; Pavlidis, N

2015-04-01

Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Known knowns, known unknowns and unknown unknowns in prokaryotic transposition.

PubMed

Siguier, Patricia; Gourbeyre, Edith; Chandler, Michael

2017-08-01

Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize. In spite of a robust understanding of transposition of some TE, there remain a number of important TE groups with potential high genome impact and unknown transposition mechanisms and yet others, only recently identified by bioinformatics, yet to be formally confirmed as mobile. Here, we point to some areas of limited understanding concerning well established important TE groups with DDE Tpases, to address central gaps in our knowledge of characterised Tn with other types of Tpases and finally, to highlight new potentially mobile DNA species. It is not exhaustive. Examples have been chosen to provide encouragement in the continued exploration of the considerable prokaryotic mobilome especially in light of the current threat to public health posed by the spread of multiple Ab R . Copyright © 2017 Elsevier Ltd. All rights reserved.

From sequence analysis of three novel ascorbate peroxidases from Arabidopsis thaliana to structure, function and evolution of seven types of ascorbate peroxidase.

PubMed Central

Jespersen, H M; Kjaersgård, I V; Ostergaard, L; Welinder, K G

1997-01-01

Ascorbate peroxidases are haem proteins that efficiently scavenge H2O2 in the cytosol and chloroplasts of plants. Database analyses retrieved 52 expressed sequence tags coding for Arabidopsis thaliana ascorbate peroxidases. Complete sequencing of non-redundant clones revealed three novel types in addition to the two cytosol types described previously in Arabidopsis. Analysis of sequence data available for all plant ascorbate peroxidases resulted in the following classification: two types of cytosol soluble ascorbate peroxidase designated cs1 and cs2; three types of cytosol membrane-bound ascorbate peroxidase, namely cm1, bound to microbodies via a C-terminal membrane-spanning segment, and cm2 and cm3, both of unknown location; two types of chloroplast ascorbate peroxidase with N-terminal transit sequences, the stromal ascorbate peroxidase (chs), and the thylakoid-bound ascorbate peroxidase showing a C-terminal transmembrane segment and designated cht. Further comparison of the patterns of conserved residues and the crystal structure of pea ascorbate peroxidase showed that active site residues are conserved, and three peptide segments implicated in interaction with reducing substrate are similar, excepting cm2 and cm3 types. A change of Phe-175 in cytosol types to Trp-175 in chloroplast types might explain the greater ascorbate specificity of chloroplast compared with cytosol ascorbate peroxidases. Residues involved in homodimeric subunit interaction are conserved only in cs1, cs2 and cm1 types. The proximal cation (K+)-binding site observed in pea ascorbate peroxidase seems to be conserved. In addition, cm1, cm2, cm3, chs and cht ascorbate peroxidases contain Asp-43, Asn-57 and Ser-59, indicative of a distal monovalent cation site. The data support the hypothesis that present-day peroxidases evolved by an early gene duplication event. PMID:9291097

DNA Misfolding Found to Cause Cancer in IDH-mutant Gliomas

Cancer.gov

Researchers studying IDH-mutant brain tumors have identified a previously unknown genetic mechanism that may contribute to cancer. A change in how DNA is arranged, or packaged, in the cell nucleus may inappropriately activate a gene associated with brain cancer.

Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

USDA-ARS?s Scientific Manuscript database

Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

ABC Transporter Genes and Risk of Type 2 Diabetes

PubMed Central

Schou, Jesper; Tybjærg-Hansen, Anne; Møller, Holger J.; Nordestgaard, Børge G.; Frikke-Schmidt, Ruth

2012-01-01

OBJECTIVE Alterations of pancreatic β-cell cholesterol content may contribute to β-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown. RESEARCH DESIGN AND METHODS We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C>T) (n = 322) and a common variant (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415). RESULTS Only one of the variants examined, ABCG1 g.-530A>G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C>T) nor ABCG1 g.-530A>G were associated with type 2 diabetes (P values >0.57 and >0.30, respectively). CONCLUSIONS Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1. PMID:23139370

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns

PubMed Central

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, “What is their role in non-seed plants?” From the studies reviewed here it can be gathered that unlike seed plants, MIKCC genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC* genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution. PMID:29720991

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns.

PubMed

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, "What is their role in non-seed plants?" From the studies reviewed here it can be gathered that unlike seed plants, MIKC C genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC * genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution.

Effects of acute insulin-induced hypoglycaemia on psychomotor function: people with type 1 diabetes are less affected than non-diabetic adults.

PubMed

Geddes, J; Deary, I J; Frier, B M

2008-10-01

We examined the effects of acute insulin-induced hypoglycaemia on psychomotor function in non-diabetic volunteers and in adults with type 1 diabetes. Non-diabetic adults (n = 20) and adults with type 1 diabetes mellitus (n = 16) each underwent a euglycaemic-hyperinsulinaemic glucose clamp on two separate occasions. Arterialised blood glucose was maintained for 1 h at either 4.5 mmol/l (euglycaemia) or 2.5 mmol/l (hypoglycaemia). During this time participants underwent neuropsychological tests to assess psychomotor function. During hypoglycaemia the non-diabetic participants showed a significant deterioration in the following: (1) four-choice reaction time (p = 0.008); (2) grooved pegboard (a test of manual dexterity; p = 0.004); (3) hand steadiness (p = 0.003); (4) pursuit rotor (a test of fine motor function, attention and coordination; p = 0.018); and (5) test of total body coordination (p = 0.004). No significant differences were observed between euglycaemia and hypoglycaemia in hand-grip (p = 0.897) and line tracing time (p = 0.480) tests. In type 1 diabetes mellitus patients, only four-choice reaction time (p = 0.023) and pursuit rotor (p = 0.045) were impaired significantly during hypoglycaemia. Although acute hypoglycaemia caused significant impairment of several psychomotor functions in non-diabetic adults, a lower magnitude of impairment was observed in those with type 1 diabetes. The mechanism underlying this discrepant effect of hypoglycaemia on psychomotor function remains unknown, but may be related to the difference in sympathoadrenal activation observed between the groups. People with type 1 diabetes may also have had a behavioural advantage of over non-diabetic participants derived from their previous exposure to hypoglycaemia or potentially the disparate results arose from hypoglycaemia-induced cerebral adaptation.

Modality of tumor endothelial VEGFR2 silencing-mediated improvement in intratumoral distribution of lipid nanoparticles.

PubMed

Yamamoto, Shoshiro; Kato, Akari; Sakurai, Yu; Hada, Tomoya; Harashima, Hideyoshi

2017-04-10

The vascular endothelial growth factor (VEGF)-mediated enhancement in vascular permeability is considered to be a major factor in tumor-targeting delivery via the enhanced permeability and retention (EPR) effect. We previously reported that the silencing of the endothelial VEGF receptor (VEGFR2) by a liposomal siRNA system (RGD-MEND) resulted in an enhanced intratumoral distribution of polyethylene glycol (PEG)-modified liposomes (LPs) in a renal cell carcinoma, a type of hypervascularized cancer, although the inhibition of VEGF signaling would be expected to decrease the permeability of the tumor vasculature. We herein report that the enhancement in the intratumoral distribution of LPs by VEGFR2 inhibition was dependent on the vascular type of the tumor (stroma vessel type; SV and tumor vessel type; TV). In the case of TV-type tumors (renal cell carcinoma and hepatocellular carcinoma), inhibiting VEGFR2 improved intratumoral distribution, while no effect was found in the case of SV-type tumors (colorectal cancer). Moreover, through a comparison of the intratumoral distribution of LPs with a variety of physical properties (100nm vs 400nm, neutral vs negative vs positive), VEGFR2 inhibition was found to alter the tumor microenvironment, including heparan sulfate proteoglycans (HSPGs). In addition, the results regarding the effect of the size of nanoparticles indicated that VEGFR2 inhibition improved the penetration of nanoparticles through the vessel wall, but not via permeability, suggesting the involvement of an unknown mechanism. Our findings suggest that a combination of anti-angiogenic therapy and delivery via the EPR effect would be useful in certain cases, and that altering the tumor microenvironment by VEGFR2 blockade has a drastic effect on the intratumoral distribution of nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytologic regression in women with atypical squamous cells of unknown significance and negative human papillomavirus test.

PubMed

Wang, Shu; Lang, Jing He; Cheng, Xue Mei

2009-12-01

The aim of this study was to investigate the cytologic regression in women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus test. The 45 women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus at baseline were analyzed about the cytologic regression during 2 years of follow-up. The cumulative rate of cytologic regression was calculated by Kaplan-Meier curves. Of 45 women, the cumulative rates were as follows: 55.6% obtained cytologic regression before 6 months, 84.4% by 1 year, and 95.6% at 2 years. Cytologic regression was not influenced by age, menopausal status, and baseline human papillomavirus load. However, the 1-year cumulative regression rate in women with previous cervical lesions was significantly lower than those without (P=.02), even much lower in women with high-grade intraepithelial neoplasia or worse (P=.008). Most women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus could obtain cytologic regression within 2 years. Women with antecedent cervical lesions need longer time to reach this regression.

GBM Observations of Be X-Ray Binary Outbursts

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.; Finger, M. H.; Jenke, P. A.

2014-01-01

Since 2008 we have been monitoring accreting pulsars using the Gamma ray Burst Monitor (GBM) on Fermi. This monitoring program includes daily blind full sky searches for previously unknown or previously quiescent pulsars and source specific analysis to track the frequency evolution of all detected pulsars. To date we have detected outbursts from 23 transient accreting pulsars, including 21 confirmed or likely Be/X-ray binaries. I will describe our techniques and highlight results for selected pulsars.

Exploring the epididymis: a personal perspective on careers in science.

PubMed

Turner, Terry T

2015-01-01

Science is a profession of inquiry. We ask ourselves what is it we see and why our observations happen the way they do. Answering those two question puts us in the company of those early explorers, who from Europe found the New World, and from Asia reached west to encounter Europe. Vasco Núñez de Balboa of Spain was such an explorer. He was the first European to see or "discover" the Pacific Ocean. One can imagine his amazement, his excitement when he first saw from a mountain top that vast ocean previously unknown to his culture. A career in science sends each of us seeking our own "Balboa Moments," those observations or results that surprise or even amaze us, those discoveries that open our eyes to new views of nature and medicine. Scientists aim to do what those early explorers did: discover what has previously been unknown, see what has previously been unseen, and reveal what has previously been hidden. Science requires the scientist to discover the facts from among many fictions and to separate the important facts from the trivial so that knowledge can be properly developed. It is only with knowledge that old dogmas can be challenged and corrected. Careers in science produce specific sets of knowledge. When pooled with other knowledge sets they eventually contribute to wisdom and it is wisdom, we hope, that will improve the human condition.

[The changing spectrum of fever of unknown origin: trends and comparison with previous series at the Salvador Zubirán National Institute of Nutrition].

PubMed

Molina-Gamboa, J; Rivera-Morales, I; Camacho-Mezquita, E; Ponce-de-León, S

1994-01-01

We reviewed 400 medical records of patients admitted because of fever at the National Institute of Nutrition Salvador Zubirán between January 1, 1988 to December 31, 1992. Patient characteristics, diagnostic methods, final diagnosis and patient progress were analyzed, comparing these data with the previous series of the institute. We found 77 cases of fever of unknown origin (FUO), 47 males and 30 females, between 14 to 87 years of age. The final diagnosis encountered were: infections (40%), neoplasias (23%), collagen diseases (13%), and other diagnosis (8%). Sixteen percent of the cases remained without a final diagnosis. The most frequent infections were HIV infection (19%), tuberculosis (19%) and endocarditis (13%). The most common neoplasia was lymphoma (55.6%), with 90% of Hodgkin's disease. SLE was the most common autoimmune disease found. The methods to establish a final diagnosis were: biopsies (52%), serology (17%), cultures (12%), image (11%), and clinical (8%). Final diagnosis by serology tests increased from 2 to 17% in comparison with previous reports. Eight laparotomies were done, which is a less frequent practice than previously (10 vs 35%). We saw only one case of amebic hepatic abscess and had no cases of malaria and salmonellosis as final diagnosis of FUO; HIV infection was found to be a new major cause of FUO.

Allocating monitoring effort in the face of unknown unknowns

USGS Publications Warehouse

Wintle, B.A.; Runge, M.C.; Bekessy, S.A.

2010-01-01

There is a growing view that to make efficient use of resources, ecological monitoring should be hypothesis-driven and targeted to address specific management questions. 'Targeted' monitoring has been contrasted with other approaches in which a range of quantities are monitored in case they exhibit an alarming trend or provide ad hoc ecological insights. The second form of monitoring, described as surveillance, has been criticized because it does not usually aim to discern between competing hypotheses, and its benefits are harder to identify a priori. The alternative view is that the existence of surveillance data may enable rapid corroboration of emerging hypotheses or help to detect important 'unknown unknowns' that, if undetected, could lead to catastrophic outcomes or missed opportunities. We derive a model to evaluate and compare the efficiency of investments in surveillance and targeted monitoring. We find that a decision to invest in surveillance monitoring may be defensible if: (1) the surveillance design is more likely to discover or corroborate previously unknown phenomena than a targeted design and (2) the expected benefits (or avoided costs) arising from discovery are substantially higher than those arising from a well-planned targeted design. Our examination highlights the importance of being explicit about the objectives, costs and expected benefits of monitoring in a decision analytic framework. ?? 2010 Blackwell Publishing Ltd/CNRS.

Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.

PubMed

Ramani, Subha; Könings, Karen; Mann, Karen V; van der Vleuten, Cees

2017-10-01

Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.

Type II Secretion Substrates of Legionella pneumophila Translocate Out of the Pathogen-Occupied Vacuole via a Semipermeable Membrane.

PubMed

Truchan, Hilary K; Christman, Harry D; White, Richard C; Rutledge, Nakisha S; Cianciotto, Nicholas P

2017-06-20

Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella- containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p.i.), which is approximately the midpoint of the intracellular life cycle. However, it is detected as early as 6 h p.i. if ProA is hyperexpressed, indicating that translocation depends on the timing of ProA expression and that any other factors necessary for translocation are in place by that time point. Translocation occurs with all L. pneumophila strains tested and in amoebae, natural hosts for L. pneumophila It was absent in murine bone marrow-derived macrophages and murine macrophage cell lines. The ChiA chitinase also associated with the cytoplasmic face of the LCVM at 6 h p.i. and in a T2S-dependent manner. Galectin-3 and galectin-8, eukaryotic proteins whose localization is influenced by damage to host membranes, appeared within the LCV of infected human but not murine macrophages beginning at 6 h p.i. Thus, we hypothesize that ProA and ChiA are first secreted into the vacuolar lumen by the activity of the T2S and subsequently traffic into the macrophage cytosol via a novel mechanism that involves a semipermeable LCVM. IMPORTANCE Infection of macrophages and amoebae plays a central role in the pathogenesis of L. pneumophila , the agent of Legionnaires' disease. We have previously demonstrated that the T2S system of L. pneumophila greatly contributes to intracellular infection. However, the location of T2S substrates within the infected host cell is unknown. This report presents the first evidence of a L. pneumophila T2S substrate in the host cell cytosol and, therefore, the first evidence of a non-T4S effector trafficking out of the LCV. We also provide the first indication that the LCV is not completely intact but is instead semipermeable and that this occurs in human but not murine macrophages. Given this permeability, we hypothesize that other T2S substrates and LCV lumenal contents can escape into the host cell cytosol. Thus, these substrates may represent a battery of previously unidentified effectors that can interact with host factors and contribute to intracellular infection by L. pneumophila . Copyright © 2017 Truchan et al.

78 FR 36089 - Airworthiness Directives; Hawker Beechcraft Corporation (Type Certificate Previously Held by...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... Corporation (Type Certificate Previously Held by Raytheon Aircraft Company) Model BAe.125 Series 800A... to Hawker Beechcraft Corporation (Type Certificate Previously Held by Raytheon Aircraft Company... Airworthiness Directives; Hawker Beechcraft Corporation (Type Certificate Previously Held by Raytheon Aircraft...

Estimating unknown input parameters when implementing the NGA ground-motion prediction equations in engineering practice

USGS Publications Warehouse

Kaklamanos, James; Baise, Laurie G.; Boore, David M.

2011-01-01

The ground-motion prediction equations (GMPEs) developed as part of the Next Generation Attenuation of Ground Motions (NGA-West) project in 2008 are becoming widely used in seismic hazard analyses. However, these new models are considerably more complicated than previous GMPEs, and they require several more input parameters. When employing the NGA models, users routinely face situations in which some of the required input parameters are unknown. In this paper, we present a framework for estimating the unknown source, path, and site parameters when implementing the NGA models in engineering practice, and we derive geometrically-based equations relating the three distance measures found in the NGA models. Our intent is for the content of this paper not only to make the NGA models more accessible, but also to help with the implementation of other present or future GMPEs.

Probabilistic and deterministic aspects of linear estimation in geodesy. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Dermanis, A.

1976-01-01

Recent advances in observational techniques related to geodetic work (VLBI, laser ranging) make it imperative that more consideration should be given to modeling problems. Uncertainties in the effect of atmospheric refraction, polar motion and precession-nutation parameters, cannot be dispensed with in the context of centimeter level geodesy. Even physical processes that have generally been previously altogether neglected (station motions) must now be taken into consideration. The problem of modeling functions of time or space, or at least their values at observation points (epochs) is explored. When the nature of the function to be modeled is unknown. The need to include a limited number of terms and to a priori decide upon a specific form may result in a representation which fails to sufficiently approximate the unknown function. An alternative approach of increasing application is the modeling of unknown functions as stochastic processes.

Streptococcus massiliensis in the human mouth: a phylogenetic approach for the inference of bacterial habitats.

PubMed

Póntigo, F; Silva, C; Moraga, M; Flores, S V

2015-12-29

Streptococcus is a diverse bacterial lineage. Species of this genus occupy a myriad of environments inside humans and other animals. Despite the elucidation of several of these habitats, many remain to be identified. Here, we explore a methodological approach to reveal unknown bacterial environments. Specifically, we inferred the phylogeny of the Mitis group by analyzing the sequences of eight genes. In addition, information regarding habitat use of species belonging to this group was obtained from the scientific literature. The oral cavity emerged as a potential, previously unknown, environment of Streptococcus massiliensis. This phylogeny-based prediction was confirmed by species-specific polymerase chain reaction (PCR) amplification. We propose employing a similar approach, i.e., use of bibliographic data and molecular phylogenetics as predictive methods, and species-specific PCR as confirmation, in order to reveal other unknown habitats in further bacterial taxa.

Levothyroxine sodium revisited: A wholistic structural elucidation approach of new impurities via HPLC-HRMS/MS, on-line H/D exchange, NMR spectroscopy and chemical synthesis.

PubMed

Ruggenthaler, M; Grass, J; Schuh, W; Huber, C G; Reischl, R J

2017-02-20

The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method ("Procedure 1") has already been extensively studied, however for the second method ("Procedure 2"), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet. Applying minor modifications to the chromatographic parameters of USP "Procedure 2" and using various comprehensive structural elucidation methods such as high resolution tandem mass spectrometry with on-line hydrogen-deuterium (H/D) exchange or two-dimensional nuclear magnetic resonance spectroscopy (NMR) we gained new insights about the complex impurity profile of the synthetic thyroid hormone. This resulted in the characterization of 24 compounds previously unknown to literature and the introduction of two new classes of Levothyroxine Sodium impurities. Five novel compounds were unambiguously identified via isolation or synthesis of reference substances and subsequent NMR spectroscopic investigation. Additionally, Collision-Induced Dissociation (CID)-type fragmentation of identified major impurities as well as neutral loss fragmentation patterns of many characterized impurities were discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Avoidance of APOBEC3B-induced mutation by error-free lesion bypass

PubMed Central

Hoopes, James I.; Hughes, Amber L.; Hobson, Lauren A.; Cortez, Luis M.; Brown, Alexander J.

2017-01-01

Abstract APOBEC cytidine deaminases mutate cancer genomes by converting cytidines into uridines within ssDNA during replication. Although uracil DNA glycosylases limit APOBEC-induced mutation, it is unknown if subsequent base excision repair (BER) steps function on replication-associated ssDNA. Hence, we measured APOBEC3B-induced CAN1 mutation frequencies in yeast deficient in BER endonucleases or DNA damage tolerance proteins. Strains lacking Apn1, Apn2, Ntg1, Ntg2 or Rev3 displayed wild-type frequencies of APOBEC3B-induced canavanine resistance (CanR). However, strains without error-free lesion bypass proteins Ubc13, Mms2 and Mph1 displayed respective 4.9-, 2.8- and 7.8-fold higher frequency of APOBEC3B-induced CanR. These results indicate that mutations resulting from APOBEC activity are avoided by deoxyuridine conversion to abasic sites ahead of nascent lagging strand DNA synthesis and subsequent bypass by error-free template switching. We found this mechanism also functions during telomere re-synthesis, but with a diminished requirement for Ubc13. Interestingly, reduction of G to C substitutions in Ubc13-deficient strains uncovered a previously unknown role of Ubc13 in controlling the activity of the translesion synthesis polymerase, Rev1. Our results highlight a novel mechanism for error-free bypass of deoxyuridines generated within ssDNA and suggest that the APOBEC mutation signature observed in cancer genomes may under-represent the genomic damage these enzymes induce. PMID:28334887

Taxonomic notes on American heriades spinola, 1808 and leioproctus smith, 1853 (hymenoptera: megachilidae colletidae)

USDA-ARS?s Scientific Manuscript database

The previously unknown males of Leioproctus rosellae and Heriades tayrona, two recently discovered bees from northern Colombia, are described and diagnostic characters illustrated. The additional material of Heriades confirms that the megachilid tribe Osmiini does reach northern South America....

CLOTHES AS A SOURCE OF PARTICLES CONTRIBUTING TO THE "PERSONAL CLOUD"

EPA Science Inventory

Previous studies such as EPA's PTEAM Study have documented increased personal exposures to particles compared to either indoor or outdoor concentrations--a finding that bas been characterized as a "personal cloud." The sources of the personal cloud are unknown, but co...

Interobserver Agreement on First-Stage Conversation Analytic Transcription

ERIC Educational Resources Information Center

Roberts, Felicia; Robinson, Jeffrey D.

2004-01-01

This investigation assesses interobserver agreement on conversation analytic (CA) transcription. Four professional CA transcribers spent a maximum of 3 hours transcribing 2.5 minutes of a previously unknown, naturally occurring, mundane telephone call. Researchers unitized transcripts into words, sounds, silences, inbreaths, outbreaths, and laugh…

Inconspicuous echolocation in hoary bats (Lasiurus cinereus)

Treesearch

Aaron J. Corcoran; Theodore J. Weller

2018-01-01

Echolocation allows bats to occupy diverse nocturnal niches. Bats almost always use echolocation, even when other sensory stimuli are available to guide navigation. Here, using arrays of calibrated infrared cameras and ultrasonic microphones, we demonstrate that hoary bats (Lasiurus cinereus) use previously unknown echolocation behaviours that...

Isolation of a hyperthermophilic archaeum predicted by in situ RNA analysis.

PubMed

Huber, R; Burggraf, S; Mayer, T; Barns, S M; Rossnagel, P; Stetter, K O

1995-07-06

A variety of hyperthermophilic bacteria and archaea have been isolated from high-temperature environments by plating and serial dilutions. However, these techniques allow only the small percentage of organisms able to form colonies, or those that are predominant within environmental samples, to be obtained in pure culture. Recently, in situ 16S ribosomal RNA analyses of samples from the Obsidian hot pool at Yellowstone National Park, Wyoming, revealed a variety of archaeal sequences, which were all different from those of previously isolated species. This suggests substantial diversity of archaea with so far unknown morphological, physiological and biochemical features, which may play an important part within high-temperature ecosystems. Here we describe a procedure to obtain pure cultures of unknown organisms harbouring specific 16S rRNA sequences identified previously within the environment. It combines visual recognition of single cells by phylogenetic staining and cloning by 'optical tweezers'. Our result validates polymerase chain reaction data on the existence of large archael communities.

Previously unknown class of metalorganic compounds revealed in meteorites

PubMed Central

Ruf, Alexander; Kanawati, Basem; Hertkorn, Norbert; Yin, Qing-Zhu; Moritz, Franco; Harir, Mourad; Lucio, Marianna; Michalke, Bernhard; Wimpenny, Joshua; Shilobreeva, Svetlana; Bronsky, Basil; Saraykin, Vladimir; Gabelica, Zelimir; Gougeon, Régis D.; Quirico, Eric; Ralew, Stefan; Jakubowski, Tomasz; Haack, Henning; Gonsior, Michael; Jenniskens, Peter; Hinman, Nancy W.; Schmitt-Kopplin, Philippe

2017-01-01

The rich diversity and complexity of organic matter found in meteorites is rapidly expanding our knowledge and understanding of extreme environments from which the early solar system emerged and evolved. Here, we report the discovery of a hitherto unknown chemical class, dihydroxymagnesium carboxylates [(OH)2MgO2CR]−, in meteoritic soluble organic matter. High collision energies, which are required for fragmentation, suggest substantial thermal stability of these Mg-metalorganics (CHOMg compounds). This was corroborated by their higher abundance in thermally processed meteorites. CHOMg compounds were found to be present in a set of 61 meteorites of diverse petrological classes. The appearance of this CHOMg chemical class extends the previously investigated, diverse set of CHNOS molecules. A connection between the evolution of organic compounds and minerals is made, as Mg released from minerals gets trapped into organic compounds. These CHOMg metalorganic compounds and their relation to thermal processing in meteorites might shed new light on our understanding of carbon speciation at a molecular level in meteorite parent bodies. PMID:28242686

On the Traceability of Commercial Saffron Samples Using ¹H-NMR and FT-IR Metabolomics.

