Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase

PubMed Central

Sareen, Archana; Chaudhury, Indrajit; Adams, Nicole; Sobeck, Alexandra

2012-01-01

Fanconi anemia (FA) pathway members, FANCD2 and FANCI, contribute to the repair of replication-stalling DNA lesions. FA pathway activation relies on phosphorylation of FANCI by the ataxia telangiectasia and Rad3-related (ATR) kinase, followed by monoubiquitination of FANCD2 and FANCI by the FA core complex. FANCD2 and FANCI are thought to form a functional heterodimer during DNA repair, but it is unclear how dimer formation is regulated or what the functions of the FANCD2–FANCI complex versus the monomeric proteins are. We show that the FANCD2–FANCI complex forms independently of ATR and FA core complex, and represents the inactive form of both proteins. DNA damage-induced FA pathway activation triggers dissociation of FANCD2 from FANCI. Dissociation coincides with FANCD2 monoubiquitination, which significantly precedes monoubiquitination of FANCI; moreover, monoubiquitination responses of FANCD2 and FANCI exhibit distinct DNA substrate specificities. A phosphodead FANCI mutant fails to dissociate from FANCD2, whereas phosphomimetic FANCI cannot interact with FANCD2, indicating that FANCI phosphorylation is the molecular trigger for FANCD2–FANCI dissociation. Following dissociation, FANCD2 binds replicating chromatin prior to—and independently of—FANCI. Moreover, the concentration of chromatin-bound FANCD2 exceeds that of FANCI throughout replication. Our results suggest that FANCD2 and FANCI function separately at consecutive steps during DNA repair in S-phase. PMID:22753026

Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage

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

Noda, Taichi; Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521; Takahashi, Akihisa

2011-01-07

The role of the Fanconi anemia (FA) repair pathway for DNA damage induced by formaldehyde was examined in the work described here. The following cell types were used: mouse embryonic fibroblast cell lines FANCA{sup -/-}, FANCC{sup -/-}, FANCA{sup -/-}C{sup -/-}, FANCD2{sup -/-} and their parental cells, the Chinese hamster cell lines FANCD1 mutant (mt), FANCGmt, their revertant cells, and the corresponding wild-type (wt) cells. Cell survival rates were determined with colony formation assays after formaldehyde treatment. DNA double strand breaks (DSBs) were detected with an immunocytochemical {gamma}H2AX-staining assay. Although the sensitivity of FANCA{sup -/-}, FANCC{sup -/-} and FANCA{sup -/-}C{sup -/-}more » cells to formaldehyde was comparable to that of proficient cells, FANCD1mt, FANCGmt and FANCD2{sup -/-} cells were more sensitive to formaldehyde than the corresponding proficient cells. It was found that homologous recombination (HR) repair was induced by formaldehyde. In addition, {gamma}H2AX foci in FANCD1mt cells persisted for longer times than in FANCD1wt cells. These findings suggest that formaldehyde-induced DSBs are repaired by HR through the FA repair pathway which is independent of the FA nuclear core complex. -- Research highlights: {yields} We examined to clarify the repair pathways of formaldehyde-induced DNA damage. Formaldehyde induces DNA double strand breaks (DSBs). {yields} DSBs are repaired through the Fanconi anemia (FA) repair pathway. {yields} This pathway is independent of the FA nuclear core complex. {yields} We also found that homologous recombination repair was induced by formaldehyde.« less

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair

PubMed Central

Yang, Hui; Zhang, Tianlong; Tao, Ye; Wang, Fang; Tong, Liang; Ding, Jianping

2013-01-01

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair. PMID:24003026

Constitutive role of the Fanconi anemia D2 gene in the replication stress response.

PubMed

Tian, Yanyan; Shen, Xi; Wang, Rui; Klages-Mundt, Naeh L; Lynn, Erica J; Martin, Sara K; Ye, Yin; Gao, Min; Chen, Junjie; Schlacher, Katharina; Li, Lei

2017-12-08

In response to DNA cross-linking damage, the Fanconi anemia (FA) core complex activates the FA pathway by monoubiquitinating Fanconi anemia complementation group D2 (FANCD2) for the initiation of the nucleolytic processing of the DNA cross-links and stabilization of stalled replication forks. Given that all the classic FA proteins coordinately monoubiquitinate FANCD2, it is unclear why losses of individual classic FA genes yield varying cellular sensitivities to cross-linking damage. To address this question, we generated cellular knock-out models of FA core complex components and FANCD2 and found that FANCD2-null mutants display higher levels of spontaneous chromosomal damage and hypersensitivity to replication-blocking lesions than Fanconi anemia complementation group L (FANCL)-null mutants, suggesting that FANCD2 provides a basal level of DNA protection countering endogenous lesions in the absence of monoubiquitination. FANCD2's ubiquitination-independent function is likely involved in optimized recruitment of nucleolytic activities for the processing and protection of stressed replication forks. Our results reveal that FANCD2 has a ubiquitination-independent role in countering endogenous levels of replication stress, a function that is critical for the maintenance of genomic stability. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Multiple TPR motifs characterize the Fanconi anemia FANCG protein.

PubMed

Blom, Eric; van de Vrugt, Henri J; de Vries, Yne; de Winter, Johan P; Arwert, Fré; Joenje, Hans

2004-01-05

The genome protection pathway that is defective in patients with Fanconi anemia (FA) is controlled by at least eight genes, including BRCA2. A key step in the pathway involves the monoubiquitylation of FANCD2, which critically depends on a multi-subunit nuclear 'core complex' of at least six FANC proteins (FANCA, -C, -E, -F, -G, and -L). Except for FANCL, which has WD40 repeats and a RING finger domain, no significant domain structure has so far been recognized in any of the core complex proteins. By using a homology search strategy comparing the human FANCG protein sequence with its ortholog sequences in Oryzias latipes (Japanese rice fish) and Danio rerio (zebrafish) we identified at least seven tetratricopeptide repeat motifs (TPRs) covering a major part of this protein. TPRs are degenerate 34-amino acid repeat motifs which function as scaffolds mediating protein-protein interactions, often found in multiprotein complexes. In four out of five TPR motifs tested (TPR1, -2, -5, and -6), targeted missense mutagenesis disrupting the motifs at the critical position 8 of each TPR caused complete or partial loss of FANCG function. Loss of function was evident from failure of the mutant proteins to complement the cellular FA phenotype in FA-G lymphoblasts, which was correlated with loss of binding to FANCA. Although the TPR4 mutant fully complemented the cells, it showed a reduced interaction with FANCA, suggesting that this TPR may also be of functional importance. The recognition of FANCG as a typical TPR protein predicts this protein to play a key role in the assembly and/or stabilization of the nuclear FA protein core complex.

[Data mining analysis of professor Li Fa-zhi AIDS itchy skin medical record].

PubMed

Wang, Dan-Ni; Li, Zhen; Xu, Li-Ran; Guo, Hui-Jun

2013-08-01

Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of itchy skin, provide the corresponding drug reference basis for Chinese medicine treatment of AIDS, skin itching. By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS patients with skin pruritus, etiology and pathogenesis analysis, skin itching AIDS syndrome differentiation of old Chinese medicine treatment and medication rule. The use of multi-dimensional query analysis, core drug skin itching AIDS treatment in this study as a windbreak, cicada slough, bupleurum, Qufeng solution table drug, licorice detoxification efficacy of drugs, Radix Scutellariae, Kochia scoparia, clearing away heat and promoting diuresis medicine; core prescription for Jingfang San streak virus. Professor Li Fa-zhi treatment of AIDS in the skin itching Qufeng solution table dehumidification antipruritic treatment.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

PubMed

Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-08-16

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

Replication Protein A (RPA) deficiency activates the Fanconi anemia DNA repair pathway.

PubMed

Jang, Seok-Won; Jung, Jin Ki; Kim, Jung Min

2016-09-01

The Fanconi anemia (FA) pathway regulates DNA inter-strand crosslink (ICL) repair. Despite our greater understanding of the role of FA in ICL repair, its function in the preventing spontaneous genome instability is not well understood. Here, we show that depletion of replication protein A (RPA) activates the FA pathway. RPA1 deficiency increases chromatin recruitment of FA core complex, leading to FANCD2 monoubiquitination (FANCD2-Ub) and foci formation in the absence of DNA damaging agents. Importantly, ATR depletion, but not ATM, abolished RPA1 depletion-induced FANCD2-Ub, suggesting that ATR activation mediated FANCD2-Ub. Interestingly, we found that depletion of hSSB1/2-INTS3, a single-stranded DNA-binding protein complex, induces FANCD2-Ub, like RPA1 depletion. More interestingly, depletion of either RPA1 or INTS3 caused increased accumulation of DNA damage in FA pathway deficient cell lines. Taken together, these results indicate that RPA deficiency induces activation of the FA pathway in an ATR-dependent manner, which may play a role in the genome maintenance.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

PubMed Central

Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-01-01

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway. PMID:27449087

Genomic instability in mice is greater in Fanconi anemia caused by deficiency of Fancd2 than Fancg.

PubMed

Reliene, Ramune; Yamamoto, Mitsuko L; Rao, P Nagesh; Schiestl, Robert H

2010-12-01

Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects, and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), nonhomologous end joining, and translesion synthesis (TLS). Fancd2(-/-) mice have a more severe phenotype than Fancg(-/-), and other FA core complex-deficient mice, although both Fancg and Fancd2 belong to the same FA pathway. We hypothesized that Fancd2 deficiency results in a more severe phenotype because Fancd2 also has a FA pathway-independent function in the maintenance of genomic integrity. To test this hypothesis, we determined the level of DNA damage and genomic instability in Fancd2(-/-), Fancg(-/-), and wild-type controls. Fancd2(-/-) mice displayed a higher magnitude of chromosomal breakage and micronucleus formation than the wild-type or Fancg(-/-) mice. Also, DNA strand breaks were increased in Fancd2(-/-) but not in Fancg(-/-) mice. In addition, Fancd2(-/-) mice displayed an elevated frequency of DNA deletions, resulting from HR at the endogenous p(un) locus. In contrast, in Fancg(-/-) mice, the frequency of DNA deletions was decreased. Thus, Fancd2 but not Fancg deficiency results in elevated chromosomal/DNA breakage and permanent genome rearrangements. This provides evidence that Fancd2 plays an additional role in the maintenance of genomic stability than Fancg, which might explain the higher predisposition to cancer seen in the Fancd2(-/-) mice.

RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway.

PubMed

Xie, Jenny; Kim, Hyungjin; Moreau, Lisa A; Puhalla, Shannon; Garber, Judy; Al Abo, Muthana; Takeda, Shunichi; D'Andrea, Alan D

2015-04-01

The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity, and the gene encoding RNF4 was epistatic with the other genes encoding members of the FA/BRCA pathway. Together, the results from our study underscore the importance of analyzing unique patient-derived mutations for dissecting complex DNA repair processes.

RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway

PubMed Central

Xie, Jenny; Kim, Hyungjin; Moreau, Lisa A.; Puhalla, Shannon; Garber, Judy; Al Abo, Muthana; Takeda, Shunichi; D’Andrea, Alan D.

2015-01-01

The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4–mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity, and the gene encoding RNF4 was epistatic with the other genes encoding members of the FA/BRCA pathway. Together, the results from our study underscore the importance of analyzing unique patient-derived mutations for dissecting complex DNA repair processes. PMID:25751062

FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

PubMed Central

Ali, Abdullah Mahmood; Singh, Thiyam Ramsing; Meetei, Amom Ruhikanta

2009-01-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and –M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins. PMID:19379763

Unifying principles in homodimeric type I photosynthetic reaction centers: properties of PscB and the FA, FB and FX iron-sulfur clusters in green sulfur bacteria.

PubMed

Jagannathan, Bharat; Golbeck, John H

2008-12-01

The photosynthetic reaction center from the green sulfur bacterium Chlorobium tepidum (CbRC) was solubilized from membranes using Triton X-100 and isolated by sucrose density ultra-centrifugation. The CbRC complexes were subsequently treated with 0.5 M NaCl and ultrafiltered over a 100 kDa cutoff membrane. The resulting CbRC cores did not exhibit the low-temperature EPR resonances from FA- and FB- and were unable to reduce NADP+. SDS-PAGE and mass spectrometric analysis showed that the PscB subunit, which harbors the FA and FB clusters, had become dissociated, and was now present in the filtrate. Attempts to rebind PscB onto CbRC cores were unsuccessful. Mössbauer spectroscopy showed that recombinant PscB contains a heterogeneous mixture of [4Fe-4S]2+,1+ and other types of Fe/S clusters tentatively identified as [2Fe-2S]2+,1+ clusters and rubredoxin-like Fe3+,2+ centers, and that the [4Fe-4S]2+,1+ clusters which were present were degraded at high ionic strength. Quantitative analysis confirmed that the amount of iron and sulfide in the recombinant protein was sub-stoichiometric. A heme-staining assay indicated that cytochrome c551 remained firmly attached to the CbRC cores. Low-temperature EPR spectroscopy of photoaccumulated CbRC complexes and CbRC cores showed resonances between g=5.4 and 4.4 assigned to a S=3/2 ground spin state [4Fe-4S]1+ cluster and at g=1.77 assigned to a S=1/2 ground spin state [4Fe-4S]1+ cluster, both from FX-. These results unify the properties of the acceptor side of the Type I homodimeric reaction centers found in green sulfur bacteria and heliobacteria: in both, the FA and FB iron-sulfur clusters are present on a salt-dissociable subunit, and FX is present as an interpolypeptide [4Fe-4S]2+,1+ cluster with a significant population in a S=3/2 ground spin state.

The Common Core State Standards: An Opportunity to Enhance Formative Assessment in History/Social Studies Classrooms

ERIC Educational Resources Information Center

Ateh, Comfort M.; Wyngowski, Aaron J.

2015-01-01

This article discusses the opportunity that the Common Core State Standards (CCSS) present for enhancing formative assessment (FA) in history and social studies classrooms. There is evidence that FA can enhance learning for students if implemented well. Unfortunately, teachers continue to be challenged in implementing FA in their classrooms. We…

Upregulated ATM gene expression and activated DNA crosslink-induced damage response checkpoint in Fanconi anemia: implications for carcinogenesis.

PubMed

Yamamoto, Kazuhiko; Nihrane, Abdallah; Aglipay, Jason; Sironi, Juan; Arkin, Steven; Lipton, Jeffrey M; Ouchi, Toru; Liu, Johnson M

2008-01-01

Fanconi anemia (FA) predisposes to hematopoietic failure, birth defects, leukemia, and squamous cell carcinoma of the head and neck (HNSCC) and cervix. The FA/BRCA pathway includes 8 members of a core complex and 5 downstream gene products closely linked with BRCA1 or BRCA2. Precancerous lesions are believed to trigger the DNA damage response (DDR), and we focused on the DDR in FA and its putative role as a checkpoint barrier to cancer. In primary fibroblasts with mutations in the core complex FANCA protein, we discovered that basal expression and phosphorylation of ATM (ataxia telangiectasia mutated) and p53 induced by irradiation (IR) or mitomycin C (MMC) were upregulated. This heightened response appeared to be due to increased basal levels of ATM in cultured FANCA-mutant cells, highlighting the new observation that ATM can be regulated at the transcriptional level in addition to its well-established activation by autophosphorylation. Functional analysis of this response using gamma-H2AX foci as markers of DNA double-stranded breaks (DSBs) demonstrated abnormal persistence of only MMC- and not IR-induced foci. Thus, we describe a processing defect that leads to general DDR upregulation but specific persistence of DNA crosslinker-induced damage response foci. Underscoring the significance of these findings, we found resistance to DNA crosslinker-induced cell cycle arrest and apoptosis in a TP53-mutant, patient-derived HNSCC cell line, whereas a lymphoblastoid cell line derived from this same individual was not mutated at TP53 and retained DNA crosslinker sensitivity. Our results suggest that cancer in FA may arise from selection for cells that escape from a chronically activated DDR checkpoint.

Assessing the Spectrum of Germline Variation in Fanconi Anemia Genes among Patients with Head and Neck Carcinoma before Age 50

PubMed Central

Chandrasekharappa, Settara C.; Chinn, Steven B.; Donovan, Frank X.; Chowdhury, Naweed I.; Kamat, Aparna; Adeyemo, Adebowale A.; Thomas, James W.; Vemulapalli, Meghana; Hussey, Caroline S.; Reid, Holly H.; Mullikin, James C.; Wei, Qingyi; Sturgis, Erich M.

2018-01-01

Patients with Fanconi anemia (FA) have increased risk for head and neck squamous cell carcinoma (HNSCC). We sought to determine the prevalence of undiagnosed FA and FA carriers in patients with HNSCC and an age cutoff for FA genetic screening. Screening germline DNA from 417 HNSCC patients under age 50 revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, nine indels, one large deletion, and one synonymous variant predicted to effect splicing. 108 patients (26%) had at least one rare variant predicted to be damaging, and 57 (14%) had at least one rare variant predicted to be damaging and previously reported. Fifteen patients carried two rare variants, or an X-linked variant, in an FA gene. Overall, we did not identify an age cutoff for FA screening among young HNSCC patients, as there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, we observed an increased burden, or mutation load, of FA gene variants in FANCD2, FANCE, and FANCL in our HNSCC patient cohort relative to the 1000 Genomes population. FANCE and FANCL, components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. FA germline functional variants offer a novel area of study in HNSCC tumorigenesis, and the increased mutation burden of critical genes indicates the importance of the FA pathway in HNSCC. PMID:28678401

RfpA, RfpB, and RfpC are the master control elements of far-red light photoacclimation (FaRLiP)

DOE PAGES

Zhao, Chi; Gan, Fei; Shen, Gaozhong; ...

2015-11-25

Terrestrial cyanobacteria often occur in niches tha tare strongly enriched in far-redlight (FRL; λ > 700nm). Some cyanobacteria exhibit a complex and extensive photoacclimation response, known as FRLphotoacclimation(FaRLiP).During the FaRLiP response, specialized paralogous proteins replace 17 core subunits of the three major photosynthetic complexes: Photosystem (PS)I, PSII,and the phycobilisome. Additionally, the cells synthesize both chlorophyll (Chl) f and Chl d.Using biparental mating from Escherichia coli, we constructed null mutants of three genes, rfpA, rfpB,and rfpC, in the cyanobacteria Chlorogloeopsis fritschii PCC 9212 and Chroococcidiopsis thermalis PCC 7203.The resulting mutants were no longer able to modify their photosynthetic apparatus to absorbmore » FRL, were no longer able to synthesize Chl f, in appropriately synthesized Chl d in white light,and were unable to transcribe genes of the FaRLiP gene cluster. We conclude that RfpA, RfpB, and RfpC constitute a FRL-activated signal transduction cascade that is the master control switch for the FaRLiP response. FRL is proposed to activate (or inactivate) the histidine kinase activity of RfpA, which leads to formation of the active state of RfpB, the key response regulator and transcription activator. RfpC may act as a phosphate shuttle between RfpA and RfpB. Our results show that reverse genetics via conjugation will be a powerful approach in detailed studies of the FaRLiP response.« less

RfpA, RfpB, and RfpC are the master control elements of far-red light photoacclimation (FaRLiP)

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

Zhao, Chi; Gan, Fei; Shen, Gaozhong

Terrestrial cyanobacteria often occur in niches tha tare strongly enriched in far-redlight (FRL; λ > 700nm). Some cyanobacteria exhibit a complex and extensive photoacclimation response, known as FRLphotoacclimation(FaRLiP).During the FaRLiP response, specialized paralogous proteins replace 17 core subunits of the three major photosynthetic complexes: Photosystem (PS)I, PSII,and the phycobilisome. Additionally, the cells synthesize both chlorophyll (Chl) f and Chl d.Using biparental mating from Escherichia coli, we constructed null mutants of three genes, rfpA, rfpB,and rfpC, in the cyanobacteria Chlorogloeopsis fritschii PCC 9212 and Chroococcidiopsis thermalis PCC 7203.The resulting mutants were no longer able to modify their photosynthetic apparatus to absorbmore » FRL, were no longer able to synthesize Chl f, in appropriately synthesized Chl d in white light,and were unable to transcribe genes of the FaRLiP gene cluster. We conclude that RfpA, RfpB, and RfpC constitute a FRL-activated signal transduction cascade that is the master control switch for the FaRLiP response. FRL is proposed to activate (or inactivate) the histidine kinase activity of RfpA, which leads to formation of the active state of RfpB, the key response regulator and transcription activator. RfpC may act as a phosphate shuttle between RfpA and RfpB. Our results show that reverse genetics via conjugation will be a powerful approach in detailed studies of the FaRLiP response.« less

RfpA, RfpB, and RfpC are the Master Control Elements of Far-Red Light Photoacclimation (FaRLiP)

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

Zhao, Chi; Gan, Fei; Shen, Gaozhong

Terrestrial cyanobacteria often occur in niches that are strongly enriched in far-red light (FRL; λ > 700 nm). Some cyanobacteria exhibit a complex and extensive photoacclimation response, known as FRL photoacclimation (FaRLiP). During the FaRLiP response, specialized paralogous proteins replace 17 core subunits of the three major photosynthetic complexes: Photosystem (PS) I, PS II, and the phycobilisome. Additionally, the cells synthesize both chlorophyll (Chl) f and Chl d. Using biparental mating from Escherichia coli, we constructed null mutants of three genes, rfpA, rfpB, and rfpC, in the cyanobacteria Chlorogloeopsis fritschii PCC 9212 and Chroococcidiopsis thermalis PCC 7203. The resulting mutantsmore » were no longer able to modify their photosynthetic apparatus to absorb FRL, were no longer able to synthesize Chl f, inappropriately synthesized Chl d in white light, and were unable to transcribe genes of the FaRLiP gene cluster. We conclude that RfpA, RfpB, and RfpC constitute a FRL-activated signal transduction cascade that is the master control switch for the FaRLiP response. FRL is proposed to activate (or inactivate) the histidine kinase activity of RfpA, which leads to formation of the active state of RfpB, the key response regulator and transcription activator. RfpC may act as a phosphate shuttle between RfpA and RfpB. Our results show that reverse genetics via conjugation will be a powerful approach in detailed studies of the FaRLiP response.« less

Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia.

PubMed

Rickman, Kimberly A; Lach, Francis P; Abhyankar, Avinash; Donovan, Frank X; Sanborn, Erica M; Kennedy, Jennifer A; Sougnez, Carrie; Gabriel, Stacey B; Elemento, Olivier; Chandrasekharappa, Settara C; Schindler, Detlev; Auerbach, Arleen D; Smogorzewska, Agata

2015-07-07

Fanconi anemia (FA) is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs). Mutations in 17 genes (FANCA-FANCS) have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2), UBE2T. UBE2T is known to interact with FANCL, the E3 ubiquitin-ligase component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following treatment with mitomycin C, and are hypersensitive to crosslinking agents. These cellular defects are complemented by expression of wild-type UBE2T, demonstrating that deficiency of the protein UBE2T can lead to Fanconi anemia. UBE2T gene gains an alias of FANCT. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Heuristic rules embedded genetic algorithm for in-core fuel management optimization

NASA Astrophysics Data System (ADS)

Alim, Fatih

The objective of this study was to develop a unique methodology and a practical tool for designing loading pattern (LP) and burnable poison (BP) pattern for a given Pressurized Water Reactor (PWR) core. Because of the large number of possible combinations for the fuel assembly (FA) loading in the core, the design of the core configuration is a complex optimization problem. It requires finding an optimal FA arrangement and BP placement in order to achieve maximum cycle length while satisfying the safety constraints. Genetic Algorithms (GA) have been already used to solve this problem for LP optimization for both PWR and Boiling Water Reactor (BWR). The GA, which is a stochastic method works with a group of solutions and uses random variables to make decisions. Based on the theories of evaluation, the GA involves natural selection and reproduction of the individuals in the population for the next generation. The GA works by creating an initial population, evaluating it, and then improving the population by using the evaluation operators. To solve this optimization problem, a LP optimization package, GARCO (Genetic Algorithm Reactor Code Optimization) code is developed in the framework of this thesis. This code is applicable for all types of PWR cores having different geometries and structures with an unlimited number of FA types in the inventory. To reach this goal, an innovative GA is developed by modifying the classical representation of the genotype. To obtain the best result in a shorter time, not only the representation is changed but also the algorithm is changed to use in-core fuel management heuristics rules. The improved GA code was tested to demonstrate and verify the advantages of the new enhancements. The developed methodology is explained in this thesis and preliminary results are shown for the VVER-1000 reactor hexagonal geometry core and the TMI-1 PWR. The improved GA code was tested to verify the advantages of new enhancements. The core physics code used for VVER in this research is Moby-Dick, which was developed to analyze the VVER by SKODA Inc. The SIMULATE-3 code, which is an advanced two-group nodal code, is used to analyze the TMI-1.

Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer drugs.

PubMed

Feng, Shini; Zhang, Huijie; Yan, Ting; Huang, Dandi; Zhi, Chunyi; Nakanishi, Hideki; Gao, Xiao-Dong

With its unique physical and chemical properties and structural similarity to carbon, boron nitride (BN) has attracted considerable attention and found many applications. Biomedical applications of BN have recently started to emerge, raising great hopes in drug and gene delivery. Here, we developed a targeted anticancer drug delivery system based on folate-conjugated BN nanospheres (BNNS) with receptor-mediated targeting. Folic acid (FA) was successfully grafted onto BNNS via esterification reaction. In vitro cytotoxicity assay showed that BNNS-FA complexes were non-toxic to HeLa cells up to a concentration of 100 μg/mL. Then, doxorubicin hydrochloride (DOX), a commonly used anticancer drug, was loaded onto BNNS-FA complexes. BNNS-FA/DOX complexes were stable at pH 7.4 but effectively released DOX at pH 5.0, which exhibited a pH sensitive and sustained release pattern. BNNS-FA/DOX complexes could be recognized and specifically internalized by HeLa cells via FA receptor-mediated endocytosis. BNNS-FA/DOX complexes exhibited greater cytotoxicity to HeLa cells than free DOX and BNNS/DOX complexes due to the increased cellular uptake of DOX mediated by the FA receptor. Therefore, BNNS-FA complexes had strong potential for targeted cancer therapy.

Talin determines the nanoscale architecture of focal adhesions.

PubMed

Liu, Jaron; Wang, Yilin; Goh, Wah Ing; Goh, Honzhen; Baird, Michelle A; Ruehland, Svenja; Teo, Shijia; Bate, Neil; Critchley, David R; Davidson, Michael W; Kanchanawong, Pakorn

2015-09-01

Insight into how molecular machines perform their biological functions depends on knowledge of the spatial organization of the components, their connectivity, geometry, and organizational hierarchy. However, these parameters are difficult to determine in multicomponent assemblies such as integrin-based focal adhesions (FAs). We have previously applied 3D superresolution fluorescence microscopy to probe the spatial organization of major FA components, observing a nanoscale stratification of proteins between integrins and the actin cytoskeleton. Here we combine superresolution imaging techniques with a protein engineering approach to investigate how such nanoscale architecture arises. We demonstrate that talin plays a key structural role in regulating the nanoscale architecture of FAs, akin to a molecular ruler. Talin diagonally spans the FA core, with its N terminus at the membrane and C terminus demarcating the FA/stress fiber interface. In contrast, vinculin is found to be dispensable for specification of FA nanoscale architecture. Recombinant analogs of talin with modified lengths recapitulated its polarized orientation but altered the FA/stress fiber interface in a linear manner, consistent with its modular structure, and implicating the integrin-talin-actin complex as the primary mechanical linkage in FAs. Talin was found to be ∼97 nm in length and oriented at ∼15° relative to the plasma membrane. Our results identify talin as the primary determinant of FA nanoscale organization and suggest how multiple cellular forces may be integrated at adhesion sites.

[Fanconi anemia: genes and function(s) revisited].

PubMed

Papadopoulo, Dora; Moustacchi, Ethel

2005-01-01

Fanconi anemia (FA), a rare inherited disorder, exhibits a complex phenotype including progressive bone marrow failure, congenital malformations and increased risk of cancers, mainly acute myeloid leukaemia. At the cellular level, FA is characterized by hypersensitivity to DNA cross-linking agents and by high frequencies of induced chromosomal aberrations, a property used for diagnosis. FA results from mutations in one of the eleven FANC (FANCA to FANCJ) genes. Nine of them have been identified. In addition, FANCD1 gene has been shown to be identical to BRCA2, one of the two breast cancer susceptibility genes. Seven of the FANC proteins form a complex, which exists in four different forms depending of its subcellular localisation. Four FANC proteins (D1(BRCA2), D2, I and J) are not associated to the complex. The presence of the nuclear form of the FA core complex is necessary for the mono-ubiquitinylation of FANCD2 protein, a modification required for its re-localization to nuclear foci, likely to be sites of DNA repair. A clue towards understanding the molecular function of the FANC genes comes from the recently identified connection of FANC to the BRCA1, ATM, NBS1 and ATR genes. Two of the FANC proteins (A and D2) directly interact with BRCA1, which in turn interacts with the MRE11/RAD50/NBS1 complex, which is one of the key components in the mechanisms involved in the cellular response to DNA double strand breaks (DSB). Moreover, ATM, a protein kinase that plays a central role in the network of DSB signalling, phosphorylates in vitro and in vivo FANCD2 in response to ionising radiations. Moreover, the NBS1 protein and the monoubiquitinated form of FANCD2 seem to act together in response to DNA crosslinking agents. Taken together with the previously reported impaired DSB and DNA interstrand crosslinks repair in FA cells, the connection of FANC genes to the ATM, ATR, NBS1 and BRCA1 links the FANC genes function to the finely orchestrated network involved in the sensing, signalling and repair of DNA replication-blocking lesions.

Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer drugs

PubMed Central

Feng, Shini; Zhang, Huijie; Yan, Ting; Huang, Dandi; Zhi, Chunyi; Nakanishi, Hideki; Gao, Xiao-Dong

2016-01-01

With its unique physical and chemical properties and structural similarity to carbon, boron nitride (BN) has attracted considerable attention and found many applications. Biomedical applications of BN have recently started to emerge, raising great hopes in drug and gene delivery. Here, we developed a targeted anticancer drug delivery system based on folate-conjugated BN nanospheres (BNNS) with receptor-mediated targeting. Folic acid (FA) was successfully grafted onto BNNS via esterification reaction. In vitro cytotoxicity assay showed that BNNS-FA complexes were non-toxic to HeLa cells up to a concentration of 100 μg/mL. Then, doxorubicin hydrochloride (DOX), a commonly used anticancer drug, was loaded onto BNNS-FA complexes. BNNS-FA/DOX complexes were stable at pH 7.4 but effectively released DOX at pH 5.0, which exhibited a pH sensitive and sustained release pattern. BNNS-FA/DOX complexes could be recognized and specifically internalized by HeLa cells via FA receptor-mediated endocytosis. BNNS-FA/DOX complexes exhibited greater cytotoxicity to HeLa cells than free DOX and BNNS/DOX complexes due to the increased cellular uptake of DOX mediated by the FA receptor. Therefore, BNNS-FA complexes had strong potential for targeted cancer therapy. PMID:27695318

The ubiquitin family meets the Fanconi anemia proteins.

