Keizer, Ron J; van Benten, Michel; Beijnen, Jos H; Schellens, Jan H M; Huitema, Alwin D R
Pharmacokinetic-pharmacodynamic modeling using non-linear mixed effects modeling (NONMEM) is a powerful yet challenging technique, as the software is generally accessed from the command line. A graphical user interface, Piraña, was developed that offers a complete modeling environment for NONMEM, enabling both novice and advanced users to increase efficiency of their workflow. Piraña provides features for the management and creation of model files, the overview of modeling results, creation of run reports and handling of datasets and output tables, and the running of custom R scripts on model output. Through the secure shell (SSH) protocol, Piraña can also be used to connect to Linux clusters (SGE, MOSIX) for distribution of workload. Modeling with NONMEM is computationally burdensome, which may be alleviated by distributing runs to computer clusters. A solution to this problem is offered here, called PCluster. This platform is easy to set up, runs in standard network environments, and can be extended with additional nodes if needed. The cluster supports the modeling toolkit Perl speaks NONMEM (PsN), and can include dedicated or non-dedicated PCs. A daemon script, written in Perl, was designed to run in the background on each node in the cluster, and to manage job distribution. The PCluster can be accessed from Piraña, and both software products have extensively been tested on a large academic network. The software is available under an open-source license. PMID:20627442
Chen, C C; Hurez, V; Brockenbrough, J S; Kubagawa, H; Cooper, M D
A diverse pattern of polymorphism is defined for the paired Ig-like receptors (PIRs) that serve as activating (PIR-A) and inhibitory (PIR-B) receptors on B lymphocytes, dendritic cells, and myeloid-lineage cells in mice. The monoclonal anti-PIR antibody 10.4 is shown to recognize an allelic PIR-A/PIR-B determinant on cells from BALB/c but not C57BL/6 mice. Other strains of inbred mice also can be typed on the basis of their expression of this PIR allelic determinant. Analysis of (BALB/c x C57BL/6) F1 hybrid offspring indicates that PIR molecules bearing the paternal PIR allotype are expressed whereas PIR-A and PIR-B molecules bearing the maternal allotype are not. The monoallelic expression of the polymorphic PIR-A and PIR-B molecules, and possibly of their human Ig-like transcript/leukocyte Ig-like receptor/monocyte/macrophage Ig-like receptor and killer cell inhibitory receptor relatives, may influence innate and specific immune responses in outbred populations. PMID:10359805
Maeda, A; Kurosaki, M; Kurosaki, T
Paired immunoglobulin-like receptor (PIR)-A and PIR-B possess similar ectodomains with six immunoglobulin-like loops, but have distinct transmembrane and cytoplasmic domains. PIR-B bears immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences in its cytoplasmic domain that recruit Src homology (SH)2 domain-containing tyrosine phosphatases SHP-1 and SHP-2, leading to inhibition of B and mast cell activation. In contrast, the PIR-A protein has a charged Arg residue in its transmembrane region and a short cytoplasmic domain that lacks ITIM sequences. Here we show that Fc receptor gamma chain, containing an immunoreceptor tyrosine-based activation motif (ITAM), associates with PIR-A. Cross-linking of this PIR-A complex results in mast cell activation such as calcium mobilization in an ITAM-dependent manner. Thus, our data provide evidence for the existence of two opposite signaling pathways upon PIR aggregation. PIR-A induces the stimulatory signal by using ITAM in the associated gamma chain, whereas PIR-B mediates the inhibitory signal through its ITIMs. PMID:9730901
Singh, O. P.; Dykes, C. L.; Sharma, G.; Das, M. K.
Leucine-to-phenylalanine substitution at residue L1014 in the voltage-gated sodium channel, target site of action for dichlorodiphenyltrichloroethane (DDT) and pyrethroids, is the most common knockdown resistance (kdr) mutation reported in several insects conferring resistance against DDT and pyrethroids. Here, we report presence of two coexisting alternative transversions, A>T and A>C, on the third codon position of L1014 residue in malaria vector Anopheles subpictus Grassi (species A) from Jamshedpur (India), both leading to the same amino acid substitution of Leu-to-Phe with allelic frequencies of 19 and 67%, respectively. A single primer-introduced restriction analysis–polymerase chain reaction (PIRA-PCR) was devised for the identification of L1014F-kdr mutation in An. subpictus resulting from either type of point mutation. Genotyping of samples with PIRA-PCR revealed high frequency (82%) of L1014F-kdr mutation in the study area. PMID:26336276
Background Mexico has the highest adult overweight and obesity prevalence in the Americas; 23.8% of children <5 years old are at risk for overweight and 9.7% are already overweight or obese. Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social (IMSS) clinics. Methods We randomized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care. We recruited 306 parent-child pairs: 168 intervention, 138 usual care. Children were 2-5 years old with WHO body mass index (BMI) z-score 0-3. We measured children’s height and weight and parents reported children’s diet and physical activity at baseline and 3 and 6-month follow-up. We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values. Results 93 (55%) intervention and 96 (70%) usual care families completed 3 and 6-month follow-up. At 3 months, intervention v. usual care children increased vegetables by 6.3 servings/week (95% CI, 1.8, 10.8). In stratified analyses, intervention participants with high program adherence (5-6 sessions) decreased snacks and screen time and increased vegetables v. usual care. No further effects on behavioral outcomes or BMI were observed. Transportation time and expenses were barriers to adherence. 90% of parents who completed the post-intervention survey were satisfied with the program. Conclusions Although satisfaction was high among participants, barriers to participation and retention included transportation cost and time. In intention to treat analyses, we found intervention effects on vegetable intake, but not other behaviors or BMI. Trial registration ClinicalTrials.gov NCT01539070. Comisión Nacional de Investigación Científica del IMSS: 2009-785-120. PMID:24649831
Using a lighthearted and simple approach, this 23-minute videotape in English and Spanish versions presents interactions between parents and children while reading books. The children in the videotape range in age from 0 to 5 years. The video is introduced by scenes of children enjoying books while narration discussing the impact of reading to…
Office of Elementary and Secondary Education (ED), Washington, DC. Safe and Drug Free Schools Program.