PubMed

Consonni, Roberto; Ordoudi, Stella A; Cagliani, Laura R; Tsiangali, Maria; Tsimidou, Maria Z

2016-02-29

In previous works on authentic samples of saffron of known history (harvest and processing year, storage conditions, and length of time) some biomarkers were proposed using both FT-IR and NMR metabolomics regarding the shelf life of the product. This work addresses the difficulties to trace back the "age" of commercial saffron samples of unknown history, sets a limit value above which these products can be considered substandard, and offers a useful tool to combat saffron mislabeling and fraud with low-quality saffron material. Investigations of authentic and commercial saffron samples of different origin and harvest year, which had been stored under controlled conditions for different lengths of time, allowed a clear-cut clustering of samples in two groups according to the storage period irrespectively of the provenience. In this respect, the four-year cut off point proposed in our previous work assisted to trace back the "age" of unknown samples and to check for possible mislabeling practices.

A chemical proteomics approach for global analysis of lysine monomethylome profiling.

PubMed

Wu, Zhixiang; Cheng, Zhongyi; Sun, Mingwei; Wan, Xuelian; Liu, Ping; He, Tieming; Tan, Minjia; Zhao, Yingming

2015-02-01

Methylation of lysine residues on histone proteins is known to play an important role in chromatin structure and function. However, non-histone protein substrates of this modification remain largely unknown. An effective approach for system-wide analysis of protein lysine methylation, particularly lysine monomethylation, is lacking. Here we describe a chemical proteomics approach for global screening for monomethyllysine substrates, involving chemical propionylation of monomethylated lysine, affinity enrichment of the modified monomethylated peptides, and HPLC/MS/MS analysis. Using this approach, we identified with high confidence 446 lysine monomethylation sites in 398 proteins, including three previously unknown histone monomethylation marks, representing the largest data set of protein lysine monomethylation described to date. Our data not only confirms previously discovered lysine methylation substrates in the nucleus and spliceosome, but also reveals new substrates associated with diverse biological processes. This method hence offers a powerful approach for dynamic study of protein lysine monomethylation under diverse cellular conditions and in human diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

PubMed

de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed; White, Jacqui; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Fray, Martin; Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl Mj; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve Dm

2015-09-01

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.

Differences in social skills performance between institutionalized juvenile male offenders and a comparable group of boys without offence records.

PubMed

Spence, S H

1981-09-01

Eighteen institutionalized young male offenders and 18 boys without criminal records, comparable in terms of age, academic performance and social background, were videotaped during a five-minute standardized interview with a previously unknown adult. The videotapes were then subjected to a behavioural analysis of 13 responses which had previously been suggested to be important social skill components. The tapes were also shown to six independent judges who rated each tape in terms of social skills performance, social anxiety, friendliness, and employability. The offender group was found to differ significantly from the non-offender group in terms of the level of eye-contact, head movements, amount spoken, fiddling movements, and gross body movements. The offender group was also rated in significantly less favourably terms on the scales of social skills performance, social anxiety, and employability, compared to the non-offender groups. No significant difference was found in terms of friendliness ratings. Correlation analyses between the specific behavioural measures and the subjective rating scales revealed statistically significant associations between six of the 13 behavioural measures and one or more of the subjective rating scales. The provides some indication of the type of responses important in determining the impression made by adolescent male in an interview situation.

Turning publicly available gene expression data into discoveries using gene set context analysis.

PubMed

Ji, Zhicheng; Vokes, Steven A; Dang, Chi V; Ji, Hongkai

2016-01-08

Gene Set Context Analysis (GSCA) is an open source software package to help researchers use massive amounts of publicly available gene expression data (PED) to make discoveries. Users can interactively visualize and explore gene and gene set activities in 25,000+ consistently normalized human and mouse gene expression samples representing diverse biological contexts (e.g. different cells, tissues and disease types, etc.). By providing one or multiple genes or gene sets as input and specifying a gene set activity pattern of interest, users can query the expression compendium to systematically identify biological contexts associated with the specified gene set activity pattern. In this way, researchers with new gene sets from their own experiments may discover previously unknown contexts of gene set functions and hence increase the value of their experiments. GSCA has a graphical user interface (GUI). The GUI makes the analysis convenient and customizable. Analysis results can be conveniently exported as publication quality figures and tables. GSCA is available at https://github.com/zji90/GSCA. This software significantly lowers the bar for biomedical investigators to use PED in their daily research for generating and screening hypotheses, which was previously difficult because of the complexity, heterogeneity and size of the data. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.

PubMed

Chiabrando, Deborah; Castori, Marco; di Rocco, Maja; Ungelenk, Martin; Gießelmann, Sebastian; Di Capua, Matteo; Madeo, Annalisa; Grammatico, Paola; Bartsch, Sophie; Hübner, Christian A; Altruda, Fiorella; Silengo, Lorenzo; Tolosano, Emanuela; Kurth, Ingo

2016-12-01

Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1) gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.

Capillary electrophoresis - Mass spectrometry metabolomics analysis revealed enrichment of hypotaurine in rat glioma tissues.

PubMed

Gao, Peng; Ji, Min; Fang, Xueyan; Liu, Yingyang; Yu, Zhigang; Cao, Yunfeng; Sun, Aijun; Zhao, Liang; Zhang, Yong

2017-11-15

Glioma is one of the most lethal brain malignancies with unknown etiologies. Many metabolomics analysis aiming at diverse kinds of samples had been performed. Due to the varied adopted analytical platforms, the reported disease-related metabolites were not consistent across different studies. Comparable metabolomics results are more likely to be acquired by analyzing the same sample types with identical analytical platform. For tumor researches, tissue samples metabolomics analysis own the unique advantage that it can gain more direct insight into disease-specific pathological molecules. In this light, a previous reported capillary electrophoresis - mass spectrometry human tissues metabolomics analysis method was employed to profile the metabolome of rat C6 cell implantation gliomas and the corresponding precancerous tissues. It was found that 9 metabolites increased in the glioma tissues. Of them, hypotaurine was the only metabolite that enriched in the malignant tissues as what had been reported in the relevant human tissues metabolomics analysis. Furthermore, hypotaurine was also proved to inhibit α-ketoglutarate-dependent dioxygenases (2-KDDs) through immunocytochemistry staining and in vitro enzymatic activity assays by using C6 cell cultures. This study reinforced the previous conclusion that hypotaurine acted as a competitive inhibitor of 2-KDDs and proved the value of metabolomics in oncology studies. Copyright © 2017. Published by Elsevier Inc.

Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor

PubMed Central

Chen, Zhaochun; Fischer, Elizabeth R.; Kouiavskaia, Diana; Hansen, Bryan T.; Ludtke, Steven J.; Bidzhieva, Bella; Makiya, Michelle; Agulto, Liane; Purcell, Robert H.; Chumakov, Konstantin

2013-01-01

Most structural information about poliovirus interaction with neutralizing antibodies was obtained in the 1980s in studies of mouse monoclonal antibodies. Recently we have isolated a number of human/chimpanzee anti-poliovirus antibodies and demonstrated that one of them, MAb A12, could neutralize polioviruses of both serotypes 1 and 2. This communication presents data on isolation of an additional cross-neutralizing antibody (F12) and identification of a previously unknown epitope on the surface of poliovirus virions. Epitope mapping was performed by sequencing of antibody-resistant mutants and by cryo-EM of complexes of virions with Fab fragments. The results have demonstrated that both cross-neutralizing antibodies bind the site located at the bottom of the canyon surrounding the fivefold axis of symmetry that was previously shown to interact with cellular poliovirus receptor CD155. However, the same antibody binds to serotypes 1 and 2 through different specific interactions. It was also shown to interact with type 3 poliovirus, albeit with about 10-fold lower affinity, insufficient for effective neutralization. Antibody interaction with the binding site of the cellular receptor may explain its broad reactivity and suggest that further screening or antibody engineering could lead to a universal antibody capable of neutralizing all three serotypes of poliovirus. PMID:24277851

Variants in MTNR1B influence fasting glucose levels

PubMed Central

Prokopenko, Inga; Langenberg, Claudia; Florez, Jose C; Saxena, Richa; Soranzo, Nicole; Thorleifsson, Gudmar; Loos, Ruth J F; Manning, Alisa K; Jackson, Anne U; Aulchenko, Yurii; Potter, Simon C; Erdos, Michael R; Sanna, Serena; Hottenga, Jouke-Jan; Wheeler, Eleanor; Kaakinen, Marika; Lyssenko, Valeriya; Chen, Wei-Min; Ahmadi, Kourosh; Beckmann, Jacques S; Bergman, Richard N; Bochud, Murielle; Bonnycastle, Lori L; Buchanan, Thomas A; Cao, Antonio; Cervino, Alessandra; Coin, Lachlan; Collins, Francis S; Crisponi, Laura; de Geus, Eco J C; Dehghan, Abbas; Deloukas, Panos; Doney, Alex S F; Elliott, Paul; Freimer, Nelson; Gateva, Vesela; Herder, Christian; Hofman, Albert; Hughes, Thomas E; Hunt, Sarah; Illig, Thomas; Inouye, Michael; Isomaa, Bo; Johnson, Toby; Kong, Augustine; Krestyaninova, Maria; Kuusisto, Johanna; Laakso, Markku; Lim, Noha; Lindblad, Ulf; Lindgren, Cecilia M; McCann, Owen T; Mohlke, Karen L; Morris, Andrew D; Naitza, Silvia; Orrù, Marco; Palmer, Colin N A; Pouta, Anneli; Randall, Joshua; Rathmann, Wolfgang; Saramies, Jouko; Scheet, Paul; Scott, Laura J; Scuteri, Angelo; Sharp, Stephen; Sijbrands, Eric; Smit, Jan H; Song, Kijoung; Steinthorsdottir, Valgerdur; Stringham, Heather M; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, André G; Voight, Benjamin F; Waterworth, Dawn; Wichmann, H-Erich; Willemsen, Gonneke; Witteman, Jacqueline C M; Yuan, Xin; Zhao, Jing Hua; Zeggini, Eleftheria; Schlessinger, David; Sandhu, Manjinder; Boomsma, Dorret I; Uda, Manuela; Spector, Tim D; Penninx, Brenda WJH; Altshuler, David; Vollenweider, Peter; Jarvelin, Marjo Riitta; Lakatta, Edward; Waeber, Gerard; Fox, Caroline S; Peltonen, Leena; Groop, Leif C; Mooser, Vincent; Cupples, L Adrienne; Thorsteinsdottir, Unnur; Boehnke, Michael; Barroso, Inês; Van Duijn, Cornelia; Dupuis, Josée; Watanabe, Richard M; Stefansson, Kari; McCarthy, Mark I; Wareham, Nicholas J; Meigs, James B; Abecasis, Gonçalo R

2009-01-01

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 = × 10−50) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 × 10−15). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 × 10−7) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 × 10−57) and GCK (rs4607517, P = 1.0 × 10−25) loci. PMID:19060907

Defending against pathogens – immunological priming and its molecular basis in a sea anemone, cnidarian

PubMed Central

Brown, Tanya; Rodriguez-Lanetty, Mauricio

2015-01-01

Cnidarians, in general, are long-lived organisms and hence may repeatedly encounter common pathogens during their lifespans. It remains unknown whether these early diverging animals possess some type of immunological reaction that strengthens the defense response upon repeated infections, such as that described in more evolutionary derived organisms. Here we show results that sea anemones that had previously encountered a pathogen under sub-lethal conditions had a higher survivorship during a subsequently lethal challenge than naïve anemones that encountered the pathogen for the first time. Anemones subjected to the lethal challenge two and four weeks after the sub-lethal exposure presented seven- and five-fold increases in survival, respectively, compared to the naïve anemones. However, anemones challenged six weeks after the sub-lethal exposure showed no increase in survivorship. We argue that this short-lasting priming of the defense response could be ecologically relevant if pathogen encounters are restricted to short seasons characterized by high stress. Furthermore, we discovered significant changes in proteomic profiles between naïve sea anemones and those primed after pathogen exposure suggesting a clear molecular signature associated with immunological priming in cnidarians. Our findings reveal that immunological priming may have evolved much earlier in the tree of life than previously thought. PMID:26628080

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

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Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

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Integration of molecular typing results into tuberculosis surveillance in Germany—A pilot study

PubMed Central

Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

2017-01-01

An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age <15 years (OR = 4.96, 95% CI: 1.69–14.55) and being born in Germany (OR = 2.01, 95% CI: 1.44–2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48–98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control. PMID:29166403

Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

PubMed

Andrés, Marta; Göhring-Zwacka, Elke; Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

2017-01-01

An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age <15 years (OR = 4.96, 95% CI: 1.69-14.55) and being born in Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control.

Biochar type and factors affecting N transformation, ammonia volatilization, and nitrous oxide emissions

USDA-ARS?s Scientific Manuscript database

Soil amendment with biochar has shown the potential to improve nitrogen (N) availability for plant uptake and reduce environmental losses via ammonia (NH3) and nitrous oxide (N2O) emissions. There are still many unknowns on how biochar type and soil conditions affect N dynamics and processes associa...

Campylobacter fetus subspecies contain conserved type IV secretion systems on multiple genomic islands and plasmids

USDA-ARS?s Scientific Manuscript database

The features contributing to the differences in pathogenicity of the C. fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode type IV secretion system (T4SS) and fic-domain (filamentation induced by cyclic AMP) proteins. In the genomes of ...

Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations

USDA-ARS?s Scientific Manuscript database

Rater reproducibility of the Bristol Stool Form Scale (BSFS), which categorizes stools into one of seven types, is unknown. We sought to determine reliability and agreement by individual stool type and when responses are categorized by Rome III clinical designation as normal or abnormal (constipatio...

Quantum Teleportation of a Two Qubit State Using GHZ- Like State

NASA Astrophysics Data System (ADS)

Nandi, Kaushik; Mazumdar, Chandan

2014-04-01

Recently Yang et al. (Int. J. Theor. Phys. 48:516, 2009) had shown that using a particular type of GHZ- Like state as quantum channel, it is possible to teleport an arbitrary unknown qubit. We investigate this channel for the teleportation of a particular type of two qubit state.

Variations in Both-Addends-Unknown Problems

ERIC Educational Resources Information Center

Champagne, Zachary M.; Schoen, Robert; Riddell, Claire M.

2014-01-01

Early elementary school students are expected to solve twelve distinct types of word problems. A math researcher and two teachers pose a structure for thinking about one problem type that has not been studied as closely as the other eleven. In this article, the authors share some of their discoveries with regard to the variety of…

An inulin-type fructan enhances calcium absorption primarily via an effect on colonic absorption in humans

USDA-ARS?s Scientific Manuscript database

Calcium absorption efficiency and bone mineral mass are increased in adolescents who regularly consume inulin-type fructans (ITF). The mechanism of action in increasing absorption is unknown but may be related to increased colonic calcium absorption. We conducted a study in young adults designed to ...

Emotional Creativity and Real-Life Involvement in Different Types of Creative Leisure Activities

ERIC Educational Resources Information Center

Trnka, Radek; Zahradnik, Martin; Kuška, Martin

2016-01-01

The role of emotional creativity in practicing creative leisure activities and in the preference of college majors remains unknown. This study aims to explore how emotional creativity measured by the Emotional Creativity Inventory (ECI; Averill, 1999) is interrelated with the real-life involvement in different types of specific creative leisure…

Career Goals and Retention-Related Factors among College Freshmen

ERIC Educational Resources Information Center

Hull-Blanks, Elva; Robinson Kurpius, Sharon E.; Befort, Christie; Sollenberger, Sonja; Nicpon, Megan Foley; Huser, Laura

2005-01-01

The relationships of four types of career goals (job related, school related, value related, and unknown) with factors of school retention, academic performance, self-esteem, educational self-efficacy, and school and career commitment are studied among 401 first-semester college freshmen. Differences in types of goals based on gender are also…

A new approach to aid the characterisation and identification of metabolites of a model drug; partial isotope enrichment combined with novel formula elucidation software.

PubMed

Hobby, Kirsten; Gallagher, Richard T; Caldwell, Patrick; Wilson, Ian D

2009-01-01

This work describes the identification of 'isotopically enriched' metabolites of 4-cyanoaniline using the unique features of the software package 'Spectral Simplicity'. The software is capable of creating the theoretical mass spectra for partially isotope-enriched compounds, and subsequently performing an elemental composition analysis to give the elemental formula for the 'isotopically enriched' metabolite. A novel mass spectral correlation method, called 'FuzzyFit', was employed. 'FuzzyFit' utilises the expected experimental distribution of errors in both mass accuracy and isotope pattern and enables discrimination between statistically probable and improbable candidate formulae. The software correctly determined the molecular formulae of ten previously described metabolites of 4-cyanoaniline confirming the technique of partial isotope enrichment can produce results analogous to standard methodologies. Six previously unknown species were also identified, based on the presence of the unique 'designer' isotope ratio. Three of the unknowns were tentatively identified as N-acetylglutamine, O-methyl-N acetylglucuronide and a putative fatty acid conjugate. The discovery of a significant number of unknown species of a model drug with a comprehensive history of investigation highlights the potential for enhancement to the analytical process by the use of 'designer' isotope ratio compounds. The 'FuzzyFit' methodology significantly aided the elucidation of candidate formulae, by provision of a vastly simplified candidate formula data set. Copyright (c) 2008 John Wiley & Sons, Ltd.

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

PubMed Central

Ramos, Caroline L.; Fonseca, Fernanda L.; Rodrigues, Jessica; Guimarães, Allan J.; Cinelli, Leonardo P.; Miranda, Kildare; Nimrichter, Leonardo; Casadevall, Arturo; Travassos, Luiz R.

2012-01-01

In prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogen Cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. The structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. In this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection by C. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on the N-acetyl amino group of chitin. Carboxyl and O-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-α). These results indicate that association of chitin-derived structures with GXM through their N-acetyl amino groups generates glycan complexes with previously unknown properties. PMID:22562469

An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

PubMed

Bhagavat, Raghu; Sankar, Santhosh; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2018-03-06

Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships. To bridge this gap, we detect pockets in proteins of known 3D structures, using computational techniques. This augmented pocketome (PocketDB) consists of 249,096 pockets, which is about seven times larger than what is currently known. We deduce possible ligand associations for about 46% of the newly identified pockets. The augmented pocketome, when subjected to clustering based on similarities among pockets, yielded 2,161 site types, which are associated with 1,037 ligand types, together providing fold-site-type-ligand-type associations. The PocketDB resource facilitates a structure-based function annotation, delineation of the structural basis of ligand recognition, and provides functional clues for domains of unknown functions, allosteric proteins, and druggable pockets. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human Cytomegalovirus Replication Is Inhibited by the Autophagy-Inducing Compounds Trehalose and SMER28 through Distinctively Different Mechanisms.

PubMed

Clark, Alex E; Sabalza, Maite; Gordts, Philip L S M; Spector, Deborah H

2018-03-15

Human cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously reported that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles and that debris, including debris with an appearance consistent with that of abnormal virions, is present in multivesicular bodies. Trehalose treatment increased the levels of Rab7, a protein required for lysosomal biogenesis and fusion, and slightly decreased the levels of Rab11, which is associated with recycling endosomes. We also present evidence that trehalose can promote autophagy without altering cellular glucose uptake. We show that SMER28 inhibits HCMV at the level of early protein production and interferes with viral genome replication in a cell type-dependent fashion. Finally, we show that SMER28 treatment does not cause the vacuolation, acidification, or redistribution of Rab7 associated with trehalose treatment and shows only a modest and cell type-dependent effect on autophagy. We propose a model in which the reciprocal effects on Rab7 and Rab11 induced by trehalose contribute to the redirection of enveloped virions from the plasma membrane to acidified compartments and subsequent degradation, and SMER28 treatment results in decreased expression levels of early and late proteins, reducing the number of virions produced without the widespread vacuolation characteristic of trehalose treatment. IMPORTANCE There is a need for less toxic HCMV antiviral drugs, and modulation of autophagy to control viral infection is a new strategy that takes advantage of virus dependence on autophagy inhibition. The present study extends our previous work on trehalose by showing a possible mechanism of action and introduces another autophagy-inducing compound, SMER28, that is effective against HCMV in several cell types. The mechanism by which trehalose induces autophagy is currently unknown, although our data show that trehalose does not inhibit cellular glucose uptake in cells relevant for HCMV replication but instead alters virion degradation by promoting acidic vacuolization. The comparison of our cell types and those used by others highlights the cell type-dependent nature of studying autophagy. Copyright © 2018 American Society for Microbiology.

Substitutions of dairy product intake and risk of stroke: a Danish cohort study.

PubMed

Laursen, Anne Sofie Dam; Dahm, Christina Catherine; Johnsen, Søren Paaske; Tjønneland, Anne; Overvad, Kim; Jakobsen, Marianne Uhre

2018-02-01

Low fat dairy products are part of dietary guidelines to prevent stroke. However, epidemiological evidence is inconclusive with regard to the association between dairy products and stroke. We therefore investigated associations for substitutions between dairy product subgroups and risk of total stroke and stroke subtypes. We included 55,211 Danish men and women aged 50-64 years without previous stroke. Baseline diet was assessed by a food frequency questionnaire. Cases were identified through a national register and subsequently verified. The associations were analyzed using Cox proportional hazard regression. During a median follow-up of 13.4 years, we identified 2272 strokes, of which 1870 were ischemic (318 large artery atherosclerotic, 839 lacunar, 102 cardioembolic, 98 other determined types, 513 of unknown type), 389 were hemorrhages (273 intracerebral, 116 subarachnoid) and 13 of unknown etiology. Substitution of semi-skimmed fermented milk or cheese for whole-fat fermented milk was associated with a higher rate of ischemic stroke [semi-skimmed fermented milk: hazard ratio (HR) = 1.20 (95% confidence interval (CI) 0.99-1.45), cheese: HR = 1.14 (95% CI 0.98-1.31) per serving/day substituted] and substitutions of whole-fat fermented milk for low-fat milk, whole-fat milk or buttermilk were associated with a lower rate [low-fat milk: HR = 0.85 (95% CI 0.74-0.99), whole-fat milk: HR = 0.84 (95% CI 0.71-0.98) and buttermilk: HR = 0.83 (95% CI 0.70-0.99)]. We observed no associations for substitutions between dairy products and hemorrhagic stroke. Our results suggest that intake of whole-fat fermented milk as a substitution for semi-skimmed fermented milk, cheese, buttermilk or milk, regardless of fat content, is associated with a lower rate of ischemic stroke.

Understanding the brain through its spatial structure

NASA Astrophysics Data System (ADS)

Morrison, Will Zachary

The spatial location of cells in neural tissue can be easily extracted from many imaging modalities, but the information contained in spatial relationships between cells is seldom utilized. This is because of a lack of recognition of the importance of spatial relationships to some aspects of brain function, and the reflection in spatial statistics of other types of information. The mathematical tools necessary to describe spatial relationships are also unknown to many neuroscientists, and biologists in general. We analyze two cases, and show that spatial relationships can be used to understand the role of a particular type of cell, the astrocyte, in Alzheimer's disease, and that the geometry of axons in the brain's white matter sheds light on the process of establishing connectivity between areas of the brain. Astrocytes provide nutrients for neuronal metabolism, and regulate the chemical environment of the brain, activities that require manipulation of spatial distributions (of neurotransmitters, for example). We first show, through the use of a correlation function, that inter-astrocyte forces determine the size of independent regulatory domains in the cortex. By examining the spatial distribution of astrocytes in a mouse model of Alzheimer's Disease, we determine that astrocytes are not actively transported to fight the disease, as was previously thought. The paths axons take through the white matter determine which parts of the brain are connected, and how quickly signals are transmitted. The rules that determine these paths (i.e. shortest distance) are currently unknown. By measurement of axon orientation distributions using three-point correlation functions and the statistics of axon turning and branching, we reveal that axons are restricted to growth in three directions, like a taxicab traversing city blocks, albeit in three-dimensions. We show how geometric restrictions at the small scale are related to large-scale trajectories. Finally we discuss the implications of this finding for experimental and theoretical connectomics.

Distributed subterranean exploration and mapping with teams of UAVs

NASA Astrophysics Data System (ADS)

Rogers, John G.; Sherrill, Ryan E.; Schang, Arthur; Meadows, Shava L.; Cox, Eric P.; Byrne, Brendan; Baran, David G.; Curtis, J. Willard; Brink, Kevin M.

2017-05-01

Teams of small autonomous UAVs can be used to map and explore unknown environments which are inaccessible to teams of human operators in humanitarian assistance and disaster relief efforts (HA/DR). In addition to HA/DR applications, teams of small autonomous UAVs can enhance Warfighter capabilities and provide operational stand-off for military operations such as cordon and search, counter-WMD, and other intelligence, surveillance, and reconnaissance (ISR) operations. This paper will present a hardware platform and software architecture to enable distributed teams of heterogeneous UAVs to navigate, explore, and coordinate their activities to accomplish a search task in a previously unknown environment.

PROGNOSTIC VALUE OF SHAPE-DESCRIPTIVE FACTORS FOR THE PROGRESSION OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PubMed

Pfau, Maximilian; Lindner, Moritz; Goerdt, Lukas; Thiele, Sarah; Nadal, Jennifer; Schmid, Matthias; Schmitz-Valckenberg, Steffen; Sadda, SriniVas R; Holz, Frank G; Fleckenstein, Monika

2018-05-16

To systematically compare the prognostic value of multiple shape-descriptive factors in the natural course of the disease. A total of 296 eyes of 201 patients (female patients 130; mean age: 72.2 ± 13.08 years) with a median follow-up of 2.38 years from 2 prospective, noninterventional natural history studies (Fundus-Autofluorescence-in-Age-related-Macular-Degeneration [clinicaltrials.gov identifier NCT00393692], Directional-Spread-in-Geographic-Atrophy [NCT02051998]) were included in the analysis. Serial fundus autofluorescence images were annotated using semiautomated image analysis software to determine the lesion area, circularity, perimeter, and caliper diameters. These variables and the fundus autofluorescence phenotype were evaluated for prediction of the future square root progression rates using linear mixed-effects models. For the combined model, leave-one-out cross validation on patient level (Scenario 1: previously unknown patient) resulted in a goodness-to-fit (R value) of 0.244 and leave-one-out cross validation on visit level (Scenario 2: previous observation of the patient) in a R value of 0.391. This indicated that shape-descriptive factors could explain 24.4% of the variance in geographic atrophy progression in previously unknown patients and 39.1% in patients with previous observation. These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.