PubMed

Renaudin, Xavier; Koch Lerner, Leticia; Menck, Carlos Frederico Martins; Rosselli, Filippo

2016-01-01

Fanconi anaemia (FA) is a hereditary disorder characterized by bone marrow failure, developmental defects, predisposition to cancer and chromosomal abnormalities. FA is caused by biallelic mutations that inactivate genes encoding proteins involved in replication stress-associated DNA damage responses. The 20 FANC proteins identified to date constitute the FANC pathway. A key event in this pathway involves the monoubiquitination of the FANCD2-FANCI heterodimer by the collective action of at least 10 different proteins assembled in the FANC core complex. The FANC core complex-mediated monoubiquitination of FANCD2-FANCI is essential to assemble the heterodimer in subnuclear, chromatin-associated, foci and to regulate the process of DNA repair as well as the rescue of stalled replication forks. Several recent works have demonstrated that the activity of the FANC pathway is linked to several other protein post-translational modifications from the ubiquitin-like family, including SUMO and NEDD8. These modifications are related to DNA damage responses but may also affect other cellular functions potentially related to the clinical phenotypes of the syndrome. This review summarizes the interplay between the ubiquitin and ubiquitin-like proteins and the FANC proteins that constitute a major pathway for the surveillance of the genomic integrity and addresses the implications of their interactions in maintaining genome stability. Copyright © 2016 Elsevier B.V. All rights reserved.

The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG.

PubMed

de Winter, J P; van der Weel, L; de Groot, J; Stone, S; Waisfisz, Q; Arwert, F; Scheper, R J; Kruyt, F A; Hoatlin, M E; Joenje, H

2000-11-01

Fanconi anemia (FA) is a chromosomal instability syndrome associated with a strong predisposition to cancer, particularly acute myeloid leukemia and squamous cell carcinoma. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. Complementation analysis has indicated that at least seven distinct genes are involved in the pathogenesis of FA. Despite the identification of four of these genes (FANCA, FANCC, FANCF and FANCG), the nature of the 'FA pathway' has remained enigmatic, as the FA proteins lack sequence homologies or motifs that could point to a molecular function. To further define this pathway, we studied the subcellular localizations and mutual interactions of the FA proteins, including the recently identified FANCF protein, in human lymphoblasts. FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. These interactions were detected in wild-type and FA-D lymphoblasts, but not in lymphoblasts of other FA complementation groups. This implies that each of the FA proteins, except FANCD, is required for these complexes to form. Similarly, we show that the interaction between FANCA and FANCC is restricted to wild-type and FA-D cells. Furthermore, we document the subcellular localization of FANCA and the FANCA/FANCG complex in all FA complementation groups. Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity.

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.

PubMed

Chandrasekharappa, Settara C; Chinn, Steven B; Donovan, Frank X; Chowdhury, Naweed I; Kamat, Aparna; Adeyemo, Adebowale A; Thomas, James W; Vemulapalli, Meghana; Hussey, Caroline S; Reid, Holly H; Mullikin, James C; Wei, Qingyi; Sturgis, Erich M

2017-10-15

Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. Germline DNA samples from 417 patients with HNSCC aged <50 years were screened for sequence variants by targeted next-generation sequencing of the entire length of 16 FA genes. The sequence revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, 9 indels, 1 large deletion, and 1 synonymous variant that was predicted to effect splicing. One hundred eight patients (26%) had at least 1 rare variant that was predicted to be damaging, and 57 (14%) had at least 1 rare variant that was predicted to be damaging and had been previously reported. Fifteen patients carried 2 rare variants or an X-linked variant in an FA gene. Overall, an age cutoff for FA screening was not identified among young patients with HNSCC, because there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, an increased burden, or mutation load, of FA gene variants was observed in carriers of the genes FA complementation group D2 (FANCD2), FANCE, and FANCL in the HNSCC patient cohort relative to the 1000 Genomes population. FA germline functional variants offer a novel area of study in HNSCC tumorigenesis. FANCE and FANCL, which are components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. In the current cohort, the increased mutation load of FANCD2, FANCE, and FANCL variants among younger patients with HNSCC indicates the importance of the FA pathway in HNSCC. Cancer 2017;123:3943-54. © 2017 American Cancer Society. © 2017 American Cancer Society.

Interaction of formic acid with nitrogen: stabilization of the higher-energy conformer.

PubMed

Marushkevich, Kseniya; Räsänen, Markku; Khriachtchev, Leonid

2010-10-07

Conformational change is an important concept in chemistry and physics. In the present work, we study conformations of formic acid (HCOOH, FA) and report the preparation and identification of the complex of the higher-energy conformer cis-FA with N(2) in an argon matrix. The cis-FA···N(2) complex was synthesized by combining annealing and vibrational excitation of the ground-state trans-FA in a FA/N(2)/Ar matrix. The assignment is based on IR spectroscopic measurements and ab initio calculations. The cis-FA···N(2) complex decay in an argon matrix is much slower compared with the cis-FA monomer. In agreement with the experimental observations, the calculations predict a substantial increase in the stabilization barrier for the cis-FA···N(2) complex compared with the uncomplexed cis-FA monomer. A number of solvation effects in an argon matrix are computationally estimated and discussed. The present results on the cis-FA···N(2) complex show that intermolecular interaction can stabilize intrinsically unstable conformers, as previously found for some other cis-FA complexes.

Subconcussive Head Impact Exposure and White Matter Tract Changes over a Single Season of Youth Football.

PubMed

Bahrami, Naeim; Sharma, Dev; Rosenthal, Scott; Davenport, Elizabeth M; Urban, Jillian E; Wagner, Benjamin; Jung, Youngkyoo; Vaughan, Christopher G; Gioia, Gerard A; Stitzel, Joel D; Whitlow, Christopher T; Maldjian, Joseph A

2016-12-01

Purpose To examine the effects of subconcussive impacts resulting from a single season of youth (age range, 8-13 years) football on changes in specific white matter (WM) tracts as detected with diffusion-tensor imaging in the absence of clinically diagnosed concussions. Materials and Methods Head impact data were recorded by using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure (RWE CP ). Twenty-five male participants were evaluated for seasonal fractional anisotropy (FA) changes in specific WM tracts: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF). Fiber tracts were segmented into a central core and two fiber terminals. The relationship between seasonal FA change in the whole fiber, central core, and the fiber terminals with RWE CP was also investigated. Linear regression analysis was conducted to determine the association between RWE CP and change in fiber tract FA during the season. Results There were statistically significant linear relationships between RWE cp and decreased FA in the whole (R 2 = 0.433; P = .003), core (R 2 = 0.3649; P = .007), and terminals (R 2 = 0.5666; P < .001) of left IFOF. A trend toward statistical significance (P = .08) in right SLF was observed. A statistically significant correlation between decrease in FA of the right SLF terminal and RWE CP was also observed (R 2 = 0.2893; P = .028). Conclusion This study found a statistically significant relationship between head impact exposure and change of FA fractional anisotropy value of whole, core, and terminals of left IFOF and right SLF's terminals where WM and gray matter intersect, in the absence of a clinically diagnosed concussion. © RSNA, 2016.

Fanconi anemia: causes and consequences of genetic instability.

PubMed

Kalb, R; Neveling, K; Nanda, I; Schindler, D; Hoehn, H

2006-01-01

Fanconi anemia (FA) is a rare recessive disease that reflects the cellular and phenotypic consequences of genetic instability: growth retardation, congenital malformations, bone marrow failure, high risk of neoplasia, and premature aging. At the cellular level, manifestations of genetic instability include chromosomal breakage, cell cycle disturbance, and increased somatic mutation rates. FA cells are exquisitely sensitive towards oxygen and alkylating drugs such as mitomycin C or diepoxybutane, pointing to a function of FA genes in the defense against reactive oxygen species and other DNA damaging agents. FA is caused by biallelic mutations in at least 12 different genes which appear to function in the maintenance of genomic stability. Eight of the FA proteins form a nuclear core complex with a catalytic function involving ubiquitination of the central FANCD2 protein. The posttranslational modification of FANCD2 promotes its accumulation in nuclear foci, together with known DNA maintenance proteins such as BRCA1, BRCA2, and the RAD51 recombinase. Biallelic mutations in BRCA2 cause a severe FA-like phenotype, as do biallelic mutations in FANCD2. In fact, only leaky or hypomorphic mutations in this central group of FA genes appear to be compatible with life birth and survival. The newly discovered FANCJ (= BRIP1) and FANCM (= Hef ) genes correspond to known DNA-maintenance genes (helicase resp. helicase-associated endonuclease for fork-structured DNA). These genes provide the most convincing evidence to date of a direct involvement of FA genes in DNA repair functions associated with the resolution of DNA crosslinks and stalled replication forks. Even though genetic instability caused by mutational inactivation of the FANC genes has detrimental effects for the majority of FA patients, around 20% of patients appear to benefit from genetic instability since genetic instability also increases the chance of somatic reversion of their constitutional mutations. Intragenic crossover, gene conversion, back mutation and compensating mutations in cis have all been observed in revertant, and, consequently, mosaic FA-patients, leading to improved bone marrow function. There probably is no other experiment of nature in our species in which causes and consequences of genetic instability, including the role of reactive oxygen species, can be better documented and explored than in FA.

Complexation of furosemide with fulvic acid extracted from shilajit: a novel approach.

PubMed

Agarwal, Suraj Prakash; Anwer, Mohammad Khalid; Aqil, Mohammad

2008-05-01

The aim of the present work was to complex furosemide (FSM) with fulvic acid (FA) extracted from shilajit with the hope of having a better understanding of the complexation behavior. The effect of FA on the aqueous solubility, dissolution rate, and permeability of FSM was investigated. Different techniques, such as grinding, freeze drying, solvent evaporation, and so forth, were used for the preparation of the complex. The complexes were prepared in molar ratios of 1:1 and 1:2 FSM:FA and were evaluated for drug inclusion, solubility, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, dissolution study, and permeation study. These methods confirm the formation of an amorphous inclusion complex of FSM with FA.

Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial.

PubMed

Obeid, Rima; Kirsch, Susanne H; Dilmann, Sarah; Klein, Cosima; Eckert, Rudolf; Geisel, Jürgen; Herrmann, Wolfgang

2016-04-01

Unmetabolized folic acid (UMFA) is common in serum of elderly individuals receiving folic acid (FA)-fortified foods or supplements. We studied the effect of supplementing FA or B-complex on serum concentrations of (6S)-5-methyltetrahydropteroylglutamate [(6S)-5-CH3-H4Pte] and UMFA in elderly people and explored factors associated with detectable UMFA post-supplementation. This is a randomized single-blind non-controlled trial on 58 elderly people using daily 400 µg FA (n = 31) or 400 µg FA, 10 µg cyanocob(III)alamin and 8 mg pyridoxine (n = 27) for a median of 23 days. Main outcome includes changes in concentrations of serum (6S)-5-CH3-H4Pte and UMFA. Total homocysteine declined by a median of 1.6 (p = 0.074) in the FA and 1.3 µmol/L (p = 0.009) in the B-complex arms (p = 0.66 between the arms). Serum (6S)-5-CH3-H4Pte significantly (p < 0.001 vs. baseline) increased by a median of 9.2 and 6.5 nmol/L in the FA and B-complex groups, respectively (p = 0.152 between the groups). Compared to FA, B-complex reduced cystathionine and caused lower post-intervention serum UMFA, percentage of UMFA to (6S)-5-CH3-H4Pte and prevalence of UMFA ≥ 0.21 nmol/L. Higher serum cystathionine and whole-blood folate predicted higher post-intervention serum UMFA. FA caused higher UMFA as compared to B-complex. Pyridoxine appears to improve folate recycling. Data on serum UMFA should be interpreted in relation to other vitamins involved in folate metabolism. Serum UMFA is suggested to play a sensory role through which the cell recognizes FA available for metabolism via dihydrofolate reductase.

Subconcussive Head Impact Exposure and White Matter Tract Changes over a Single Season of Youth Football

PubMed Central

Bahrami, Naeim; Sharma, Dev; Rosenthal, Scott; Davenport, Elizabeth M.; Urban, Jillian E.; Wagner, Benjamin; Jung, Youngkyoo; Vaughan, Christopher G.; Gioia, Gerard A.; Stitzel, Joel D.; Maldjian, Joseph A.

2016-01-01

Purpose To examine the effects of subconcussive impacts resulting from a single season of youth (age range, 8–13 years) football on changes in specific white matter (WM) tracts as detected with diffusion-tensor imaging in the absence of clinically diagnosed concussions. Materials and Methods Head impact data were recorded by using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure (RWECP). Twenty-five male participants were evaluated for seasonal fractional anisotropy (FA) changes in specific WM tracts: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus, and superior longitudinal fasciculus (SLF). Fiber tracts were segmented into a central core and two fiber terminals. The relationship between seasonal FA change in the whole fiber, central core, and the fiber terminals with RWECP was also investigated. Linear regression analysis was conducted to determine the association between RWECP and change in fiber tract FA during the season. Results There were statistically significant linear relationships between RWEcp and decreased FA in the whole (R2 = 0.433; P = .003), core (R2 = 0.3649; P = .007), and terminals (R2 = 0.5666; P < .001) of left IFOF. A trend toward statistical significance (P = .08) in right SLF was observed. A statistically significant correlation between decrease in FA of the right SLF terminal and RWECP was also observed (R2 = 0.2893; P = .028). Conclusion This study found a statistically significant relationship between head impact exposure and change of FAfractional anisotropy value of whole, core, and terminals of left IFOF and right SLF’s terminals where WM and gray matter intersect, in the absence of a clinically diagnosed concussion. © RSNA, 2016 PMID:27775478

Characterization of mature maize (Zea mays L.) root system architecture and complexity in a diverse set of Ex-PVP inbreds and hybrids.

PubMed

Hauck, Andrew L; Novais, Joana; Grift, Tony E; Bohn, Martin O

2015-01-01

The mature root system is a vital plant organ, which is critical to plant performance. Commercial maize (Zea mays L.) breeding has resulted in a steady increase in plant performance over time, along with noticeable changes in above ground vegetative traits, but the corresponding changes in the root system are not presently known. In this study, roughly 2500 core root systems from field trials of a set of 10 diverse elite inbreds formerly protected by Plant Variety Protection plus B73 and Mo17 and the 66 diallel intercrosses among them were evaluated for root traits using high throughput image-based phenotyping. Overall root architecture was modeled by root angle (RA) and stem diameter (SD), while root complexity, the amount of root branching, was quantified using fractal analysis to obtain values for fractal dimension (FD) and fractal abundance (FA). For each trait, per se line effects were highly significant and the most important contributor to trait performance. Mid-parent heterosis and specific combining ability was also highly significant for FD, FA, and RA, while none of the traits showed significant general combining ability. The interaction between the environment and the additive line effect was also significant for all traits. Within the inbred and hybrid generations, FD and FA were highly correlated (rp ≥ 0.74), SD was moderately correlated to FD and FA (0.69 ≥ rp ≥ 0.48), while the correlation between RA and other traits was low (0.13 ≥ rp ≥ -0.40). Inbreds with contrasting effects on complexity and architecture traits were observed, suggesting that root complexity and architecture traits are inherited independently. A more comprehensive understanding of the maize root system and the way it interacts with the environment will be useful for defining adaptation to nutrient acquisition and tolerance to stress from drought and high plant densities, critical factors in the yield gains of modern hybrids.

"Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.

PubMed

Bano, Shazia; Nazir, Samina; Munir, Saeeda; AlAjmi, Mohamed Fahad; Afzal, Muhammad; Mazhar, Kehkashan

2016-01-01

We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

Experimental determination and modeling of arsenic complexation with humic and fulvic acids.

PubMed

Fakour, Hoda; Lin, Tsair-Fuh

2014-08-30

The complexation of humic acid (HA) and fulvic acid (FA) with arsenic (As) in water was studied. Experimental results indicate that arsenic may form complexes with HA and FA with a higher affinity for arsenate than for arsenite. With the presence of iron oxide based adsorbents, binding of arsenic to HA/FA in water was significantly suppressed, probably due to adsorption of As and HA/FA. A two-site ligand binding model, considering only strong and weak site types of binding affinity, was successfully developed to describe the complexation of arsenic on the two natural organic fractions. The model showed that the numbers of weak sites were more than 10 times those of strong sites on both HA and FA for both arsenic species studied. The numbers of both types of binding sites were found to be proportional to the HA concentrations, while the apparent stability constants, defined for describing binding affinity between arsenic and the sites, are independent of the HA concentrations. To the best of our knowledge, this is the first study to characterize the impact of HA concentrations on the applicability of the ligand binding model, and to extrapolate the model to FA. The obtained results may give insights on the complexation of arsenic in HA/FA laden groundwater and on the selection of more effective adsorption-based treatment methods for natural waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced anticancer activity of DM1-loaded star-shaped folate-core PLA-TPGS nanoparticles

NASA Astrophysics Data System (ADS)

Tang, Xiaolong; Liang, Yong; Zhu, Yongqiang; Cai, Shiyu; Sun, Leilei; Chen, Tianyi

2014-10-01

The efficient delivery of therapeutic drugs into interested cells is a critical challenge to broad application of nonviral vector systems. In this research, emtansine (DM1)-loaded star-shaped folate-core polylactide- d-α-tocopheryl polyethylene glycol 1000 succinate (FA-PLA-TPGS-DM1) copolymer which demonstrated superior anticancer activity in vitro/ vivo in comparison with linear FA-PLA-TPGS nanoparticles was applied to be a vector of DM1 for FR+ breast cancer therapy. The DM1- or coumarin 6-loaded nanoparticles were fabricated, and then characterized in terms of size, morphology, drug encapsulation efficiency, and in vitro drug release. And the viability of MCF-7/HER2 cells treated with FA-DM1-nanoparticles (NPs) was assessed. Severe combined immunodeficient mice carrying MCF-7/HER2 tumor xenografts were treated in several groups including phosphate-buffered saline control, DM1, DM1-NPs, and FA-DM1-NPs. The antitumor activity was then assessed by survival time and solid tumor volume. All the specimens were prepared for formalin-fixed and paraffin-embedded tissue sections for hematoxylin-eosin staining. The data showed that the FA-DM1-NPs could efficiently deliver DM1 into MCF-7/HER2 cells. The cytotoxicity of DM1 to MCF-7/HER2 cells was significantly increased by FA-DM1-NPs when compared with the control groups. In conclusion, the FA-DM1-NPs offered a considerable potential formulation for FR+ tumor-targeting biotherapy.

FaCSI: A block parallel preconditioner for fluid-structure interaction in hemodynamics

NASA Astrophysics Data System (ADS)

Deparis, Simone; Forti, Davide; Grandperrin, Gwenol; Quarteroni, Alfio

2016-12-01

Modeling Fluid-Structure Interaction (FSI) in the vascular system is mandatory to reliably compute mechanical indicators in vessels undergoing large deformations. In order to cope with the computational complexity of the coupled 3D FSI problem after discretizations in space and time, a parallel solution is often mandatory. In this paper we propose a new block parallel preconditioner for the coupled linearized FSI system obtained after space and time discretization. We name it FaCSI to indicate that it exploits the Factorized form of the linearized FSI matrix, the use of static Condensation to formally eliminate the interface degrees of freedom of the fluid equations, and the use of a SIMPLE preconditioner for saddle-point problems. FaCSI is built upon a block Gauss-Seidel factorization of the FSI Jacobian matrix and it uses ad-hoc preconditioners for each physical component of the coupled problem, namely the fluid, the structure and the geometry. In the fluid subproblem, after operating static condensation of the interface fluid variables, we use a SIMPLE preconditioner on the reduced fluid matrix. Moreover, to efficiently deal with a large number of processes, FaCSI exploits efficient single field preconditioners, e.g., based on domain decomposition or the multigrid method. We measure the parallel performances of FaCSI on a benchmark cylindrical geometry and on a problem of physiological interest, namely the blood flow through a patient-specific femoropopliteal bypass. We analyze the dependence of the number of linear solver iterations on the cores count (scalability of the preconditioner) and on the mesh size (optimality).

The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

PubMed

Garcia-Higuera, I; Kuang, Y; Denham, J; D'Andrea, A D

2000-11-01

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FA-A cell line, with a reciprocal increase in the half-life of FANCG. Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm. The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA.

Assessment of a field-aligned ICRF antenna

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

Wukitch, S. J.; Brunner, D.; Ennever, P.

Impurity contamination and localized heat loads associated with ion cyclotron range of frequency (ICRF) antenna operation are among the most challenging issues for ICRF utilization.. Another challenge is maintaining maximum coupled power through plasma variations including edge localized modes (ELMs) and confinement transitions. Here, we report on an experimental assessment of a field aligned (FA) antenna with respect to impurity contamination, impurity sources, RF enhanced heat flux and load tolerance. In addition, we compare the modification of the scrape of layer (SOL) plasma potential of the FA antenna to a conventional, toroidally aligned (TA) antenna, in order to explore themore » underlying physics governing impurity contamination linked to ICRF heating. The FA antenna is a 4-strap ICRF antenna where the current straps and antenna enclosure sides are perpendicular to and the Faraday screen rods are parallel to the total magnetic field. In principle, alignment with respect to the total magnetic field minimizes integrated E∥ (electric field along a magnetic field line) via symmetry. Consistent with expectations, we observed that the impurity contamination and impurity source at the FA antenna are reduced compared to the TA antenna. In both L and H-mode discharges, the radiated power is 20–30% lower for a FA-antenna heated discharge than a discharge heated with the TA-antennas. Further we observe that the fraction of RF energy deposited upon the antenna is less than 0.4 % of the total injected RF energy in dipole phasing. The total deposited energy increases significantly when the FA antenna is operated in monopole phasing. The FA antenna also exhibits an unexpected load tolerance for ELMs and confinement transitions compared to the TA antennas. However, inconsistent with expectations, we observe RF induced plasma potentials to be nearly identical for FA and TA antennas when operated in dipole phasing. In monopole phasing, the FA antenna has the highest plasma potentials and poor heating efficiency despite calculations indicating low integrated E∥. In mode conversion heating scenario, no core waves were detected in the plasma core indicating poor wave penetration. For monopole phasing, simulations suggest the antenna spectrum is peaked at very short wavelength and full wave simulations show the short wavelength has poor wave penetration to the plasma core.« less

Highly robust hydrogen generation by bio-inspired Ir complexes for dehydrogenation of formic acid in water: Experimental and theoretical mechanistic investigations at different pH

DOE PAGES

Wang, Wan -Hui; Fujita, Etsuko; Ertem, Mehmed Z.; ...

2015-07-30

Hydrogen generation from formic acid (FA), one of the most promising hydrogen storage materials, has attracted much attention due to the demand for the development of renewable energy carriers. Catalytic dehydrogenation of FA in an efficient and green manner remains challenging. Here, we report a series of bio-inspired Ir complexes for highly robust and selective hydrogen production from FA in aqueous solutions without organic solvents or additives. One of these complexes bearing an imidazoline moiety (complex 6) achieved a turnover frequency (TOF) of 322,000 h⁻¹ at 100 °C, which is higher than ever reported. The novel catalysts are very stablemore » and applicable in highly concentrated FA. For instance, complex 3 (1 μmol) affords an unprecedented turnover number (TON) of 2,050,000 at 60 °C. Deuterium kinetic isotope effect experiments and density functional theory (DFT) calculations employing a “speciation” approach demonstrated a change in the rate-determining step with increasing solution pH. This study provides not only more insight into the mechanism of dehydrogenation of FA but also offers a new principle for the design of effective homogeneous organometallic catalysts for H₂ generation from FA.« less

Substrate Type and Free Ammonia Determine Bacterial Community Structure in Full-Scale Mesophilic Anaerobic Digesters Treating Cattle or Swine Manure.

PubMed

Li, Jiabao; Rui, Junpeng; Yao, Minjie; Zhang, Shiheng; Yan, Xuefeng; Wang, Yuanpeng; Yan, Zhiying; Li, Xiangzhen

2015-01-01

The microbial-mediated anaerobic digestion (AD) process represents an efficient biological process for the treatment of organic waste along with biogas harvest. Currently, the key factors structuring bacterial communities and the potential core and unique bacterial populations in manure anaerobic digesters are not completely elucidated yet. In this study, we collected sludge samples from 20 full-scale anaerobic digesters treating cattle or swine manure, and investigated the variations of bacterial community compositions using high-throughput 16S rRNA amplicon sequencing. Clustering and correlation analysis suggested that substrate type and free ammonia (FA) play key roles in determining the bacterial community structure. The COD: [Formula: see text] (C:N) ratio of substrate and FA were the most important available operational parameters correlating to the bacterial communities in cattle and swine manure digesters, respectively. The bacterial populations in all of the digesters were dominated by phylum Firmicutes, followed by Bacteroidetes, Proteobacteria and Chloroflexi. Increased FA content selected Firmicutes, suggesting that they probably play more important roles under high FA content. Syntrophic metabolism by Proteobacteria, Chloroflexi, Synergistetes and Planctomycetes are likely inhibited when FA content is high. Despite the different manure substrates, operational conditions and geographical locations of digesters, core bacterial communities were identified. The core communities were best characterized by phylum Firmicutes, wherein Clostridium predominated overwhelmingly. Substrate-unique and abundant communities may reflect the properties of manure substrate and operational conditions. These findings extend our current understanding of the bacterial assembly in full-scale manure anaerobic digesters.

Substrate Type and Free Ammonia Determine Bacterial Community Structure in Full-Scale Mesophilic Anaerobic Digesters Treating Cattle or Swine Manure

PubMed Central

Li, Jiabao; Rui, Junpeng; Yao, Minjie; Zhang, Shiheng; Yan, Xuefeng; Wang, Yuanpeng; Yan, Zhiying; Li, Xiangzhen

2015-01-01

The microbial-mediated anaerobic digestion (AD) process represents an efficient biological process for the treatment of organic waste along with biogas harvest. Currently, the key factors structuring bacterial communities and the potential core and unique bacterial populations in manure anaerobic digesters are not completely elucidated yet. In this study, we collected sludge samples from 20 full-scale anaerobic digesters treating cattle or swine manure, and investigated the variations of bacterial community compositions using high-throughput 16S rRNA amplicon sequencing. Clustering and correlation analysis suggested that substrate type and free ammonia (FA) play key roles in determining the bacterial community structure. The COD: NH4+-N (C:N) ratio of substrate and FA were the most important available operational parameters correlating to the bacterial communities in cattle and swine manure digesters, respectively. The bacterial populations in all of the digesters were dominated by phylum Firmicutes, followed by Bacteroidetes, Proteobacteria and Chloroflexi. Increased FA content selected Firmicutes, suggesting that they probably play more important roles under high FA content. Syntrophic metabolism by Proteobacteria, Chloroflexi, Synergistetes and Planctomycetes are likely inhibited when FA content is high. Despite the different manure substrates, operational conditions and geographical locations of digesters, core bacterial communities were identified. The core communities were best characterized by phylum Firmicutes, wherein Clostridium predominated overwhelmingly. Substrate-unique and abundant communities may reflect the properties of manure substrate and operational conditions. These findings extend our current understanding of the bacterial assembly in full-scale manure anaerobic digesters. PMID:26648921

A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA.

PubMed

Yagasaki, H; Adachi, D; Oda, T; Garcia-Higuera, I; Tetteh, N; D'Andrea, A D; Futaki, M; Asano, S; Yamashita, T

2001-12-15

Fanconi anemia (FA) is an autosomal recessive disease with congenital anomalies, bone marrow failure, and susceptibility to leukemia. Patient cells show chromosome instability and hypersensitivity to DNA cross-linking agents. At least 8 complementation groups (A-G) have been identified and 6 FA genes (for subtypes A, C, D2, E, F, and G) have been cloned. Increasing evidence indicates that a protein complex assembly of multiple FA proteins, including FANCA and FANCG, plays a crucial role in the FA pathway. Previously, it was reported that FANCA was phosphorylated in lymphoblasts from normal controls, whereas the phosphorylation was defective in those derived from patients with FA of multiple complementation groups. The present study examined phosphorylation of FANCA ectopically expressed in FANCA(-) cells. Several patient-derived mutations abrogated in vivo phosphorylation of FANCA in this system, suggesting that FANCA phosphorylation is associated with its function. In vitro phosphorylation studies indicated that a physiologic protein kinase for FANCA (FANCA-PK) forms a complex with the substrate. Furthermore, at least a part of FANCA-PK as well as phosphorylated FANCA were included in the FANCA/FANCG complex. Thus, FANCA-PK appears to be another component of the FA protein complex and may regulate function of FANCA. FANCA-PK was characterized as a cytoplasmic serine kinase sensitive to wortmannin. Identification of the protein kinase is expected to elucidate regulatory mechanisms that control the FA pathway.

Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance

NASA Astrophysics Data System (ADS)

Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Yuan, Gongdao; Zhuo, Renxi; Li, Feng

2017-02-01

Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

Boronic Acid vs. Folic Acid: A Comparison of the bio-recognition performances by Impedimetric Cytosensors based on Ferrocene cored dendrimer.

PubMed

Dervisevic, Muamer; Şenel, Mehmet; Sagir, Tugba; Isik, Sevim

2017-05-15

A comparative study is reported where folic acid (FA) and boronic acid (BA) based cytosensors and their analytical performances in cancer cell detection were analyzed by using electrochemical impedance spectroscopy (EIS) method. Cytosensors were fabricated using self-assembled monolayer principle by modifying Au electrode with cysteamine (Cys) and immobilization of ferrocene cored polyamidiamine dendrimers second generation (Fc-PAMAM (G2)), after which electrodes were modified with FA and BA. Au/Fc-PAMAM(G2)/FA and Au/Fc-PAMAM(G2)/BA based cytosensors showed extremely good analytical performances in cancer cell detection with linear range of 1×10 2 to 1×10 6 cellsml -1 , detection limit of 20cellsml -1 with incubation time of 20min for FA based electrode, and for BA based electrode detection limit was 28cellsml -1 with incubation time of 10min. Next to excellent analytical performances, cytosensors showed high selectivity towards cancer cells which was demonstrated in selectivity study using human embryonic kidney 293 cells (HEK 293) as normal cells and Au/Fc-PAMAM(G2)/FA electrode showed two times better selectivity than BA modified electrode. These cytosensors are promising for future applications in cancer cell diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of a JA-Ile Biosynthesis Inhibitor to Methyl Jasmonate-Treated Strawberry Fruit Induces Upregulation of Specific MBW Complex-Related Genes and Accumulation of Proanthocyanidins.