This publication is part of the Department of Education's ongoing effort to provide information to emerging populations in their native language on how to create and maintain drug-free and safe schools across the nation. Throughout the publication are personal stories and artwork of elementary and secondary school students that promote the message…
The bibliography contains citations concerning chlorofluorocarbons (CFC's), and efforts to find substitute materials in response to the need to lessen the environmental impact of CFC on the ozone layer, as agreed to in the international Montreal Protocol. CFC alternatives are expected to be used as aerosol propellants, blowing agents, refrigerants, fire extinguishants, and solvents. References to the effects of CFC on ozone are found in separate bibliographies. (Contains 250 citations and includes a subject term index and title list.)
Ono, M; Yuasa, T; Ra, C; Takai, T
Paired Ig-like receptors (PIR) are polymorphic type I transmembrane proteins belonging to an Ig superfamily encoded by multiple isotypic genes. They are expressed on immune cells such as mast cells, macrophages, and B lymphocytes. Two subtypes of PIR have been classified according to the difference in the primary structure of the PIR transmembrane and cytoplasmic regions. These subtypes are designated as PIR-A and PIR-B. In this study, the transmembrane and cytoplasmic regions of the PIR-A subtype were shown to mediate activation signal events such as cytoplasmic calcium mobilization, protein tyrosine phosphorylations, and degranulation in rat mast cell line RBL-2H3. The association of the Fc receptor gamma and beta subunits with PIR-A was shown to be responsible for PIR-A function but not required for membrane expression of PIR-A on COS-7 cells. We further revealed the role of two charged amino acid residues in the transmembrane region, namely arginine and glutamic acid, in PIR-A function and its association with the above subunits. In contrast to the inhibitory nature of the PIR-B subtype, present findings reveal that PIR-A potentially acts as a stimulatory receptor in mast cells, suggesting a mechanism for regulation of mast cell functions by the PIR family. PMID:10514523
Jo, Yong Hun; Patnaik, Bharat Bhusan; Kang, Se Won; Chae, Sung-Hwa; Oh, Seunghan; Kim, Dong Hyun; Noh, Mi Young; Seo, Gi Won; Jeong, Heon Cheon; Noh, Ju Young; Jeong, Ji Eun; Hwang, Hee Ju; Ko, Kisung; Han, Yeon Soo; Lee, Yong Seok
Background Most traditional genome sequencing projects involving viruses include the culture and purification of the virus particles. However, purification of virions may yield insufficient material for traditional sequencing. The electrophoretic method described here provides a strategy whereby the genomic DNA of the Korean isolate of Pieris rapae granulovirus (PiraGV-K) could be recovered in sufficient amounts for sequencing by purifying it directly from total host DNA by pulse-field gel electrophoresis (PFGE). Methodology/Principal Findings The total genomic DNA of infected P. rapae was embedded in agarose plugs, treated with restriction nuclease and methylase, and then PFGE was used to separate PiraGV-K DNA from the DNA of P. rapae, followed by mapping of fosmid clones of the purified viral DNA. The double-stranded circular genome of PiraGV-K was found to encode 120 open reading frames (ORFs), which covered 92% of the sequence. BLAST and ORF arrangement showed the presence of 78 homologs to other genes in the database. The mean overall amino acid identity of PiraGV-K ORFs was highest with the Chinese isolate of PiraGV (∼99%), followed up with Choristoneura occidentalis ORFs at 58%. PiraGV-K ORFs were grouped, according to function, into 10 genes involved in transcription, 11 involved in replication, 25 structural protein genes, and 15 auxiliary genes. Genes for Chitinase (ORF 10) and cathepsin (ORF 11), involved in the liquefaction of the host, were found in the genome. Conclusions/Significance The recovery of PiraGV-K DNA genome by pulse-field electrophoretic separation from host genomic DNA had several advantages, compared with its isolation from particles harvested as virions or inclusions from the P. rapae host. We have sequenced and analyzed the 108,658 bp PiraGV-K genome purified by the electrophoretic method. The method appears to be generally applicable to the analysis of genomes of large viruses. PMID:24391907
Kubagawa, Hiromi; Burrows, Peter D.; Cooper, Max D.