Metastatic brain tumor

MedlinePlus

... the brain, the type of tissue involved, the original location of the tumor, and other factors. In rare cases, doctors do not know the original location. This is called cancer of unknown primary ( ...

Seeing the Body Distorts Tactile Size Perception

ERIC Educational Resources Information Center

Longo, Matthew R.; Sadibolova, Renata

2013-01-01

Vision of the body modulates somatosensation, even when entirely non-informative about stimulation. For example, seeing the body increases tactile spatial acuity, but reduces acute pain. While previous results demonstrate that vision of the body modulates somatosensory sensitivity, it is unknown whether vision also affects metric properties of…

Diesel particle-induced transcriptional expression of P21 involves activation of EGFR, SRC, and STAT3

EPA Science Inventory

Exposure to diesel exhaust particles (DEP) has been associated with adverse health outcomes such as inflammation, adjuvancy, and mutagenesis. However, the molecular mechanisms by which DEP inhalation exerts these effects are still largely unknown. We previously reported that expo...

Magical Thinking in Narratives of Adolescent Cutters

ERIC Educational Resources Information Center

Gregory, Robert J.; Mustata, Georgian T.

2012-01-01

Adolescents sometimes cut themselves to relieve distress; however, the mechanism is unknown. Previous studies have linked self-injury to deficits in processing emotions symbolically through language. To investigate expressive language of adolescent cutters, the authors analyzed 100 narratives posted on the Internet. Most narratives (n = 66)…

Orthographic Facilitation in Chinese Spoken Word Recognition: An ERP Study

ERIC Educational Resources Information Center

Zou, Lijuan; Desroches, Amy S.; Liu, Youyi; Xia, Zhichao; Shu, Hua

2012-01-01

Orthographic influences in spoken word recognition have been previously examined in alphabetic languages. However, it is unknown whether orthographic information affects spoken word recognition in Chinese, which has a clean dissociation between orthography (O) and phonology (P). The present study investigated orthographic effects using event…

Description of Lutzomyia (Trichophoromyia) pabloi n. sp. and the female of L. howardi (Diptera: Psychodidae) from Colombia.

PubMed

Barreto, Mauricio; Burbano, María Elena; Young, David G

2002-07-01

A new Lutzomyia species in the subgenus Trichophoromyia, L. pabloi, is described and illustrated. A description of the previously unknown female of L. howardi Young is also presented. These specimens were captured in the Amazon region of Colombia.

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

PubMed Central

Koch, Janne; Hau, Jann; Pravsgaard Christensen, Jan; Elvang Jensen, Henrik; Bagge Hansen, Morten; Rieneck, Klaus

2013-01-01

Few experimental models are available for the study of natural resistance to cancer. One of them is the SR/CR (spontaneous regression/complete resistance) mouse model in which natural resistance to a variety of cancer types appeared to be inherited in SR/CR strains of BALB/c and C57BL/6 mice. The genetic, cellular, and molecular effector mechanisms in this model are largely unknown, but cells from the innate immune system may play a significant role. In contrast to previous observations, the cancer resistance was limited to S180 sarcoma cancer cells. We were unable to confirm previous observations of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant BALB/c mice as well as C57BL/6 mice after depletion of both CD4+/CD8+ leukocytes and B-cells from SR/CR mice. In the responding recipient mice, the cancer disappeared gradually following infiltration of a large number of polymorphonuclear granulocytes and remarkably few lymphocytes in the remaining tumor tissues. This study confirmed that the in vivo growth and spread of cancer cells depend on a complex interplay between the cancer cells and the host organism. Here, hereditary components of the immune system, most likely the innate part, played a crucial role in this interplay and lead to resistance to a single experimental cancer type. The fact that leukocytes depleted of both CD4+/CD8+ and B cells from the cancer resistant donor mice could be transferred to inhibit S180 cancer cell growth in susceptible recipient mice support the vision of an efficient and adverse event free immunotherapy in future selected cancer types. PMID:23555858

Gender Differences in Hiccup Patients: Analysis of Published Case Reports and Case-Control Studies.

PubMed

Lee, Gyeong-Won; Kim, Rock Bum; Go, Se Il; Cho, Hyun Seop; Lee, Seung Jun; Hui, David; Bruera, Eduardo; Kang, Jung Hun

2016-02-01

Although sporadic male predominance in hiccup patients has been reported, the association between gender differences and triggering factors has rarely been evaluated in patients with hiccups. The aim of this study was to investigate whether gender differences exist in hiccup patients by analyzing all previously published hiccup literature containing gender and etiology information. Published literature on this topic was identified using a standardized search strategy in the PubMed, SCOPUS, and CINAHL electronic databases. The literature search included studies published from January 1990 to December 2013. Searches were limited to English-language publications. Of 476 identified studies, 318 studies were eligible including eight case-control studies that contained nonhiccup control groups. Triggering factors for hiccups were categorized into two types: central nervous system (CNS) and non-CNS causes. Odds ratios (ORs) were calculated for the eight case-control studies and event rates for the other studies by meta-analysis. In addition, gender differences and mean ages were analyzed for the case studies. Pooled OR was 2.42 (95% confidence interval [CI] 1.40-4.17) with inclination for male predominance. Subgroup analysis by cause showed clear male predominance in the non-CNS type with OR of 11.72 (95% CI 3.16-43.50), whereas indistinct in the CNS type with OR of 1.74 (95% CI 0.95-3.16). Of the remaining 310 studies with 864 patients, previous findings were consistent. Male predominance was consistent in non-CNS (85.1%, 95% CI 78.2-90.2) and unknown origin (82.2%, 95% CI 75.8-87.2) patients, whereas mitigating the sex discrepancy in those with CNS origin (65.8%, 95% CI 53.1-76.5). We demonstrated male predominance in hiccup patients. This gender difference for hiccups was more pronounced in patients with non-CNS causes, whereas indistinct in patients with CNS causes. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction.

PubMed

Goyal, Akash; Yu, Francois T H; Tenwalde, Mathea G; Chen, Xucai; Althouse, Andrew; Villanueva, Flordeliza S; Pacella, John J

2017-07-01

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi. Venous- and arterial-type microthrombi were infused onto a mesh with 40-μm pores to simulate MVO. Pulsed US (1 MHz) was delivered with inertial cavitation (IC) (1.0 MPa, 1000 cycles, 0.33 Hz) and stable cavitation (SC) US (0.23 MPa, 20% duty cycle, 0.33 Hz) regimes while MB suspension (2 × 10 6  MBs/mL) was infused. The efficacy of sonoreperfusion with these parameters was tested with and without tPA. Sonoreperfusion efficacy was significantly greater for IC + tPA compared with tPA alone, IC, SC and SC + tPA, suggesting lytic synergism between tPA and US for both venous- and arterial-type microthrombi. In contrast to our previous in vitro studies using 1.5 MPa at 5000 US cycles without tPA, the IC regime employed herein used 90% less US energy. These findings suggest an IC regime can be used with tPA synergistically to achieve a high degree of fibrinolysis for both thrombus types. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Patterns of call communication between group-housed zebra finches change during the breeding cycle

PubMed Central

Gill, Lisa F; Goymann, Wolfgang; Ter Maat, Andries; Gahr, Manfred

2015-01-01

Vocal signals such as calls play a crucial role for survival and successful reproduction, especially in group-living animals. However, call interactions and call dynamics within groups remain largely unexplored because their relation to relevant contexts or life-history stages could not be studied with individual-level resolution. Using on-bird microphone transmitters, we recorded the vocalisations of individual zebra finches (Taeniopygia guttata) behaving freely in social groups, while females and males previously unknown to each other passed through different stages of the breeding cycle. As birds formed pairs and shifted their reproductive status, their call repertoire composition changed. The recordings revealed that calls occurred non-randomly in fine-tuned vocal interactions and decreased within groups while pair-specific patterns emerged. Call-type combinations of vocal interactions changed within pairs and were associated with successful egg-laying, highlighting a potential fitness relevance of calling dynamics in communication systems. DOI: http://dx.doi.org/10.7554/eLife.07770.001 PMID:26441403

Multiple exaggerated weapon morphs: a novel form of male polymorphism in harvestmen.

PubMed

Painting, Christina J; Probert, Anna F; Townsend, Daniel J; Holwell, Gregory I

2015-11-06

Alternative reproductive tactics in animals are commonly associated with distinct male phenotypes resulting in polymorphism of sexually selected weapons such as horns and spines. Typically, morphs are divided between small (unarmed) and large (armed) males according to one or more developmental thresholds in association with body size. Here, we describe remarkable weapon trimorphism within a single species, where two exaggerated weapon morphs and a third morph with reduced weaponry are present. Male Pantopsalis cheliferoides harvestmen display exaggerated chelicerae (jaws) which are highly variable in length among individuals. Across the same body size spectrum, however, some males belong to a distinct second exaggerated morph which possesses short, broad chelicerae. Multiple weapon morphs in a single species is a previously unknown phenomenon and our findings have significant implications for understanding weapon diversity and maintenance of polymorphism. Specifically, this species will be a valuable model for testing how weapons diverge by being able to test directly for the circumstances under which a certain weapon type is favoured and how weapon shape relates to performance.

Supercritical carbon dioxide extraction of electrolyte from spent lithium ion batteries and its characterization by gas chromatography with chemical ionization

NASA Astrophysics Data System (ADS)

Mönnighoff, Xaver; Friesen, Alex; Konersmann, Benedikt; Horsthemke, Fabian; Grützke, Martin; Winter, Martin; Nowak, Sascha

2017-06-01

The aging products of the electrolyte from a commercially available state-of-the-art 18650-type cell were investigated. During long term cycling a huge difference in their performance and lifetime at different temperatures was observed. By interpretation of a strong capacity fading of cells cycled at 20 °C compared to cells cycled at 45 °C a temperature depending aging mechanism was determined. To investigate the influence of the electrolyte on this fading, the electrolyte was extracted by supercritical fluid extraction (SFE) and then analyzed by gas chromatography (GC) with electron impact (EI) ionization and mass selective detection. To obtain more information with regard to the identification of unknown decomposition products further analysis with positive chemical ionization (PCI) and negative chemical ionization (NCI) was performed. 17 different volatile organic aging products were detected and identified. So far, seven of them were not yet known in literature and several formation pathways were postulated taking previously published literature into account.

Pan-Cancer Analysis of Mutation Hotspots in Protein Domains.

PubMed

Miller, Martin L; Reznik, Ed; Gauthier, Nicholas P; Aksoy, Bülent Arman; Korkut, Anil; Gao, Jianjiong; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

2015-09-23

In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain mutation analysis also sharpens the functional interpretation of the impact of mutations, as domains more succinctly embody function than entire genes. By mapping mutations in 22 different tumor types to equivalent positions in multiple sequence alignments of domains, we confirm well-known functional mutation hotspots, identify uncharacterized rare variants in one gene that are equivalent to well-characterized mutations in another gene, detect previously unknown mutation hotspots, and provide hypotheses about molecular mechanisms and downstream effects of domain mutations. With the rapid expansion of cancer genomics projects, protein domain hotspot analysis will likely provide many more leads linking mutations in proteins to the cancer phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

PubMed

Manning, Alisa K; Hivert, Marie-France; Scott, Robert A; Grimsby, Jonna L; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E; Navarro, Pau; Perry, John R B; Rasmussen-Torvik, Laura J; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J; Tanaka, Toshiko; van Duijn, Cornelia M; An, Ping; de Andrade, Mariza; Andrews, Jeanette S; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S; Beilby, John P; Bellis, Claire; Bergman, Richard N; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L; Boomsma, Dorret I; Borecki, Ingrid B; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S; Clarke, Robert; Collins, Francis S; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo-Riitta; Jhun, Min A; Johnson, Paul C D; Jukema, J Wouter; Jula, Antti; Kao, W H; Kaprio, Jaakko; Kardia, Sharon L R; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J F; Luan, Jian'an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K E; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L; Mooser, Vincent; Morken, Mario A; Miljkovic, Iva; Narisu, Narisu; O'Connell, Jeff; Ong, Ken K; Oostra, Ben A; Palmer, Lyle J; Palotie, Aarno; Pankow, James S; Peden, John F; Pedersen, Nancy L; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P; Province, Michael A; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R; Sijbrands, Eric J G; Siscovick, David S; Smit, Johannes H; Small, Kerrin S; Smith, Nicholas L; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V; Swift, Amy J; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H; Willems, Sara M; Willemsen, Gonneke; Wilson, James F; Witteman, Jacqueline C M; Wright, Alan F; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J; McCarthy, Mark I; Barroso, Ines; Watanabe, Richard M; Florez, Jose C; Dupuis, Josée; Meigs, James B; Langenberg, Claudia

2012-05-13

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins.