PubMed

Delgado, Laura D; Zúñiga, Paz E; Figueroa, Nicolás E; Pastene, Edgar; Escobar-Sepúlveda, Hugo F; Figueroa, Pablo M; Garrido-Bigotes, Adrián; Figueroa, Carlos R

2018-06-13

Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the jasmonate pathway and anthocyanin and PA biosynthesis in fruits remains to be understood. Anthocyanin and PA accumulation is mainly regulated at the transcriptional level through R2R3-MYB and bHLH transcription factors in different plant species and organs. Here, the effect of jarin-1, a specific inhibitor of bioactive JA (jasmonoyl-isoleucine, JA-Ile) biosynthesis, on anthocyanin and PA accumulation was evaluated during strawberry ( Fragaria × ananassa ) fruit development using an in vitro ripening system for 48 h. Also, we observed the effects of MeJA and the application of jarin-1 to MeJA-treated fruits (MeJA + jarin-1 treatment). We assessed changes of expression levels for the JA-Ile and MeJA biosynthetic ( FaJAR1.2 and FaJMT ), JA signaling-related ( FaMYC2 and FaJAZ1 ), MYB-bHLH-WD40 (MBW) complex-related ( FabHLH3/33 , FaMYB9/10/11 , and repressor FaMYB1 ), and anthocyanin and PA biosynthetic (FaANS , FaUFGT , FaANR , and FaLAR ) genes. In addition, the promoter region of MBW complex-related MYB genes was isolated and sequenced. We found a higher redness of strawberry fruit skin and anthocyanin content in MeJA-treated fruits with respect to jarin-1-treated ones concomitant with an upregulation of FaANS and FaUFGT genes. Inversely, the PA content was higher in jarin-1- and MeJA + jarin-1-treated than in MeJA-treated fruits. MeJA + jarin-1 treatment resulted in an upregulation of FaANR and associated transcription factors such as FabHLH33 and FaMYB9/11 along with FaJMT and FaJAR1.2 . Finally, we found JA-responsive elements in the promoter regions of FaMYB1/9/10/11 genes. It is proposed that PA biosynthesis-related genes can be upregulated by the application of jarin-1 to MeJA-treated fruit, thus increasing PA accumulation in strawberry.

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

PubMed Central

Wolfenson, Haguy; Lubelski, Ariel; Regev, Tamar; Klafter, Joseph; Henis, Yoav I.; Geiger, Benjamin

2009-01-01

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization. PMID:19172999

Host-guest inclusion system of ferulic acid with p-Sulfonatocalix[n]arenes: Preparation, characterization and antioxidant activity

NASA Astrophysics Data System (ADS)

Chao, Jianbin; Wang, Huijuan; Song, Kailun; Wang, Yongzhao; Zuo, Ying; Zhang, Liwei; Zhang, Bingtai

2017-02-01

The inclusion complexes of ferulic acid (FA) with p-Sulfonatocalix[n]arenes (SCXn, n = 4, 6, 8) were prepared and characterized both in the solid state and in solution using fluorescence spectroscopy, 1H nuclear magnetic resonance (1H NMR), attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM) and differential scanning calorimetry (DSC). The results show that FA is able to form inclusion complexes with SCXn in a molar ratio of 1:1, causing a significant decrease in the fluorescence intensity of FA. The association constant of the inclusion complexes was calculated from the fluorescence titration data. 1H NMR spectroscopy analysis demonstrates that the aromatic ring and methoxy group of FA are partially covered by SCXn.

Functional manganese dioxide nanosheet for targeted photodynamic therapy and bioimaging in vitro and in vivo

NASA Astrophysics Data System (ADS)

Kim, Seongchan; Ahn, Seong Min; Lee, Ji-Seon; Kim, Tae Shik; Min, Dal-Hee

2017-06-01

Photodynamic therapy (PDT) has been widely studied as a promising non-invasive therapeutic strategy for the treatment of cancer. However, the poor solubility of photosensitizer (PS) in aqueous solution and inefficient cell-penetrating capability have limited the target-specific PDT. Herein, we develop a novel targeted photodynamic therapeutic and bioimaging system based on folic acid (FA)-conjugated MnO2 (FA-MnO2) nanosheet as a new carrier of PS, zinc phthalocyanine (ZnPc). ZnPc loaded FA-MnO2 nanosheet (FA-MnO2/ZnPc) complex is successfully formed by electrostatic interaction and coordination. We find that FA-MnO2/ZnPc complex exhibits excellent targeted delivery of ZnPc into folate receptor positive cancer cells and the ZnPc is released out from the complex via endogenous glutathione (GSH) stimulus, facilitating simultaneous bioimaging and targeted PDT by singlet oxygen (SO) generation upon light irradiation, showing high efficacy with only one tenth of conventional PS dosage in vitro and in vivo.

The Fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation

PubMed Central

Yamashita, Takayuki; Kupfer, Gary M.; Naf, Dieter; Suliman, Ahmed; Joenje, Hans; Asano, Shigetaka; D’Andrea, Alan D.

1998-01-01

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A–H). Two FA genes, corresponding to complementation groups A and C, have been cloned, but the function of the FAA and FAC proteins remains unknown. We have recently shown that the FAA and FAC proteins bind and form a nuclear complex. In the current study, we analyzed the FAA and FAC proteins in normal lymphoblasts and lymphoblasts from multiple FA complementation groups. In contrast to normal controls, FA cells derived from groups A, B, C, E, F, G, and H were defective in the formation of the FAA/FAC protein complex, the phosphorylation of the FAA protein, and the accumulation of the FAA/FAC protein complex in the nucleus. These biochemical events seem to define a signaling pathway required for the maintenance of genomic stability and normal hematopoiesis. Our results support the idea that multiple gene products cooperate in the FA Pathway. PMID:9789045

Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance.

PubMed

Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Yuan, Gongdao; Zhuo, Renxi; Li, Feng

2017-02-24

Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

Sorption of Eu(III) on humic acid or fulvic acid bound to hydrous alumina studied by SEM-EDS, XPS, TRLFS, and batch techniques.

PubMed

Tan, X L; Wang, X K; Geckeis, H; Rabung, Th

2008-09-01

To identify the effect of humic acid (HA) and fulvic acid (FA) on the sorption mechanism of Eu(III) on organic--inorganic colloids in the environment at a molecular level, surface adsorbed/ complexed Eu(III) on hydrous alumina, HA-, and FA-hydrous alumina hybrids were characterized by using X-ray photoelectron spectroscopy (XPS) and time-resolved laser fluorescence spectroscopy (TRLFS). The experiments were performed in 0.1 mol/L KNO3 or 0.1 mol/L NaClO4 under ambient conditions. The pH values were varied between 2 and 11 at a fixed Eu(III) concentration of 6.0 x 10(-7) mol/L and 4.3 x 10(-5) mol/L. The different Eu(III)/FA(HA)/hydrous alumina complexes were characterized by their fluorescence emission spectra ((5D0-F1)/ (5D0 --> 7F2)) and binding energy of Eu(III). Inner-sphere surface complexation may contribute mainly to Eu(III) sorption on hydrous alumina, and a ternary surface complex is formed at the HA/ FA-hydrous alumina hybrid surfaces. The sorption and species of Eu(III) in ternary Eu-HA/FA-hydrous alumina systems are not dominated by either HA/FA or hydrous alumina, but are dominated by both HA/FA and hydrous alumina. The results are important for understanding the sorption mechanisms and the nature of surface adsorbed Eu(III) species and trivalent chemical homologues of Eu(III) in the natural environment.

Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein.

PubMed

Chen, Junjie; van Dongen, Mallory A; Merzel, Rachel L; Dougherty, Casey A; Orr, Bradford G; Kanduluru, Ananda Kumar; Low, Philip S; Marsh, E Neil G; Banaszak Holl, Mark M

2016-03-14

Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ∼80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching.

Plasmon effects in light scalar and pseudo-scalar emission from a supernova.

NASA Astrophysics Data System (ADS)

Altherr, T.

1991-05-01

The emission of light scalars and pseudo-scalars (axion-like particles) coupled to the chromo/electric field from a QCD/AED plasma at high temperature and very high density is studied in detail. The calculation is then applied to the SN 1987A event for which new bounds on the Peccei-Quinn symmetry breaking scale fa are derived, fa ⪆ 3×109GeV in presence of a quark-gluon core and fa ⪆ 107GeV, which is the same bound as the one obtained from red giant stars, by considering axion emission from the electron gas.

Development of a General Aza-Cope Reaction Trigger Applied to Fluorescence Imaging of Formaldehyde in Living Cells.

PubMed

Bruemmer, Kevin J; Walvoord, Ryan R; Brewer, Thomas F; Burgos-Barragan, Guillermo; Wit, Niek; Pontel, Lucas B; Patel, Ketan J; Chang, Christopher J

2017-04-19

Formaldehyde (FA) is a reactive signaling molecule that is continuously produced through a number of central biological pathways spanning epigenetics to one-carbon metabolism. On the other hand, aberrant, elevated levels of FA are implicated in disease states ranging from asthma to neurodegenerative disorders. In this context, fluorescence-based probes for FA imaging are emerging as potentially powerful chemical tools to help disentangle the complexities of FA homeostasis and its physiological and pathological contributions. Currently available FA indicators require direct modification of the fluorophore backbone through complex synthetic considerations to enable FA detection, often limiting the generalization of designs to other fluorophore classes. To address this challenge, we now present the rational, iterative development of a general reaction-based trigger utilizing 2-aza-Cope reactivity for selective and sensitive detection of FA in living systems. Specifically, we developed a homoallylamine functionality that can undergo a subsequent self-immolative β-elimination, creating a FA-responsive trigger that is capable of masking a phenol on a fluorophore or any other potential chemical scaffold for related imaging and/or therapeutic applications. We demonstrate the utility of this trigger by creating a series of fluorescent probes for FA with excitation and emission wavelengths that span the UV to visible spectral regions through caging of a variety of dye units. In particular, Formaldehyde Probe 573 (FAP573), based on a resorufin scaffold, is the most red-shifted and FA sensitive in this series in terms of signal-to-noise responses and enables identification of alcohol dehydrogenase 5 (ADH5) as an enzyme that regulates FA metabolism in living cells. The results provide a starting point for the broader use of 2-aza-Cope reactivity for probing and manipulating FA biology.

Interobserver variation in the diagnosis of fibroepithelial lesions of the breast: a multicentre audit by digital pathology.

PubMed

Dessauvagie, Benjamin F; Lee, Andrew H S; Meehan, Katie; Nijhawan, Anju; Tan, Puay Hoon; Thomas, Jeremy; Tie, Bibiana; Treanor, Darren; Umar, Seemeen; Hanby, Andrew M; Millican-Slater, Rebecca

2018-02-13

Fibroepithelial lesions (FELs) of the breast span a morphological continuum including lesions where distinction between cellular fibroadenoma (FA) and benign phyllodes tumour (PT) is difficult. The distinction is clinically important with FAs managed conservatively while equivocal lesions and PTs are managed with surgery. We sought to audit core biopsy diagnoses of equivocal FELs by digital pathology and to investigate whether digital point counting is useful in clarifying FEL diagnoses. Scanned slide images from cores and subsequent excisions of 69 equivocal FELs were examined in a multicentre audit by eight pathologists to determine the agreement and accuracy of core needle biopsy (CNB) diagnoses and by digital point counting of stromal cellularity and expansion to determine if classification could be improved. Interobserver variation was high on CNB with a unanimous diagnosis from all pathologists in only eight cases of FA, diagnoses of both FA and PT on the same CNB in 15 and a 'weak' mean kappa agreement between pathologists (k=0.36). 'Moderate' agreement was observed on CNBs among breast specialists (k=0.44) and on excision samples (k=0.49). Up to 23% of lesions confidently diagnosed as FA on CNB were PT on excision and up to 30% of lesions confidently diagnosed as PT on CNB were FA on excision. Digital point counting did not aid in the classification of FELs. Accurate and reproducible diagnosis of equivocal FELs is difficult, particularly on CNB, resulting in poor interobserver agreement and suboptimal accuracy. Given the diagnostic difficulty, and surgical implications, equivocal FELs should be reported in consultation with experienced breast pathologists as a small number of benign FAs can be selected out from equivocal lesions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Appraising the uptake and use of recommendations for a common outcome data set for clinical trials: a case study in fall injury prevention.

PubMed

Copsey, Bethan; Hopewell, Sally; Becker, Clemens; Cameron, Ian D; Lamb, Sarah E

2016-03-10

Many researchers and professional bodies are seeking consensus for core outcomes for clinical trials. The Prevention of Falls Network Europe (ProFaNE) developed a common outcome data set for fall injury prevention trials 10 years ago. This study assesses the impact of these recommendations. A systematic search (up to 16 January 2015) was performed using Web of Science, Scopus and PubMed for articles citing the ProFaNE recommendations. Randomised trials on fall prevention in older people were selected for further analysis. Data were extracted on study characteristics and adherence to the key domains recommended by the ProFaNE consensus: falls, fall injury, physical activity, psychological consequences and health-related quality of life. Details of non-recommended outcome measures used were also recorded. The ProFaNE recommendations were cited in a total of 464 published articles, of which 34 were randomised trials on fall prevention in older people. Only one study (3 %) reported on all core domains. Most of the trials reported on falls (n = 32/34, 94 %) as a core outcome measure. Most of the recommendations within the falls domain were well-followed. Around half of the trials reported on fall-related injury (n = 16/34, 47 %). However, none reported the number of radiologically confirmed peripheral fracture events, which is the recommended outcome measure for injury. The other key domains (quality of life, physical activity and psychological consequences) were less frequently reported on, with a lack of consistency in the outcome measures used. The ProFaNE recommendations had a limited effect on standardising the reporting of outcomes in randomised trials on fall injury prevention in older people during the search period. Authors of consensus guidelines should consider maximising buy-in by including a diversity of geographic areas and academic disciplines at the development stage and using a solid dissemination strategy.

Colloidal diatomite, radionickel, and humic substance interaction: a combined batch, XPS, and EXAFS investigation.

PubMed

Sheng, Guodong; Shen, Runpu; Dong, Huaping; Li, Yimin

2013-06-01

This work determined the influence of humic acid (HA) and fulvic acid (FA) on the interaction mechanism and microstructure of Ni(II) onto diatomite by using batch experiments, X-ray photoelectron spectroscopy (XPS), and extended X-ray absorption fine structure (EXAFS) methods. Macroscopic and spectroscopic experiments have been combined to see the evolution of the interaction mechanism and microstructure of Ni(II) in the presence of HA/FA as compared with that in the absence of HA/FA. The results indicated that the interaction of Ni(II) with diatomite presents the expected solution pH edge at 7.0, which is modified by addition of HA/FA. In the presence of HA/FA, the interaction of Ni(II) with diatomite increased below solution pH 7.0, while Ni(II) interaction decreased above solution pH 7.0. XPS analysis suggested that the enrichment of Ni(II) onto diatomite may be due to the formation of (≡SO)2Ni. EXAFS results showed that binary surface complexes and ternary surface complexes of Ni(II) can be simultaneously formed in the presence of HA/FA, whereas only binary surface complexes of Ni(II) are formed in the absence of HA/FA, which contribute to the enhanced Ni(II) uptake at low pH values. The results observed in this work are important for the evaluation of Ni(II) and related radionuclide physicochemical behavior in the natural soil and water environment.

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

PubMed Central

Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

2016-01-01

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

Multiple Hydrogen Bond Tethers for Grazing Formic Acid in Its Complexes with Phenylacetylene.

PubMed

Karir, Ginny; Kumar, Gaurav; Kar, Bishnu Prasad; Viswanathan, K S

2018-03-01

Complexes of phenylacetylene (PhAc) and formic acid (FA) present an interesting picture, where the two submolecules are tethered, sometimes multiply, by hydrogen bonds. The multiple tentacles adopted by PhAc-FA complexes stem from the fact that both submolecules can, in the same complex, serve as proton acceptors and/or proton donors. The acetylenic and phenyl π systems of PhAc can serve as proton acceptors, while the ≡C-H or -C-H of the phenyl ring can act as a proton donor. Likewise, FA also is amphiprotic. Hence, more than 10 hydrogen-bonded structures, involving O-H···π, C-H···π, and C-H···O contacts, were indicated by our computations, some with multiple tentacles. Interestingly, despite the multiple contacts in the complexes, the barrier between some of the structures is small, and hence, FA grazes around PhAc, even while being tethered to it, with hydrogen bonds. We used matrix isolation infrared spectroscopy to experimentally study the PhAc-FA complexes, with which we located global and a few local minima, involving primarily an O-H···π interaction. Experiments were corroborated by ab initio computations, which were performed using MP2 and M06-2X methods, with 6-311++G (d,p) and aug-cc-pVDZ basis sets. Single-point energy calculations were also done at MP2/CBS and CCSD(T)/CBS levels. The nature, strength, and origin of these noncovalent interactions were studied using AIM, NBO, and LMO-EDA analysis.

The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents.

PubMed

Chen, Clark C; Taniguchi, Toshiyasu; D'Andrea, Alan

2007-05-01

DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of gliomas. Despite their frequent use, the therapeutic efficacy of these agents is limited by the development of resistance. Previous studies suggest that the mechanism of this resistance is complex and involves multiple DNA repair pathways. To better define the pathways contributing to the mechanisms underlying glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose- and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci formation, both hallmarks of FA pathway activation. The FA-deficient cells were more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To test whether these observations were pertinent to glioma biology, we screened a panel of glioma cell lines and identified one (HT16) that was deficient in the FA repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA pathway activation by a small molecule inhibitor (curcumin) or by small interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87 glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive to that of methyl-guanine methyl transferase inhibition. The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance.

Modeling the binding of fulvic acid by goethite: the speciation of adsorbed FA molecules

NASA Astrophysics Data System (ADS)

Filius, Jeroen D.; Meeussen, Johannes C. L.; Lumsdon, David G.; Hiemstra, Tjisse; van Riemsdijk, Willem H.

2003-04-01

Under natural conditions, the adsorption of ions at the solid-water interface may be strongly influenced by the adsorption of organic matter. In this paper, we describe the adsorption of fulvic acid (FA) by metal(hydr)oxide surfaces with a heterogeneous surface complexation model, the ligand and charge distribution (LCD) model. The model is a self-consistent combination of the nonideal competitive adsorption (NICA) equation and the CD-MUSIC model. The LCD model can describe simultaneously the concentration, pH, and salt dependency of the adsorption with a minimum of only three adjustable parameters. Furthermore, the model predicts the coadsorption of protons accurately for an extended range of conditions. Surface speciation calculations show that almost all hydroxyl groups of the adsorbed FA molecules are involved in outer sphere complexation reactions. The carboxylic groups of the adsorbed FA molecule form inner and outer sphere complexes. Furthermore, part of the carboxylate groups remain noncoordinated and deprotonated.

Preparation, Characterization, and Optimization of Folic Acid-Chitosan-Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery.

PubMed

Naghibi Beidokhti, Hamid Reza; Ghaffarzadegan, Reza; Mirzakhanlouei, Sasan; Ghazizadeh, Leila; Dorkoosh, Farid Abedin

2017-01-01

The objective of this study was to investigate the combined influence of independent variables in the preparation of folic acid-chitosan-methotrexate nanoparticles (FA-Chi-MTX NPs). These NPs were designed and prepared for targeted drug delivery in tumor. The NPs of each batch were prepared by coaxial electrospray atomization method and evaluated for particle size (PS) and particle size distribution (PSD). The independent variables were selected to be concentration of FA-chitosan, ratio of shell solution flow rate to core solution flow rate, and applied voltage. The process design of experiments (DOE) was obtained with three factors in three levels by Design expert software. Box-Behnken design was used to select 15 batches of experiments randomly. The chemical structure of FA-chitosan was examined by FTIR. The NPs of each batch were collected separately, and morphologies of NPs were investigated by field emission scanning electron microscope (FE-SEM). The captured pictures of all batches were analyzed by ImageJ software. Mean PS and PSD were calculated for each batch. Polynomial equation was produced for each response. The FE-SEM results showed the mean diameter of the core-shell NPs was around 304 nm, and nearly 30% of the produced NPs are in the desirable range. Optimum formulations were selected. The validation of DOE optimization results showed errors around 2.5 and 2.3% for PS and PSD, respectively. Moreover, the feasibility of using prepared NPs to target tumor extracellular pH was shown, as drug release was greater in the pH of endosome (acidic medium). Finally, our results proved that FA-Chi-MTX NPs were active against the human epithelial cervical cancer (HeLa) cells.

Fanconi anemia and the cell cycle: new perspectives on aneuploidy

PubMed Central

2014-01-01

Fanconi anemia (FA) is a complex heterogenic disorder of genomic instability, bone marrow failure, cancer predisposition, and congenital malformations. The FA signaling network orchestrates the DNA damage recognition and repair in interphase as well as proper execution of mitosis. Loss of FA signaling causes chromosome instability by weakening the spindle assembly checkpoint, disrupting centrosome maintenance, disturbing resolution of ultrafine anaphase bridges, and dysregulating cytokinesis. Thus, the FA genes function as guardians of genome stability throughout the cell cycle. This review discusses recent advances in diagnosis and clinical management of Fanconi anemia and presents the new insights into the origins of genomic instability in FA. These new discoveries may facilitate the development of rational therapeutic strategies for FA and for FA-deficient malignancies in the general population. PMID:24765528

Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.

PubMed

Futaki, M; Watanabe, S; Kajigaya, S; Liu, J M

2001-02-23

Fanconi anemia (FA) is a genetic syndrome characterized by bone marrow failure, birth defects, and a predisposition to malignancy. At this time, six FA genes have been identified, and several gene products have been found to interact in a protein complex. FA cells appear to overexpress the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). We therefore examined the effects of TNF-alpha on the regulation of FA complementation group proteins, FANCG and FANCA. We found that treatment with TNF-alpha induced FANCG protein expression. FANCA was induced concurrently with FANCG, and the FANCA/FANCG complex was increased in the nucleus following TNF-alpha treatment. Inactivation of inhibitory kappa B kinase-2 modulated the expression of FANCG. We also found that both nuclear and cytoplasmic FANCG fractions were phosphorylated. These results show that FANCG is a phosphoprotein and suggest that the cellular accumulation of FA proteins is subject to regulation by TNF-alpha signaling.

Folic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery.

PubMed

Xu, Zhenhua; Jin, Jiefu; Siu, Leo K S; Yao, Hong; Sze, Johnny; Sun, Hongzhe; Kung, Hsiang-Fu; Poon, Wai Sang; Ng, Samuel S M; Lin, Marie C

2012-04-15

In this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. (1)H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine2000 and Linear PEI 22 kDa (L-PEI 22 kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis and photoluminescence properties of novel Schiff base type polymer-rare earth complexes containing furfural-based bidentate Schiff base ligands

NASA Astrophysics Data System (ADS)

Gao, Baojiao; Zhang, Dandan; Li, Yanbin

2018-03-01

Luminescent polymer-rare earth complexes are an important class of photoluminescence and electroluminescence materials. Via molecular design, two furfural-based bidentate Schiff base ligands, furfural-aniline (FA) type ligand and furfural-cyclohexylamine (FC) type ligand, were bonded on the side chains of polysulfone (PSF), respectively, forming two functionalized macromolecules, PSF-FA and PSF-FC. And then through respective coordination reactions of the two functionalized macromolecules with Eu(Ⅲ) ion and Tb(Ⅲ) ion, novel luminescent binary and ternary (with 1,10-phenanthroline as the second ligand) polymer-rare earth complexes were synthesized. For these complexes, on basis of the characterization of their chemical structures, they photoluminescence properties were main researched, and the relationship between their luminescent properties and structures was explored. The experimental results show that the complexes coming from PSF-FA and Eu(Ⅲ) ion including binary and ternary complexes emit strong red luminescence, indicating that the bonded bidentate Schiff base ligand FA can sensitize the fluorescence emission of Eu(III) ion. While the complexes coming from PSF-FC and Tb(Ⅲ) ion produce green luminescence, displaying that the bonded bidentate Schiff base ligand FC can sensitize the fluorescence emission of Tb(Ⅲ) ion. The fluorescence emission intensities of the ternary complexes were stronger than that of binary complexes, reflecting the important effect of the second ligand. The fluorescence emission of the solid film of complexes is much stronger than that of the solutions of complexes. Besides, by comparison, it is found that the furfural (as a heteroaromatic compound)-based Schiff base type polymer-rare earth complexes have stronger fluorescence emission and higher energy transfer efficiency than salicylaldehyde (as a common aromatic compound)-based Schiff base type polymer-rare earth complexes.

TRIM.FaTE Evaluation Report

EPA Pesticide Factsheets

The TRIM.FaTE Evaluation Report is composed of three volumes. Volume I presents conceptual, mechanistic, and structural complexity evaluations of various aspects of the model. Volumes II and III present performance evaluation.

The effect of natural organic matter on the adsorption of mercury to bacterial cells

NASA Astrophysics Data System (ADS)

Dunham-Cheatham, Sarrah; Mishra, Bhoopesh; Myneni, Satish; Fein, Jeremy B.

2015-02-01

We investigated the ability of non-metabolizing Bacillus subtilis, Shewanella oneidensis MR-1, and Geobacter sulfurreducens bacterial species to adsorb mercury in the absence and presence of Suwanee River fulvic acid (FA). Bulk adsorption and X-ray absorption spectroscopy (XAS) experiments were conducted at three pH conditions, and the results indicate that the presence of FA decreases the extent of Hg adsorption to biomass under all of the pH conditions studied. Hg XAS results show that the presence of FA does not alter the binding environment of Hg adsorbed onto the biomass regardless of pH or FA concentration, indicating that ternary bacteria-Hg-FA complexes do not form to an appreciable extent under the experimental conditions, and that Hg binding on the bacteria is dominated by sulfhydryl binding. We used the experimental results to calculate apparent partition coefficients, Kd, for Hg under each experimental condition. The calculations yield similar coefficients for Hg onto each of the bacterial species studies, suggesting there is no significant difference in Hg partitioning between the three bacterial species. The calculations also indicate similar coefficients for Hg-bacteria and Hg-FA complexes. S XAS measurements confirm the presence of sulfhydryl sites on both the FA and bacterial cells, and demonstrate the presence of a wide range of S moieties on the FA in contrast to the bacterial biomass, whose S sites are dominated by thiols. Our results suggest that although FA can compete with bacterial binding sites for aqueous Hg, because of the relatively similar partition coefficients for the types of sorbents, the competition is not dominated by either bacteria or FA unless the concentration of one type of site greatly exceeds that of the other.

Cortactin as a Target for FAK in the Regulation of Focal Adhesion Dynamics

PubMed Central

Ghassemian, Majid; Schlaepfer, David D.

2012-01-01

Background Efficient cell movement requires the dynamic regulation of focal adhesion (FA) formation and turnover. FAs are integrin-associated sites of cell attachment and establish linkages to the cellular actin cytoskeleton. Cells without focal adhesion kinase (FAK), an integrin-activated tyrosine kinase, exhibit defects in FA turnover and cell motility. Cortactin is an actin binding adaptor protein that can influence FA dynamics. FAK and cortactin interact, but the cellular role of this complex remains unclear. Principal Findings Using FAK-null fibroblasts stably reconstituted with green fluorescent protein (GFP) tagged FAK constructs, we find that FAK activity and FAK C-terminal proline-rich region 2 (PRR2) and PRR3 are required for FA turnover and cell motility. Cortactin binds directly to FAK PRR2 and PRR3 sites via its SH3 domain and cortactin expression is important in promoting FA turnover and GFP-FAK release from FAs. FAK-cortactin binding is negatively-regulated by FAK activity and associated with cortactin tyrosine phosphorylation. FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility. However, phospho-mimetic cortactin mutated to glutamic acid (3YE) did not affect FA dynamics and did not rescue FA turnover defects in cells with inhibited FAK activity or with PRR2-mutated FAK that does not bind cortactin. Conclusions Our results support a model whereby FAK-mediated FA remodeling may occur through the formation of a FAK-cortactin signaling complex. This involves a cycle of cortactin binding to FAK, cortactin tyrosine phosphorylation, and subsequent cortactin-FAK dissociation accompanied by FA turnover and cell movement. PMID:22952866

Imaging, biodistribution and in vitro study of smart 99mTc-PAMAM G4 dendrimer as novel nano-complex.

PubMed

Narmani, Asghar; Yavari, Kamal; Mohammadnejad, Javad

2017-11-01

Overexpression of folic acid receptor in various human tumors cells makes it as good candidate for targeting delivery of chemotherapeutic and radiopharmaceutical agents. In this research, FA used for functionalization of PEG modified PAMAM G4 dendrimer as a smart delivery of 5-FU and 99m Tc for the breast carcinoma in order to chemotherapeutic and imaging goals. One aim of this research was assess the FA-mediated cell viability assay of PEG-PAMAM G4-FA-5FU- 99m Tc and in vitro uptake of PEG-PAMAM G4-FA- 99m Tc as the novel nano-complex determined on C2Cl2 (normal cell) and MCF-7 (breast cancer cell) cell lines. Other main goals were studied. Morover, an investigation in to in vivo imaging and biodistribution was carried out via a novel radio tracer by which tumor accumulation and site were obviously detected. The targeted tumor images taken by tail intravenous injection demonstrated that nano-complex can be smartly used in imaging study of the clinical practices. Also, the biodistribution of this nano-complex was investigated and the organ predestination of 99m Tc labeled nano-complex (%ID/g) was ascertained. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins.

PubMed

Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

2011-12-01

Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex.

Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway.