An Fcα receptor probe of human origin was used to identify novel members of the Ig gene superfamily in mice. Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDNAs isolated from a mouse splenic library. Both type I transmembrane proteins possess similar ectodomains with six Ig-like loops, but have different transmembrane and cytoplasmic regions. The predicted PIR-A protein has a short cytoplasmic tail and a charged Arg residue in the transmembrane region that, by analogy with the FcαR relative, suggests the potential for association with an additional transmembrane protein to form a signal transducing unit. In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs. These features are shared by the related killer inhibitory receptors. PIR-A proteins appear to be highly variable, in that predicted peptide sequences differ for seven randomly selected PIR-A clones, whereas PIR-B cDNA clones are invariant. Southern blot analysis with PIR-B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A genes. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid lineage cells, wherein both are expressed simultaneously. The characteristics of the highly-conserved PIR-A and PIR-B genes and their coordinate cellular expression suggest a potential regulatory role in humoral, inflammatory, and allergic responses. PMID:9144225
Kubagawa, H; Burrows, P D; Cooper, M D
An Fcalpha receptor probe of human origin was used to identify novel members of the Ig gene superfamily in mice. Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDNAs isolated from a mouse splenic library. Both type I transmembrane proteins possess similar ectodomains with six Ig-like loops, but have different transmembrane and cytoplasmic regions. The predicted PIR-A protein has a short cytoplasmic tail and a charged Arg residue in the transmembrane region that, by analogy with the FcalphaR relative, suggests the potential for association with an additional transmembrane protein to form a signal transducing unit. In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs. These features are shared by the related killer inhibitory receptors. PIR-A proteins appear to be highly variable, in that predicted peptide sequences differ for seven randomly selected PIR-A clones, whereas PIR-B cDNA clones are invariant. Southern blot analysis with PIR-B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A genes. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid lineage cells, wherein both are expressed simultaneously. The characteristics of the highly-conserved PIR-A and PIR-B genes and their coordinate cellular expression suggest a potential regulatory role in humoral, inflammatory, and allergic responses. PMID:9144225
Hoover, Ryan E.
This study examines (1) subject content, (2) file size, (3) types of documents indexed, (4) range of years spanned, and (5) level of indexing and abstracting in five databases which collectively provide extensive coverage of the forestry and forest products industries: AGRICOLA, CAB ABSTRACTS, FOREST PRODUCTS (AIDS), PAPERCHEM, and PIRA. The…
Nakamura, Akira; Kobayashi, Eiji; Takai, Toshiyuki
Immune responses are often regulated by opposing receptor pairs that recognize the same ligand but deliver either activating or inhibitory signals. Paired immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells comprise a major histocompatibility complex class I recognition system that regulates the responsiveness of these cells. Here, activating PIR-A and inhibitory PIR-B bound various mouse major histocompatibility complex class I (H-2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A on macrophages induced intracellular phosphotyrosine signaling. After transfer of allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated graft-versus-host disease, which was due to augmented activation of recipient dendritic cells with concomitant upregulation of PIR-A and increased interferon-gamma production. PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions. PMID:15146181
The immunoglobulin-like receptors provide positive and negative regulation of immune cells upon recognition of various ligands, thus enabling those cells to respond properly to extrinsic stimuli. Murine paired immunoglobulin-like receptor (PIR)-A and PIR-B, a typical receptor pair of the immunoglobulin-like receptor family, are expressed on a wide range of cells in the immune system, such as B cells, mast cells, macrophages and dendritic cells, mostly in a pair-wise fashion. The PIR-A requires the homodimeric Fc receptor common gamma chain for its efficient cell-surface expression and for the delivery of an activation signal. In contrast, PIR-B inhibits receptor-mediated activation signals in vitro upon engagement with other activating-type receptors, such as the antigen receptor on B cells and the high-affinity Fc receptor for immunoglobulin E on mast cells. Recent identification of major histocompatibility complex (MHC) class I molecules as the physiological ligands for PIR has enabled us to attribute various immunological phenotypes observed in PIR-B-deficient mice to the consequences of the absence of a balanced interaction between PIR and MHC class I molecules expressed ubiquitously. Thus, PIR-A and PIR-B constitute a novel and physiologically important MHC class I recognition system. PMID:16011512
Asal, Victor; Rethemeyer, R. Karl; Horgan, John
This paper presents an analysis of the Provisional Irish Republican Army's (PIRA) brigade level behavior during the Northern Ireland Conflict (1970-1998) and identifies the organizational factors that impact a brigade's lethality as measured via terrorist attacks. Key independent variables include levels of technical expertise, cadre age, counter-terrorism policies experienced, brigade size, and IED components and delivery methods. We find that technical expertise within a brigade allows for careful IED usage, which significantly minimizes civilian casualties (a specific strategic goal of PIRA) while increasing the ability to kill more high value targets with IEDs. Lethal counter-terrorism events also significantly affect a brigade's likelihood of killing both civilians and high-value targets but in different ways. Killing PIRA members significantly decreases IED fatalities but also significantly decreases the possibility of zero civilian IED-related deaths in a given year. Killing innocent Catholics in a Brigade's county significantly increases total and civilian IED fatalities. Together the results suggest the necessity to analyze dynamic situational variables that impact terrorist group behavior at the sub-unit level. PMID:25838603
Torii, Ikuko; Oka, Satoshi; Hotomi, Muneki; Benjamin, William H.; Takai, Toshiyuki; Kearney, John F.; Briles, David E.; Kubagawa, Hiromi
Paired immunoglobulin-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many hematopoietic cells including B lymphocytes and myeloid cells. To determine the functional roles of PIR-A and PIR-B in primary bacterial infection, PIR-B-deficient (PIR-B-/-) and wild-type (WT) control mice were injected intravenously with an attenuated strain of Salmonella enterica Typhimurium (WB335). PIR-B-/- mice were found to be more susceptible to Salmonella infection than WT mice as evidenced by high mortality rate, high bacterial loads in the liver and spleen, and a failure to clear bacteria from the circulation. While blood levels of major cytokines and Salmonella-specific antibodies were mostly comparable in the two groups of mice, distinct patterns of inflammatory lesions were found in their livers at 7- to 14-d post-infection: diffuse spreading along the sinusoids in PIR-B-/- mice versus nodular restricted localization in WT mice. PIR-B-/- mice have more inflammatory cells in the liver but fewer B cells and CD8+ T cells in the spleen than WT mice at 14-d post-infection. PIR-B-/- bone marrow-derived macrophages (BMMφ) failed to control intracellular replication of Salmonella in vitro, in part due to inefficient phagosomal oxidant production, when compared with WT BMMφ. PIR-B-/- BMMφ also produced more nitrite and TNFα upon exposure to Salmonella than WT BMMφ. These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection. PMID:18768880
Adhya, Sriya; Noé, John W.