PubMed

Mayr, Gerald; De Pietri, Vanesa L; Paul Scofield, R

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

Synthesis and properties of acetamidinium salts

PubMed Central

2011-01-01

Background Acetamidines are starting materials for synthesizing many chemical substances, such as imidazoles, pyrimidines and triazines, which are further used for biochemically active compounds as well as energetic materials. The aim of this study was to synthesise and characterise a range of acetamidinium salts in order to overcome the inconvenience connected with acetamidinium chloride, which is the only commercially available acetamidinium salt. Results Acetamidinium salts were synthesised and characterised by elemental analysis, mass spectrometry, NMR and - in the case of energetic salts - DTA. The structures of previously unknown acetamidinium salts were established by X-ray diffraction analysis. Hygroscopicities in 90% humidity of eight acetamidinium salts were evaluated. Conclusions The different values of hygroscopicity are corroborated by the structures determined by X-ray analysis. The acetamidinium salts with 2D layered structures (acetamidinium nitrate, formate, oxalate and dinitromethanide) show a lack of hygroscopicity, and the compounds with 3D type of structure (acetamidinium chloride, acetate, sulphate and perchlorate) and possessing rather large cavities are quite hygroscopic. PMID:22152129

A stable quasi-periodic 4.18-d oscillation and mysterious occultations in the 2011 MOST light-curve of TW Hya

NASA Astrophysics Data System (ADS)

Siwak, Michal; Rucinski, Slavek M.; Matthews, Jaymie M.; Guenther, David B.; Kuschnig, Rainer; Moffat, Anthony F. J.; Rowe, Jason F.; Sasselov, Dimitar; Weiss, Werner W.

2014-10-01

We present an analysis of the 2011 photometric observations of TW Hya by the MOST satellite; this is the fourth continuous series of this type. The large-scale light variations are dominated by a strong, quasi-periodic 4.18-d oscillation with superimposed, apparently chaotic flaring activity. The former is probably produced by stellar rotation with one large hotspot created by a stable accretion funnel, while the latter may be produced by small hotspots, created at moderate latitudes by unstable accretion tongues. A new, previously unnoticed feature is a series of semiperiodic, well-defined brightness dips of unknown nature, of which 19 were observed during 43 d of our nearly continuous observations. Re-analysis of the 2009 MOST light-curve revealed the presence of three similar dips. On the basis of recent theoretical results, we tentatively conclude that the dips may represent occultations of the small hotspots created by unstable accretion tongues by hypothetical optically thick clumps of dust.

Interatomic Coulombic decay cascades in multiply excited neon clusters

PubMed Central

Nagaya, K.; Iablonskyi, D.; Golubev, N. V.; Matsunami, K.; Fukuzawa, H.; Motomura, K.; Nishiyama, T.; Sakai, T.; Tachibana, T.; Mondal, S.; Wada, S.; Prince, K. C.; Callegari, C.; Miron, C.; Saito, N.; Yabashi, M.; Demekhin, Ph. V.; Cederbaum, L. S.; Kuleff, A. I.; Yao, M.; Ueda, K.

2016-01-01

In high-intensity laser light, matter can be ionized by direct multiphoton absorption even at photon energies below the ionization threshold. However on tuning the laser to the lowest resonant transition, the system becomes multiply excited, and more efficient, indirect ionization pathways become operative. These mechanisms are known as interatomic Coulombic decay (ICD), where one of the species de-excites to its ground state, transferring its energy to ionize another excited species. Here we show that on tuning to a higher resonant transition, a previously unknown type of interatomic Coulombic decay, intra-Rydberg ICD occurs. In it, de-excitation of an atom to a close-lying Rydberg state leads to electron emission from another neighbouring Rydberg atom. Moreover, systems multiply excited to higher Rydberg states will decay by a cascade of such processes, producing even more ions. The intra-Rydberg ICD and cascades are expected to be ubiquitous in weakly-bound systems exposed to high-intensity resonant radiation. PMID:27917867

GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs).

PubMed

Uehara, Eriko; Hokazono, Hideki; Hida, Mariko; Sasaki, Takako; Yoshioka, Hidekatsu; Matsuo, Noritaka

2017-06-01

The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner. Additionally, the expression of fibrillin-1, fibrillin-2, and fibulin-5/DANCE, but not lysyl oxidase and latent transforming factor-β-binding protein 4, were also significantly increased in HDFs. Finally, immunohistochemical analysis confirmed that treatment with GABA dramatically increased the formation of elastic fibers in HDFs. Taken together, our results showed that GABA improves skin elasticity in HDFs by upregulating elastin synthesis and elastin fiber formation.

Three-dimensional aspects of the shrinking phenomenon of ArF resist

NASA Astrophysics Data System (ADS)

Laufer, Ido; Eytan, Giora E.; Dror, Ophir

2002-07-01

Previous studies of the interaction of electron beams with different types of ArF resists have shown the undesired phenomenon of the resist shrinkage. The lateral component of this shrinkage has been detected and quantified easily by SEM CD measurements. However, the vertical extent of this phenomenon has to date remained unknown. In this work we present measurements of the changes in height and sidewall angles of an ArF line by using a new e-beam tilting ability of the Vera SEM 3D. The 3D measurement results show that the height of the line shrinks in similar proportions to the top and bottom CDs, with a difference in the magnitude. Due to higher penetration depth of the e-beam on the top of the line than on the sidewall, the vertical shrinkage reaches steady state more rapidly than the lateral shrinkage. We also found a slight reduction in sidewall angle, which is less than one degree even under high e-beam exposure.

Vinpocetine inhibits breast cancer cells growth in vitro and in vivo.

PubMed

Huang, Er-Wen; Xue, Sheng-Jiang; Zhang, Zheng; Zhou, Jia-Guo; Guan, Yong-Yuan; Tang, Yong-Bo

2012-10-01

Vinpocetine is a clinically used drug for cerebrovascular disorders as well as age-related memory impairment. Of note, vinpocetine has been recently identified as a novel anti-inflammatory agent; however, its effects on cancer cells remain to be investigated. In the present study, we found that vinpocetine potently inhibited proliferation of multiple types of human breast cancer cells by arresting cell cycle at G(0)/G(1) phase. It was also revealed that vinpocetine induced cell apoptosis via mitochondria-dependent pathway. Moreover, vinpocetine impaired the migration of the strongly metastatic cell MDA-MB-231. In xenograft model of human breast cancer in nude mice, both systemic and local administration of vinpocetine significantly suppressed the tumor growth without observed toxicity. Interestingly, vinpocetine markedly attenuated the activation of Akt and signal transducer and activator of transcription factor 3 (STAT3), but had no effects on MAP kinases pathways. Collectively, the data suggest that vinpocetine possesses significant yet previously unknown antitumor properties that may be utilized for the treatment of breast cancer.

Trapping toxins within lipid droplets is a resistance mechanism in fungi

PubMed Central

Chang, Wenqiang; Zhang, Ming; Zheng, Sha; Li, Ying; Li, Xiaobin; Li, Wei; Li, Gang; Lin, Zhaomin; Xie, Zhiyu; Zhao, Zuntian; Lou, Hongxiang

2015-01-01

Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. However, the role of LDs in resistance to toxins in fungi remains largely unknown. Here, we show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. We found that an endolichenic fungus that generates phototoxic perylenequinones (PQs) trapped the PQs inside LDs. Using a model that incorporates the fungicidal action of hypocrellin A (HA), a PQ derivative, we showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery. PMID:26463663

Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain

PubMed Central

Okamura-Oho, Yuko; Shimokawa, Kazuro; Nishimura, Masaomi; Takemoto, Satoko; Sato, Akira; Furuichi, Teiichi; Yokota, Hideo

2014-01-01

Using a recently invented technique for gene expression mapping in the whole-anatomy context, termed transcriptome tomography, we have generated a dataset of 36,000 maps of overall gene expression in the adult-mouse brain. Here, using an informatics approach, we identified a broad co-expression network that follows an inverse power law and is rich in functional interaction and gene-ontology terms. Our framework for the integrated analysis of expression maps and graphs of co-expression networks revealed that groups of combinatorially expressed genes, which regulate cell differentiation during development, were present in the adult brain and each of these groups was associated with a discrete cell types. These groups included non-coding genes of unknown function. We found that these genes specifically linked developmentally conserved groups in the network. A previously unrecognized robust expression pattern covering the whole brain was related to the molecular anatomy of key biological processes occurring in particular areas. PMID:25382412

Numerical approximation abilities correlate with and predict informal but not formal mathematics abilities

PubMed Central

Libertus, Melissa E.; Feigenson, Lisa; Halberda, Justin

2013-01-01

Previous research has found a relationship between individual differences in children’s precision when nonverbally approximating quantities and their school mathematics performance. School mathematics performance emerges from both informal (e.g., counting) and formal (e.g., knowledge of mathematics facts) abilities. It remains unknown whether approximation precision relates to both of these types of mathematics abilities. In the present study we assessed the precision of numerical approximation in 85 3- to 7-year-old children four times over a span of two years. Additionally, at the last time point, we tested children’s informal and formal mathematics abilities using the Test of Early Mathematics Ability (TEMA-3; Ginsburg & Baroody, 2003). We found that children’s numerical approximation precision correlated with and predicted their informal, but not formal, mathematics abilities when controlling for age and IQ. These results add to our growing understanding of the relationship between an unlearned, non-symbolic system of quantity representation and the system of mathematical reasoning that children come to master through instruction. PMID:24076381

Ribosome protection by antibiotic resistance ATP-binding cassette protein.

PubMed

Su, Weixin; Kumar, Veerendra; Ding, Yichen; Ero, Rya; Serra, Aida; Lee, Benjamin Sian Teck; Wong, Andrew See Weng; Shi, Jian; Sze, Siu Kwan; Yang, Liang; Gao, Yong-Gui

2018-05-15

The ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer resistance to ribosome-targeting antibiotics through a yet unknown mechanism. Among them, MsrE has been implicated in macrolide resistance. Here, we report the cryo-EM structure of ATP form MsrE bound to the ribosome. Unlike previously characterized ribosomal protection proteins, MsrE is shown to bind to ribosomal exit site. Our structure reveals that the domain linker forms a unique needle-like arrangement with two crossed helices connected by an extended loop projecting into the peptidyl-transferase center and the nascent peptide exit tunnel, where numerous antibiotics bind. In combination with biochemical assays, our structure provides insight into how MsrE binding leads to conformational changes, which results in the release of the drug. This mechanism appears to be universal for the ABC-F type ribosome protection proteins. Copyright © 2018 the Author(s). Published by PNAS.

Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations

PubMed Central

Sun, Jiying; Shi, Lin; Kinomura, Aiko; Fukuto, Atsuhiko; Horikoshi, Yasunori; Oma, Yukako; Harata, Masahiko; Ikura, Masae; Ikura, Tsuyoshi; Kanaar, Roland

2018-01-01

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. PMID:29759113

A rare genetic disorder causing persistent severe neonatal hypoglycaemia the diagnostic workup.

PubMed

Francescato, Gaia; Salvatoni, Alessandro; Persani, Luca; Agosti, Massimo

2012-07-19

We report a case of familial glucocorticoid deficiency (FGD), a rare genetic autosomal-recessive disorder with typical hyperpigmentation of the skin and mucous membranes, severe hypoglycaemia, occasionally leading to seizures and coma, feeding difficulties, failure to thrive and infections. A newborn child was admitted, on his second day of life, to our neonatal intensive care unit because of seizures and respiratory insufficiency. Hyperpigmentation was not evident due to his Senegalese origin. The clinical presentation led us to consider a wide range of diagnostic hypothesis. Laboratory findings brought us to the diagnosis of FGD that was confirmed by molecular analysis showing an MC2R:p.Y254C mutation previously reported as causative of type 1 FGD and two novel heterozygous non-synonymous single-nucleotide polymorphisms in exon 2 and 3 of melanocortin 2 receptor accessory protein-α, whose role in the disease is currently unknown. The importance of an early collection and storage of blood samples during hypoglycaemic event is emphasised.

HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses

PubMed Central

Col, Edwige; Caron, Cécile; Chable-Bessia, Christine; Legube, Gaelle; Gazzeri, Sylvie; Komatsu, Yasuhiko; Yoshida, Minoru; Benkirane, Monsef; Trouche, Didier; Khochbin, Saadi

2005-01-01

HIV-1 transactivator Tat uses cellular acetylation signalling by targeting several cellular histone acetyltransferases (HAT) to optimize its various functions. Although Tip60 was the first HAT identified to interact with Tat, the biological significance of this interaction has remained obscure. We had previously shown that Tat represses Tip60 HAT activity. Here, a new mechanism of Tip60 neutralization by Tat is described, where Tip60 is identified as a substrate for the newly reported p300/CBP-associated E4-type ubiquitin-ligase activity, and Tat uses this mechanism to induce the polyubiquitination and degradation of Tip60. Tip60 targeting by Tat results in a dramatic impairment of the Tip60-dependent apoptotic cell response to DNA damage. These data reveal yet unknown strategies developed by HIV-1 to increase cell resistance to genotoxic stresses and show a role of Tat as a modulator of cellular protein ubiquitination. PMID:16001085

Halococcus salifodinae sp. nov., an Archaeal Isolate from an Austrian Salt Mine

NASA Technical Reports Server (NTRS)

Denner, Ewald B. M.; McGenity, Terry J.; Busse, Hans-Jurgen; Grant, William D.; Wanner, Gerhard; Stan-Lotter, Helga

1994-01-01

A novel extremely halophilic archaeon (archaebacterium) was isolated from rock salt obtained from an Austrian salt mine. The deposition of the salt is thought to have occurred during the Permian period (225 x 106 to 280 x 10(exp 6) years ago). This organism grew over a pH range of 6.8 to 9.5. Electron microscopy revealed cocci in tetrads or larger clusters. The partial 16S rRNA sequences, polar lipid composition, and menaquinone content suggested that this organism was related to members of the genus Halococcus, while the whole-cell protein patterns, the presence of several unknown lipids, and the presence of pink pigmentation indicated that it was different from previously described coccoid halophiles. We propose that this isolate should be recognized as a new species and should be named Halococcus salifodinae. The type strain is Bl(sub p) (= ATCC 51437 = DSM 8989). A chemotaxonomically similar microorganism was isolated from a British salt mine.

Patterns in spontaneous adverse event reporting among branded and generic antiepileptic drugs.

PubMed

Bohn, J; Kortepeter, C; Muñoz, M; Simms, K; Montenegro, S; Dal Pan, G

2015-05-01

Spontaneous adverse event reports constitute an important source of information on previously unknown adverse reactions to marketed medicines. However, the dynamics of such reporting following generic introduction are poorly understood. Using adverse event reports on five antiepileptic drugs from the US Food and Drug Administration's Adverse Event Reporting System, we describe temporal trends in adverse event reporting before and after generic introduction, and survey the quality of product-identifying information contained therein. The majority of reports were sent by innovator drug manufacturers while few were sent by generic manufacturers, even when generics accounted for >90% of dispensed prescriptions. We manually reviewed narratives from 2,500 reports and found that the suspect product type (brand or generic) could not be determined in 84% of reports, while generic products (16%) were identified more often than brand-name products (<1%). These results suggest that pharmacovigilance stakeholders should act to promote more detailed reporting practices. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Developmental differences in relations between parent-reported executive function and unitized and non-unitized memory representations during childhood

PubMed Central

Blankenship, Sarah L.; Riggins, Tracy

2015-01-01

Previous research has documented an association between executive functioning (EF) and memory for bound details. However, it is unknown if this relation varies as a function of the type of bound information (i.e., unitized versus non-unitized) and whether this association changes as a function of age during childhood, when both EF and memory undergo rapid development. The current study sought to address these gaps by examining whether relations between parent-reported EF differed for unitized versus non-unitized memory representations and if these relations differed between children who were 4, 6, or 8 years of age. Results revealed that EF was selectively associated with non-unitized associative memory in 8-year-old children; no significant relations between EF and either memory condition were evident in 4- or 6-year-olds. These results suggest relations between EF and memory may be specific to non-unitized representations and that this association may emerge across childhood as both EF and memory abilities develop. PMID:26347683

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)*

PubMed Central

Sun, Cen-Cen; Dong, Wei-Ren; Zhao, Jing; Nie, Li; Xiang, Li-Xin; Zhu, Guan; Shao, Jian-Zhong

2015-01-01

Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins that are known as thioredoxin peroxidases. Here we report that Prx1 proteins from Tetraodon nigroviridis and humans also possess a previously unknown catalase-like activity that is independent of Cys residues and reductants but dependent on iron. We identified that the GVL motif was essential to the catalase (CAT)-like activity of Prx1 but not to the Cys-dependent thioredoxin peroxidase (POX) activity, and we generated mutants lacking POX and/or CAT activities for individually delineating their functional features. We discovered that the TnPrx1 POX and CAT activities possessed different kinetic features in reducing H2O2. The overexpression of wild-type TnPrx1 and mutants differentially regulated the intracellular levels of reactive oxygen species and p38 phosphorylation in HEK-293T cells treated with H2O2. These observations suggest that the dual antioxidant activities of Prx1 may be crucial for organisms to mediate intracellular redox homeostasis. PMID:26088136

A Novel Locus For Dilated Cardiomyopathy Maps to Canine Chromosome 8

PubMed Central

Werner, Petra; Raducha, Michael G.; Prociuk, Ulana; Sleeper, Meg M.; Henthorn, Paula S.

2008-01-01

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint LOD scores of 10.8 and 14, respectively. The locus maps to a 3.9 Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure. PMID:18442891

Facial soft tissue thickness differences among three skeletal classes in Japanese population.

PubMed

Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko

2014-03-01

Facial reconstruction is used in forensic anthropology to recreate the face from unknown human skeletal remains, and to elucidate the antemortem facial appearance. This requires accurate assessment of the skull (age, sex, ancestry, etc.) and thickness data. However, additional information is required to reconstruct the face as the information obtained from the skull is limited. Here, we aimed to examine the information from the skull that is required for accurate facial reconstruction. The human facial profile is classified into 3 shapes: straight, convex, and concave. These facial profiles facilitate recognition of individuals. The skeletal classes used in orthodontics are classified according to these 3 facial types. We have previously reported the differences between Japanese females. In the present study, we applied this classification for facial tissue measurement, compared the differences in tissue depth of each skeletal class for both sexes in the Japanese population, and elucidated the differences between the skeletal classes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants

PubMed Central

De Rosa, Veronica; Galgani, Mario; Porcellini, Antonio; Colamatteo, Alessandra; Santopaolo, Marianna; Zuchegna, Candida; Romano, Antonella; De Simone, Salvatore; Procaccini, Claudio; La Rocca, Claudia; Carrieri, Pietro Biagio; Maniscalco, Giorgia Teresa; Salvetti, Marco; Buscarinu, Maria Chiara; Franzese, Adriana; Mozzillo, Enza; La Cava, Antonio; Matarese, Giuseppe

2016-01-01

Human regulatory T cells (Treg cells) that develop from conventional T cells (Tconv cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced Treg cells (iTreg cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iTreg cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2–related suppressive activity of iTreg cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of Treg cells in health and in autoimmunity. PMID:26414764

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.

PubMed

Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

2017-09-01

Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-β family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

PubMed Central

Cortez, Victor S; Ulland, Tyler K; Cervantes-Barragan, Luisa; Bando, Jennifer K; Robinette, Michelle L; Wang, Qianli; White, Andrew J; Gilfillan, Susan; Cella, Marina; Colonna, Marco

2017-01-01

Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of ‘imprinting’ by cytokines of the TGF-β family. We examined mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGF-βR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells. PMID:28759002

Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

PubMed

Koike-Yusa, Hiroko; Li, Yilong; Tan, E-Pien; Velasco-Herrera, Martin Del Castillo; Yusa, Kosuke

2014-03-01

Identification of genes influencing a phenotype of interest is frequently achieved through genetic screening by RNA interference (RNAi) or knockouts. However, RNAi may only achieve partial depletion of gene activity, and knockout-based screens are difficult in diploid mammalian cells. Here we took advantage of the efficiency and high throughput of genome editing based on type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems to introduce genome-wide targeted mutations in mouse embryonic stem cells (ESCs). We designed 87,897 guide RNAs (gRNAs) targeting 19,150 mouse protein-coding genes and used a lentiviral vector to express these gRNAs in ESCs that constitutively express Cas9. Screening the resulting ESC mutant libraries for resistance to either Clostridium septicum alpha-toxin or 6-thioguanine identified 27 known and 4 previously unknown genes implicated in these phenotypes. Our results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins

NASA Astrophysics Data System (ADS)

Mayr, Gerald; De Pietri, Vanesa L.; Paul Scofield, R.

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

Light intensity affects RNA silencing of a transgene in Nicotiana benthamiana plants.

PubMed

Kotakis, Christos; Vrettos, Nicholas; Kotsis, Dimitrios; Tsagris, Mina; Kotzabasis, Kiriakos; Kalantidis, Kriton

2010-10-12

Expression of exogenous sequences in plants is often suppressed through one of the earliest described RNA silencing pathways, sense post-transcriptional gene silencing (S-PTGS). This type of suppression has made significant contributions to our knowledge of the biology of RNA silencing pathways and has important consequences in plant transgenesis applications. Although significant progress has been made in recent years, factors affecting the stability of transgene expression are still not well understood. It has been shown before that the efficiency of RNA silencing in plants is influenced by various environmental factors. Here we report that a major environmental factor, light intensity, significantly affects the induction and systemic spread of S-PTGS. Moreover, we show that photoadaptation to high or low light intensity conditions differentially affects mRNA levels of major components of the RNA silencing machinery. Light intensity is one of the previously unknown factors that affect transgene stability at the post-transcriptional level. Our findings demonstrate an example of how environmental conditions could affect RNA silencing.

Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle.

PubMed

Hartman, Emily C; Jakobson, Christopher M; Favor, Andrew H; Lobba, Marco J; Álvarez-Benedicto, Ester; Francis, Matthew B; Tullman-Ercek, Danielle

2018-04-11

Self-assembling proteins are critical to biological systems and industrial technologies, but predicting how mutations affect self-assembly remains a significant challenge. Here, we report a technique, termed SyMAPS (Systematic Mutation and Assembled Particle Selection), that can be used to characterize the assembly competency of all single amino acid variants of a self-assembling viral structural protein. SyMAPS studies on the MS2 bacteriophage coat protein revealed a high-resolution fitness landscape that challenges some conventional assumptions of protein engineering. An additional round of selection identified a previously unknown variant (CP[T71H]) that is stable at neutral pH but less tolerant to acidic conditions than the wild-type coat protein. The capsids formed by this variant could be more amenable to disassembly in late endosomes or early lysosomes-a feature that is advantageous for delivery applications. In addition to providing a mutability blueprint for virus-like particles, SyMAPS can be readily applied to other self-assembling proteins.

Estrogen receptor alpha modulates toll-like receptor signaling in murine lupus

PubMed Central

Cunningham, Melissa A.; Naga, Osama S.; Eudaly, Jackie G.; Scott, Jennifer L.; Gilkeson, Gary S.

2013-01-01

Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. Despite significant research effort, the mechanisms underlying the female predominance in this disease are largely unknown. Previously, we showed that estrogen receptor alpha knockout (ERαKO) lupus prone female mice had significantly less pathologic renal disease and proteinuria, and significantly prolonged survival. Since autoantibody levels and number and percentage of B/T cells were not significantly impacted by ERα genotype, we hypothesized that the primary benefit of ERα deficiency in lupus nephritis was via modulation of the innate immune response. Using BMDCs and spleen cells/B cells from female wild-type or ERαKO mice, we found that ERαKO-derived cells have a significantly reduced inflammatory response after stimulation with TLR agonists. Our results indicate that the inflammatory response to TLR ligands is significantly impacted by the presence of ERα despite the absence of estradiol, and may partially explain the protective effect of ERα deficiency in lupus-prone animals. PMID:22659029

A novel analytical technique suitable for the identification of plastics.

PubMed

Nečemer, Marijan; Kump, Peter; Sket, Primož; Plavec, Janez; Grdadolnik, Jože; Zvanut, Maja

2013-01-01

The enormous development and production of plastic materials in the last century resulted in increasing numbers of such kinds of objects. Development of a simple and fast technique to classify different types of plastics could be used in many activities dealing with plastic materials such as packaging of food, sorting of used plastic materials, and also, if technique would be non-destructive, for conservation of plastic artifacts in museum collections, a relatively new field of interest since 1990. In our previous paper we introduced a non-destructive technique for fast identification of unknown plastics based on EDXRF spectrometry,1 using as a case study some plastic artifacts archived in the Museum in order to show the advantages of the nondestructive identification of plastic material. In order to validate our technique it was necessary to apply for this purpose the comparison of analyses with some of the analytical techniques, which are more suitable and so far rather widely applied in identifying some most common sorts of plastic materials.

Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.

PubMed

Sun, Jiying; Shi, Lin; Kinomura, Aiko; Fukuto, Atsuhiko; Horikoshi, Yasunori; Oma, Yukako; Harata, Masahiko; Ikura, Masae; Ikura, Tsuyoshi; Kanaar, Roland; Tashiro, Satoshi

2018-05-08

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. © 2018, Sun et al.

Numerical approximation abilities correlate with and predict informal but not formal mathematics abilities.

PubMed

Libertus, Melissa E; Feigenson, Lisa; Halberda, Justin

2013-12-01

Previous research has found a relationship between individual differences in children's precision when nonverbally approximating quantities and their school mathematics performance. School mathematics performance emerges from both informal (e.g., counting) and formal (e.g., knowledge of mathematics facts) abilities. It remains unknown whether approximation precision relates to both of these types of mathematics abilities. In the current study, we assessed the precision of numerical approximation in 85 3- to 7-year-old children four times over a span of 2years. In addition, at the final time point, we tested children's informal and formal mathematics abilities using the Test of Early Mathematics Ability (TEMA-3). We found that children's numerical approximation precision correlated with and predicted their informal, but not formal, mathematics abilities when controlling for age and IQ. These results add to our growing understanding of the relationship between an unlearned nonsymbolic system of quantity representation and the system of mathematics reasoning that children come to master through instruction. Copyright © 2013 Elsevier Inc. All rights reserved.