PubMed

Luo, Cheng-Qiong; Jang, Yoonjeong; Xing, Lei; Cui, Peng-Fei; Qiao, Jian-Bin; Lee, Ah Young; Kim, Hyeon-Jeong; Cho, Myung-Haing; Jiang, Hu-Lin

2016-11-20

Lung cancer has been a leading cause of cancer mortality worldwide and aerosol-mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized. Gel electrophoresis study elucidated that the designed polymer was capable to condense DNA and protect it from degradation by DNase I. Cell viability and transfection efficiency assay in vitro and in vivo indicated its increased transfection performance with lower toxicity. Furthermore, reduced tumor numbers and down-regulation of Akt1 protein after aerosol treatment containing FA-HPSPE/shAkt1 complexes proved its therapeutic potential for lung cancer suppression. Results obtained in this study suggested that FA-HPSPE with highly biocompatibility and targeting capability while forming complexes with shAkt1 and administrated through noninvasive aerosol could be prospective for inhibiting lung tumorigenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased mitochondrial matrix directed superoxide production by fatty acid hydroperoxides in skeletal muscle mitochondria

PubMed Central

Bhattacharya, Arunabh; Lustgarten, Michael; Shi, Yun; Liu, Yuhong; Jang, Youngmok C; Pulliam, Daniel; Jernigan, Amanda L; Van Remmen, Holly

2013-01-01

Previous studies have shown that muscle atrophy is associated with mitochondrial dysfunction and an increased rate of mitochondrial reactive oxygen species production. We recently demonstrated that fatty acid hydroperoxides (FA-OOH) are significantly elevated in mitochondria isolated from atrophied muscles. The purpose of the current study is to determine whether FA-OOH can alter skeletal muscle mitochondrial function. We found that FA-OOH (at low micromolar concentrations) induces mitochondrial dysfunction assessed by decrease in the rate of ATP production, oxygen consumption and activity of respiratory chain complexes I and III. Using methods to distinguish superoxide release towards the matrix and inter-membrane space, we demonstrate that FA-OOH significantly elevates oxidative stress in the mitochondrial matrix (and not the inter-membrane space) with complex I as the major site of superoxide production (most likely from a site upstream of the ubiquinone binding site but downstream from the flavin binding site-the iron sulfur clusters). Our results are the first to indicate that FA-OOH’s are important modulators of mitochondrial function and oxidative stress in skeletal muscle mitochondria and may play an important role in muscle atrophies that are associated with increased generation of FA-OOH’s, e.g., denervation-induced muscle atrophy. PMID:21172427

The FANCJ/MutLα interaction is required for correction of the cross-link response in FA-J cells

PubMed Central

Peng, Min; Litman, Rachel; Xie, Jenny; Sharma, Sudha; Brosh, Robert M; Cantor, Sharon B

2007-01-01

FANCJ also called BACH1/BRIP1 was first linked to hereditary breast cancer through its direct interaction with BRCA1. FANCJ was also recently identified as a Fanconi anemia (FA) gene product, establishing FANCJ as an essential tumor suppressor. Similar to other FA cells, FANCJ-null (FA-J) cells accumulate 4N DNA content in response to DNA interstrand crosslinks (ICLs). This accumulation is corrected by reintroduction of wild-type FANCJ. Here, we show that FANCJ interacts with the mismatch repair complex MutLα, composed of PMS2 and MLH1. Specifically, FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain. Genetic studies reveal that FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs. These results suggest that the FANCJ/MutLα interaction, but not FANCJ/BRCA1 interaction, is essential for establishment of a normal ICL-induced response. The functional role of the FANCJ/MutLα complex demonstrates a novel link between FA and MMR, and predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1. PMID:17581638

Synthesis of Core-Shell Nanoparticle Composites

DTIC Science & Technology

2010-08-17

Mawson Institute, University of South Australia 1 Final Report Contract Number FA2386-09-1-4043 Synthesis of Core-Shell Nanoparticle Composites...CI: Peter Majewski, School of Advanced Manufacturing and Mechanical Engineering, Mawson Institute, University of South Australia, peter.majewski...5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) University of South Australia, Mawson Lakes Blvd., Mawson Lakes SA, Australia

Fatty acid composition of porcine cumulus oocyte complexes (COC) during maturation: effect of the lipid modulators trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) and forskolin.

PubMed

Prates, E G; Alves, S P; Marques, C C; Baptista, M C; Horta, A E M; Bessa, R J B; Pereira, R M

2013-05-01

The effect of maturation and of two lipid modulators supplementation along in vitro maturation (IVM) on fatty acid (FA) and dimethylacetal (DMA) composition of porcine cumulus oocyte complexes (COC) were studied. Abattoir-derived immature COC were analyzed for FA and DMA or submitted to IVM as follows: control group; t10,c12 CLA group, t10,c12 CLA supplementation for 44 h; Forskolin group, forskolin supplementation during the initial 2 h; t10,c12 CLA + forskolin group, t10,c12 CLA for 44 h and forskolin for just 2h. Each experimental group had five replicates. FA analysis of oocytes, cumulus cells (CC), follicular fluid, and culture media were performed by gas-liquid chromatography. Oocytes and their CC had different FA composition. Oocytes were richer in saturated FA (SFA) preferentially maintaining their FA profile during maturation. Mature CC had the highest polyunsaturated FA (PUFA) content. Five individual and total SFA, and monounsaturated FA (MUFA), notably oleic acid (c9-18:1), percentages were lower (P ≤ 0.023) in mature than in immature CC. t10,c12 CLA was accumulated by COC from t10,c12 CLA and t10,c12 CLA + forskolin groups, mostly in CC where MUFA and an eicosatrienoic isomer decreased (P ≤ 0.043). Nevertheless, PUFA or FA and DMA total content were not affected. Arachidonic acid was reduced in t10,c12 CLA + forskolin CC and hexadecanal-DMA-16:0 in t10,c12 CLA CC. Forskolin alone increased (P ≤ 0.043) c9-18:1 in oocytes. In conclusion, maturation process clearly changed porcine COC FA and DMA profiles, mostly of CC, also more susceptible to modifications induced by t10,c12 CLA. This possibility of manipulating COC lipid composition during IVM could be used to improve oocyte quality/cryopreservation efficiency.

Natural organic matter and the event horizon of mass spectrometry.

PubMed

Hertkorn, N; Frommberger, M; Witt, M; Koch, B P; Schmitt-Kopplin, Ph; Perdue, E M

2008-12-01

Soils, sediments, freshwaters, and marine waters contain natural organic matter (NOM), an exceedingly complex mixture of organic compounds that collectively exhibit a nearly continuous range of properties (size-reactivity continuum). NOM is composed mainly of carbon, hydrogen, and oxygen, with minor contributions from heteroatoms such as nitrogen, sulfur, and phosphorus. Suwannee River fulvic acid (SuwFA) is a fraction of NOM that is relatively depleted in heteroatoms. Ultrahigh resolution Fourier transform ion cyclotron (FTICR) mass spectra of SuwFA reveal several thousand molecular formulas, corresponding in turn to several hundred thousand distinct chemical environments of carbon even without accountancy of isomers. The mass difference deltam among adjoining C,H,O-molecules between and within clusters of nominal mass is inversely related to molecular dissimilarity: any decrease of deltam imposes an ever growing mandatory difference in molecular composition. Molecular formulas that are expected for likely biochemical precursor molecules are notably absent from these spectra, indicating that SuwFA is the product of diagenetic reactions that have altered the major components of biomass beyond the point of recognition. The degree of complexity of SuwFA can be brought into sharp focus through comparison with the theoretical limits of chemical complexity, as constrained and quantized by the fundamentals of chemical binding. The theoretical C,H,O-compositional space denotes the isomer-filtered complement of the entire, very vast space of molecular structures composed solely of carbon, hydrogen, and oxygen. The molecular formulas within SuwFA occupy a sizable proportion of the theoretical C,H,O-compositional space. A 100 percent coverage of the theoretically feasible C,H,O-compositional space by SuwFA molecules is attained throughout a sizable range of mass and H/C and O/C elemental ratios. The substantial differences between (and complementarity of) the SuwFA molecular formulas that are observed using six different modes of ionization (APCI, APPI, and ESI in positive and negative modus) imply considerable selectivity of the ionization process and suggest that the observed mass spectra represent simplified projections of still more complex mixtures.

Helicobacter pylori purine nucleoside phosphorylase shows new distribution patterns of open and closed active site conformations and unusual biochemical features.

PubMed

Narczyk, Marta; Bertoša, Branimir; Papa, Lucija; Vuković, Vedran; Leščić Ašler, Ivana; Wielgus-Kutrowska, Beata; Bzowska, Agnieszka; Luić, Marija; Štefanić, Zoran

2018-04-01

Even with decades of research, purine nucleoside phosphorylases (PNPs) are enzymes whose mechanism is yet to be fully understood. This is especially true in the case of hexameric PNPs, and is probably, in part, due to their complex oligomeric nature and a whole spectrum of active site conformations related to interactions with different ligands. Here we report an extensive structural characterization of the apo forms of hexameric PNP from Helicobacter pylori (HpPNP), as well as its complexes with phosphate (P i ) and an inhibitor, formycin A (FA), together with kinetic, binding, docking and molecular dynamics studies. X-ray structures show previously unseen distributions of open and closed active sites. Microscale thermophoresis results indicate that a two-site model describes P i binding, while a three-site model is needed to characterize FA binding, irrespective of P i presence. The latter may be related to the newly found nonstandard mode of FA binding. The ternary complex of the enzyme with P i and FA shows, however, that P i binding stabilizes the standard mode of FA binding. Surprisingly, HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that P i moves out of most active sites, in accordance with its weak binding. Conformational changes between nonstandard and standard binding modes of nucleoside are observed during the simulations. Altogether, these findings show some unique features of HpPNP and provide new insights into the functioning of the active sites, with implications for understanding the complex mechanism of catalysis of this enzyme. The atomic coordinates and structure factors have been deposited in the Protein Data Bank: with accession codes 6F52 (HpPNPapo_1), 6F5A (HpPNPapo_2), 6F5I (HpPNPapo_3), 5LU0 (HpPNP_PO4), 6F4W (HpPNP_FA) and 6F4X (HpPNP_PO4_FA). Purine nucleoside orthophosphate ribosyl transferase, EC2.4.2.1, UniProtID: P56463. © 2018 Federation of European Biochemical Societies.

The Fanconi anemia ID2 complex: dueling saxes at the crossroads.

PubMed

Boisvert, Rebecca A; Howlett, Niall G

2014-01-01

Fanconi anemia (FA) is a rare recessive genetic disease characterized by congenital abnormalities, bone marrow failure and heightened cancer susceptibility in early adulthood. FA is caused by biallelic germ-line mutation of any one of 16 genes. While several functions for the FA proteins have been ascribed, the prevailing hypothesis is that the FA proteins function cooperatively in the FA-BRCA pathway to repair damaged DNA. A pivotal step in the activation of the FA-BRCA pathway is the monoubiquitination of the FANCD2 and FANCI proteins. Despite their importance for DNA repair, the domain structure, regulation, and function of FANCD2 and FANCI remain poorly understood. In this review, we provide an overview of our current understanding of FANCD2 and FANCI, with an emphasis on their posttranslational modification and common and unique functions.

The Fanconi anemia ID2 complex: Dueling saxes at the crossroads

PubMed Central

Boisvert, Rebecca A; Howlett, Niall G

2014-01-01

Fanconi anemia (FA) is a rare recessive genetic disease characterized by congenital abnormalities, bone marrow failure and heightened cancer susceptibility in early adulthood. FA is caused by biallelic germ-line mutation of any one of 16 genes. While several functions for the FA proteins have been ascribed, the prevailing hypothesis is that the FA proteins function cooperatively in the FA-BRCA pathway to repair damaged DNA. A pivotal step in the activation of the FA-BRCA pathway is the monoubiquitination of the FANCD2 and FANCI proteins. Despite their importance for DNA repair, the domain structure, regulation, and function of FANCD2 and FANCI remain poorly understood. In this review, we provide an overview of our current understanding of FANCD2 and FANCI, with an emphasis on their posttranslational modification and common and unique functions. PMID:25486561

Bioconjugated iron oxide nanocubes: synthesis, functionalization, and vectorization.

PubMed

Wortmann, Laura; Ilyas, Shaista; Niznansky, Daniel; Valldor, Martin; Arroub, Karim; Berger, Nadja; Rahme, Kamil; Holmes, Justin; Mathur, Sanjay

2014-10-08

A facile bottom-up approach for the synthesis of inorganic/organic bioconjugated nanoprobes based on iron oxide nanocubes as the core with a nanometric silica shell is demonstrated. Surface coating and functionalization protocols developed in this work offered good control over the shell thickness (8-40 nm) and enabled biovectorization of SiO2@Fe3O4 core-shell structures by covalent attachment of folic acid (FA) as a targeting unit for cellular uptake. The successful immobilization of folic acid was investigated both quantitatively (TGA, EA, XPS) and qualitatively (AT-IR, UV-vis, ζ-potential). Additionally, the magnetic behavior of the nanocomposites was monitored after each functionalization step. Cell viability studies confirmed low cytotoxicity of FA@SiO2@Fe3O4 conjugates, which makes them promising nanoprobes for targeted internalization by cells and their imaging.

Multifunctional Fe3O4 @ Au core/shell nanostars: a unique platform for multimode imaging and photothermal therapy of tumors

PubMed Central

Hu, Yong; Wang, Ruizhi; Wang, Shige; Ding, Ling; Li, Jingchao; Luo, Yu; Wang, Xiaolin; Shen, Mingwu; Shi, Xiangyang

2016-01-01

We herein report the development of multifunctional folic acid (FA)-targeted Fe3O4 @ Au nanostars (NSs) for targeted multi-mode magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. In this present work, citric acid-stabilized Fe3O4/Ag composite nanoparticles prepared by a mild reduction route were utilized as seeds and exposed to the Au growth solution to induce the formation of Fe3O4 @ Au core/shell NSs. Followed by successive decoration of thiolated polyethyleneimine (PEI-SH), FA via a polyethylene glycol spacer, and acetylation of the residual PEI amines, multifunctional Fe3O4 @ Au NSs were formed. The designed multifunctional NSs possess excellent colloidal stability, good cytocompatibility in a given concentration range, and specific recognition to cancer cells overexpressing FA receptors. Due to co-existence of Fe3O4 core and star-shaped Au shell, the NSs can be used for MR and CT imaging of tumors, respectively. Likewise, the near infrared plasmonic absorption feature also enables the NSs to be used for PA imaging and PTT of tumors. Our study clearly demonstrates a unique theranostic nanoplatform that can be used for high performance multi-mode imaging-guided PTT of tumors, which may be extendable for theranostics of different diseases in translational medicine. PMID:27325015

Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

PubMed

Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

2012-07-03

Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective detection of small molecules by means of FA in complex biological samples.

New insights into the operative network of FaEO, an enone oxidoreductase from Fragaria x ananassa Duch.

PubMed

Collu, Gabriella; Farci, Domenica; Esposito, Francesca; Pintus, Francesca; Kirkpatrick, Joanna; Piano, Dario

2017-05-01

The 2-methylene-furan-3-one reductase or Fragaria x ananassa Enone Oxidoreductase (FaEO) catalyses the last reductive step in the biosynthesis of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a major component in the characteristic flavour of strawberries. In the present work, we describe the association between FaEO and the vacuolar membrane of strawberry fruits. Even if FaEO lacks epitopes for stable or transient membrane-interactions, it contains a calmodulin-binding region, suggesting that in vivo FaEO may be associated with the membrane via a peripheral protein complex with calmodulin. Moreover, we also found that FaEO occurs in dimeric form in vivo and, as frequently observed for calmodulin-regulated proteins, it may be expressed in different isoforms by alternative gene splicing. Further mass spectrometry analysis confirmed that the isolated FaEO consists in the already known isoform and that it is the most characteristic during ripening. Finally, a characterization by absorption spectroscopy showed that FaEO has specific flavoprotein features. The relevance of these findings and their possible physiological implications are discussed.

Fitting modular reconnaissance systems into modern high-performance aircraft

NASA Astrophysics Data System (ADS)

Stroot, Jacquelyn R.; Pingel, Leslie L.

1990-11-01

The installation of the Advanced Tactical Air Reconnaissance System (ATARS) in the F/A-18D(RC) presented a complex set of design challenges. At the time of the F/A-18D(RC) ATARS option exercise, the design and development of the ATARS subsystems and the parameters of the F/A-18D(RC) were essentially fixed. ATARS is to be installed in the gun bay of the F/A-18D(RC), taking up no additional room, nor adding any more weight than what was removed. The F/A-18D(RC) installation solution required innovations in mounting, cooling, and fit techniques, which made constant trade study essential. The successful installation in the F/A-18D(RC) is the result of coupling fundamental design engineering with brainstorming and nonstandard approaches to every situation. ATARS is sponsored by the Aeronautical Systems Division, Wright-Patterson AFB, Ohio. The F/A-18D(RC) installation is being funded to the Air Force by the Naval Air Systems Command, Washington, D.C.

Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.

PubMed

Lakhi, Nisha A; Mizejewski, Gerald J

2017-02-01

Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair. An impaired cascade in these events imparts an increased breast cancer susceptibility to female FA patients. Elevations of sAFP have availed this fetal protein to serve as a biomarker for FA disease. However, the origin of the synthesis of sAFA has not been determined in FA patients. We hypothesize that hematopoietic multipotent progenitor stem cells in the bone marrow are the source of sAFP production in FA patients.

Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.

PubMed

Ravera, Silvia; Vaccaro, Daniele; Cuccarolo, Paola; Columbaro, Marta; Capanni, Cristina; Bartolucci, Martina; Panfoli, Isabella; Morelli, Alessandro; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo

2013-10-01

Fanconi anemia (FA) is a rare and complex inherited blood disorder of the child. At least 15 genes are associated with the disease. The highest frequency of mutations belongs to groups A, C and G. Genetic instability and cytokine hypersensitivity support the selection of leukemic over non-leukemic stem cells. FA cellular phenotype is characterized by alterations in red-ox state, mitochondrial functionality and energy metabolism as reported in the past however a clear picture of the altered biochemical phenotype in FA is still elusive and the final biochemical defect(s) still unknown. Here we report an analysis of the respiratory fluxes in FANCA primary fibroblasts, lymphocytes and lymphoblasts. FANCA mutants show defective respiration through Complex I, diminished ATP production and metabolic sufferance with an increased AMP/ATP ratio. Respiration in FANCC mutants is normal. Treatment with N-acetyl-cysteine (NAC) restores oxygen consumption to normal level. Defective respiration in FANCA mutants appear correlated with the FA pro-oxidative phenotype which is consistent with the altered morphology of FANCA mitochondria. Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Comparative evaluation of humic substances in oral drug delivery.

PubMed

Mirza, Mohd Aamir; Ahmad, Niyaz; Agarwal, Suraj Prakash; Mahmood, Danish; Khalid Anwer, M; Iqbal, Z

2011-05-01

Major and biologically most explored components of natural organic matter (NOM) are humic acid (HA) and fulvic acid (FA). We have explored rock shilajit as a source of NOM. On the other hand carbamazepine (CBZ) is a well known anticonvulsant drug and has a limited accessibility to brain. Bioavailability and pharmacokinetic profiles of CBZ have been improved by complexation and different techniques also. Present study has assessed the comparative abilities of FA and HA as complexing agent for CBZ in order to enhance pharmacokinetic profile of CBZ and accessibility to the brain. These two complexing agents have been compared on various indices such as their abilities to cause complexation and enhance solubility, permeability and dissolution. The present study also compared pharmacodynamic and biochemical profiles after oral administration of complexes. With the help of various pharmaceutical techniques such as freeze drying, physical mixture, kneading and solvent evaporation, two molar ratios (1:1 and 1:2) were selected for complexation and evaluated for conformational analysis (molecular modeling). Complex formed was further characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), mass spectroscopy and X-ray diffraction (XRD). Preclinical study on rodents with CBZ-HA and CBZ-FA has yielded appreciable results in terms of their anticonvulsant and antioxidants activities. However, CBZ-HA (1:2) demonstrated better result than any other complex.

Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.

PubMed

Wong, Pamela T; Chen, Dexin; Tang, Shengzhuang; Yanik, Sean; Payne, Michael; Mukherjee, Jhindan; Coulter, Alexa; Tang, Kenny; Tao, Ke; Sun, Kang; Baker, James R; Choi, Seok Ki

2015-12-02

Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

PubMed

Michalski, M C; Genot, C; Gayet, C; Lopez, C; Fine, F; Joffre, F; Vendeuvre, J L; Bouvier, J; Chardigny, J M; Raynal-Ljutovac, K

2013-10-01

On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen. Copyright © 2013 Elsevier Ltd. All rights reserved.

Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes.

PubMed

Cruz, Maysa M; Lopes, Andressa B; Crisma, Amanda R; de Sá, Roberta C C; Kuwabara, Wilson M T; Curi, Rui; de Andrade, Paula B M; Alonso-Vale, Maria I C

2018-03-20

We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 μM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.

A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release

PubMed Central

Yang, Yi; Zhao, Hang; Jia, YanPeng; Guo, QingFa; Qu, Ying; Su, Jing; Lu, XiaoLing; Zhao, YongXiang; Qian, ZhiYong

2016-01-01

Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release. PMID:26883682

Patients undergoing PCI from the femoral route by default radial operators are at high risk of vascular access-site complications.

PubMed

Rafie, Ihsan M; Uddin, Muez M; Ossei-Gerning, Nicholas; Anderson, Richard A; Kinnaird, Timothy D

2014-02-01

Radial artery (RA) access for PCI has a lower incidence of vascular access-site (VAS) complications than the femoral artery (FA) approach. However, even for default radial operators certain patients are intervened upon from the FA. We examined the demographics and incidence of VAS complications when default radial operators resort to the FA for PCI. The demographics and VAS complications were compared by access site retrospectively for all PCI cases performed by default radial operators (n=1,392). A modified ACUITY trial definition of major VAS complication was used. FA puncture occurred in 25.2% (351/1,392) of cases. Patients were more likely to be female, older and weigh less than patients undergoing PCI from the RA. The FA procedure was likely to be more complex with larger sheaths, more left main stem, graft and multivessel intervention, and there was a greater proportion of emergency cases. Despite increased case complexity, glycoprotein inhibitors were used less frequently in femoral cases (26.5% vs. 36.8%, p<0.001). A VAS complication occurred in 12.5% (44/351) of cases. The risk factors for access-site bleeding are disproportionately high in the population requiring FA puncture by default radial operators, and as a result such patients have a high rate of vascular access-site complications.

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery.

PubMed

Xin, Yu; Liu, Tie; Yang, Chenlong

We have prepared novel poly(d,l-lactide- co -glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold ( t 1/2 ), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

PubMed Central

Xin, Yu; Liu, Tie; Yang, Chenlong

2016-01-01

We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy. PMID:27853366

Targeting property and toxicity of a novel ultrasound contrast agent microbubble carrying the targeting and drug-loaded complex FA-CNTs-PTX on MCF7 cells.

PubMed

Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua

2017-10-01

The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Ionic complexation as a non-covalent approach for the design of folate anchored rifampicin Gantrez nanoparticles.

PubMed

Date, Praveen V; Patel, Mitesh D; Majee, Sharmila B; Samad, Abdul; Devarajan, Padma V

2013-05-01

The present study discloses the design of folate anchored Rifampicin-Poly methylvinylether maleic anhydride copolymer (Gantrez AN-119, Gantrez) nanoparticles (RFMGzFa) by ionic complexation. Folic acid was anchored to the preformed drug loaded nanoparticles. Folic acid was anchored in different concentration by simply varying the amount of folic acid added during preparation. RFMGzFa nanoparticles were prepared by emulsion solvent diffusion method. Gantrez AN-119 rapidly hydrolyzes in aqueous medium releasing carboxylic acid groups, to create an acidic environment. This facilitates protonation and subsequent ionic complexation of folic acid with the carboxylic groups, to enable anchoring. FTIR spectra confirmed this interaction. Infrared imaging revealed distribution of folic acid across the nanoparticle surface. Nanoparticles were obtained in the size range 350-450 nm with RFM loading of 12-14% w/w. Zeta potential confirmed colloidal stability. TEM/SEM revealed spherical morphology. RFMGzFa nanoparticles exhibited sustained release of RFM and folic acid. Folic acid showed sustained release upto 12 h, which was ion exchange mediated. A 480% enhancement in RFM uptake with RFMGzFa nanoparticles compared to 300% with RFMGz nanoparticles in-vitro, in human macrophage cell line U-937, suggested the role of folic acid in folate receptor mediated uptake. Ionic complexation represents a simple non-covalent approach for anchoring folic acid on polymeric nanoparticles of Gantrez.

Fluctuating asymmetry in broiler chickens: a decision protocol for trait selection in seven measuring methods.

PubMed

Van Nuffel, A; Tuyttens, F A M; Van Dongen, S; Talloen, W; Van Poucke, E; Sonck, B; Lens, L

2007-12-01

Nonidentical development of bilateral traits due to disturbing genetic or developmental factors is called fluctuating asymmetry (FA) if such deviations are continuously distributed. Fluctuating asymmetry is believed to be a reliable indicator of the fitness and welfare of an animal. Despite an increasing body of research, the link between FA and animal performance or welfare is reported to be inconsistent, possibly, among other reasons, due to inaccurate measuring protocols or incorrect statistical analyses. This paper reviews problems of interpreting FA results in poultry and provides guidelines for the measurement and analysis of FA, applied to broilers. A wide range of morphological traits were measured by 7 different techniques (ranging from measurements on living broilers or intact carcasses to X-rays, bones, and digital images) and evaluated for their applicability to estimate FA. Following 4 selection criteria (significant FA, absence of directional asymmetry or antisymmetry, absence of between-trait correlation in signed FA values, and high signal-to-noise ratio), from 3 to 14 measurements per method were found suitable for estimating the degree of FA. The accuracy of FA estimates was positively related to the complexity and time investment of the measuring method. In addition, our study clearly shows the importance of securing adequate statistical power when designing FA studies. Repeatability analyses of FA estimates indicated the need for larger sample sizes, more repeated measurements, or both, than are commonly used in FA studies.

Formation of ethyl ferulate from feruloylated oligosaccharide by transesterification of rice koji enzyme under sake mash conditions.

PubMed

Suzuki, Nobukazu; Ito, Toshihiko; Hiroshima, Kai; Tokiwano, Tetsuo; Hashizume, Katsumi

2016-03-01

Formation of ethyl ferulate (EF) and ferulic acid (FA) under sake mash conditions was studied using feruloylated oligosaccharide (FO), prepared from rice grains, as the substrate for rice koji enzyme. EF and FA were produced from FO over six times faster than from alkyl ferulates however, under the same ethanol concentration, only small differences were observed between the EF/FA ratios when either FO or methyl ferulate were used as substrates. Esterification and hydrolysis of FO or methyl ferulate showed similar pH dependencies and similar EF/FA ratios for each substrate in all of the pH ranges tested. Ethanol concentration clearly affected the EF/FA ratio; the ratio increased as ethanol concentration increased. Formation of EF and FA in the sake mash simulated rice digest was accelerated by addition of exogenous FO. These results indicated that supply of FO to sake mash is a crucial step for EF and FA formation, and ethanol is an influencing factor in the EF/FA ratio. The rice koji enzyme reaction suggested that EF and FA are formed through a common feruloylated enzyme intermediate complex by transesterification or hydrolysis, and these reactions occur competitively. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Fluorescence anisotropy (polarization): from drug screening to precision medicine

PubMed Central

Zhang, Hairong; Wu, Qian; Berezin, Mikhail Y.

2016-01-01

Introduction Fluorescence anisotropy (FA) is one of the major established methods accepted by industry and regulatory agencies for understanding the mechanisms of drug action and selecting drug candidates utilizing a high-throughput format. Areas covered This review covers the basics of FA and complementary methods, such as fluorescence lifetime anisotropy and their roles in the drug discovery process. The authors highlight the factors affecting FA readouts, fluorophore selection, and instrumentation. Furthermore, the authors describe the recent development of a successful, commercially valuable FA assay for Long QT syndrome drug toxicity to illustrate the role that FA can play in the early stages of drug discovery. Expert opinion Despite the success in drug discovery, the FA-based technique experiences competitive pressure from other homogeneous assays. That being said, FA is an established yet rapidly developing technique, recognized by academic institutions, the pharmaceutical industry, and regulatory agencies across the globe. The technical problems encountered in working with small molecules in homogeneous assays are largely solved, and new challenges come from more complex biological molecules and nanoparticles. With that, FA will remain one of the major work-horse techniques leading to precision (personalized) medicine. PMID:26289575

Comparative evaluation of humic substances in oral drug delivery

PubMed Central

Mirza, Mohd. Aamir; Ahmad, Niyaz; Agarwal, Suraj Prakash; Mahmood, Danish; Khalid Anwer, M.; Iqbal, Z.

2011-01-01

Major and biologically most explored components of natural organic matter (NOM) are humic acid (HA) and fulvic acid (FA). We have explored rock shilajit as a source of NOM. On the other hand carbamazepine (CBZ) is a well known anticonvulsant drug and has a limited accessibility to brain. Bioavailability and pharmacokinetic profiles of CBZ have been improved by complexation and different techniques also. Present study has assessed the comparative abilities of FA and HA as complexing agent for CBZ in order to enhance pharmacokinetic profile of CBZ and accessibility to the brain. These two complexing agents have been compared on various indices such as their abilities to cause complexation and enhance solubility, permeability and dissolution. The present study also compared pharmacodynamic and biochemical profiles after oral administration of complexes. With the help of various pharmaceutical techniques such as freeze drying, physical mixture, kneading and solvent evaporation, two molar ratios (1:1 and 1:2) were selected for complexation and evaluated for conformational analysis (molecular modeling). Complex formed was further characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), mass spectroscopy and X-ray diffraction (XRD). Preclinical study on rodents with CBZ–HA and CBZ–FA has yielded appreciable results in terms of their anticonvulsant and antioxidants activities. However, CBZ–HA (1:2) demonstrated better result than any other complex. PMID:25755978

Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment.

PubMed

Pan, Changqie; Liu, Yuqing; Zhou, Minyu; Wang, Wensheng; Shi, Min; Xing, Malcolm; Liao, Wangjun

2018-01-01

A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical ( 1 H nuclear magnetic resonance) and physical (morphology and super-magnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients

PubMed Central

2014-01-01

Background Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. Methods We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Results Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients’ clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Conclusions Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology. PMID:24885126

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients.

PubMed

Chang, Lixian; Yuan, Weiping; Zeng, Huimin; Zhou, Quanquan; Wei, Wei; Zhou, Jianfeng; Li, Miaomiao; Wang, Xiaomin; Xu, Mingjiang; Yang, Fengchun; Yang, Yungui; Cheng, Tao; Zhu, Xiaofan

2014-05-15

Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients' clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology.

The effects of noise in cardiac diffusion tensor imaging and the benefits of averaging complex data.

PubMed

Scott, Andrew D; Nielles-Vallespin, Sonia; Ferreira, Pedro F; McGill, Laura-Ann; Pennell, Dudley J; Firmin, David N

2016-05-01

There is growing interest in cardiac diffusion tensor imaging (cDTI), but, unlike other diffusion MRI applications, there has been little investigation of the effects of noise on the parameters typically derived. One method of mitigating noise floor effects when there are multiple image averages, as in cDTI, is to average the complex rather than the magnitude data, but the phase contains contributions from bulk motion, which must be removed first. The effects of noise on the mean diffusivity (MD), fractional anisotropy (FA), helical angle (HA) and absolute secondary eigenvector angle (E2A) were simulated with various diffusion weightings (b values). The effect of averaging complex versus magnitude images was investigated. In vivo cDTI was performed in 10 healthy subjects with b = 500, 1000, 1500 and 2000 s/mm(2). A technique for removing the motion-induced component of the image phase present in vivo was implemented by subtracting a low-resolution copy of the phase from the original images before averaging the complex images. MD, FA, E2A and the transmural gradient in HA were compared for un-averaged, magnitude- and complex-averaged reconstructions. Simulations demonstrated an over-estimation of FA and MD at low b values and an under-estimation at high b values. The transition is relatively signal-to-noise ratio (SNR) independent and occurs at a higher b value for FA (b = 1000-1250 s/mm(2)) than MD (b ≈ 250 s/mm(2)). E2A is under-estimated at low and high b values with a transition at b ≈ 1000 s/mm(2), whereas the bias in HA is comparatively small. The under-estimation of FA and MD at high b values is caused by noise floor effects, which can be mitigated by averaging the complex data. Understanding the parameters of interest and the effects of noise informs the selection of the optimal b values. When complex data are available, they should be used to maximise the benefit from the acquisition of multiple averages. The combination of complex data is also a valuable step towards segmented acquisitions. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of natural organic matter on arsenic removal by modified granular natural siderite: Evidence of ternary complex formation by HPSEC-UV-ICP-MS.