The `Mirage' (Opti-Gone International) is a well-known optics demonstration (PIRA index number 6A20.35) that uses two opposed concave mirrors to project a real image of a small object into space. We studied image formation in the Mirage by standard 2x2 matrix methods and by exact ray tracing, with particular attention to additional real images that can be observed when the mirror separation is increased beyond one focal length. We find that the three readily observed secondary images correspond to 4, 6, or 8 reflections, respectively, contrary to previous reports.
Lee, Chung-Te; Chen, I-Tung; Yang, Yi-Ting; Ko, Tzu-Ping; Huang, Yun-Tzu; Huang, Jiun-Yan; Huang, Ming-Fen; Lin, Shin-Jen; Chen, Chien-Yu; Lin, Shih-Shun; Lightner, Donald V.; Wang, Han-Ching; Wang, Andrew H.-J.; Wang, Hao-Ching; Hor, Lien-I; Lo, Chu-Fang
Acute hepatopancreatic necrosis disease (AHPND) is a severe, newly emergent penaeid shrimp disease caused by Vibrio parahaemolyticus that has already led to tremendous losses in the cultured shrimp industry. Until now, its disease-causing mechanism has remained unclear. Here we show that an AHPND-causing strain of V. parahaemolyticus contains a 70-kbp plasmid (pVA1) with a postsegregational killing system, and that the ability to cause disease is abolished by the natural absence or experimental deletion of the plasmid-encoded homologs of the Photorhabdus insect-related (Pir) toxins PirA and PirB. We determined the crystal structure of the V. parahaemolyticus PirA and PirB (PirAvp and PirBvp) proteins and found that the overall structural topology of PirAvp/PirBvp is very similar to that of the Bacillus Cry insecticidal toxin-like proteins, despite the low sequence identity (<10%). This structural similarity suggests that the putative PirABvp heterodimer might emulate the functional domains of the Cry protein, and in particular its pore-forming activity. The gene organization of pVA1 further suggested that pirABvp may be lost or acquired by horizontal gene transfer via transposition or homologous recombination. PMID:26261348
Barhwal, Kalpana; Das, Saroj K; Kumar, Ashish; Hota, Sunil K; Srivastava, Ravi B
Hypoxia has been reported to cause hippocampal neurodegeneration resulting in learning and memory deficits. In the present study, we investigated the potential of salidroside, a glucoside derivative of tyrosol, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Morris water maze test showed improvement in learning and spatial memory of salidroside-treated hypoxic rats correlating with increased dendritic intersections and arborization. Salidroside administration increased phosphorylation of insulin receptor subunit A (IRA) at Y972, Y1162/63, and Y1146 sites and subsequent activation of AMP-activated protein kinase (AMPK) α subunit isoforms pAMPKα1 and pAMPKα2 resulting in mitochondrial biogenesis. Contrarily, silencing of IRA in salidroside-supplemented hypoxic hippocampal cells could not improve cell viability or alter pAMPKα1 and pAMPKα2 expression. Rats administered with salidroside showed elevated expression of phosphorylated cAMP response element-binding protein in the hippocampus. Salidroside administration also resulted in increased sirtuin 1 (SIRT1) activity through a cytochrome P4502E1 (CYP2E1)-regulated mechanism that was independent of pIRA. Taken together, these findings suggest a synergistic role of pIRA and SIRT1 in salidroside-mediated neuroprotection, mitochondrial biogenesis, and cognitive improvement during hypoxia. We propose a novel mechanism for salidroside-mediated neuroprotection in hypoxia. PMID:26173704
Acuña, M; Eaton, L; Ramírez, N R; Cifuentes, L; Llop, E
We estimated the frequencies of serum butyrylcholinesterase (BChE) alleles in three tribes of Mapuche Indians from southern Chile, using enzymatic methods, and we estimated the frequency of allele BCHE*K in one tribe using primer reduced restriction analysis (PCR-PIRA). The three tribes have different degrees of European admixture, which is reflected in the observed frequencies of the atypical allele BCHE*A: 1.11% in Huilliches, 0.89% in Cuncos, and 0% in Pehuenches. This result is evidence in favor of the hypothesis that BCHE*A is absent in native Amerindians. The frequencies of BCHE*F were higher than in most reported studies (3.89%, 5.78%, and 4.41%, respectively). These results are probably due to an overestimation of the frequency of allele BCHE*F, since none of the 20 BCHE UF individuals (by the enzymatic test) individuals analyzed showed either of the two DNA base substitutions associated with this allele. Although enzymatic methods rarely detect the presence of allele BCHE*K, PCR-PIRA found the allele in an appreciable frequency (5.76%), although lower than that found in other ethnic groups. Since observed frequencies of unusual alleles correspond to estimated percentages of European admixture, it is likely that none of these unusual alleles were present in Mapuche Indians before the arrival of Europeans. PMID:12687586
Most new teachers walk into their new classroom territory and find at least some equipment. Perhaps there are items there that you don't recognize. One way to get those types of questions answered is to post a question and/or picture on the TAP-L (Teaching Apparatus List) listserv (see: http://www.pira-online.org for more information). Within a few short minutes, the sender will receive at least a couple of responses. But what if a new teacher walks into a totally empty prep room? Now that teacher is tasked with purchasing useful equipment, and we know that the opportunity for a similar acquisition in the near future is slim. So you better choose wisely! Whether my new stockroom is well equipped or completely empty, I would make sure to have the following six items in my arsenal.