Nucleocytoplasmic shuttling of hexokinase II in a cancer cell

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

Neary, Catherine L., E-mail: nearycl@umdnj.edu; Pastorino, John G.

2010-04-16

In yeast, the hexokinase type II enzyme (HXKII) translocates to the nucleus in the presence of excess glucose, and participates in glucose repression. However, no evidence has suggested a nuclear function for HXKII in mammalian cells. Herein, we present data showing nuclear localization of HXKII in HeLa cells, both by immunocytochemistry and subcellular fractionation. HXKII is extruded from the nucleus, at least in part, by the activity of the exportin 1/CrmA system, as demonstrated by increased nuclear expression and decreased cytoplasmic expression after incubation with leptomycin B, a bacterially-derived exportin inhibitor. Furthermore, cytoplasmic localization of HXKII is dependent on itsmore » enzymatic activity, as inhibiting HXKII activity using 2-deoxy-D-glucose (2DG) increased nuclear localization. This effect was more significant in cells incubated in the absence of glucose for 24 h prior to addition of 2DG. Regulated translocation of HXKII to the nucleus of mammalian cells could represent a previously unknown glucose-sensing mechanism.« less

Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts.

PubMed

Oravecz-Wilson, Katherine I; Kiel, Mark J; Li, Lina; Rao, Dinesh S; Saint-Dic, Djenann; Kumar, Priti D; Provot, Melissa M; Hankenson, Kurt D; Reddy, Venkat N; Lieberman, Andrew P; Morrison, Sean J; Ross, Theodora S

2004-04-15

Huntingtin Interacting Protein 1 (HIP1) binds clathrin and AP2, is overexpressed in multiple human tumors, and transforms fibroblasts. The function of HIP1 is unknown although it is thought to play a fundamental role in clathrin trafficking. Gene-targeted Hip1-/- mice develop premature testicular degeneration and severe spinal deformities. Yet, although HIP1 is expressed in many tissues including the spleen and bone marrow and was part of a leukemogenic translocation, its role in hematopoiesis has not been examined. In this study we report that three different mutations of murine Hip1 lead to hematopoietic abnormalities reflected by diminished early progenitor frequencies and resistance to 5-FU-induced bone marrow toxicity. Two of the Hip1 mutant lines also display the previously described spinal defects. These observations indicate that, in addition to being required for the survival/proliferation of cancer cells and germline progenitors, HIP1 is also required for the survival/proliferation of diverse types of somatic cells, including hematopoietic progenitors.

Styrene-Associated Health Outcomes at a Windblade Manufacturing Plant

PubMed Central

McCague, Anna-Binney; Cox-Ganser, Jean M.; Harney, Joshua M.; Alwis, K. Udeni; Blount, Benjamin C.; Cummings, Kristin J.; Edwards, Nicole; Kreiss, Kathleen

2015-01-01

Background Health risks of using styrene to manufacture windblades for the green energy sector are unknown. Methods Using data collected from 355 (73%) current windblade workers and regression analysis, we investigated associations between health outcomes and styrene exposure estimates derived from urinary styrene metabolites. Results The median current styrene exposure was 53.6 mg/g creatinine (interquartile range: 19.5–94.4). Color blindness in men and women (standardized morbidity ratios 2.3 and 16.6, respectively) was not associated with exposure estimates, but was the type previously reported with styrene. Visual contrast sensitivity decreased and chest tightness increased (odds ratio 2.9) with increasing current exposure. Decreases in spirometric parameters and FeNO, and increases in the odds of wheeze and asthma-like symptoms (odds ratios 1.3 and 1.2, respectively) occurred with increasing cumulative exposure. Conclusions Despite styrene exposures below the recommended 400 mg/g creatinine, visual and respiratory effects indicate the need for additional preventative measures in this industry. PMID:26305283

Blue whales respond to simulated mid-frequency military sonar.

PubMed

Goldbogen, Jeremy A; Southall, Brandon L; DeRuiter, Stacy L; Calambokidis, John; Friedlaender, Ari S; Hazen, Elliott L; Falcone, Erin A; Schorr, Gregory S; Douglas, Annie; Moretti, David J; Kyburg, Chris; McKenna, Megan F; Tyack, Peter L

2013-08-22

Mid-frequency military (1-10 kHz) sonars have been associated with lethal mass strandings of deep-diving toothed whales, but the effects on endangered baleen whale species are virtually unknown. Here, we used controlled exposure experiments with simulated military sonar and other mid-frequency sounds to measure behavioural responses of tagged blue whales (Balaenoptera musculus) in feeding areas within the Southern California Bight. Despite using source levels orders of magnitude below some operational military systems, our results demonstrate that mid-frequency sound can significantly affect blue whale behaviour, especially during deep feeding modes. When a response occurred, behavioural changes varied widely from cessation of deep feeding to increased swimming speed and directed travel away from the sound source. The variability of these behavioural responses was largely influenced by a complex interaction of behavioural state, the type of mid-frequency sound and received sound level. Sonar-induced disruption of feeding and displacement from high-quality prey patches could have significant and previously undocumented impacts on baleen whale foraging ecology, individual fitness and population health.

[Efflux systems in Serratia marcescens].

PubMed

Mardanova, A M; Bogomol'naia, L M; Romanova, Iu D; Sharipova, M R

2014-01-01

A widespread bacterium Serratia marcescens (family Enterobacteriaceae) is an opportunistic and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from pathogen and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from the cells by efflux systems is one of the mechanisms responsible for microbial resistance to these compounds. Among enterobacteria, efflux systems of Escherichia coli and Salmonella enterica var. Typhimurium have been studied most extensively. Few efflux systems that belong to different families have been reported for S. marcescens. In this review, we analyzed available literature about S. marcescens efflux systems and carried out the comparative analysis of the genes encoding the RND type systems in different Serratia species and in other enterobacteria. Bioinformatical analysis of the S. marcescens genome allowed us to identify the previously unknown efflux systems based on their homology with the relevant E. coli genes. Identification of additional efflux systems in S. marcescens genome will promote our understanding of physiology of these bacteria, will detect new molecular mechanisms of resistance and will reveal their resistance potential.

Active music classes in infancy enhance musical, communicative and social development.

PubMed

Gerry, David; Unrau, Andrea; Trainor, Laurel J

2012-05-01

Previous studies suggest that musical training in children can positively affect various aspects of development. However, it remains unknown as to how early in development musical experience can have an effect, the nature of any such effects, and whether different types of music experience affect development differently. We found that random assignment to 6 months of active participatory musical experience beginning at 6 months of age accelerates acquisition of culture-specific knowledge of Western tonality in comparison to a similar amount of passive exposure to music. Furthermore, infants assigned to the active musical experience showed superior development of prelinguistic communicative gestures and social behaviour compared to infants assigned to the passive musical experience. These results indicate that (1) infants can engage in meaningful musical training when appropriate pedagogical approaches are used, (2) active musical participation in infancy enhances culture-specific musical acquisition, and (3) active musical participation in infancy impacts social and communication development. © 2012 Blackwell Publishing Ltd.

Lower gastrointestinal symptoms are associated with worse glycemic control and quality of life in type 1 diabetes mellitus.

PubMed

Leeds, John S; Hadjivassiliou, Marios; Tesfaye, Solomon; Sanders, David S

2018-01-01

Lower gastrointestinal symptoms are not well characterized in people with type 1 diabetes, and the effects on quality of life and glycemic control are unknown. This study aimed to determine the prevalence of lower gastrointestinal symptoms and the effects on glycemic control and quality of life, and to investigate for underlying causes. This is a prospective, cohort study in secondary care. Patients with type 1 diabetes completed a gastrointestinal symptom questionnaire and the Short Form 36 V.2 quality of life questionnaire and had their hemoglobin A1c measured. Patients with diarrhea were offered reassessment and investigation as per the national guidelines. Controls without diabetes were used to compare symptom prevalence and quality of life scores. 706 with type 1 diabetes (mean age 41.9 years) and 604 controls (mean age 41.9 years) were enrolled. Gastrointestinal symptoms were significantly more frequent in type 1 diabetes compared with controls, in particular constipation (OR 2.4), diarrhea (OR 2.5), alternating bowel habit (OR 2.1), abdominal pain (OR 1.4), floating stools (OR 2.7), bloating (OR 1.4) and flatulence (OR 1.3) (all p<0.05). Previous pancreatitis was more frequent in type 1 diabetes (OR 4.6), but other gastrointestinal conditions were not. Gastrointestinal symptoms were associated with poorer glycemic control (p<0.01) and worse quality of life particularly in those with diarrhea. Investigation of those with diarrhea, including those with alternating bowel habit, (n=105), identified a cause in 72.3% with subsequent change in management. Gastrointestinal symptoms are twice as common in type 1 diabetes and associated with poorer quality of life and glycemic control. Investigation of diarrhea in people with type 1 diabetes leads to a high yield of treatable conditions and a change in management in about three-quarters.

Taxonomic description of in situ bee pollen from the middle Eocene of Germany.

PubMed

Grímsson, FriĐgeir; Zetter, Reinhard; Labandeira, Conrad C; Engel, Michael S; Wappler, Torsten

2017-01-02

The middle Eocene Messel and Eckfeld localities are renowned for their excellently preserved faunas and diverse floras. Here we describe for the first time pollen from insect-pollinated plants found in situ on well-preserved ancient bees using light and scanning electron microscopy. There have been 140 pollen types reported from Messel and 162 pollen types from Eckfeld. Here we document 23 pollen types, six from Messel and 18 from Eckfeld (one is shared). The taxa reported here are all pollinated by insects and mostly not recovered in the previously studied dispersed fossil pollen records. Typically, a single or two pollen types are found on each fossil bee specimen, the maximum number of distinct pollen types on a single individual is five. Only five of the 23 pollen types obtained are angiosperms of unknown affinity, the remainder cover a broad taxonomic range of angiosperm trees and include members of several major clades: monocots (1 pollen type), fabids (7), malvids (4), asterids (5) and other core eudicots (1). Seven types each can be assigned to individual genera or infrafamilial clades. Since bees visit only flowers in the relative vicinity of their habitat, the recovered pollen provides a unique insight into the autochthonous palaeo-flora. The coexistence of taxa such as Decodon, Elaeocarpus, Mortoniodendron and other Tilioideae, Mastixoideae, Olax, Pouteria and Nyssa confirms current views that diverse, thermophilic forests thrived at the Messel and Eckfeld localities, probably under a warm subtropical, fully humid climate. Our study calls for increased attention to pollen found in situ on pollen-harvesting insects such as bees, which can provide new insights on insect-pollinated plants and complement even detailed palaeo-palynological knowledge obtained mostly from pollen of wind-pollinated plants in the dispersed pollen record of sediments. In the case of Elaeocarpus, Mortoniodendron, Olax and Pouteria the pollen collected by the middle Eocene bees represent the earliest unambiguous records of their respective genera.

Taxonomic description of in situ bee pollen from the middle Eocene of Germany

PubMed Central

Grímsson, FriĐgeir; Zetter, Reinhard; Labandeira, Conrad C.; Engel, Michael S.; Wappler, Torsten

2017-01-01

Abstract The middle Eocene Messel and Eckfeld localities are renowned for their excellently preserved faunas and diverse floras. Here we describe for the first time pollen from insect-pollinated plants found in situ on well-preserved ancient bees using light and scanning electron microscopy. There have been 140 pollen types reported from Messel and 162 pollen types from Eckfeld. Here we document 23 pollen types, six from Messel and 18 from Eckfeld (one is shared). The taxa reported here are all pollinated by insects and mostly not recovered in the previously studied dispersed fossil pollen records. Typically, a single or two pollen types are found on each fossil bee specimen, the maximum number of distinct pollen types on a single individual is five. Only five of the 23 pollen types obtained are angiosperms of unknown affinity, the remainder cover a broad taxonomic range of angiosperm trees and include members of several major clades: monocots (1 pollen type), fabids (7), malvids (4), asterids (5) and other core eudicots (1). Seven types each can be assigned to individual genera or infrafamilial clades. Since bees visit only flowers in the relative vicinity of their habitat, the recovered pollen provides a unique insight into the autochthonous palaeo-flora. The coexistence of taxa such as Decodon, Elaeocarpus, Mortoniodendron and other Tilioideae, Mastixoideae, Olax, Pouteria and Nyssa confirms current views that diverse, thermophilic forests thrived at the Messel and Eckfeld localities, probably under a warm subtropical, fully humid climate. Our study calls for increased attention to pollen found in situ on pollen-harvesting insects such as bees, which can provide new insights on insect-pollinated plants and complement even detailed palaeo-palynological knowledge obtained mostly from pollen of wind-pollinated plants in the dispersed pollen record of sediments. In the case of Elaeocarpus, Mortoniodendron, Olax and Pouteria the pollen collected by the middle Eocene bees represent the earliest unambiguous records of their respective genera. PMID:28057943