PubMed

Li, Fulan; Guo, Huaming; Zhou, Xiaoqian; Zhao, Kai; Shen, Jiaxing; Liu, Fei; Wei, Chao

2017-02-01

High arsenic (As) groundwater usually has high concentrations of natural organic matter (NOM). Effects of NOM on arsenic adsorption were investigated to evaluate the efficiency of modified granular natural siderite (MGNS) as an adsorbent for groundwater arsenic remediation. Humic and fulvic acids (HA/FA) were selected as model NOM compounds. In batch tests, HA or FA was either first adsorbed onto the MGNS, or applied together with dissolved arsenic to investigate effects of both adsorbed and dissolved NOM on arsenic removal. The kinetic data showed no significant effects of both adsorbed and dissolved HA/FA on As(III) adsorption. However, As(V) removal was inhibited, whereby the adsorbed NOM compounds had greater inhibitory effect. The inhibitory effect on As(V) removal increased with increasing NOM concentrations. FA exhibited higher inhibitory effect than HA at the same concentration. Steric Exclusion Chromatography-HPLC (SEC-HPLC), and High-Performance Size Exclusion Chromatography-UV-Inductively Coupled Plasma Mass Spectrometry (HPSEC-UV-ICP-MS) revealed that As(V) removal was mostly achieved by the oxyanion adsorption and adversely affected by dissolved FA via competitive adsorption for surface sites. In addition to oxyanion adsorption, removal of As(V) was related to scavenging of ternary HA-As-Fe complexes, which led to the less inhibitory effect of dissolved HA on As(V) removal than dissolved FA via competitive adsorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Performance evaluation of firefly algorithm with variation in sorting for non-linear benchmark problems

NASA Astrophysics Data System (ADS)

Umbarkar, A. J.; Balande, U. T.; Seth, P. D.

2017-06-01

The field of nature inspired computing and optimization techniques have evolved to solve difficult optimization problems in diverse fields of engineering, science and technology. The firefly attraction process is mimicked in the algorithm for solving optimization problems. In Firefly Algorithm (FA) sorting of fireflies is done by using sorting algorithm. The original FA is proposed with bubble sort for ranking the fireflies. In this paper, the quick sort replaces bubble sort to decrease the time complexity of FA. The dataset used is unconstrained benchmark functions from CEC 2005 [22]. The comparison of FA using bubble sort and FA using quick sort is performed with respect to best, worst, mean, standard deviation, number of comparisons and execution time. The experimental result shows that FA using quick sort requires less number of comparisons but requires more execution time. The increased number of fireflies helps to converge into optimal solution whereas by varying dimension for algorithm performed better at a lower dimension than higher dimension.

Formic acid catalyzed hydrolysis of SO3 in the gas phase: a barrierless mechanism for sulfuric acid production of potential atmospheric importance.

PubMed

Hazra, Montu K; Sinha, Amitabha

2011-11-02

Computational studies at the B3LYP/6-311++G(3df,3pd) and MP2/6-311++G(3df,3pd) levels are performed to explore the changes in reaction barrier height for the gas phase hydrolysis of SO(3) to form H(2)SO(4) in the presence of a single formic acid (FA) molecule. For comparison, we have also performed calculations for the reference reaction involving water assisted hydrolysis of SO(3) at the same level. Our results show that the FA assisted hydrolysis of SO(3) to form H(2)SO(4) is effectively a barrierless process. The barrier heights for the isomerization of the SO(3)···H(2)O···FA prereactive collision complex, which is the rate limiting step in the FA assisted hydrolysis, are found to be respectively 0.59 and 0.08 kcal/mol at the B3LYP/6-311++G(3df,3pd) and MP2/6-311++G(3df,3pd) levels. This is substantially lower than the ~7 kcal/mol barrier for the corresponding step in the hydrolysis of SO(3) by two water molecules--which is currently the accepted mechanism for atmospheric sulfuric acid production. Simple kinetic analysis of the relative rates suggests that the reduction in barrier height facilitated by FA, combined with the greater stability of the prereactive SO(3)···H(2)O···FA collision complex compared to SO(3)···H(2)O···H(2)O and the rather plentiful atmospheric abundance of FA, makes the formic acid mediated hydrolysis reaction a potentially important pathway for atmospheric sulfuric acid production.

Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1

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

Gwon, Gwang Hyeon; Kim, Youngran; Liu, Yaqi

2014-10-15

Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5' flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domainmore » playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.« less

Effects of Chain Length and Degree of Unsaturation of Fatty Acids on Structure and in Vitro Digestibility of Starch-Protein-Fatty Acid Complexes.

PubMed

Zheng, Mengge; Chao, Chen; Yu, Jinglin; Copeland, Les; Wang, Shuo; Wang, Shujun

2018-02-28

The effects of chain length and degree of unsaturation of fatty acids (FAs) on structure and in vitro digestibility of starch-protein-FA complexes were investigated in model systems. Studies with the rapid visco analyzer (RVA) showed that the formation of ternary complex resulted in higher viscosities than those of binary complex during the cooling and holding stages. The results of differential scanning calorimetry (DSC), Raman, and X-ray diffraction (XRD) showed that the structural differences for ternary complexes were much less than those for binary complexes. Starch-protein-FA complexes presented lower in vitro enzymatic digestibility compared with starch-FAs complexes. We conclude that shorter chain and lower unsaturation FAs favor the formation of ternary complexes but decrease the thermal stability of these complexes. FAs had a smaller effect on the ordered structures of ternary complexes than on those of binary complexes and little effect on enzymatic digestibility of both binary and ternary complexes.

White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus

PubMed Central

Price, Gary; Cercignani, Mara; Parker, Geoffrey J.M.; Altmann, Daniel R.; Barnes, Thomas R.E.; Barker, Gareth J.; Joyce, Eileen M.; Ron, Maria A.

2008-01-01

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the symptoms and cognitive abnormalities of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail, and we present here a study of patients with first-episode psychosis using this technique. We studied the uncinate fasciculus (UF), the largest white matter tract that connects the frontal and temporal lobes, two brain regions significantly implicated in schizophrenia. Nineteen patients with first-episode schizophrenia and 23 controls were studied using a probabilistic tractography algorithm (PICo). Fractional anisotropy (FA) and probability of connection were obtained for every voxel in the tract, and the group means and distributions of these variables were compared. The spread of the FA distribution in the upper tail, as measured by the squared coefficient of variance (SCV), was reduced in the left UF in the patient group, indicating that the number of voxels with high FA values was reduced in the core of the tract and suggesting the presence of changes in fibre alignment and tract coherence in the patient group. The SCV of FA was lower in females across both groups and there was no correlation between the SCV of FA and clinical ratings. PMID:17988894

The optimal community detection of software based on complex networks

NASA Astrophysics Data System (ADS)

Huang, Guoyan; Zhang, Peng; Zhang, Bing; Yin, Tengteng; Ren, Jiadong

2016-02-01

The community structure is important for software in terms of understanding the design patterns, controlling the development and the maintenance process. In order to detect the optimal community structure in the software network, a method Optimal Partition Software Network (OPSN) is proposed based on the dependency relationship among the software functions. First, by analyzing the information of multiple execution traces of one software, we construct Software Execution Dependency Network (SEDN). Second, based on the relationship among the function nodes in the network, we define Fault Accumulation (FA) to measure the importance of the function node and sort the nodes with measure results. Third, we select the top K(K=1,2,…) nodes as the core of the primal communities (only exist one core node). By comparing the dependency relationships between each node and the K communities, we put the node into the existing community which has the most close relationship. Finally, we calculate the modularity with different initial K to obtain the optimal division. With experiments, the method OPSN is verified to be efficient to detect the optimal community in various softwares.

Neutronics, steady-state, and transient analyses for the Poland MARIA reactor for irradiation testing of LEU lead test fuel assemblies from CERCA : ANL independent verification results.

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

Garner, P. L.; Hanan, N. A.

The MARIA reactor at the Institute of Atomic Energy (IAE) in Swierk (30 km SE of Warsaw) in the Republic of Poland is considering conversion from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel assemblies (FA). The FA design in MARIA is rather unique; a suitable LEU FA has never been designed or tested. IAE has contracted with CERCA (the fuel supply portion of AREVA in France) to supply 2 lead test assemblies (LTA). The LTAs will be irradiated in MARIA to burnup level of at least 40% for both LTAs and to 60% for one LTA. IAE may decidemore » to purchase additional LEU FAs for a full core conversion after the test irradiation. The Reactor Safety Committee within IAE and the National Atomic Energy Agency in Poland (PAA) must approve the LTA irradiation process. The approval will be based, in part, on IAE submitting revisions to portions of the Safety Analysis Report (SAR) which are affected by the insertion of the LTAs. (A similar process will be required for the full core conversion to LEU fuel.) The analysis required was established during working meetings between Argonne National Laboratory (ANL) and IAE staff during August 2006, subsequent email correspondence, and subsequent staff visits. The analysis needs to consider the current high-enriched uranium (HEU) core and 4 core configurations containing 1 and 2 LEU LTAs in various core positions. Calculations have been performed at ANL in support of the LTA irradiation. These calculations are summarized in this report and include criticality, burn-up, neutronics parameters, steady-state thermal hydraulics, and postulated transients. These calculations have been performed at the request of the IAE staff, who are performing similar calculations to be used in their SAR amendment submittal to the PAA. The ANL analysis has been performed independently from that being performed by IAE and should only be used as one step in the verification process.« less

Orientations of Iron-Sulfur Clusters FA and FB in the Homodimeric Type-I Photosynthetic Reaction Center of Heliobacterium modesticaldum.

PubMed

Kondo, Toru; Matsuoka, Masahiro; Azai, Chihiro; Itoh, Shigeru; Oh-Oka, Hirozo

2016-05-12

Orientations of the FA and FB iron-sulfur (FeS) clusters in a structure-unknown type-I homodimeric heriobacterial reaction center (hRC) were studied in oriented membranes of the thermophilic anaerobic photosynthetic bacterium Heliobacterium modesticaldum by electron paramagnetic resonance (EPR), and compared with those in heterodimeric photosystem I (PS I). The Rieske-type FeS center in the cytochrome b/c complex showed a well-oriented EPR signal. Illumination at 14 K induced an FB(-) signal with g-axes of gz = 2.066, gy = 1.937, and gx = 1.890, tilted at angles of 60°, 60°, and 45°, respectively, with respect to the membrane normal. Chemical reduction with dithionite produced an additional signal of FA(-), which magnetically interacted with FB(-), with gz = 2.046, gy = 1.942, and gx = 1.911 at 30°, 60°, and 90°, respectively. The angles and redox properties of FA(-) and FB(-) in hRC resemble those of FB(-) and FA(-), respectively, in PS I. Therefore, FA and FB in hRC, named after their g-value similarities, seem to be located like FB and FA, not like FA and FB, respectively, in PS I. The reducing side of hRC could resemble those in PS I, if the names of FA and FB are interchanged with each other.

pH-responsive unimolecular micelles self-assembled from amphiphilic hyperbranched block copolymer for efficient intracellular release of poorly water-soluble anticancer drugs.

PubMed

Tabatabaei Rezaei, Seyed Jamal; Abandansari, Hamid Sadeghi; Nabid, Mohammad Reza; Niknejad, Hassan

2014-07-01

Novel unimolecular micelles from amphiphilic hyperbranched block copolymer H40-poly(ε-caprolactone)-b-poly(acrylic acid)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-b-PAA-b'-MPEG/PEG-FA (HCAE-FA)) as new multifunctional nanocarriers to pH-induced accelerated release and tumor-targeted delivery of poorly water-soluble anticancer drugs were developed. The hydrophobic core of the unimolecular micelle was hyperbranched polyester (H40-poly(ε-caprolactone) (H40-PCL)). The inner hydrophilic layer was composed of PAA segments, while the outer hydrophilic shell was composed of PEG segments. This copolymer formed unimolecular micelles in the aqueous solution with a mean particle size of 33 nm, as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). To study the feasibility of micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, paclitaxel (PTX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 10.35 wt.%. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to acidic environments which would trigger the release of encapsulated drugs. Flow cytometry and fluorescent microscope studies revealed that the cellular binding of the FA-conjugated micelles against HeLa cells was higher than that of the neat micelles (without FA). The in vitro cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol®. All of these results show that these unique unimolecular micelles may offer a very promising approach for targeted cancer therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of fulvic acid surface coatings on plutonium sorption and desorption kinetics on goethite

DOE PAGES

Tinnacher, Ruth M.; Begg, James D.; Mason, Harris; ...

2015-01-21

The rates and extent of plutonium (Pu) sorption and desorption onto mineral surfaces are important parameters for predicting Pu mobility in subsurface environments. The presence of natural organic matter, such as fulvic acid (FA), may influence these parameters. We investigated the effects of FA on Pu(IV) sorption/desorption onto goethite in two scenarios: when FA was (1) initially present in solution or (2) found as organic coatings on the mineral surface. A low pH was used to maximize FA coatings on goethite. Experiments were combined with kinetic modeling and speciation calculations to interpret variations in Pu sorption rates in the presencemore » of FA. Our results indicate that FA can change the rates and extent of Pu sorption onto goethite at pH 4. Differences in the kinetics of Pu sorption were observed as a function of the concentration and initial form of FA. The fraction of desorbed Pu decreased in the presence of FA, indicating that organic matter can stabilize sorbed Pu on goethite. These results suggest that ternary Pu–FA–mineral complexes could enhance colloid-facilitated Pu transport. In conclusion, more representative natural conditions need to be investigated to quantify the relevance of these findings.« less

Decipher the dynamic coordination between enzymatic activity and structural modulation at focal adhesions in living cells

NASA Astrophysics Data System (ADS)

Lu, Shaoying; Seong, Jihye; Wang, Yi; Chang, Shiou-Chi; Eichorst, John Paul; Ouyang, Mingxing; Li, Julie Y.-S.; Chien, Shu; Wang, Yingxiao

2014-07-01

Focal adhesions (FAs) are dynamic subcellular structures crucial for cell adhesion, migration and differentiation. It remains an enigma how enzymatic activities in these local complexes regulate their structural remodeling in live cells. Utilizing biosensors based on fluorescence resonance energy transfer (FRET), we developed a correlative FRET imaging microscopy (CFIM) approach to quantitatively analyze the subcellular coordination between the enzymatic Src activation and the structural FA disassembly. CFIM reveals that the Src kinase activity only within the microdomain of lipid rafts at the plasma membrane is coupled with FA dynamics. FA disassembly at cell periphery was linearly dependent on this raft-localized Src activity, although cells displayed heterogeneous levels of response to stimulation. Within lipid rafts, the time delay between Src activation and FA disassembly was 1.2 min in cells seeded on low fibronectin concentration ([FN]) and 4.3 min in cells on high [FN]. CFIM further showed that the level of Src-FA coupling, as well as the time delay, was regulated by cell-matrix interactions, as a tight enzyme-structure coupling occurred in FA populations mediated by integrin αvβ3, but not in those by integrin α5β1. Therefore, different FA subpopulations have distinctive regulation mechanisms between their local kinase activity and structural FA dynamics.

Is excision biopsy of fibroadenomas based solely on size criteria warranted?

PubMed

Neville, Grace; Neill, Cathleen O'; Murphy, Rosemary; Corrigan, Mark; Redmond, Paul H; Feeley, Linda; Bennett, Michael W; O'Connell, Fionnuala; Browne, Tara Jane

2018-05-25

Fibroadenomas (FA) are the most common benign tumor in the female breast. Most are managed conservatively provided there is clinical, radiologic, and pathologic concordance. However, surgical excision is typically recommended for cellular fibroepithelial lesions or those lesions with clinical, radiologic, or pathologic features concerning for phyllodes tumor (PT). Some studies have suggested surgical excision in all FA >30 mm to reduce core needle biopsy (CNB) sampling errors. The aim of our study was to evaluate, in the absence of any other concerning clinicopathologic features, whether surgical excision of FA was warranted based on size criteria alone. Cork University Hospital is a large academic center in Southern Ireland. Its breast cancer center provides both a screening and symptomatic service and diagnoses approximately 600 cancers per year. The breast histopathological data base was reviewed for all CNBs from January 1, 2010, to June 30, 2015, with a diagnosis of FA that went on to have excision at our institution. We excluded all cellular fibroepithelial lesions and those cases with co-existent lobular neoplasia, ductal carcinoma in situ, invasive carcinoma, atypical ductal hyperplasia, or lesions which would require excision in their own right. Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. Patient demographics and preoperative radiologic size and the radiologic target were recorded in each case. All radiology was reviewed by a breast radiologist prior to inclusion in the study, and there was histologic radiologic concordance with a diagnosis of FA in all cases. A total of 12,109 consecutive radiologically guided CNB were performed January 2010-June 2015; 3438 with a diagnosis of FA were identified of which 290 cases went on to have surgical excision. Of those 290 cases; 98.28% (n = 285) were confirmed as FA on excision. The remaining 1.72% (n = 5) had atypical features-FA with LCIS (n = 1), benign PT (n = 3), and invasive ductal carcinoma (n = 1). Our study suggests that, excision based solely on size is not warranted in clinical and radiologically concordant cases with a diagnosis of FA on CNB. © 2018 Wiley Periodicals, Inc.

Effect of fulvic and humic acids on copper and zinc homeostasis in rats.

PubMed

Hullár, István; Vucskits, András Valentin; Berta, Erzsébet; Andrásofszky, Emese; Bersényi, András; Szabó, József

2018-03-01

The objective of this study was to investigate the effects of fulvic acid (FA) and humic acid (HA), the two main compounds of humic substances (HSs), on copper (Cu) and zinc (Zn) homeostasis. Seventy-two male Wistar rats were randomly divided into nine experimental groups. The control diet (AIN-93G formula) and the diets supplemented with 0.1%, 0.2%, 0.4% and 0.8% FA or HA were fed for 26 days. Cu and Zn concentrations of the large intestinal content (LIC), liver, kidney, femur and hair were determined. FA and HA did not influence significantly the Cu or Zn contents of the experimental diets, the rats' feed intake, weight gain and the feed to gain ratio. Both FA and HA decreased the Cu concentrations of the LIC significantly and in a dose-related manner; however the absorption-stimulating effect of HA was more pronounced. FA increased the Cu content of the liver, but neither FA nor HA had a dose-dependent effect on it. FA or HA supplementations had no significant effect on the Cu concentration of the kidney. At the concentrations used, dietary FA or HA supplementations are not promising growth promoters. FA influences the Cu homeostasis unlike HA, because FA not only stimulates Cu absorption, but the extra quantity of absorbed Cu is retained in the organism. The stimulatory effect of HA on Zn absorption may not be manifested in Cu and Zn homeostasis, because of the tight connection of these microelements to FA and HA, which prevents the transmission of Zn from the ZnHA complex to the organs. As regards the effect of FA and HA on Cu and Zn homeostasis, both FA and HA stimulated the absorption of these microelements, but only FA increased the retention of Cu (in the liver) and Zn (in the kidney).

Fanconi Anemia Proteins and Their Interacting Partners: A Molecular Puzzle

PubMed Central

Kaddar, Tagrid; Carreau, Madeleine

2012-01-01

In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these “other” nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle. PMID:22737580

The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters.

PubMed

Du, Wei; Rani, Reena; Sipple, Jared; Schick, Jonathan; Myers, Kasiani C; Mehta, Parinda; Andreassen, Paul R; Davies, Stella M; Pang, Qishen

2012-05-03

Oxidative stress has been implicated in the pathogenesis of many human diseases including Fanconi anemia (FA), a genetic disorder associated with BM failure and cancer. Here we show that major antioxidant defense genes are down-regulated in FA patients, and that gene down-regulation is selectively associated with increased oxidative DNA damage in the promoters of the antioxidant defense genes. Assessment of promoter activity and DNA damage repair kinetics shows that increased initial damage, rather than a reduced repair rate, contributes to the augmented oxidative DNA damage. Mechanistically, FA proteins act in concert with the chromatin-remodeling factor BRG1 to protect the promoters of antioxidant defense genes from oxidative damage. Specifically, BRG1 binds to the promoters of the antioxidant defense genes at steady state. On challenge with oxidative stress, FA proteins are recruited to promoter DNA, which correlates with significant increase in the binding of BRG1 within promoter regions. In addition, oxidative stress-induced FANCD2 ubiquitination is required for the formation of a FA-BRG1-promoter complex. Taken together, these data identify a role for the FA pathway in cellular antioxidant defense.

Slicing Method for curved façade and window extraction from point clouds

NASA Astrophysics Data System (ADS)

Iman Zolanvari, S. M.; Laefer, Debra F.

2016-09-01

Laser scanning technology is a fast and reliable method to survey structures. However, the automatic conversion of such data into solid models for computation remains a major challenge, especially where non-rectilinear features are present. Since, openings and the overall dimensions of the buildings are the most critical elements in computational models for structural analysis, this article introduces the Slicing Method as a new, computationally-efficient method for extracting overall façade and window boundary points for reconstructing a façade into a geometry compatible for computational modelling. After finding a principal plane, the technique slices a façade into limited portions, with each slice representing a unique, imaginary section passing through a building. This is done along a façade's principal axes to segregate window and door openings from structural portions of the load-bearing masonry walls. The method detects each opening area's boundaries, as well as the overall boundary of the façade, in part, by using a one-dimensional projection to accelerate processing. Slices were optimised as 14.3 slices per vertical metre of building and 25 slices per horizontal metre of building, irrespective of building configuration or complexity. The proposed procedure was validated by its application to three highly decorative, historic brick buildings. Accuracy in excess of 93% was achieved with no manual intervention on highly complex buildings and nearly 100% on simple ones. Furthermore, computational times were less than 3 sec for data sets up to 2.6 million points, while similar existing approaches required more than 16 hr for such datasets.

Diatom valve distribution and sedimentary fatty acid composition in Larsen Bay, Eastern Antarctica Peninsula

NASA Astrophysics Data System (ADS)

Sañé, E.; Isla, E.; Pruski, A. M.; Bárcena, M. A.; Vétion, G.; DeMaster, D.

2011-08-01

During austral summer 2006-2007, five sediment cores were recovered from the Eastern Antarctic Peninsula (EAP) continental shelf. Microscopic observations and sediment fatty acid (FA) composition analyses were carried out to investigate whether the drastic changes at the sea surface in EAP may be reflected in the sedimentary record. A sharp decrease in the number of diatom valves was observed below 2 cm depth. This difference between the upper 2 cm of sediment and the deeper part of the sediment column was attributed to the drastic change in the upper water column conditions after the collapse of the ice shelves, which allowed the arrival of phytoplankton debris and fresh organic matter to the sea floor in EAP. The presence of bacterial-, zooplankton- and detrital-related FA throughout EAP cores suggests that there has been an input of older and more refractory organic matter into the region, presumably by lateral transport before the Larsen ice shelves disintegration.

Sedimentologic characteristics of recent washover deposits from Assateague Island, Maryland

USGS Publications Warehouse

Bernier, Julie C.; Zaremba, Nicholas J.; Wheaton, Cathryn J.; Ellis, Alisha M.; Marot, Marci E.; Smith, Christopher G.

2016-06-08

This report describes sediment data collected using sand augers in active overwash zones on Assateague Island in Maryland. Samples were collected by the U.S. Geological Survey (USGS) during two surveys in March/April and October 2014 (USGS Field Activity Numbers [FAN] 2014-301-FA and 2014-322-FA, respectively). The physical characteristics (for example, sediment texture or bedding structure) of and spatial differences among these deposits will provide information about overwash processes and sediment transport from the sandy barrier-island reaches to the back-barrier environments. Metrics derived from these data, such as mean grain size or deposit thicknesses, can be used to ground-truth remote sensing and geophysical data and can also be incorporated into sediment transport models. Data products, including sample location tables, descriptive core logs, core photographs and x-radiographs, the results of sediment grain-size analyses, and Geographic Information System (GIS) data files with accompanying formal Federal Geographic Data Committee (FGDC) metadata can be downloaded from the Data Downloads page.

Effect of soil humic and fulvic acids, pH and ionic strength on Th(IV) sorption to TiO2 nanoparticles.

PubMed

Tan, Xiaoli; Wang, Xiangke; Chen, Changlun; Sun, Aihua

2007-04-01

Thorium is considered as a chemical analog of other tetravalent actinides. Herein, the sorption of Th(IV) on TiO(2) in the presence or absence of soil fulvic acid (FA)/humic acid (HA) as a function of pH, ionic strength and FA/HA concentration has been studied by a batch method. The morphology was characterized by scanning electron microscopy (SEM). The results indicate that sorption of Th(IV) on TiO(2) increases from 0% to approximately 94% at pH 1 approximately 4, and then maintains level with increasing pH values. Both FA and HA have a positive effect on Th(IV) sorption at low pH values and the contribution of FA on Th(IV) sorption is rather higher than that of HA at pH<4. The sorption is weakly dependent on the concentration of KNO(3) in solution, but the cations K(+), Na(+) and Li(+) influence Th(IV) sorption more obviously. The batch results indicate that the inner sphere complex formation is formed at bare surfaces or FA/HA-bound TiO(2) particle surfaces. Results of SEM analysis show that the particle sizes of TiO(2), Th-TiO(2) and Th-HA-TiO(2) colloids are quite different. Surface complexation may be considered as the main sorption mechanism.

FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.

PubMed

Liu, Ting; Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie; Huang, Jun

2010-08-06

Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. Here, we characterize a previously unrecognized nuclease, Fanconi anemia-associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links.

Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

PubMed Central

Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix

2017-01-01

Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic. PMID:28875066

Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

PubMed

Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix; Hoi, Herbert

2017-01-01

A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. To do this we used captive house sparrows ( Passer domesticus ) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

Co-opting the Fanconi Anemia Genomic Stability Pathway Enables Herpesvirus DNA Synthesis and Productive Growth

PubMed Central

Karttunen, Heidi; Savas, Jeffrey N.; McKinney, Caleb; Chen, Yu-Hung; Yates, John R.; Hukkanen, Veijo; Huang, Tony T.; Mohr, Ian

2015-01-01

SUMMARY DNA damage associated with viral DNA synthesis can result in double strand breaks that threaten genome integrity and must be repaired. Here, we establish that the cellular Fanconi Anemia (FA) genomic stability pathway is exploited by HSV1 to promote viral DNA synthesis and enable its productive growth. Potent FA pathway activation in HSV1-infected cells resulted in monoubiquitination of FA effector proteins, FANCI and FANCD2 (FANCI-D2) and required the viral DNA polymerase. FANCD2 relocalized to viral replication compartments and FANCI-D2 interacted with a multi-subunit complex containing the virus-encoded single-stranded DNA-binding protein ICP8. Significantly, while HSV1 productive growth was impaired in monoubiquitination-defective FA patient cells, this restriction was partially surmounted by antagonizing the DNA-dependent protein kinase (DNA-PK), a critical enzyme required for non-homologous end-joining (NHEJ). This identifies the FA-pathway as a new cellular factor required for herpesvirus productive growth and suggests that FA-mediated suppression of NHEJ is a fundamental step in the viral lifecycle. PMID:24954902

Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats.

PubMed

Langley, S C; York, D A

1990-09-01

The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid-responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat.

Investigation of Pb species in soils, celery and duckweed by synchrotron radiation X-ray absorption near-edge structure spectrometry

NASA Astrophysics Data System (ADS)

Luo, Liqiang; Shen, Yating; Liu, Jian; Zeng, Yuan

2016-08-01

The Pb species play a key role in its translocation in biogeochemical cycles. Soils, sediments and plants were collected from farmlands around Pb mines, and the Pb species in them was identified by X-ray absorption near-edge structure spectrometry. In soils, Pb5(PO4)3Cl and Pb3(PO4)2 were detected, and in sediments, Pb-fulvic acids (FAs) complex was identified. A Pb complex with FA fragments was also detected in celery samples. We found that (1) different Pb species were present in soils and sediments; (2) the Pb species in celery, which was grown in sediments, was different from the species present in duckweed, which grew in water; and (3) a Pb-FA-like compound was present in celery roots. The newly identified Pb species, the Pb-FA-like compound, may play a key role in Pb tolerance and translocation within plants.

Early Life Precursors, Epigenetics, and the Development of Food Allergy1

PubMed Central

Hong, Xiumei; Wang, Xiaobin

2012-01-01

Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene-environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of non-genetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birthweight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene-environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early-life environmental exposures and gene-environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the inter-relationships of early life exposures, genetic susceptibility, epigenomic alterations and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA, and will provide essential information to develop more effective new paradigms in the diagnosis, prevention and management of FA. PMID:22777545

Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction.

PubMed

Amil-Ruiz, Francisco; Garrido-Gala, José; Gadea, José; Blanco-Portales, Rosario; Muñoz-Mérida, Antonio; Trelles, Oswaldo; de Los Santos, Berta; Arroyo, Francisco T; Aguado-Puig, Ana; Romero, Fernando; Mercado, José-Ángel; Pliego-Alfaro, Fernando; Muñoz-Blanco, Juan; Caballero, José L

2016-01-01

Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria × ananassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutatum spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen.

Determination of folates by HPLC-chemiluminescence using a ruthenium(II)-cerium(IV) system, and its application to pharmaceutical preparations and supplements.

PubMed

Ikeda, Rie; Ichiyama, Kosuke; Tabuchi, Naoto; Wada, Mitsuhiro; Kuroda, Naotaka; Nakashima, Kenichiro

2014-11-01

A chemiluminescence (CL) reaction of folic acid (FA) with ruthenium (II) and cerium (IV) was applied to quantify FA-related compounds such as FA, dihydrofolic acid, tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid and methotrexate (MTX). Among the FAs, 5-methyltetrahydrofolic acid provided the highest CL intensity. HPLC-CL detection of FA was applied to quantify FA in pharmaceutical preparations and supplements. Analytical samples were separated on a semi-micro ODS column with a mixture of 20 mM phosphate buffer (pH 5.7) and acetonitrile (94 : 6, v/v %). The separated samples were mixed with a post-column CL reagent consisting of 1.5 mM Ru(bipy)3 (2+) and 1.0 mM Ce(SO4)2 , then the generated CL was monitored. The calibration range for FA was 10-100 μM and the limit of detection was 1.34 μM (signal-to-noise ratio of 3). Repeatabilities were 4.2, 4.6 and 5.0 RSD% (10, 25, 50 μM), and the recoveries for FA supplement, vitamin B complex supplement and FA-containing medication (tablet) were 102.4 ± 10.5, 103.3 ± 13.3 and 100.3 ± 8.5%, respectively. The described method is robust against changes in the chromatographic parameters of ± 3.3 or ± 1.5%. The measured FA content corresponded well to the labeled content of FA-containing products (100.6-104.9%), demonstrating the precision and accuracy of this method for the evaluation of FA pharmaceutical preparations. Copyright © 2014 John Wiley & Sons, Ltd.

Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction

PubMed Central

Amil-Ruiz, Francisco; Garrido-Gala, José; Gadea, José; Blanco-Portales, Rosario; Muñoz-Mérida, Antonio; Trelles, Oswaldo; de los Santos, Berta; Arroyo, Francisco T.; Aguado-Puig, Ana; Romero, Fernando; Mercado, José-Ángel; Pliego-Alfaro, Fernando; Muñoz-Blanco, Juan; Caballero, José L.

2016-01-01

Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria × ananassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutatum spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen. PMID:27471515

pH-sensitive Au–BSA–DOX–FA nanocomposites for combined CT imaging and targeted drug delivery

PubMed Central

Huang, He; Yang, Da-Peng; Liu, Minghuan; Wang, Xiangsheng; Zhang, Zhiyong; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie; Wang, Xiansong

2017-01-01

Albumin-based nanoparticles (NPs) as a drug delivery system have attracted much attention owing to their nontoxicity, non-immunogenicity, great stability and ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA) was utilized as a template to prepare Au–BSA core/shell NPs. The outer layer BSA was subsequently conjugated with cis-aconityl doxorubicin (DOX) and folic acid (FA) to create Au–BSA–DOX–FA nanocomposites. A list of characterizations was undertaken to identify the successful conjugation of drug molecules and targeted agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8) assay indicated that Au–BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells in the concentration range of 0–100 μg/mL, which can therefore be used as a safe drug delivery carrier. Furthermore, compared with free DOX, Au–BSA–DOX–FA nanocomposites exhibited a pH-sensitive drug release ability and superior antitumor activity in a drug concentration-dependent manner. In vivo computed tomography (CT) imaging experiments showed that Au–BSA–DOX–FA nanocomposites could be used as an efficient and durable CT contrast agent for targeted CT imaging of the folate receptor (FR) overexpressed in cancer tissues. In vivo antitumor experiments demonstrated that Au–BSA–DOX–FA nanocomposites have selective antitumor activity effects on FR-overexpressing tumors and no adverse effects on normal tissues and organs. In conclusion, the Au–BSA–DOX–FA nanocomposite exhibits selective targeting activity, X-ray attenuation activity and pH-sensitive drug release activity. Therefore, it can enhance CT imaging and improve the targeting therapeutic efficacy of FR-overexpressing gastric cancers. Our findings suggest that Au–BSA–DOX–FA nanocomposite is a novel drug delivery carrier and a promising candidate for cancer theranostic applications. PMID:28435261

Spectrometric determination of clinically relevant fatty acids in the blood serum

NASA Astrophysics Data System (ADS)

Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

2017-01-01

The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights

PubMed Central

Thompson, Larry H.; Hinz, John M.

2009-01-01

The Fanconi anemia (FA) molecular network consists of 15 “FANC” proteins, of which 13 are associated with mutations in patients with this cancer-prone chromosome instability disorder. Whereas historically the common phenotype associated with FA mutations is marked sensitivity to DNA interstrand crosslinking agents, the literature supports a more global role for FANC proteins in coping with diverse stresses encountered by replicative polymerases. We have attempted to reconcile and integrate numerous observations into a model in which FANC proteins coordinate the following physiological events during DNA crosslink repair: (a) activating a FANCM-ATR-dependent S-phase checkpoint; (b) mediating enzymatic replication-fork breakage and crosslink unhooking; (c) filling the resulting gap by translesion synthesis (TLS) by error-prone polymerase(s); and (d) restoring the resulting one-ended double-strand break by homologous recombination repair (HRR). The FANC core subcomplex (FANCA, B, C, E, F, G, L, FAAP100) promotes TLS for both crosslink and non-crosslink damage such as spontaneous oxidative base damage, UV-C photoproducts, and alkylated bases. TLS likely helps prevent stalled replication forks from breaking, thereby maintaining chromosome continuity. Diverse DNA damages and replication inhibitors result in monoubiquitination of the FANCD2-FANCI complex by the FANCL ubiquitin ligase activity of the core subcomplex upon its recruitment to chromatin by the FANCM-FAAP24 heterodimeric translocase. We speculate that this translocase activity acts as the primary damage sensor and helps remodel blocked replication forks to facilitate checkpoint activation and repair. Monoubiquitination of FANCD2-FANCI is needed for promoting HRR, in which the FANCD1/BRCA2 and FANCN/PALB2 proteins act at an early step. We conclude that the core subcomplex is required for both TLS and HRR occurring separately for non-crosslink damages and for both events during crosslink repair. The FANCJ/BRIP1/BACH1 helicase functions in association with BRCA1 and may remove structural barriers to replication, such as guanine quadruplex structures, and/or assist in crosslink unhooking. PMID:19622404

Development of an EORTC quality of life phase III module measuring cancer-related fatigue (EORTC QLQ-FA13).

PubMed

Weis, Joachim; Arraras, Juan Ignacio; Conroy, Thierry; Efficace, Fabio; Fleissner, Claudia; Görög, Attila; Hammerlid, Eva; Holzner, Bernhard; Jones, Louise; Lanceley, Anne; Singer, Susanne; Wirtz, Markus; Flechtner, Henning; Bottomley, Andrew

2013-05-01

European Organisation for Research and Treatment of Cancer (EORTC) has developed a new multidimensional instrument measuring cancer-related fatigue that can be used in conjunction with the quality of life core questionnaire, EORTC QLQ-C30. The paper focuses on the development of the phase III module, collaborating with seven European countries, including a patient sample of 318 patients. The methodology followed the EORTC guidelines for developing phase III modules. Patients were assessed by questionnaires (EORTC QLQ-C30 with the EORTC Fatigue Module FA15) followed by an interview, asking for their opinions on the difficulty in understanding, on annoyance and on intrusiveness. The phase II FA15 was revised on the basis of qualitative analyses (comments of the patients), quantitative results (descriptive statistics) as well as the multi-item response theory analyses. The three dimensions (physical, emotional and cognitive) of the scale could be confirmed. As a result, EORTC QLQ-FA13 is now available as a valid phase III module measuring cancer-related fatigue in clinical trials and will be psychometrically improved in the upcoming phase IV. Copyright © 2012 John Wiley & Sons, Ltd.

Mechanism of Elongation Factor-G-mediated Fusidic Acid Resistance and Fitness Compensation in Staphylococcus aureus *

PubMed Central

Koripella, Ravi Kiran; Chen, Yang; Peisker, Kristin; Koh, Cha San; Selmer, Maria; Sanyal, Suparna

2012-01-01

Antibiotic resistance in bacteria is often associated with fitness loss, which is compensated by secondary mutations. Fusidic acid (FA), an antibiotic used against pathogenic bacteria Staphylococcus aureus, locks elongation factor-G (EF-G) to the ribosome after GTP hydrolysis. To clarify the mechanism of fitness loss and compensation in relation to FA resistance, we have characterized three S. aureus EF-G mutants with fast kinetics and crystal structures. Our results show that a significantly slower tRNA translocation and ribosome recycling, plus increased peptidyl-tRNA drop-off, are the causes for fitness defects of the primary FA-resistant mutant F88L. The double mutant F88L/M16I is three to four times faster than F88L in both reactions and showed no tRNA drop-off, explaining its fitness compensatory phenotype. The M16I mutation alone showed hypersensitivity to FA, higher activity, and somewhat increased affinity to GTP. The crystal structures demonstrate that Phe-88 in switch II is a key residue for FA locking and also for triggering interdomain movements in EF-G essential for its function, explaining functional deficiencies in F88L. The mutation M16I loosens the hydrophobic core in the G domain and affects domain I to domain II contact, resulting in improved activity both in the wild-type and F88L background. Thus, FA-resistant EF-G mutations causing fitness loss and compensation operate by affecting the conformational dynamics of EF-G on the ribosome. PMID:22767604

Core Engine Noise Program. Volume III. Prediction Methods -- Supplement I. - Extension of Prediction Methods

DTIC Science & Technology

1976-03-01

frequency noise transmission through turbine blade rows and addition of engine and component data to the prediction method for core noise. " Phase VI...lower turbine blade row attenuation for this low bypass engine . When the blade row attenuation is accounted for by means of a turbine work extrac...component and engine data. Currently, an in-depth program to investigate turbine blade row attenuation is underway (NAS3-19435 and DOT-FA75WA-3688). The

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

PubMed Central

Li, Chao; Ni, Juan; Liu, Yao-Xian; Wang, Han; Liang, Zi-Qing; Wang, Xu

2017-01-01

Background/Aims Folic acid (FA) is a core micronutrient involved in DNA synthesis/methylation, and the metabolism of FA is responsible for genomic stability. MicroRNAs may affect gene expression during folate metabolism when cellular homeostasis is changed. This study aimed to reveal the relationship between FA deficiency and the expression of miR-22-p/miR-149-5p and the targeted regulation of miR-22-3p/miR-149-5p on the key folate metabolic gene Methylenetetrahydrofolate reductase (MTHFR). Methods Normal (HL-7702 cells) and cancerous (QGY-7703 cells) human hepatocytes were intervened in modified RPMI 1640 with FA deficiency for 21 days. The interaction between MTHFR and the tested miRNAs was verified by Dual-Luciferase Reporter Assays. The changes in the expression of miR-22-3p/miR-149-5p in response to FA deficiency were detected by Poly (A) Tailing RT-qPCR, and the expression of MTHFR at both the transcriptional and translational levels was determined by RT-qPCR and Western blotting, respectively. Result MiR-22-3p/miR-149-5p directly targeted the 3’UTR sequence of the MTHFR gene. FA deficiency led to an upregulation of miR-22-3p/miR-149-5p expression in QGY-7703/HL-7702 cells, while the transcription of MTHFR was decreased in QGY-7703 cells but elevated in HL-7702 cells. Western blotting showed that FA deficiency resulted in a decline of the MTHFR protein in QGY-7703 cells, whereas in HL-7702 cells, the MTHFR protein level remained constant. Conclusion The results suggested that miR-22-3p/miR-149-5p exert different post-transcriptional effects on MTHFR under conditions of FA deficiency in normal and cancerous human hepatocytes. The results also implied that miR-22-3p/miR-149-5p might exert anticancer effects in cases of long-term FA deficiency. PMID:28045918

Novel Variations of FANCA Gene Provokes Fanconi Anemia: Molecular Diagnosis in a Special Chinese Family.

PubMed

Li, Niu; Song, Aiyun; Ding, Lixia; Zhu, Hua; Li, Guoqiang; Miao, Yan; Wang, Jian; Li, Benshang; Chen, Jing

2018-07-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder with highly variable clinical manifestations and an incidence of ∼1 to 5 in 1 million births. To date, 15 bona fide FA genes have been reported to be responsible for the known FA complementation groups and the FANCA gene accounts for almost 60%. In the present study, we report a special Chinese family, which has 2 children with classic FA characteristics. Via 2-step analysis of the whole-exome sequencing data and verification using multiplex ligation-dependent probe amplification test, one child was found to have a novel compound heterozygous mutation of a splicing variant (c.1471-1G>A) and a large intragenic deletion (exons 23-30 del) of the FANCA gene. The other child had the same splicing variant and another novel large deletion (exons 1-18 del) in the FANCA gene. Clone sequencing showed the c.1471-1G>A variant generate an altered transcript with 1 cryptic splice site in intron 15, resulting in a premature termination codon (p.Val490HisfsX6). This study not only shows the complexity of FA molecular diagnosis via comprehensively studying the FA pathogenic genes and the mutational spectrum, but also has significant reference value for the future molecular diagnosis of FA.

Adsorption characterizations of fulvic acid fractions onto kaolinite.

PubMed

Li, Aimin; Xu, Minjuan; Li, Wenhui; Wang, Xuejun; Dai, Jingyu

2008-01-01

Fulvic acids extracted from a typical rice-production region near Taihu Lake of China were fractionated into three fractions including F4.8, F7.0 and F11.0 (eluted by pH 4.8 buffer, pH 7.0 buffer and pH 11.0 buffer, respectively). Sorption of fulvic acid (FA) fractions onto kaolinite was studied by batch adsorption experiments, and characterizations of kaolinite before and after adsorption were investigated using scanning electron microscopy (SEM). Adsorption isotherms of kaolinite for three FA fractions fit well with the Langmuir adsorption model. The adsorption density of the three fractions was positively correlated with the ratio of the amount of the alkyl carbon to that of carboxyl and carbonyl carbon in FA fractions and followed an order of F11.0 > F7.0 > F4.8. Hydrophobic interaction was one of the control mechanisms for the sorption of FA fraction onto kaolinite. SEM images confirmed that compared to blank kaolinite samples, kaolinite samples coated by a FA fraction displayed an opener and more dispersed conformation resulting from the disruption of the floc structure in complex. Dispersion of kaolinite after adsorption was due to the repulsion between negatively charged FA-coated particles, which is closely related to the amount of FA fractions absorbed on kaolinite.

Uncertainty analysis of the nonideal competitive adsorption-donnan model: effects of dissolved organic matter variability on predicted metal speciation in soil solution.

PubMed

Groenenberg, Jan E; Koopmans, Gerwin F; Comans, Rob N J

2010-02-15

Ion binding models such as the nonideal competitive adsorption-Donnan model (NICA-Donnan) and model VI successfully describe laboratory data of proton and metal binding to purified humic substances (HS). In this study model performance was tested in more complex natural systems. The speciation predicted with the NICA-Donnan model and the associated uncertainty were compared with independent measurements in soil solution extracts, including the free metal ion activity and fulvic (FA) and humic acid (HA) fractions of dissolved organic matter (DOM). Potentially important sources of uncertainty are the DOM composition and the variation in binding properties of HS. HS fractions of DOM in soil solution extracts varied between 14 and 63% and consisted mainly of FA. Moreover, binding parameters optimized for individual FA samples show substantial variation. Monte Carlo simulations show that uncertainties in predicted metal speciation, for metals with a high affinity for FA (Cu, Pb), are largely due to the natural variation in binding properties (i.e., the affinity) of FA. Predictions for metals with a lower affinity (Cd) are more prone to uncertainties in the fraction FA in DOM and the maximum site density (i.e., the capacity) of the FA. Based on these findings, suggestions are provided to reduce uncertainties in model predictions.

Beneficial effects of ω-3 PUFA in children on cardiovascular risk factors during childhood and adolescence.

PubMed

Bonafini, Sara; Antoniazzi, Franco; Maffeis, Claudio; Minuz, Pietro; Fava, Cristiano

2015-07-01

Omega-3 polyunsatured fatty acids (ω-3 PUFA) are essential nutrients mainly derived from fish and seafood but present also in vegetables such as nuts and seed-oils. Some epidemiological and clinical studies indicate a protection of ω-3 FA against cardiovascular disease and a favourable effect on cardiovascular risk factors control in adults. The evidences of their effects in children and adolescents are scanty but a possible beneficial role, especially for insulin sensitivity and blood pressure control, has been proposed. In this review we want to focus especially on the evidences, which could justify the assumption of ω-3 in children and adolescents, and to underline the aspects which need further investigation. Mechanisms through which ω-3 FA act are manifolds and still a matter of investigation: beside their interaction with ion channel and their influence on plasma membrane fluidity, probably the main effect is acting as competitor for cytochrome P-450 (CYP) with respect to ω-6 FA. Thus, they can modulate the biosynthesis of eicosanoids and other lipid mediators, which likely exert a protective action. Another suggestive hypothesis is that their beneficial effect is not dependent only on the intake of ω-3 FA, but also on the complex interaction between different nutrients including ω-3 and other FAs with polymorphisms in genes involved in ω-3 FA modulation. This complex interaction has seldom been explored in children and adolescents. Further studies are needed to investigate all these points in order to find a better collocation of ω-3 FA on the available armamentarium for preventive, possibly individualized, medicine. Copyright © 2015 Elsevier Inc. All rights reserved.

Adsorption of aquatic humic substances on colloidal-size aluminum oxide particles: Influence of solution chemistry

NASA Astrophysics Data System (ADS)

Schlautman, Mark A.; Morgan, James J.

1994-10-01

The adsorption of Suwannee River humic substances (HS) on colloidal-size aluminum oxide particles was examined as a function of solution chemistry. The amount of humic acid (HA) or fulvic acid (FA) adsorbed decreased with increasing pH for all solutions of constant ionic strength. In NaCl solutions at fixed pH values, the adsorption of HA and FA increased with increasing ionic strength. The presence of Ca 2+ enhanced the adsorption of HA but had little effect on FA. For identical solution conditions, the amount (by mass) of HA adsorbed to alumina was always greater than FA. Adsorption densities for both HA and FA showed good agreement with the Langmuir equation, and interpretations of adsorption processes were made from the model parameters. For FA, ligand exchange appears to be the dominant adsorption reaction for the conditions studied here. Ligand exchange is also a major adsorption reaction for HA; however, other reactions contribute to adsorption for some solution compositions. At high pH, cation and water bridging become increasingly important for HA adsorption with increasing amounts of Na + and Ca 2+, respectively. At low to neutral pH values, increases in these same two cations make hydrophobic bonding more effective. Calculations of HS carboxyl group densities in the adsorbed layer support the proposed adsorption reactions. From the adsorption data it appears that fewer than 3.3 HS-COO - groups per nm 2 can be bound directly as inner-sphere complexes by the alumina surface. We propose that the influence of aqueous chemistry on HS adsorption reactions, and therefore on the types of HS surface complexes formed, affects the formation and nature of organic coatings on mineral surfaces.

Pavement/sub-grade condition assessment I-65 approximate milepost 97.5 (transition from asphalt) to 102.5 (KY 313 overpass).

DOT National Transportation Integrated Search

2005-06-01

In efforts to perform an assessment of both the existing pavement and the underlying subgrade conditions, the Kentucky Transportation Center employed the use of three types of equipment/infrastructure analyzers: drill truck for taking field cores; fa...

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.

PubMed

Kalsbeek, Anya; Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A; O'Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C; Harris, William S; Tintle, Nathan L

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort

PubMed Central

Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A.; O’Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C.; Harris, William S.; Tintle, Nathan L.

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis. PMID:29652918

Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

PubMed

Niu, Xufeng; Liu, Zhongning; Hu, Jiang; Rambhia, Kunal J; Fan, Yubo; Ma, Peter X

2016-07-01

To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Fanconi Anemia Pathway: Repairing the Link Between DNA Damage and Squamous Cell Carcinoma

PubMed Central

Romick-Rosendale, Lindsey E.; Lui, Vivian W. Y.; Grandis, Jennifer R.; Wells, Susanne I.

2013-01-01

Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components. In response to DNA damage, nuclear FA proteins associate into high molecular weight complexes through a cascade of post-translational modifications and physical interactions, followed by the repair of damaged DNA. Hematopoietic cells are particularly sensitive to the loss of these interactions, and bone marrow failure occurs almost universally in FA patients. FA as a disease is further characterized by cancer susceptibility, which highlights the importance of the FA pathway in tumor suppression, and will be the focus of this review. Acute myeloid leukemia is the most common cancer type, often subsequent to bone marrow failure. However, FA patients are also at an extreme risk of squamous cell carcinoma (SCC) of the head and neck and gynecological tract, with an even greater incidence in those individuals who have received a bone marrow transplant and recovered from hematopoietic disease. FA tumor suppression in hematopoietic versus epithelial compartments could be mechanistically similar or distinct. Definition of compartment specific FA activities is now critical to assess the effects of today’s bone marrow failure treatments on tomorrow’s solid tumor development. It is our hope that current therapies can then be optimized to decrease the risk of malignant transformation in both hematopoietic and epithelial cells. Here we review our current understanding of the mechanisms of action of the Fanconi anemia pathway as it contributes to stress responses, DNA repair and squamous cell carcinoma susceptibility. PMID:23333482

Cryoinsulation Material Development to Mitigate Obsolescence Risk for Global Warming Potential Foams

NASA Technical Reports Server (NTRS)

Protz, Alison; Bruyns, Roland; Nettles, Mindy

2015-01-01

Cryoinsulation foams currently being qualified for the Space Launch System (SLS) core stage are nonozone- depleting substances (ODP) and are compliant with current environmental regulations. However, these materials contain the blowing agent HFC-245fa, a hydrofluorocarbon (HFC), which is a Global Warming Potential (GWP) substance. In August 2014, the Environmental Protection Agency (EPA) proposed a policy change to reduce or eliminate certain HFCs, including HFC-245fa, in end-use categories including foam blowing agents beginning in 2017. The policy proposes a limited exception to allow continued use of HFC and HFC-blend foam blowing agents for military or space- and aeronautics-related applications, including rigid polyurethane spray foams, but only until 2022.

HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.

PubMed

Shi, Xiangyang; Bi, Xiangdong; Ganser, T Rose; Hong, Seungpyo; Myc, Lukasz A; Desai, Ankur; Holl, Mark M Banaszak; Baker, James R

2006-07-01

Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl, acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate were separated and analyzed using reverse-phase high performance liquid chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the separation of mixed generations can be achieved using a linear gradient 0-50% acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with defined acetylation and carboxylation degrees can be analyzed using HPLC. Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes acetyl) was analyzed and its specific binding with a bovine folic acid binding protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much higher specific binding capability with FBP than those without FA moieties. Findings from this study indicate that HPLC is an effective technique not only for characterization and separation of functionalized PAMAM dendrimers and conjugates but also for investigation of the interaction between dendrimers and biomolecules.

Theoretical studies of weak interactions of formamide with methanol and its derivates

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Wen; Wang, Lu; Han, Shu-Min; Cui, Xiang-Yang; Du, Chong-Yang; Liu, Tao

2015-08-01

Theoretical calculations have been performed for the complexes of formamide (FA) with methanol and its derivates (MAX, X = F, Cl, Br, NO2, H, OH, CH3, and NH2) to study their structures and properties. Substituent effects on the hydrogen bond (H-bond) strength and cooperative effect by using water and its derivatives (HOZ, Z = H, NH2, and Br) as weak interaction probe were also explored. The calculation results show that electron-donating groups strengthen the weak interaction between formamide with methanol whereas electron-withdrawing groups weaken it. The cooperativity is present for the N-HïO H-bond in MAX-FA-HOZ and the cooperative effect increases in a series HONH2, HOH, and HOBr. In addition, we investigated the interaction between FA with hypohalous acids HOY (Y = F, Cl, and Br). It was found that the weak interaction between FA and HOY became stronger with the increase of the size of halogen atom. The nature of the halogen atom has negligible impact on the strength of the H-bond in MAX-FA (X = F, Cl, and Br), whereas it has an obvious influence on the strength of the H-bond in HOY-FA (Y = F, Cl, and Br).

Capacity of humic substances to complex with iron at different salinities in the Yangtze River estuary and East China Sea.

PubMed

Yang, Rujun; Su, Han; Qu, Shenglu; Wang, Xuchen

2017-05-03

The iron binding capacities (IBC) of fulvic acid (FA) and humic acid (HA) were determined in the salinity range from 5 to 40. The results indicated that IBC decreased while salinity increased. In addition, dissolved iron (dFe), FA and HA were also determined along the Yangtze River estuary's increasing salinity gradient from 0.14 to 33. The loss rates of dFe, FA and HA in the Yangtze River estuary were up to 96%, 74%, and 67%, respectively. The decreases in dFe, FA and HA, as well as the change in IBC of humic substances (HS) along the salinity gradient in the Yangtze River estuary were all well described by a first-order exponential attenuation model: y(dFe/FA/HA, S) = a 0 × exp(kS) + y 0 . These results indicate that flocculation of FA and HA along the salinity gradient resulted in removal of dFe. Furthermore, the exponential attenuation model described in this paper can be applied in the major estuaries of the world where most of the removal of dFe and HS occurs where freshwater and seawater mix.

Function allocation for humans and automation in the context of team dynamics

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

Jeffrey C. Joe; John O'Hara; Jacques Hugo

Within Human Factors Engineering, a decision-making process called function allocation (FA) is used during the design life cycle of complex systems to distribute the system functions, often identified through a functional requirements analysis, to all human and automated machine agents (or teammates) involved in controlling the system. Most FA methods make allocation decisions primarily by comparing the capabilities of humans and automation, but then also by considering secondary factors such as cost, regulations, and the health and safety of workers. The primary analysis of the strengths and weaknesses of humans and machines, however, is almost always considered in terms ofmore » individual human or machine capabilities. Yet, FA is fundamentally about teamwork in that the goal of the FA decision-making process is to determine what are the optimal allocations of functions among agents. Given this framing of FA, and the increasing use of and sophistication of automation, there are two related social psychological issues that current FA methods need to address more thoroughly. First, many principles for effective human teamwork are not considered as central decision points or in the iterative hypothesis and testing phase in most FA methods, when it is clear that social factors have numerous positive and negative effects on individual and team capabilities. Second, social psychological factors affecting team performance and can be difficult to translate to automated agents, and most FA methods currently do not account for this effect. The implications for these issues are discussed.« less

Assembly and mechanosensory function of focal adhesions: experiments and models.

PubMed

Bershadsky, Alexander D; Ballestrem, Christoph; Carramusa, Letizia; Zilberman, Yuliya; Gilquin, Benoit; Khochbin, Saadi; Alexandrova, Antonina Y; Verkhovsky, Alexander B; Shemesh, Tom; Kozlov, Michael M

2006-04-01

Initial integrin-mediated cell-matrix adhesions (focal complexes) appear underneath the lamellipodia, in the regions of the "fast" centripetal flow driven by actin polymerization. Once formed, these adhesions convert the flow behind them into a "slow", myosin II-driven mode. Some focal complexes then turn into elongated focal adhesions (FAs) associated with contractile actomyosin bundles (stress fibers). Myosin II inhibition does not suppress formation of focal complexes but blocks their conversion into mature FAs and further FA growth. Application of external pulling force promotes FA growth even under conditions when myosin II activity is blocked. Thus, individual FAs behave as mechanosensors responding to the application of force by directional assembly. We proposed a thermodynamic model for the mechanosensitivity of FAs, taking into account that an elastic molecular aggregate subject to pulling forces tends to grow in the direction of force application by incorporating additional subunits. This simple model can explain a variety of processes typical of FA behavior. Assembly of FAs is triggered by the small G-protein Rho via activation of two major targets, Rho-associated kinase (ROCK) and the formin homology protein, Dia1. ROCK controls creation of myosin II-driven forces, while Dia1 is involved in the response of FAs to these forces. Expression of the active form of Dia1, allows the external force-induced assembly of mature FAs, even in conditions when Rho is inhibited. Conversely, downregulation of Dia1 by siRNA prevents FA maturation even if Rho is activated. Dia1 and other formins cap barbed (fast growing) ends of actin filaments, allowing insertion of the new actin monomers. We suggested a novel mechanism of such "leaky" capping based on an assumption of elasticity of the formin/barbed end complex. Our model predicts that formin-mediated actin polymerization should be greatly enhanced by application of external pulling force. Thus, the formin-actin complex might represent an elementary mechanosensing device responding to force by enhancement of actin assembly. In addition to its role in actin polymerization, Dia1 seems to be involved in formation of links between actin filaments and microtubules affecting microtubule dynamics. Alpha-tubulin deacetylase HDAC6 cooperates with Dia1 in formation of such links. Since microtubules are known to promote FA disassembly, the Dia1-mediated effect on microtubule dynamics may possibly play a role in the negative feedback loop controlling size and turnover of FAs.

Dissolved Organic Matter Quality in a Shallow Aquifer of Bangladesh: Implications for Arsenic Mobility.

PubMed

Mladenov, Natalie; Zheng, Yan; Simone, Bailey; Bilinski, Theresa M; McKnight, Diane M; Nemergut, Diana; Radloff, Kathleen A; Rahman, M Moshiur; Ahmed, Kazi Matin

2015-09-15

In some high arsenic (As) groundwater systems, correlations are observed between dissolved organic matter (DOM) and As concentrations, but in other systems, such relationships are absent. The role of labile DOM as the main driver of microbial reductive dissolution is not sufficient to explain the variation in DOM-As relationships. Other processes that may also influence As mobility include complexation of As by dissolved humic substances, and competitive sorption and electron shuttling reactions mediated by humics. To evaluate such humic DOM influences, we characterized the optical properties of filtered surface water (n = 10) and groundwater (n = 24) samples spanning an age gradient in Araihazar, Bangladesh. Further, we analyzed large volume fulvic acid (FA) isolates (n = 6) for optical properties, C and N content, and (13)C NMR spectroscopic distribution. Old groundwater (>30 years old) contained primarily sediment-derived DOM and had significantly higher (p < 0.001) dissolved As concentration than groundwater that was younger than 5 years old. Younger groundwater had DOM spectroscopic signatures similar to surface water DOM and characteristic of a sewage pollution influence. Associations between dissolved As, iron (Fe), and FA concentration and fluorescence properties of isolated FA in this field study suggest that aromatic, terrestrially derived FAs promote As-Fe-FA complexation reactions that may enhance As mobility.

Mineralogy and Petrology of Amoeboid Olivine Inclusions in CO3 Chondrites: Relationship to Parent-Body Aqueous Alteration

NASA Technical Reports Server (NTRS)

Chizmadia, Lysa J.; Rubin, Alan E.; Wasson, John T.

2003-01-01

Petrographic and mineralogic studies of amoeboid olivine inclusions (AOIs) in CO3 carbonaceous chondrites reveal that they are sensitive indicators of parent-body aqueous and thermal alteration. As the petrologic subtype increases from 3.0 to 3.8, forsteritic olivine (Fa(sub 0-1)) is systematically converted into ferroan olivine (Fa(sub 60-75)). We infer that the Fe, Si and O entered the assemblage along grain boundaries, forming ferroan olivine that filled fractures and voids. As temperatures increased, Fe(+2) from the new olivine exchanged with Mg(+2) from the original AOI to form diffusive haloes around low-FeO cores. Cations of Mn(+2), Ca(+2) and Cr(+3) were also mobilized. The systematic changes in AOI textures and olivine compositional distributions can be used to refine the classification of CO3 chondrites into subtypes. In subtype 3.0, olivine occurs as small forsterite grains (Fa(sub 0-1)), free of ferroan olivine. In petrologic subtype 3.2, narrow veins of FeO-rich olivine have formed at forsterite grain boundaries. With increasing alteration, these veins thicken to form zones of ferroan olivine at the outside AOI margin and within the AOI interior. By subtype 3.7, there is a fairly broad olivine compositional distribution in the range Fa(sub 63-70), and by subtype 3.8, no forsterite remains and the high-Fa peak has narrowed, Fa(sub 64-67). Even at this stage, there is incomplete equilibration in the chondrite as a whole (e.g., data for coarse olivine grains in Isna (CO3.8) chondrules and lithic clasts show a peak at Fa(sub39)). We infer that the mineral changes in A01 identified in the low petrologic types required aqueous or hydrothermal fluids whereas those in subtypes greater than or equal to 3.3 largely reflect diffusive exchange within and between mineral grains without the aid of fluids.