Sirikharin, Ratchanok; Taengchaiyaphum, Suparat; Sanguanrut, Piyachat; Chi, Thanh Duong; Mavichak, Rapeepat; Proespraiwong, Porranee; Nuangsaeng, Bunlung; Thitamadee, Siripong; Flegel, Timothy W.; Sritunyalucksana, Kallaya
Unique isolates of Vibrio parahaemolyticus (VPAHPND) have previously been identified as the causative agent of acute hepatopancreatic necrosis disease (AHPND) in shrimp. AHPND is characterized by massive sloughing of tubule epithelial cells of the hepatopancreas (HP), proposed to be induced by soluble toxins released from VPAHPND that colonize the shrimp stomach. Since these toxins (produced in broth culture) have been reported to cause AHPND pathology in reverse gavage bioassays with shrimp, we used ammonium sulfate precipitation to prepare protein fractions from broth cultures of VPAHPND isolates for screening by reverse gavage assays. The dialyzed 60% ammonium sulfate fraction caused high mortality within 24–48 hours post-administration, and histological analysis of the moribund shrimp showed typical massive sloughing of hepatopancreatic tubule epithelial cells characteristic of AHPND. Analysis of the active fraction by SDS-PAGE revealed two major bands at marker levels of approximately 16 kDa (ToxA) and 50 kDa (ToxB). Mass spectrometry analysis followed by MASCOT analysis revealed that both proteins had similarity to hypothetical proteins of V. parahaemolyticus M0605 (contig034 GenBank accession no. JALL01000066.1) and similarity to known binary insecticidal toxins called 'Photorhabdus insect related' proteins A and B (Pir-A and Pir-B), respectively, produced by the symbiotic, nematode bacterium Photorhabdus luminescens. In in vivo tests, it was shown that recombinant ToxA and ToxB were both required in a dose dependent manner to cause AHPND pathology, indicating further similarity to Pir-A and -B. A single-step PCR method was designed for detection of the ToxA gene and was validated using 104 bacterial isolates consisting of 51 VPAHPND isolates, 34 non-AHPND VP isolates and 19 other isolates of bacteria commonly found in shrimp ponds (including other species of Vibrio and Photobacterium). The results showed 100% specificity and sensitivity for detection of
Lazardi, K; Urbina, J A; de Souza, W
We report the ultrastructural alterations induced during the proliferative stages of Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, which had previously been shown to be potent growth inhibitors whose effects are potentiated when used in combination (J. A. Urbina, K. Lazardi, T. Aguirre, M. M. Piras, and R. Piras, Antimicrob. Agents Chemother. 32:1237-1242, 1988). Epimastigotes treated with a low concentration of ketoconazole (1 microM), which blocks ergosterol biosynthesis at the level of C-14 demethylation of lanosterol and induces cell lysis coincident with total ergosterol depletion, showed gross alterations of the kinetoplast-mitochondrion complex, which swelled and lost the organization of its inner membrane and the electron-dense bodies of its matrix. Thus, coincident with the beginning of cell lysis, the kinetoplast-mitochondrion complex occupied greater than 80% of the cell volume, while other subcellular structures such as the nucleus and subpellicular microtubules were not affected. Terbinafine, which blocks ergosterol synthesis in these cells at the level of squalene synthetase and thus leads to almost immediate arrest of growth at concentrations greater than 1 microM, produced proliferation of glycosomelike bodies, binucleated cells (arrest at cytokinesis), and eventually massive vacuolization. When the drugs were combined, the predominant effect was mitochondrial swelling, which was more drastic and took place earlier than that observed in cells treated with ketoconazole alone. In amastigotes proliferating in Vero cells, ketoconazole at the concentration required to eradicate the parasites (10 nM) produced mitochondrial swelling, the appearance of autophagic vacuoles containing partially degraded subcellular material, and finally a general breakdown of the subcellular structures. Terbinafine at 3 microM induced more limited ultrastructural damage to
Restrepo, Leda; Bayot, Bonny; Betancourt, Irma; Pinzón, Andres
Vibrio parahaemolyticus is a pathogenic bacteria which has been associated to the early mortality syndrome (EMS) also known as hepatopancreatic necrosis disease (AHPND) causing high mortality in shrimp farms. Pathogenic strains contain two homologous genes related to insecticidal toxin genes, PirA and PirB, these toxin genes are located on a plasmid contained within the bacteria. Genomic sequences have allowed the finding of two strains with a divergent structure related to the geographic region from where they were found. The isolates from the geographic collection of Southeast Asia and Mexico show variable regions on the plasmid genome, indicating that even though they are not alike they still conserve the toxin genes. In this paper, we report for the first time, a pathogenic V. parahaemolyticus strain in shrimp from South America that showed symptoms of AHPND. The genomic analysis revealed that this strain of V. parahaemolyticus found in South America appears to be more related to the Southeast Asia as compared to the Mexican strains. This finding is of major importance for the shrimp industry, especially in regards to the urgent need for disease control strategies to avoid large EMS outbreaks and economic loss, and to determine its dispersion in South America. The whole-genome shotgun project of V. parahaemolyticus strain Ba94C2 have been deposited at DDBJ/EMBL/GenBank under the accession PRJNA335761. PMID:27570736
Villazon, M. F.