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

PubMed Central

Näf, Dieter; Kupfer, Gary M.; Suliman, Ahmed; Lambert, Kathleen; D’Andrea, Alan D.

1998-01-01

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability. PMID:9742112

Head-camera video recordings of trauma core competency procedures can evaluate surgical resident's technical performance as well as colocated evaluators.

PubMed

Mackenzie, Colin F; Pasley, Jason; Garofalo, Evan; Shackelford, Stacy; Chen, Hegang; Longinaker, Nyaradzo; Granite, Guinevere; Pugh, Kristy; Hagegeorge, George; Tisherman, Samuel A

2017-07-01

Unbiased evaluation of trauma core competency procedures is necessary to determine if residency and predeployment training courses are useful. We tested whether a previously validated individual procedure score (IPS) for individual procedure vascular exposure and fasciotomy (FAS) performance skills could discriminate training status by comparing IPS of evaluators colocated with surgeons to blind video evaluations. Performance of axillary artery (AA), brachial artery (BA), and femoral artery (FA) vascular exposures and lower extremity FAS on fresh cadavers by 40 PGY-2 to PGY-6 residents was video-recorded from head-mounted cameras. Two colocated trained evaluators assessed IPS before and after training. One surgeon in each pretraining tertile of IPS for each procedure was randomly identified for blind video review. The same 12 surgeons were video-recorded repeating the procedures less than 4 weeks after training. Five evaluators independently reviewed all 96 randomly arranged deidentified videos. Inter-rater reliability/consistency, intraclass correlation coefficients were compared by colocated versus video review of IPS, and errors. Study methodology and bias were judged by Medical Education Research Study Quality Instrument and the Quality Assessment of Diagnostic Accuracy Studies criteria. There were no differences (p ≥ 0.5) in IPS for AA, FA, FAS, whether evaluators were colocated or reviewed video recordings. Evaluator consistency was 0.29 (BA) - 0.77 (FA). Video and colocated evaluators were in total agreement (p = 1.0) for error recognition. Intraclass correlation coefficient was 0.73 to 0.92, dependent on procedure. Correlations video versus colocated evaluations were 0.5 to 0.9. Except for BA, blinded video evaluators discriminated (p < 0.002) whether procedures were performed before training versus after training. Study methodology by Medical Education Research Study Quality Instrument criteria scored 15.5/19, Quality Assessment of Diagnostic Accuracy Studies 2 showed low bias risk. Video evaluations of AA, FA, and FAS procedures with IPS are unbiased, valid, and have potential for formative assessments of competency. Prognostic study, level II.

The influence of fatty acids on theophylline binding to human serum albumin. Comparative fluorescence study

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Szkudlarek-Haśnik, A.; Zubik-Skupień, I.; Góra, A.; Dubas, M.; Korzonek-Szlacheta, I.; Wielkoszyński, T.; Żurawiński, W.; Sosada, K.

2012-04-01

Theophylline, popular diuretic, is used to treat asthma and bronchospasm. In blood it forms complexes with albumin, which is also the main transporter of fatty acids. The aim of the present study was to describe the influence of fatty acids (FA) on binding of theophylline (Th) to human serum albumin (HSA) in the high affinity binding sites. Binding parameters have been obtained on the basis of the fluorescence analysis. The data obtained for the complex of Th and natural human serum albumin (nHSA) obtained from blood of obese patients qualified for surgical removal of stomach was compared with our previous studies on the influence of FA on the complex of Th and commercially available defatted human serum albumin (dHSA).

You are what you eat: describing the foraging ecology of southern elephant seals (Mirounga leonina) using blubber fatty acids.

PubMed Central

Bradshaw, Corey J A; Hindell, Mark A; Best, Narelle J; Phillips, Katrina L; Wilson, Gareth; Nichols, Peter D

2003-01-01

Understanding the trophodynamics of marine ecosystems requires data on the temporal and spatial variation in predator diet but, particularly for wide-ranging species, these data are often unavailable. The southern elephant seal (Mirounga leonina) consumes large quantities of fish and squid prey in the Southern Ocean relative to other marine mammals; however, how diet varies relative to seasonal and spatial foraging behaviour is unknown. We used fatty acid (FA) signature analysis of 63 blubber cores from adult female M. leonina over three seasons (winter 1999, summer 2000 and winter 2001) to determine diet structure. We detected significant differences between seasons and between the main foraging regions (Antarctic continental shelf versus pelagic). We used the FA profiles from 53 fish, squid and krill species to construct a discriminant function that would classify each seal, from its blubber sample as having a fish- or squid-FA profile. We determined that a higher proportion of M. leonina had fish-dominated diets during the winter and when foraging around the Antarctic continental shelf, and the majority had more squid-dominated diets during the summer when foraging pelagically. Thus, we were able to measure the coarse-scale diet structure of a major marine predator using FA profiles, and estimate its associated seasonal and temporal variation. PMID:12816642

Liposomes as fatty acids carriers in isolated rat liver: effect on energy metabolism and on isolated mitochondria activity.

PubMed

Delmas-Beauvieux, M C; Leducq, N; Thiaudière, E; Diolez, P; Gin, H; Canioni, P; Gallis, J L

2000-02-01

The effects of fatty acids (FA)-carrier, egg-lecithin liposomes (LIPO) as alternative to BSA, on ATP, glycogen and glucose contents in isolated perfused liver of fed rats were non-invasively studied using 31P/13C nuclear magnetic resonance (NMR). Oxidative phosphorylation was studied in isolated mitochondria from the same liver consecutively to the NMR experiments. ATP content decreased slowly and ATP turnover was similar during the perfusion with saline solution (KHB) or LIPO. However, LIPO induced an enhancement of respiratory control ratio in isolated mitochondria. Tissue glycogen and glucose content decreased when FA (linoleate or linolenate) were perfused with defatted BSA (3%) or LIPO (600 mg/l) whereas glucose excretion level was unchanged and lactate excretion tended to increase, reflecting changes in the cytosolic redox state and/or an enhancement of glycolysis. Addition of FA (0.5 or 1.5 mM) to LIPO caused a dramatic fall in liver ATP, a mitochondrial uncoupling and an impairment of the phosphorylation activity. Perfusion with FA (1.5 mM) carried by BSA significantly increased the ATP degradation without change of mitochondrial function. Owing to the higher affinity of BSA than LIPO for FA, these latter could be more easily released from complex LIPO-FA, increasing their uncoupling effect. Hence, the FA concentrations have to be largely decreased from the above currently used concentrations to avoid this effect. It will then be possible to minimize the effector action of FA and to study their more specific metabolic function as fuel. It was concluded that LIPO were appropriate carriers to study the different metabolic effects of FA.

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

PubMed Central

Vangestel, Carl; Mergeay, Joachim; Dawson, Deborah A.; Vandomme, Viki; Lens, Luc

2011-01-01

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed. PMID:21747940

Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain.

PubMed

Kruyt, F A; Abou-Zahr, F; Mok, H; Youssoufian, H

1999-11-26

Fanconi anemia (FA) is a genetically heterogeneous disorder characterized by bone marrow failure, birth defects, and chromosomal instability. Because FA cells are sensitive to mitomycin C (MMC), FA gene products could be involved in cellular defense mechanisms. The FANCA and FANCG proteins deficient in FA groups A and G interact directly with each other. We have localized the mutual interaction domains of these proteins to amino acids 18-29 of FANCA and to two noncontiguous carboxyl-terminal domains of FANCG encompassing amino acids 400-475 and 585-622. Site-directed mutagenesis of FANCA residues 18-29 revealed a novel arginine-rich interaction domain (RRRAWAELLAG). By alanine mutagenesis, Arg(1), Arg(2), and Leu(8) but not Arg(3), Trp(5), and Glu(7) appeared to be critical for binding to FANCG. Similar immunolocalization for FANCA and FANCG suggested that these proteins interact in vivo. Moreover, targeting of FANCA to the nucleus or the cytoplasm with nuclear localization and nuclear export signals, respectively, showed concordance between the localization patterns of FANCA and FANCG. The complementation function of FANCA was abolished by mutations in its FANCG-binding domain. Conversely, stable expression of FANCA mutants encoding intact FANCG interaction domains induced hypersensitivity to MMC in HeLa cells. These results demonstrate that FANCA-FANCG complexes are required for cellular resistance to MMC. Because the FANCC protein deficient in FA group C works within the cytoplasm, we suggest that FANCC and the FANCA-FANCG complexes suppress MMC cytotoxicity within distinct cellular compartments.

Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study.

PubMed

Cardenas, Agustin M; Sarlls, Joelle E; Kwan, Justin Y; Bageac, Devin; Gala, Zachary S; Danielian, Laura E; Ray-Chaudhury, Abhik; Wang, Hao-Wei; Miller, Karla L; Foxley, Sean; Jbabdi, Saad; Welsh, Robert C; Floeter, Mary Kay

2017-01-01

The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters. The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with C9orf72 mutations, and increased reactive astrocytes throughout the callosum. Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role.

Investigation of aluminum gate CMP in a novel alkaline solution

NASA Astrophysics Data System (ADS)

Cuiyue, Feng; Yuling, Liu; Ming, Sun; Wenqian, Zhang; Jin, Zhang; Shuai, Wang

2016-01-01

Beyond 45 nm, due to the superior CMP performance requirements with the metal gate of aluminum in the advanced CMOS process, a novel alkaline slurry for an aluminum gate CMP with poly-amine alkali slurry is investigated. The aluminum gate CMP under alkaline conditions has two steps: stock polishing and fine polishing. A controllable removal rate, the uniformity of aluminum gate and low corrosion are the key challenges for the alkaline polishing slurry of the aluminum gate CMP. This work utilizes the complexation-soluble function of FA/O II and the preference adsorption mechanism of FA/O I nonionic surfactant to improve the uniformity of the surface chemistry function with the electrochemical corrosion research, such as OCP-TIME curves, Tafel curves and AC impedance. The result is that the stock polishing slurry (with SiO2 abrasive) contains 1 wt.% H2O2,0.5 wt.% FA/O II and 1.0 wt.% FA/O I nonionic surfactant. For a fine polishing process, 1.5 wt.% H2O2, 0.4 wt.% FA/O II and 2.0 wt.% FA/O I nonionic surfactant are added. The polishing experiments show that the removal rates are 3000 ± 50 Å/min and 1600 ± 60 Å/min, respectively. The surface roughnesses are 2.05 ± 0.128 nm and 1.59 ± 0.081 nm, respectively. A combination of the functions of FA/O II and FA/O I nonionic surfactant obtains a controllable removal rate and a better surface roughness in alkaline solution.

Stem Cell Genetic Therapy for Fanconi Anemia - A New Hope.

PubMed

Hanenberg, Helmut; Roellecke, Katharina; Wiek, Constanze

2017-01-01

Fanconi anemia (FA) is a rare inherited DNA disorder clinically characterized by congenital malformations, progressive bone marrow failure, and cancer susceptibility. Due to a strong survival advantage of spontaneously corrected 'normal' hematopoietic stem cells (HSCs) in a few patients, FA is considered a model disorder for genetic correction of autologous stem cells, where genetically corrected stem cells and their progeny have a strong in vivo selective advantage, ultimately leading to normal hematopoiesis. Despite these apparently ideal circumstances, three HSC gene therapy trials with gammaretroviral vectors (stage I) designed to cure the hematological manifestation of FA completely failed to provide long-term clinical benefits for patients, predominantly due to the combination of insufficient gene transfer technologies and incompletely understood FA HSC pathobiology. Currently, FA gene therapy is in stage II where, based on an improved understanding of the cellular defects in FA HSCs, consequently adapted transduction protocols are being used in two phase I/II trials for in vitro genetic correction of FANCA-deficient hematopoietic stem cells. These results are eagerly awaited. Independent from the outcome of these studies, technologies are already available that seem highly attractive for testing in FA. In stage III, this would ultimately include targeted in vivo correction of autologous HSCs by overexpression of nonintegrating lentiviral vectors with scaffold/matrix attachment region elements using specific envelopes as pseudotypes. Although currently still challenging, in a few years in vivo genome editing approaches will be readily available in stage IV, in which the delivery of the editing machinery/ complex is targeted to the autologous FA HSCs by the nonintegrating lentiviral vectors established in stage III. Even low levels of corrected stem cells will then quickly repopulate the entire hematopoiesis of the patient. We therefore are sanguine that in the future, genetic therapy can be used clinically for the correction of FA HSCs in the standard care of FA patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Familial aggregation of food allergy and sensitization to food allergens: a family-based study.

PubMed

Tsai, H-J; Kumar, R; Pongracic, J; Liu, X; Story, R; Yu, Y; Caruso, D; Costello, J; Schroeder, A; Fang, Y; Demirtas, H; Meyer, K E; O'Gorman, M R G; Wang, X

2009-01-01

The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown. This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens. This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut-offs for > or =95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements. FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2-5.6, P=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens. This family-based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE-mediated FA.

Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis

PubMed Central

Back, Seung Keun; Lee, Hyunkyoung; Lee, JaeHee; Kim, Hye young; Kim, Hee Jin; Na, Heung Sik

2016-01-01

Atopic dermatitis is a complex disease of heterogeneous pathogenesis, in particular, genetic predisposition, environmental triggers, and their interactions. Indoor air pollution, increasing with urbanization, plays a role as environmental risk factor in the development of AD. However, we still lack a detailed picture of the role of air pollution in the development of the disease. Here, we examined the effect of formaldehyde (FA) exposure on the manifestation of atopic dermatitis and the underlying molecular mechanism in naive rats and in a rat model of atopic dermatitis (AD) produced by neonatal capsaicin treatment. The AD and naive rats were exposed to 0.8 ppm FA, 1.2 ppm FA, or fresh air (Air) for 6 weeks (2 hours/day and 5 days/week). So, six groups, namely the 1.2 FA-AD, 0.8 FA-AD, Air-AD, 1.2 FA-naive, 0.8 FA-naive and Air-naive groups, were established. Pruritus and dermatitis, two major symptoms of atopic dermatitis, were evaluated every week for 6 weeks. After that, samples of the blood, the skin and the thymus were collected from the 1.2 FA-AD, the Air-AD, the 1.2 FA-naive and the Air-naive groups. Serum IgE levels were quantified with ELISA, and mRNA expression levels of inflammatory cytokines from extracts of the skin and the thymus were calculated with qRT-PCR. The dermatitis and pruritus significantly worsened in 1.2 FA-AD group, but not in 0.8 FA-AD, compared to the Air-AD animals, whereas FA didn't induce any symptoms in naive rats. Consistently, the levels of serum IgE were significantly higher in 1.2 FA-AD than in air-AD, however, there was no significant difference following FA exposure in naive animals. In the skin, mRNA expression levels of Th1 cytokines such as TNF-α and IL-1β were significantly higher in the 1.2 FA-AD rats compared to the air-AD rats, whereas mRNA expression levels of Th2 cytokines (IL-4, IL-5, IL-13), IL-17A and TSLP were significantly higher in 1.2 FA-naive group than in the Air-naive group. These results suggested that 1.2 ppm of FA penetrated the injured skin barrier, and exacerbated Th1 responses and serum IgE level in the AD rats so that dermatitis and pruritus were aggravated, while the elevated expression of Th2 cytokines by 1.2 ppm of FA in naive rats was probably insufficient for clinical manifestation. In conclusion, in a rat model of atopic dermatitis, exposure to 1.2 ppm of FA aggravated pruritus and skin inflammation, which was associated with the elevated expression of Th1 cytokines. PMID:28005965

Joint Fire Support

DTIC Science & Technology

2010-06-30

intelligence application package for theater battle management core system ( TBMCS ) functionality at wing and squadron levels. The automated four... TBMCS , Joint Surveillance and Target Attack Radar System (Ground Control Station), and Global Command and Control System, as well as with Allied FA...The TBMCS is a force level integrated air C2 system. TBMCS provides hardware, software, and communications interfaces to support the preparation

AFRL/Cornell Information Assurance Institute

DTIC Science & Technology

2007-03-01

revewing this colection ofinformation . Send connents regarding this burden estimate or any other aspect of this collection of information, indcudng...collabora- tions involving Cornell and AFRL researchers, with * AFRL researchers able to participate in Cornell research projects, fa- cilitating technology ...approach to developing a science base and technology for supporting large-scale reliable distributed systems. First, so- lutions to core problems were

A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window.

PubMed

Biju, Silvanose; Gallo, Juan; Bañobre-López, M; Manshian, Bella B; Soenen, Stefaan J; Himmelreich, Uwe; Vander Elst, Luce; Parac-Vogt, Tatjana N

2018-05-23

A novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent was developed, based on core-shell lanthanide fluoride nanoparticles composed of a β-NaHoF4 core plus a β-NaGdF4:Yb 3+ , Tm 3+ shell with an average size of ∼24 nm. The biocompatibility of the particles was ensured by a surface modification with poly acrylic acid (PAA) and further functionalization with an affinity ligand, folic acid (FA). When excited using 980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense emission at 802 nm with lifetime of 791±3 μs, due to the transition 3 H 4 → 3 H 6 of Tm 3+ . Proton nuclear magnetic relaxation dispersion ( 1 H-NMRD) studies and magnetic resonance (MR) phantom imaging showed that the newly synthesized nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface (NP-PAA-FA), can act mainly as a T 1 -weighted contrast agent below 1.5 T, a T 1 /T 2 dual-weighted contrast agent at 3 T, and as highly efficient T 2 -weighted contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low cytotoxicity and no detectable cellular damage up to a dose of 500 μg mL -1 . © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform.

PubMed

Li, Xia; Szewczuk, Myron R; Malardier-Jugroot, Cecile

2016-01-01

Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells.

Solvent Dependence of Double Proton Transfer in the Formic Acid-Formamidine Complex: Path Integral Molecular Dynamics Investigation.

PubMed

Kungwan, Nawee; Ngaojampa, Chanisorn; Ogata, Yudai; Kawatsu, Tsutomu; Oba, Yuki; Kawashima, Yukio; Tachikawa, Masanori

2017-10-05

Solvent dependence of double proton transfer in the formic acid-formamidine (FA-FN) complex at room temperature was investigated by means of ab initio path integral molecular dynamics (AIPIMD) simulation with taking nuclear quantum and thermal effects into account. The conductor-like screening model (COSMO) was applied for solvent effect. In comparison with gas phase, double proton delocalization between two heavy atoms (O and N) in FA-FN were observed with reduced proton transfer barrier height in low dielectric constant medium (<4.8). For dielectric constant medium at 4.8, the chance of finding these two protons are more pronounced due to the solvent effect which completely washes out the proton transfer barrier. In the case of higher dielectric constant medium (>4.8), the ionic species becomes more stable than the neutral ones and the formate anion and formamidium cation are thermodynamically stable. For ab initio molecular dynamics simulation, in low dielectric constant medium (<4.8) a reduction of proton transfer barrier with solvent effect is found to be less pronounced than the AIPIMD due to the absence of nuclear quantum effect. Moreover, the motions of FA-FN complex are significantly different with increasing dielectric constant medium. Such a difference is revealed in detail by the principal component analysis.

Multi level optimization of burnable poison utilization for advanced PWR fuel management

NASA Astrophysics Data System (ADS)

Yilmaz, Serkan

The objective of this study was to develop an unique methodology and a practical tool for designing burnable poison (BP) pattern for a given PWR core. Two techniques were studied in developing this tool. First, the deterministic technique called Modified Power Shape Forced Diffusion (MPSFD) method followed by a fine tuning algorithm, based on some heuristic rules, was developed to achieve this goal. Second, an efficient and a practical genetic algorithm (GA) tool was developed and applied successfully to Burnable Poisons (BPs) placement optimization problem for a reference Three Mile Island-1 (TMI-1) core. This thesis presents the step by step progress in developing such a tool. The developed deterministic method appeared to perform as expected. The GA technique produced excellent BP designs. It was discovered that the Beginning of Cycle (BOC) Kinf of a BP fuel assembly (FA) design is a good filter to eliminate invalid BP designs created during the optimization process. By eliminating all BP designs having BOC Kinf above a set limit, the computational time was greatly reduced since the evaluation process with reactor physics calculations for an invalid solution is canceled. Moreover, the GA was applied to develop the BP loading pattern to minimize the total Gadolinium (Gd) amount in the core together with the residual binding at End-of-Cycle (EOC) and to keep the maximum peak pin power during core depletion and Soluble boron concentration at BOC both less than their limit values. The number of UO2/Gd2O3 pins and Gd 2O3 concentrations for each fresh fuel location in the core are the decision variables and the total amount of the Gd in the core and maximum peak pin power during core depletion are in the fitness functions. The use of different fitness function definition and forcing the solution movement towards to desired region in the solution space accelerated the GA runs. Special emphasize is given to minimizing the residual binding to increase core lifetime as well as minimizing the total Gd amount in the core. The GA code developed many good solutions that satisfy all of the design constraints. For these solutions, the EOC soluble boron concentration changes from 68.9 to 97.2 ppm. It is important to note that the difference of 28.3 ppm between the best and the worst solution in the good solutions region represent the potential of 12.5 Effective-Full-Power-Day (EPFD) savings in cycle length. As a comparison, the best BP loading design has 97.2 ppm soluble boron concentration at EOC while the BP loading with available vendors' U/Gd FA designs has 94.4 ppm SOB at EOC. It was estimated that the difference of 2.8 ppm reflected the potential savings of 1.25 EFPD in cycle length. Moreover, the total Gd amount was reduced by 6.89% in mass that provided extra savings in fuel cost compared to the BP loading pattern with available vendor's U/Gd FA designs. (Abstract shortened by UMI.)

Quantitative dermatoglyphic asymmetry: a comparative study between schizophrenic patients and control groups of West Bengal, India.

PubMed

Karmakar, B; Sengupta, M

2012-01-01

Quantitative Fluctuating (FA) and Directional asymmetry (DA) of dermatoglyphics on digito-palmar complex were analyzed in a group of 111 patients (males: 61, females: 50) with schizophrenia (SZ), and compared to an ethnically matched phenotypically healthy control (males: 60, females: 60) through MANOVA, ANOVA and canonical Discriminant analyses. With few exceptions, asymmetries are higher among patients, and this is more prominent in FA than DA. Statistically significant differences were observed between patient and control groups, especially in males. In both sexes, FA of combined dermatoglyphic traits (e.g. total finger ridge count, total palmar pattern ridge count) are found to be a strong discriminator between the two groups with a correct classification of over 83% probability.

Lipids of the Tail Gland, Body and Muzzle Fur of the Red Fox, Vulpes vulpes.

PubMed

McLean, Stuart; Davies, Noel W; Nichols, David S

2017-07-01

The tail gland of the red fox (Vulpes vulpes) secretes lipids containing volatile terpenes used in social communication. We have analysed lipids extracted from fur of the tail gland, body (flanks) and muzzle of foxes. GC-MS showed a novel group of iso-valerate and tiglate monoesters of alkane-1,2-diols (C18:0-22:0). There was also a larger group of Type II diesters in which a second, longer chain, fatty acid (FA) was attached to the free alcohol group. LC-MS showed the full range of diol diesters, mostly C36:0-50:0, with smaller amounts of the corresponding mono-unsaturated tiglate esters. An additional group of diesters with higher MW (C49:0-62:0) containing two long-chain FA was present in the lipids of body and muzzle fur. After saponification and GC-MS, 98 fatty acids were characterized as their methyl esters. Apart from the C5 FA, most were saturated n-, iso-, anteiso- or other methyl-branched FA (C12:0-28:0) whose structures were determined by a combination of their mass spectra and Kovats retention indices. Several FA have not previously been found in nature or in vertebrates. Thirty-four alkane-1,2-diols were found as their TMS derivatives, mostly n-, iso- or anteiso-isomers of C16:0-25:0. The tail gland had the greatest amount of wax esters, from a greater variety of FA and diols, but lacked the esters with two long-chain FA. These findings show that fox skin lipids comprise mono- and di-esters of alkane-1,2-diols, and exhibit enormous complexity due to the diversity of their constituent FA, diols and the many possible isomers of their esters.

Poorly crystalline hydroxyapatite: A novel adsorbent for enhanced fulvic acid removal from aqueous solution

NASA Astrophysics Data System (ADS)

Wei, Wei; Yang, Lei; Zhong, Wenhui; Cui, Jing; Wei, Zhenggui

2015-03-01

In this study, poorly crystalline hydroxyapatite (HAP) was developed as an efficient adsorbent for the removal of fulvic acid (FA) from aqueous solution. Surface functionality, crystallinity, and morphology of the synthetic adsorbent were studied by Fourier-transformation infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). The effects of various parameters such as crystallinity of adsorbent, contact time, adsorbent dosage, pH, initial adsorbate concentration, temperature, ionic strength and the presence of alkaline earth metal ions on FA adsorption were investigated. Results indicated that the nanosized HAP calcined at lower temperature was poorly crystalline (Xc = 0.23) and had better adsorption capacity for FA than those (Xc = 0.52, 0.86) calcined at higher temperature. FA removal was increased with increases of adsorbent dosage, temperature, ionic strength and the presence of alkali earth metal ions, but decreased as the pH increased. Kinetic studies showed that pseudo-second-order kinetic model better described the adsorption process. Equilibrium data were best described by Sips models, and the estimated maximum adsorption capacity of poorly crystalline HAP was 90.20 mg/g at 318 K, displaying higher efficiency for FA removal than previously reported adsorbents. FT-IR results revealed that FA adsorption over the adsorbent could be attributed to the surface complexation between the oxygen atom of functional groups of FA and calcium ions of HAP. Regeneration studies indicated that HAP could be recyclable for a long term. Findings of the present work highlight the potential for using poorly crystalline HAP nanoparticles as an effective and recyclable adsorbent for FA removal from aqueous solution.

Structural and functional insights into the interaction between the Cas family scaffolding protein p130Cas and the focal adhesion-associated protein paxillin

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

Zhang, Chi; Miller, Darcie J.; Guibao, Cristina D.

The Cas family scaffolding protein p130Cas is a Src substrate localized in focal adhesions (FAs) and functions in integrin signaling to promote cell motility, invasion, proliferation, and survival. p130Cas targeting to FAs is essential for its tyrosine phosphorylation and downstream signaling. Although the N-terminal SH3 domain is important for p130Cas localization, it has also been reported that the C-terminal region is involved in p130Cas FA targeting. The C-terminal region of p130Cas or Cas family homology domain (CCHD) has been reported to adopt a structure similar to that of the focal adhesion kinase C-terminal focal adhesion-targeting domain. The mechanism by whichmore » the CCHD promotes FA targeting of p130Cas, however, remains unclear. In this study, using a calorimetry approach, we identified the first LD motif (LD1) of the FA-associated protein paxillin as the binding partner of the p130Cas CCHD (in a 1:1 stoichiometry with a Kd ~4.2 μM) and elucidated the structure of the p130Cas CCHD in complex with the paxillin LD1 motif by X-ray crystallography. Of note, a comparison of the CCHD/LD1 complex with a previously solved structure of CCHD in complex with the SH2-containing protein NSP3 revealed that LD1 had almost identical positioning of key hydrophobic and acidic residues relative to NSP3. Because paxillin is one of the key scaffold molecules in FAs, we propose that the interaction between the p130Cas CCHD and the LD1 motif of paxillin plays an important role in p130Cas FA targeting.« less

Comparative adsorption of Eu(III) and Am(III) on TPD.

PubMed

Fan, Q H; Zhao, X L; Ma, X X; Yang, Y B; Wu, W S; Zheng, G D; Wang, D L

2015-09-01

Comparative adsorption behaviors of Eu(III) and Am(III) on thorium phosphate diphosphate (TPD), i.e., Th4(PO4)4P2O7, have been studied using a batch approach and surface complexation model (SCM) in this study. The results showed that Eu(III) and Am(III) adsorption increased to a large extent with the increase in TPD dose. Strong pH-dependence was observed in both Eu(III) and Am(III) adsorption processes, suggesting that inner-sphere complexes (ISCs) were possibly responsible for the adsorption of Eu(III) and Am(III). Meanwhile, the adsorption of Eu(III) and Am(III) decreased to a different extent with the increase in ion strength, which was possibly related to outer-sphere complexes and/or ion exchange. In the presence of fulvic acid (FA), the adsorption of Eu(III) and Am(III) showed high enhancement mainly due to the ternary surface complexes of TPD-FA-Eu(3+) and TPD-FA-Am(3+). The SCM showed that one ion exchange (≡S3Am/Eu) and two ISCs (≡(XO)2Am/EuNO3 and ≡(YO)2Am/EuNO3) seemed more reasonable to quantitatively describe the adsorption edges of both Eu(III) and Am(III). Our findings obviously showed that Eu(III) could be a good analogue to study actinide behaviors in practical terms. However, it should be kept in mind that there are still obvious differences between the characteristics of Eu(III) and Am(III) in some special cases, for instance, the complex ability with organic matter and adsorption affinity to a solid surface.

Chemical properties of peat used in balneology

NASA Astrophysics Data System (ADS)

Szajdak, L.; Hładoń, T.