Santa Cruz city is built along the Piraí River, part of the Amazonas basin, which has tremendous discharge variability from10 to almost 2000 m3/s. The width goes from 50 to 500 metres. Inflows were calculated and calibrated using a conceptual rainfall-runoff model in hourly time step for 14 years. A hydrodynamic model (Mike11) of the river is implemented and calibrated with two stations. It was found that the roughness coefficient decreases with increasing water level; therefore bed resistance equation in function of the velocity were calibrated for different historical events. The last part of the river has important morphological process during flood events, conceptual modification of the wet area and the hydraulic radio (in different cross sections) is proposed in order to estimate in a better way the water level changes. Even when the model (Mike11) is running with fixed bed, the water levels are well represented. The shape and the time of occurrence of the peak flow in outlet station were well represented with EF greater than 0,7.
Neige, Pascal; Lapierre, Hervé; Merle, Didier
New coleoid cephalopods are described from statolith remains from the Middle Eocene (Middle Lutetian) of the Paris Basin. Fifteen fossil statoliths are identified and assigned to the Sepiidae (Sepia boletzkyi sp. nov.,? Sepia pira sp. nov.), Loliginidae (Loligo clarkei sp. nov.), and Ommastrephidae (genus indet.) families. The sediments containing these fossils indicate permanent aquatic settings in the infralittoral domain. These sediments range in age from 46 Mya to 43 Mya. Analysis of the fossil record of statoliths (from findings described here, together with a review of previously published data) indicates marked biases in our knowledge. Fossil statoliths are known from as far back as the Early Jurassic (199.3 to 190.8 Mya) but surprisingly, to the best of our knowledge, no record occurs in the Cretaceous. This is a “knowledge bias” and clearly calls for further studies. Finally, we attempt to compare findings described here with fossils previously used to constrain divergence and/or diversification ages of some coleoid subclades in molecular phylogenies. This comparison clearly indicates that the new records detailed here will challenge some estimated divergence times of coleoid cephalopod subclades. PMID:27192490
Kraemer, Kathleen E.; Lisse, C. M.; Price, Stephan D.; Mizuno, D.; Walker, R. G.; Farnham, T. L.; Mäkinen, T.
Eight comets, two transition objects (extinct comet candidates), and two near-Earth asteroids were imaged in four infrared bands with the SPIRIT III instrument on the Midcourse Space Experiment, namely, C/1996 B2 (Hyakutake), C/1995 O1 (Hale-Bopp), C/1996 Q1 (Tabur), 126P/IRAS, 22P/Kopff, 46P/Wirtanen, (3200) Phaethon, (4015) 107P/Wilson-Harrington, (4179) Toutatis, (4197) 1982 TA, 125P/Spacewatch, and 55P/Tempel-Tuttle. We present maps of each object detected and a description of their characteristics. Five of the comets had extended dust tails, all of which show evidence for silicate emission in the 8.3 μm band. The comet C/Hyakutake had a strong secondary dust tail along the direction of the comet's motion, which the dynamical models showed was consistent with emission from large particles. The dust trail from P/Kopff was detected more than 2° from the coma in three of the four bands and is probably composed of large particles emitted during the 1996 apparition.
Neige, Pascal; Lapierre, Hervé; Merle, Didier
New coleoid cephalopods are described from statolith remains from the Middle Eocene (Middle Lutetian) of the Paris Basin. Fifteen fossil statoliths are identified and assigned to the Sepiidae (Sepia boletzkyi sp. nov.,? Sepia pira sp. nov.), Loliginidae (Loligo clarkei sp. nov.), and Ommastrephidae (genus indet.) families. The sediments containing these fossils indicate permanent aquatic settings in the infralittoral domain. These sediments range in age from 46 Mya to 43 Mya. Analysis of the fossil record of statoliths (from findings described here, together with a review of previously published data) indicates marked biases in our knowledge. Fossil statoliths are known from as far back as the Early Jurassic (199.3 to 190.8 Mya) but surprisingly, to the best of our knowledge, no record occurs in the Cretaceous. This is a "knowledge bias" and clearly calls for further studies. Finally, we attempt to compare findings described here with fossils previously used to constrain divergence and/or diversification ages of some coleoid subclades in molecular phylogenies. This comparison clearly indicates that the new records detailed here will challenge some estimated divergence times of coleoid cephalopod subclades. PMID:27192490
Fröhlich, Siegmund; Sewing, Dirk
The first large-scale battery recycling facility implementing the hydrometallurgical BATENUS technology is expected to go into operation by 1996. The plant will be situated in Schönebeck/Sachsen-Anhalt, and has a projected maximum capacity of 7500 tons of spent batteries per year. The engineering is being carried out by Keramchemie GmbH and the plant will be operated by Batterierecycling Schönebeck GmbH. The BATENUS process was developed by Pira GmbH, a research institute in Stühlingen, Germany, during a period of five years. This new process combines hydrometallurgical operations in a nearly closed reagent cycle that involves electrochemical and membrane techniques. Effluent emissions are minimized to the greatest possible extent. Process validity has been proven in a series of pilot plant testings. After mechanical separation of the casing materials like ferrous and nonferrous metals, paper and plastics, the subsequent hydrometallurgical recovery yields zinc, copper, nickel and cadmium. The other products are manganese carbonate and a mixture of manganese oxide with carbon black. Mercury is immobilized by absorption on a selective ion-exchange resin. The BATENUS process is a master process for the hydrometallurgical reclamation of metals from secondary raw materials. It has found its first application in the treatment of spent consumer batteries (i.e., mixtures of zinc-carbon, alkaline manganese, lithium, nickel-cadmium cells, etc.). As a result of its modular process design, the individual steps can be modified easily and adapted to accommodate variations in the contents of the secondary raw materials. Further applications of this highly flexible technology are planned for the future.
Montero-Herradón, Sara; García-Ceca, Javier; Sánchez Del Collado, Beatriz; Alfaro, David; Zapata, Agustín G
Thymus development is a complex process in which cell-to-cell interactions between thymocytes and thymic epithelial cells (TECs) are essential to allow a proper maturation of both thymic cell components. Although signals that control thymocyte development are well known, mechanisms governing TEC maturation are poorly understood, especially those that regulate the maturation of immature TEC populations during early fetal thymus development. In this study, we show that EphB2-deficient, EphB2LacZ and EphB3-deficient fetal thymuses present a lower number of cells and delayed maturation of DN cell subsets compared to WT values. Moreover, deficits in the production of chemokines, known to be involved in the lymphoid seeding into the thymus, contribute in decreased proportions of intrathymic T cell progenitors (PIRA/B(+)) in the mutant thymuses from early stages of development. These features correlate with increased proportions of MTS20(+) cells but fewer MTS20(-) cells from E13.5 onward in the deficient thymuses, suggesting a delayed development of the first epithelial cells. In addition, in vitro the lack of thymocytes or the blockade of Eph/ephrin-B-mediated cell-to-cell interactions between either thymocytes-TECs or TECs-TECs in E13.5 fetal thymic lobes coursed with increased proportions of MTS20(+) TECs. This confirms, for the first time, that the presence of CD45(+) cells, corresponding at these stages to DN1 and DN2 cells, and Eph/ephrin-B-mediated heterotypic or homotypic cell interactions between thymocytes and TECs, or between TECs and themselves, contribute to the early maturation of MTS20(+) TECs. PMID:27060907
Hegg, Jens C.; Giarrizzo, Tommaso; Kennedy, Brian P.
Animal migrations provide important ecological functions and can allow for increased biodiversity through habitat and niche diversification. However, aquatic migrations in general, and those of the world’s largest fish in particular, are imperiled worldwide and are often poorly understood. Several species of large Amazonian catfish carry out some of the longest freshwater fish migrations in the world, travelling from the Amazon River estuary to the Andes foothills. These species are important apex predators in the main stem rivers of the Amazon Basin and make up the region’s largest fishery. They are also the only species to utilize the entire Amazon Basin to complete their life cycle. Studies indicate both that the fisheries may be declining due to overfishing, and that the proposed and completed dams in their upstream range threaten spawning migrations. Despite this, surprisingly little is known about the details of these species’ migrations, or their life history. Otolith microchemistry has been an effective method for quantifying and reconstructing fish migrations worldwide across multiple spatial scales and may provide a powerful tool to understand the movements of Amazonian migratory catfish. Our objective was to describe the migratory behaviors of the three most populous and commercially important migratory catfish species, Dourada (Brachyplatystoma rousseauxii), Piramutaba (Brachyplatystoma vaillantii), and Piraíba (Brachyplatystoma filamentosum). We collected fish from the mouth of the Amazon River and the Central Amazon and used strontium isotope signatures (87Sr/86Sr) recorded in their otoliths to determine the location of early rearing and subsequent. Fish location was determined through discriminant function classification, using water chemistry data from the literature as a training set. Where water chemistry data was unavailable, we successfully in predicted 87Sr/86Sr isotope values using a regression-based approach that related the geology of
Background The kynurenine (KYN) pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS) including infectious diseases such as bacterial meningitis (BM). The aim of this study was to assess single nucleotide polymorphisms (SNPs) in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM. Methods One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene), kynureninase (KYNU gene), kynurenine aminotransferase I (CCBL1 gene), and kynurenine aminotransferase II (AADAT gene). SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR) followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG) by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay. Results The variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p < 0.05) in TNF-α, IL-1β, IL-6, MIP-1αCCL3 and MIP-1β/CCL4 levels was observed in BM patients homozygous (TT) to the SNP AADAT+401C/T. Furthermore, a significant (p < 0.05) decrease in cell count was observed in cerebrospinal fluid (CSF) from patients with TT genotype. In addition, an increase in the IgG level in adults (p < 0.05) was observed. The variant allele for KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population. Conclusions This study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM. PMID:21473761
Hegg, Jens C; Giarrizzo, Tommaso; Kennedy, Brian P
Animal migrations provide important ecological functions and can allow for increased biodiversity through habitat and niche diversification. However, aquatic migrations in general, and those of the world's largest fish in particular, are imperiled worldwide and are often poorly understood. Several species of large Amazonian catfish carry out some of the longest freshwater fish migrations in the world, travelling from the Amazon River estuary to the Andes foothills. These species are important apex predators in the main stem rivers of the Amazon Basin and make up the region's largest fishery. They are also the only species to utilize the entire Amazon Basin to complete their life cycle. Studies indicate both that the fisheries may be declining due to overfishing, and that the proposed and completed dams in their upstream range threaten spawning migrations. Despite this, surprisingly little is known about the details of these species' migrations, or their life history. Otolith microchemistry has been an effective method for quantifying and reconstructing fish migrations worldwide across multiple spatial scales and may provide a powerful tool to understand the movements of Amazonian migratory catfish. Our objective was to describe the migratory behaviors of the three most populous and commercially important migratory catfish species, Dourada (Brachyplatystoma rousseauxii), Piramutaba (Brachyplatystoma vaillantii), and Piraíba (Brachyplatystoma filamentosum). We collected fish from the mouth of the Amazon River and the Central Amazon and used strontium isotope signatures ((87)Sr/(86)Sr) recorded in their otoliths to determine the location of early rearing and subsequent. Fish location was determined through discriminant function classification, using water chemistry data from the literature as a training set. Where water chemistry data was unavailable, we successfully in predicted (87)Sr/(86)Sr isotope values using a regression-based approach that related the geology
Rodríguez-Rodríguez, Laura; Jiménez-Sánchez, Montserrat; Domínguez-Cuesta, María Jose; Rinterknecht, Vincent; Pallàs, Raimon; Braucher, Régis; Bourlès, Didier; Valero-Garcés, Blas
., 2011. Last deglaciation in northwestern Spain: New chronological and geomorphologic evidence from the Sanabria region. Geomorphology 135, 48-65. Palacios, D., Andrés, N., Úbeda, J., Alcalá, J., Marcos, J., Vázquez-Selem, L., 2012. The importance of poligenic moraines in the paleoclimatic interpretation from cosmogenic dating. Geophysical Research Abstracts 14, EGU2012-3759-1. Pérez-Alberti, A., Valcárcel-Díaz, M., Martini, I.P., Pascucci, V., Andrucci, S., 2011. Upper Pleistocene glacial valley-junction sediments at Pias, Trevinca Mountains, NW Spain. In: Martini, I.P., French, H.M., Pérez-Alberti, A. (Eds.), Ice-Marginal and Periglacial Processes and Sediments. Geological Society (London) Special Publication 354, pp. 93-110. Research funded by the projects LIMNOCLIBER (REN2003-09130-C02-02), IBERLIMNO (CGL2005-20236-E/CLI), LIMNOCAL (CGL2006-13327-C04-01) and GRACCIE (CSD2007-00067) of the Spanish Inter-Ministry Commission of Science and Technology (CICYT). Additional funding was provided by the Fundación Patrimonio Natural de Castilla y León through the project "La investigacion en el Lago de Sanabria dentro del proyecto CALIBRE: perspectivas y posibilidades", and by the projects Consolider Ingenio 2006 (CSD2006-0041, Topo-Iberia), 2003 PIRA 00256, HF02.4, and RISKNAT (2009SGR520). L. Rodríguez-Rodríguez has developed her research under a Severo Ochoa Programme fellowship (FICYT- Asturias).
Concerning comets: C/1984 N1 (Austin), C/1984 V1 (Levy-Rudenko), C/1991 B1 (Shoemaker-Levy), C/1993 Q1 (Mueller), C/1995 O1 (Hale-Bopp), C/1995 Q1 (Bradfield), C/1995 Q2 (Hartley-Drinkwater), C/1996 B2 (Hyakutake), C/1996 E1 (NEAT), C/1997 D1 (Mueller), C/1997 J1 (Mueller), C/1997 J2 (Meunier-Dupouy), C/1997 L1 (Zhu-Balam), C/1997 P2 (Spacewatch), C/1997 T1 (Utsunomiya), C/1998 H1 (Stonehouse), C/1998 J1 (SOHO), C/1998 K1 (Mueller), C/1998 K3 (LINEAR), C/1998 K5 (LINEAR), C/1998 M1 (LINEAR), C/1998 M2 (LINEAR), C/1998 M3 (Larsen), C/1998 M4 (LINEAR), C/1998 M5 (LINEAR), C/1998 M6 (Montani), C/1998 P1 (Williams), C/1998 Q1 (LINEAR), C/1998 T1 (LINEAR), C/1998 U1 (LINEAR), C/1998 U5 (LINEAR), 2P/Encke, 4P/Faye, 6P/d'Arrest, 7P/Pons-Winnecke, 8P/Tuttle, 9P/Tempel 1, 10P/Tempel 2, 15P/Finlay, 16P/Brooks 2, 19P/Borrelly, 21P/Giacobini-Zinner, 22P/Kopff, 23P/Brorsen-Metcalf, 29P/Schwassmann-Wachmann 1, 30P/Reinmuth 1, 31P/Schwassmann-Wachmann 2, 32P/Comas Solá, 36P/Whipple, 37P/Forbes, 41P/Tuttle-Giacobini-Kresák, 42P/Neujmin, 43P/Wolf-Harrington, 45P/Honda-Mrkos-Pajdušáková, 46P/Wirtanen, 47P/Ashbrook-Jackson, 49P/Arend-Rigaux, 51P/Harrington, 52P/Harrington-Abell, 55P/Tempel-Tuttle, 58P/Jackson-Neujmin, 59P/Kearns-Kwee, 62P/Tsuchinshan 1, 65P/Gunn, 67P/Churyumov-Gerasimenko, 68P/Klemola, 69P/Taylor, 70P/Kojima, 73P/Schwassmann-Wachmann 3, 74P/Smirnova-Chernykh, 75P/Kohoutek, 78P/Gehrels 2, 81P/Wild 2, 82P/Gehrels 3, 85P/Boethin, 86P/Wild 3, 87P/Bus, 88P/Howell, 89P/Russell 2, 91P/Russell 3, 93P/Lovas 1, 94P/Russell 4, 96P/Machholz 1, 103P/Hartley 2, 104P/Kowal 2, 111P/Helin-Roman-Crockett, 112P/Urata-Niijima, 114P/Wiseman-Skiff, 115P/Maury, 117P/Helin-Roman-Alu 1, 118P/Shoemaker-Levy 4, 119P/Parker-Hartley, 120P/Mueller 1, 123P/West-Hartley, 124P/Mrkos, 125P/Spacewatch, 126P/IRAS, 127P/Holt-Olmstead, 128P/Shoemaker-Holt 1, 129P/Shoemaker-Levy 3, 130P/McNaught-Hughes, 132P/Helin-Roman-Alu 2, 136P/Mueller 3, 138P/Shoemaker-Levy 7, P/1988 V1 (Ge-Wang), P/1993 X1