2009-04-01

The physiological activity of peats is observed in human peat-bath therapy and in the promotion of growth in some plants. Balneological peat as an ecologically clean and natural substance is perceived as being more 'human friendly' than synthetic compounds. Poland has a long tradition of using balneological peat for therapeutic purposes. Balneological peat reveals a physical effect by altering temperature and biochemical effects through biologically active substances. It is mainly used for the treatment of rheumatic diseases that are quite common in Poland. Peat represents natural product. Physico-chemical properties of peat in particular surface-active, sorption and ion exchanges, defining their biological function, depend mainly on the chemical composition and molecular structure of humic substances representing the major constituent of organic soil (peat). The carbon of organic matter of peats is composed of 10 to 20% carbohydrates, primarily of microbial origin; 20% nitrogen-containing constituents, such as amino acids and amino sugars; 10 to 20% aliphatic fatty acids, alkanes, etc.; with the rest of carbon being aromatic. For balneology peat should be highly decomposed (preferably H8), natural and clean. The content of humic acids should exceed 20% of dry weight, ash content will be less than 15 15% of dry weight, sulphur content less than 0.3% of dry weight and the amount of water more than 85%. It will not contain harmful bacteria and heavy metals. Humic substances (HS) of peat are known to be macromolecular polydisperse biphyllic systems including both hydrophobic domains (saturated hydrocarbon chains, aromatic structural units) and hydrophilic functional groups, i. e having amphiphilic character. Amphiphilic properties of FA are responsible for their solubility, viscosity, conformation, surfactant-like character and a variety of physicochemical properties of considerable biologically practical significance. The chemical composition of peats depends significantly on the genesis of peatlands and the depth of sampling. The chemical properties of peat fulvic acids (FA) have some genetic peculiarities due to the specific conditions of the process of humification of peat-forming plants in mires. The process of humification in mires takes place in the top-forming layer under amphibious moisture conditions. Substances of microbial origin are water-soluble and can participate in the formation of peat FA to a little extent. So a main source of structural units for the peat HA and FA is suggested to be organic constituents of peat forming plants of various botanical composition. The content of aromatic units in peat FA was shown to depend on the content of lignin in peat-forming plants and also of the aromatization of polysaccharides mainly due to the transformation of cellulose. FA characterized lower than humic acids molecular weight (1000-30,000). FA's are composed of a series of highly oxidized aromatic rings with a large number of side chains. Building blocks are benzene carboxylic acids and phenolic acids. These are held together by hydrogen bonding van der Waals' forces and ionic bonding. FA contains larger concentrations of nitrogen. This fraction also contains a great deal of polysaccharide materials, as well as low molecular fatty acids and cytoplasmic constituents of microorganisms. These compounds are linear, flexible colloids at low concentrations, and spherical colloids at high solution concentrations and low pH values. A more adequate knowledge of the chemical structure of humic materials will assist us in better understanding the physiological effects and also the function of these macromolecules on the health that these materials are know to exert. This improved knowledge provides us better information on chemical structure of humic substances from peats, which are responsible for pharmacotherapeutic, pharmacokinetic and biopharmaceutical effect. This structure of FA creates proper conditions for uptake of nutrient as well as bioavailability of biologically active substances. The solubilization in water by humic materials of organic substances which are otherwise water-insoluble is a matter of considerable interest to chemist deals with the problem of the function of organic matter. There has been considerable evidence that humic substances can "complex" with several biologically active substances and so modify their physiological activity. It has been noteworthy that FA can "fix" high-molecular weight water-insoluble organic compounds and make them water-soluble. FA may so act as a vehicle for the mobilization, transport and immobilization of such substances in physiological conditions. Analysis of HA and FA carried out by several analytical methods revealed that there were no chemical interaction among biologically active substances but that latter was firmly adsorbed, possible by hydrogen-bonding, on the FA surfaces. Amino acids account for the majority of organic N fraction in humic substances. Most of the amino acids in organic matter occur in bound form in the humino-peptides fraction. These amino acids are commonly bound to the central core of FA. These humino-peptides fraction of FA mediate in respiration and act as hydrogen acceptors, thus affecting oxidation-reaction reactions. Thus, what is needed at this time is more fundamental research in order to solve practical pharmacological, pharmacokinetic and biopharmaceutical problem of great significance for human health.

Prediction of fatty acid-binding residues on protein surfaces with three-dimensional probability distributions of interacting atoms.

PubMed

Mahalingam, Rajasekaran; Peng, Hung-Pin; Yang, An-Suei

2014-08-01

Protein-fatty acid interaction is vital for many cellular processes and understanding this interaction is important for functional annotation as well as drug discovery. In this work, we present a method for predicting the fatty acid (FA)-binding residues by using three-dimensional probability density distributions of interacting atoms of FAs on protein surfaces which are derived from the known protein-FA complex structures. A machine learning algorithm was established to learn the characteristic patterns of the probability density maps specific to the FA-binding sites. The predictor was trained with five-fold cross validation on a non-redundant training set and then evaluated with an independent test set as well as on holo-apo pair's dataset. The results showed good accuracy in predicting the FA-binding residues. Further, the predictor developed in this study is implemented as an online server which is freely accessible at the following website, http://ismblab.genomics.sinica.edu.tw/. Copyright © 2014 Elsevier B.V. All rights reserved.

Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics.

PubMed

Rambold, Angelika S; Cohen, Sarah; Lippincott-Schwartz, Jennifer

2015-03-23

Fatty acids (FAs) provide cellular energy under starvation, yet how they mobilize and move into mitochondria in starved cells, driving oxidative respiration, is unclear. Here, we clarify this process by visualizing FA trafficking with a fluorescent FA probe. The labeled FA accumulated in lipid droplets (LDs) in well-fed cells but moved from LDs into mitochondria when cells were starved. Autophagy in starved cells replenished LDs with FAs, increasing LD number over time. Cytoplasmic lipases removed FAs from LDs, enabling their transfer into mitochondria. This required mitochondria to be highly fused and localized near LDs. When mitochondrial fusion was prevented in starved cells, FAs neither homogeneously distributed within mitochondria nor became efficiently metabolized. Instead, FAs reassociated with LDs and fluxed into neighboring cells. Thus, FAs engage in complex trafficking itineraries regulated by cytoplasmic lipases, autophagy, and mitochondrial fusion dynamics, ensuring maximum oxidative metabolism and avoidance of FA toxicity in starved cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Generation and esterification of electrophilic fatty acid nitroalkenes in triacylglycerides

PubMed Central

Fazzari, Marco; Khoo, Nicholas; Woodcock, Steven R.; Li, Lihua; Freeman, Bruce A.; Schopfer, Francisco J.

2015-01-01

Electrophilic fatty acid nitroalkenes (NO2-FA) are products of nitric oxide and nitrite-mediated unsaturated fatty acid nitration. These electrophilic products induce pleiotropic signaling actions that modulate metabolic and inflammatory responses in cell and animal models. The metabolism of NO2-FA includes reduction of the vinyl nitro moiety by prostaglandin reductase-1, mitochondrial β–oxidation and Michael addition with low molecular weight nucleophilic amino acids. Complex lipid reactions of fatty acid nitroalkenes are not well defined. Herein we report the detection and characterization of NO2-FA-containing triacylglycerides (NO2-FA-TAG) via mass spectrometry-based methods. In this regard, unsaturated fatty acids of dietary triacylglycerides are targets for nitration reactions during gastric acidification, where NO2-FA-TAG can be detected in rat plasma after oral administration of nitro-oleic acid (NO2-OA). Furthermore, the characterization and profiling of these species, including the generation of beta oxidation and dehydrogenation products, could be detected in NO2-OA supplemented adipocytes. These data revealed that NO2-FA-TAG, formed by either the direct nitration of esterified unsaturated fatty acids or the incorporation of nitrated free fatty acids into triacylglycerides, contribute to the systemic distribution of these reactive electrophilic mediators and may serve as a depot for subsequent mobilization by lipases to in turn impact adipocyte homeostasis and tissue signaling events. PMID:26066303

Preparation macroconstants to simulate the core of VVER-1000 reactor

NASA Astrophysics Data System (ADS)

Seleznev, V. Y.

2017-01-01

Dynamic model is used in simulators of VVER-1000 reactor for training of operating staff and students. As a code for the simulation of neutron-physical characteristics is used DYNCO code that allows you to perform calculations of stationary, transient and emergency processes in real time to a different geometry of the reactor lattices [1]. To perform calculations using this code, you need to prepare macroconstants for each FA. One way of getting macroconstants is to use the WIMS code, which is based on the use of its own 69-group macroconstants library. This paper presents the results of calculations of FA obtained by the WIMS code for VVER-1000 reactor with different parameters of fuel and coolant, as well as the method of selection of energy groups for further calculation macroconstants.

Nanoscale Ionic Liquids

DTIC Science & Technology

2006-11-01

Technical Report 11 December 2005 - 30 November 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Nanoscale Ionic Liquids 5b. GRANT NUMBER FA9550-06-1-0012...Title: Nanoscale Ionic Liquids Principal Investigator: Emmanuel P. Giannelis Address: Materials Science and Engineering, Bard Hall, Cornell University...based fluids exhibit high ionic conductivity. The NFs are typically synthesized by grafting a charged, oligomeric corona onto the nanoparticle cores

Differentiation of brain infection from necrotic glioblastoma using combined analysis of diffusion and perfusion MRI.

PubMed

Chawla, Sanjeev; Wang, Sumei; Mohan, Suyash; Nasrallah, MacLean; Verma, Gaurav; Brem, Steven; O'Rourke, Donald M; Wolf, Ronald L; Poptani, Harish; Nabavizadeh, S Ali

2018-04-20

Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently. To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs. Retrospective. Fourteen patients with brain infections and 21 patients with necrotic GBMs. 3T MRI, DTI, and DSC-PWI. Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast T 1 -weighted and FLAIR images. All lesions were segmented into the central core and enhancing region. For each region, median values of MD, FA, CL, CP, relative CBV (rCBV), and top 90 th percentile of rCBV (rCBV max ) were measured. All parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions. From the central core, significantly lower MD (0.90 × 10 -3  ± 0.44 × 10 -3 mm 2 /s vs. 1.66 × 10 -3  ± 0.62 × 10 -3 mm 2 /s, P = 0.001), significantly higher FA (0.15 ± 0.06 vs. 0.09 ± 0.03, P < 0.001), and CP (0.07 ± 0.03 vs. 0.04 ± 0.02, P = 0.009) were observed in brain infections compared to those in necrotic GBMs. Additionally, from the contrast-enhancing region, significantly lower rCBV (1.91 ± 0.95 vs. 2.76 ± 1.24, P = 0.031) and rCBV max (3.46 ± 1.41 vs. 5.89 ± 2.06, P = 0.001) were observed from infective lesions compared to necrotic GBMs. FA from the central core and rCBV max from enhancing region provided the best classification model in distinguishing brain infections from necrotic GBMs, with a sensitivity of 91% and a specificity of 93%. Combined analysis of DTI and DSC-PWI may provide better performance in differentiating brain infections from necrotic GBMs. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

The nanostructural characterization of strawberry pectins in pectate lyase or polygalacturonase silenced fruits elucidates their role in softening.

PubMed

Posé, Sara; Kirby, Andrew R; Paniagua, Candelas; Waldron, Keith W; Morris, Victor J; Quesada, Miguel A; Mercado, José A

2015-11-05

To ascertain the role of pectin disassembly in fruit softening, chelated- (CSP) and sodium carbonate-soluble (SSP) pectins from plants with a pectate lyase, FaplC, or a polygalacturonase, FaPG1, downregulated by antisense transformation were characterized at the nanostructural level. Fruits from transgenic plants were firmer than the control, although FaPG1 suppression had a greater effect on firmness. Size exclusion chromatography showed that the average molecular masses of both transgenic pectins were higher than that of the control. Atomic force microscopy analysis of pectins confirmed the higher degree of polymerization as result of pectinase silencing. The mean length values for CSP chains increased from 84 nm in the control to 95.5 and 101 nm, in antisense FaplC and antisense FaPG1 samples, respectively. Similarly, SSP polyuronides were longer in transgenic fruits (61, 67.5 and 71 nm, in the control, antisense FaplC and antisense FaPG1 samples, respectively). Transgenic pectins showed a more complex structure, with a higher percentage of branched chains than the control, especially in the case of FaPG1 silenced fruits. Supramolecular pectin aggregates, supposedly formed by homogalacturonan and rhamnogalacturonan I, were more frequently observed in antisense FaPG1 samples. The larger modifications in the nanostructure of pectins in FaPG1 silenced fruits when compared with antisense pectate lyase plants correlate with the higher impact of polygalacturonase silencing on reducing strawberry fruit softening. Copyright © 2015 Elsevier Ltd. All rights reserved.

Consumer Preferences for Written and Oral Information about Allergens When Eating Out.

PubMed

Begen, Fiona M; Barnett, Julie; Payne, Ros; Roy, Debbie; Gowland, M Hazel; Lucas, Jane S

2016-01-01

Avoiding food allergens when eating outside the home presents particular difficulties for food allergic (FA) and intolerant (FI) consumers and a lack of allergen information in restaurants and takeaways causes unnecessary restrictions. Across Europe, legislation effective from December 2014, aims to improve allergen information by requiring providers of non-prepacked foods to supply information related to allergen content within their foods. Using in-depth interviews with 60 FA/FI adults and 15 parents/carers of FA/FI children, we aimed to identify FA/FI consumers' preferences for written and/or verbal allergen information when eating out or ordering takeaway food. A complex and dynamic set of preferences and practices for written and verbal allergen information was identified. Overwhelmingly, written information was favoured in the first instance, but credible personal/verbal communication was highly valued and essential to a good eating out experience. Adequate written information facilitated implicit trust in subsequent verbal information. Where written information was limited, FA/FIs depended on social cues to assess the reliability of verbal information resources, and defaulted to tried and tested allergen avoidance strategies when these were deemed unreliable. Understanding the subtle negotiations and difficulties encountered by FA/FIs when eating out can serve as a guide for legislators and food providers; by encouraging provision of clear written and verbal allergen information, and training of proactive, allergen-aware staff. This, in tandem with legal requirements for allergen information provision, paves the way for FA/FIs to feel more confident in eating out choices; and to experience improved eating out experiences.

Consumer Preferences for Written and Oral Information about Allergens When Eating Out

PubMed Central

Begen, Fiona M.; Barnett, Julie; Payne, Ros; Roy, Debbie; Gowland, M. Hazel; Lucas, Jane S.

2016-01-01

Background Avoiding food allergens when eating outside the home presents particular difficulties for food allergic (FA) and intolerant (FI) consumers and a lack of allergen information in restaurants and takeaways causes unnecessary restrictions. Across Europe, legislation effective from December 2014, aims to improve allergen information by requiring providers of non-prepacked foods to supply information related to allergen content within their foods. Methods Using in-depth interviews with 60 FA/FI adults and 15 parents/carers of FA/FI children, we aimed to identify FA/FI consumers’ preferences for written and/or verbal allergen information when eating out or ordering takeaway food. Results A complex and dynamic set of preferences and practices for written and verbal allergen information was identified. Overwhelmingly, written information was favoured in the first instance, but credible personal/verbal communication was highly valued and essential to a good eating out experience. Adequate written information facilitated implicit trust in subsequent verbal information. Where written information was limited, FA/FIs depended on social cues to assess the reliability of verbal information resources, and defaulted to tried and tested allergen avoidance strategies when these were deemed unreliable. Conclusion Understanding the subtle negotiations and difficulties encountered by FA/FIs when eating out can serve as a guide for legislators and food providers; by encouraging provision of clear written and verbal allergen information, and training of proactive, allergen-aware staff. This, in tandem with legal requirements for allergen information provision, paves the way for FA/FIs to feel more confident in eating out choices; and to experience improved eating out experiences. PMID:27223698

Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery.

PubMed

Xu, Leyuan; Yeudall, W Andrew; Yang, Hu

2017-07-15

The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic siRNA against green fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is difficult to transfect for gene therapy. We developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene delivery and transfection in head and neck squamous cancer cells can be enhanced via FR-targeted PAMAM dendrimers. The results we report here are encouraging and present latest advances in using dendrimers for cancer therapies, in particular for HNSCC. Our work has demonstrated that localized delivery of FR-targeted PAMAM dendrimer G4 complexed with siVEGFA resulted in pronounced tumor suppression in an HN12 xenograft tumor model. Tumor suppression was attributed to enhanced tumor uptake of siRNA and prolonged nanoparticle retention in the tumor. Taken together, G4-FA shows high tumor uptake and sustained highly localized retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex.

PubMed

Otsuki, T; Furukawa, Y; Ikeda, K; Endo, H; Yamashita, T; Shinohara, A; Iwamatsu, A; Ozawa, K; Liu, J M

2001-11-01

Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was demonstrated to associate with the endogenous SWI/SNF complex. We also found a significant increase in the molecular chaperone, glucose-regulated protein 94 (GRP94) among BRG1-associated factors isolated from a FANCA-mutant cell line, which was not seen in either a normal control cell line or the mutant line complemented by wild-type FANCA. Despite this specific difference, FANCA did not appear to be absolutely required for in vitro chromatin remodeling. Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1. The physiological action of FANCA on the SWI/SNF complex remains to be clarified, but our work suggests that FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair.

Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria

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

Kazakov, Alexey E.; Rodionov, Dmitry A.; Arkin, Adam Paul

2008-10-31

Bacteria can use branched-chain amino acids (ILV, i.e. isoleucine, leucine, valine) and fatty acids (FA) as sole carbon and energy sources convering ILV into acetyl-CoA, propanoyl-CoA and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR and GntR families binding tomore » eleven distinct DNA motifs. The ILV degradation genes in gamma- and beta-proteobacteria are mainly regulated by anovel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species), in addition, the TetR-type regulator LiuQ was identified in some beta-proteobacteria (8 species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in the Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gamma-proteobacteria (34 species), PsrA in gamma- and beta-proteobacteria (45 species), FadP in beta-proteobacteria (14 species), and LiuR orthologs in alpha-proteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from the functional and evolutionary points of view.« less

Association mapping of seed quality traits using the Canadian flax (Linum usitatissimum L.) core collection.

PubMed

Soto-Cerda, Braulio J; Duguid, Scott; Booker, Helen; Rowland, Gordon; Diederichsen, Axel; Cloutier, Sylvie

2014-04-01

The identification of stable QTL for seed quality traits by association mapping of a diverse panel of linseed accessions establishes the foundation for assisted breeding and future fine mapping in linseed. Linseed oil is valued for its food and non-food applications. Modifying its oil content and fatty acid (FA) profiles to meet market needs in a timely manner requires clear understanding of their quantitative trait loci (QTL) architectures, which have received little attention to date. Association mapping is an efficient approach to identify QTL in germplasm collections. In this study, we explored the quantitative nature of seed quality traits including oil content (OIL), palmitic acid, stearic acid, oleic acid, linoleic acid (LIO) linolenic acid (LIN) and iodine value in a flax core collection of 390 accessions assayed with 460 microsatellite markers. The core collection was grown in a modified augmented design at two locations over 3 years and phenotypic data for all seven traits were obtained from all six environments. Significant phenotypic diversity and moderate to high heritability for each trait (0.73-0.99) were observed. Most of the candidate QTL were stable as revealed by multivariate analyses. Nine candidate QTL were identified, varying from one for OIL to three for LIO and LIN. Candidate QTL for LIO and LIN co-localized with QTL previously identified in bi-parental populations and some mapped nearby genes known to be involved in the FA biosynthesis pathway. Fifty-eight percent of the QTL alleles were absent (private) in the Canadian cultivars suggesting that the core collection possesses QTL alleles potentially useful to improve seed quality traits. The candidate QTL identified herein will establish the foundation for future marker-assisted breeding in linseed.

Hydrometallurgical recovery of germanium from coal gasification fly ash: pilot plant scale evaluation

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

Arroyo, F.; Fernandez-Pereira, C.; Olivares, J.

2009-04-15

In this article, a hydrometallurgical method for the selective recovery of germanium from fly ash (FA) has been tested at pilot plant scale. The pilot plant flowsheet comprised a first stage of water leaching of FA, and a subsequent selective recovery of the germanium from the leachate by solvent extraction method. The solvent extraction method was based on Ge complexation with catechol in an aqueous solution followed by the extraction of the Ge-catechol complex (Ge(C{sub 6}H{sub 4}O{sub 2}){sub 3}{sup 2-}) with an extracting organic reagent (trioctylamine) diluted in an organic solvent (kerosene), followed by the subsequent stripping of the organicmore » extract. The process has been tested on a FA generated in an integrated gasification with combined cycle (IGCC) process. The paper describes the designed 5 kg/h pilot plant and the tests performed on it. Under the operational conditions tested, approximately 50% of germanium could be recovered from FA after a water extraction at room temperature. Regarding the solvent extraction method, the best operational conditions for obtaining a concentrated germanium-bearing solution practically free of impurities were as follows: extraction time equal to 20 min; aqueous phase/organic phase volumetric ratio equal to 5; stripping with 1 M NaOH, stripping time equal to 30 min, and stripping phase/organic phase volumetric ratio equal to 5. 95% of germanium were recovered from water leachates using those conditions.« less

Lesson from the stoichiometry determination of the cohesin complex: a short protease mediated elution increases the recovery from cross-linked antibody-conjugated beads.

PubMed

Holzmann, Johann; Fuchs, Johannes; Pichler, Peter; Peters, Jan-Michael; Mechtler, Karl

2011-02-04

Affinity purification of proteins using antibodies coupled to beads and subsequent mass spectrometric analysis has become a standard technique for the identification of protein complexes. With the recent transfer of the isotope dilution mass spectrometry principle (IDMS) to the field of proteomics, quantitative analyses-such as the stoichiometry determination of protein complexes-have become achievable. Traditionally proteins were eluted from antibody-conjugated beads using glycine at low pH or using diluted acids such as HCl, TFA, or FA, but elution was often found to be incomplete. Using the cohesin complex and the anaphase promoting complex/cyclosome (APC/C) as examples, we show that a short 15-60 min predigestion with a protease such as LysC (modified on-bead digest termed protease elution) increases the elution efficiency 2- to 3-fold compared to standard acid elution protocols. While longer incubation periods-as performed in standard on-bead digestion-led to partial proteolysis of the cross-linked antibodies, no or only insignificant cleavage was observed after 15-60 min protease mediated elution. Using the protease elution method, we successfully determined the stoichiometry of the cohesin complex by absolute quantification of the four core subunits using LC-SRM analysis and 19 reference peptides generated with the EtEP strategy. Protease elution was 3-fold more efficient compared to HCl elution, but measurements using both elution techniques are in agreement with a 1:1:1:1 stoichiometry. Furthermore, using isoform specific reference peptides, we determined the exact STAG1:STAG2 stoichiometry within the population of cohesin complexes. In summary, we show that the protease elution protocol increases the recovery from affinity beads and is compatible with quantitative measurements such as the stoichiometry determination of protein complexes.

Effect of Natural Organic Matter on Plutonium Sorption to Goethite

DOE PAGES

Conroy, Nathan A.; Zavarin, Mavrik; Kersting, Annie B.; ...

2016-11-21

For this research, the effect of citric acid (CA), desferrioxamine B (DFOB), fulvic acid (FA), and humic acid (HA) on plutonium (Pu) sorption to goethite was studied as a function of organic carbon concentration and pH using batch sorption experiments at 5 mg C·L –1 and 50 mg C·L –1 natural organic matter (NOM), 10 –9–10 –10 M 238Pu, and 0.1 g·L –1 goethite concentrations, at pH 3, 5, 7, and 9. Low sorption of ligands coupled with strong Pu complexation decreased Pu sorption at pH 5 and 7, relative to a ligand-free system. Conversely, CA, FA, and HA increasedmore » Pu sorption to goethite at pH 3, suggesting ternary complex formation or, in the case of humic acid, incorporation into HA aggregates. Mechanisms for ternary complex formation were characterized by Fourier transform infrared spectroscopy in the absence of Pu. CA and FA demonstrated clear surface interactions at pH 3, HA appeared unchanged suggesting HA aggregates had formed, and no DFOB interactions were observed. Plutonium sorption decreased in the presence of DFOB (relative to a ligand free system) at all pH values examined. Thus, DFOB does not appear to facilitate formation of ternary Pu-DFOB-goethite complexes. At pH 9, Pu sorption in the presence of all NOM increased relative to pH 5 and 7; speciation models attributed this to Pu(IV) hydrolysis competing with ligand complexation, increasing sorption. In conclusion, the results indicate that in simple Pu-NOM-goethite ternary batch systems, NOM will decrease Pu sorption to goethite at all but particularly low pH conditions.« less

Effect of Natural Organic Matter on Plutonium Sorption to Goethite

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

Conroy, Nathan A.; Zavarin, Mavrik; Kersting, Annie B.

For this research, the effect of citric acid (CA), desferrioxamine B (DFOB), fulvic acid (FA), and humic acid (HA) on plutonium (Pu) sorption to goethite was studied as a function of organic carbon concentration and pH using batch sorption experiments at 5 mg C·L –1 and 50 mg C·L –1 natural organic matter (NOM), 10 –9–10 –10 M 238Pu, and 0.1 g·L –1 goethite concentrations, at pH 3, 5, 7, and 9. Low sorption of ligands coupled with strong Pu complexation decreased Pu sorption at pH 5 and 7, relative to a ligand-free system. Conversely, CA, FA, and HA increasedmore » Pu sorption to goethite at pH 3, suggesting ternary complex formation or, in the case of humic acid, incorporation into HA aggregates. Mechanisms for ternary complex formation were characterized by Fourier transform infrared spectroscopy in the absence of Pu. CA and FA demonstrated clear surface interactions at pH 3, HA appeared unchanged suggesting HA aggregates had formed, and no DFOB interactions were observed. Plutonium sorption decreased in the presence of DFOB (relative to a ligand free system) at all pH values examined. Thus, DFOB does not appear to facilitate formation of ternary Pu-DFOB-goethite complexes. At pH 9, Pu sorption in the presence of all NOM increased relative to pH 5 and 7; speciation models attributed this to Pu(IV) hydrolysis competing with ligand complexation, increasing sorption. In conclusion, the results indicate that in simple Pu-NOM-goethite ternary batch systems, NOM will decrease Pu sorption to goethite at all but particularly low pH conditions.« less

Low-dimensional and Data Fusion Techniques Applied to a Rectangular Supersonic Multi-stream Jet

NASA Astrophysics Data System (ADS)

Berry, Matthew; Stack, Cory; Magstadt, Andrew; Ali, Mohd; Gaitonde, Datta; Glauser, Mark

2017-11-01

Low-dimensional models of experimental and simulation data for a complex supersonic jet were fused to reconstruct time-dependent proper orthogonal decomposition (POD) coefficients. The jet consists of a multi-stream rectangular single expansion ramp nozzle, containing a core stream operating at Mj , 1 = 1.6 , and bypass stream at Mj , 3 = 1.0 with an underlying deck. POD was applied to schlieren and PIV data to acquire the spatial basis functions. These eigenfunctions were projected onto their corresponding time-dependent large eddy simulation (LES) fields to reconstruct the temporal POD coefficients. This reconstruction was able to resolve spectral peaks that were previously aliased due to the slower sampling rates of the experiments. Additionally, dynamic mode decomposition (DMD) was applied to the experimental and LES datasets, and the spatio-temporal characteristics were compared to POD. The authors would like to acknowledge AFOSR, program manager Dr. Doug Smith, for funding this research, Grant No. FA9550-15-1-0435.

Photonic Crystal Fibers

DTIC Science & Technology

2005-12-01

passive and active versions of each fiber designed under this task. Crystal Fibre shall provide characteristics of the fiber fabricated to include core...passive version of multicore fiber iteration 2. 15. SUBJECT TERMS EOARD, Laser physics, Fibre Lasers, Photonic Crystal, Multicore, Fiber Laser 16...9 00* 0 " CRYSTAL FIBRE INT ODUCTION This report describes the photonic crystal fibers developed under agreement No FA8655-o5-a- 3046. All

Bell Inequalities for Complex Networks

DTIC Science & Technology

2015-10-26

AFRL-AFOSR-VA-TR-2015-0355 YIP Bell Inequalities for Complex Networks Greg Ver Steeg UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES Final Report 10/26...performance report PI: Greg Ver Steeg Young Investigator Award Grant Title: Bell Inequalities for Complex Networks Grant #: FA9550-12-1-0417 Reporting...October 20, 2015 Final Report for “Bell Inequalities for Complex Networks” Greg Ver Steeg Abstract This effort studied new methods to understand the effect

Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells

PubMed Central

Aubé, Michel; Lafrance, Matthieu; Brodeur, Isabelle; Delisle, Marie-Chantal; Carreau, Madeleine

2003-01-01

Background Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. Methods Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. Results We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34- stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. Conclusions These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+ cells correlates with a role at the CD34+ differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism. PMID:12809565

The role of abnormalities in the corpus callosum in social cognition deficits after Traumatic Brain Injury.

PubMed

McDonald, Skye; Rushby, Jacqueline A; Dalton, Katie I; Allen, Samantha K; Parks, Nicklas

2018-08-01

The corpus callosum (CC) is vulnerable to severe traumatic brain injury (TBI). Social cognition requires integration of non-verbal and verbal information in order to understand social behaviour and may be compromised if the CC is damaged. 17 adults with severe, chronic TBI and 17 control participants underwent structural MRI and Diffusion Tensor Imaging. A region of interest analysis examined fractional anisotropy (FA) and mean diffusivity (MD) across regions of the CC. Performance on The Awareness of Social Inference Test (TASIT): part 1 (emotion recognition) and parts 2 and 3 (social inference), was examined in relation to FA and MD. Across participants, higher genu FA values were related to higher TASIT part 3 scores. Increased splenium FA was associated with better performance for TASIT parts 1-3. There was no association between DTI values and TASIT in the controls alone. In the TBI group, FA of the genu and splenium was correlated with TASIT part 3. The pattern of performance was similar when controlling for non-social cognitive ability. In conclusion, social information is complex and multi-modal requiring inter-hemispheric connection. People with TBI, regardless of focal grey matter injury, may lose social cognitive ability due to trauma related changes to the corpus callosum.

Preferential solvation of Brooker's merocyanine in binary solvent mixtures composed of formamides and hydroxylic solvents.

PubMed

Bevilaqua, Tharly; da Silva, Domingas C; Machado, Vanderlei G

2004-03-01

The ET polarity values of 4-[(1-methyl-4(1H)-pyridinylidene)-ethylidene]-2,5-cyclohexadien-1-one (Brooker's merocyanine) were collected in mixed-solvent systems comprising a formamide [N,N-dimethylformamide (DMF), N-methylformamide (NMF) or formamide (FA)] and a hydroxylic (water, methanol, ethanol, propan-2-ol or butan-1-ol) solvent. Binary mixtures involving DMF and the other formamides (NMF and FA) as well as NMF and FA were also studied. These data were employed in the investigation of the preferential solvation (PS) of the probe. Each solvent system was analyzed in terms of both solute-solvent and solvent-solvent interactions. These latter interactions were responsible for the synergism observed in many binary mixtures. This synergistic behaviour was observed for DMF-propan-2-ol, DMF-butan-1-ol, FA-methanol, FA-ethanol and for the mixtures of the alcohols with NMF. All data were successfully fitted to a model based on solvent-exchange equilibria, which allowed the separation of the different contributions of the solvent species in the solvation shell of the dye. The results suggest that both hydrogen bonding and solvophobic interactions contribute to the formation of the solvent complexes responsible for the observed synergistic effects in the PS of the dye.

Simultaneous optimization of loading pattern and burnable poison placement for PWRs

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

Alim, F.; Ivanov, K.; Yilmaz, S.

2006-07-01

To solve in-core fuel management optimization problem, GARCO-PSU (Genetic Algorithm Reactor Core Optimization - Pennsylvania State Univ.) is developed. This code is applicable for all types and geometry of PWR core structures with unlimited number of fuel assembly (FA) types in the inventory. For this reason an innovative genetic algorithm is developed with modifying the classical representation of the genotype. In-core fuel management heuristic rules are introduced into GARCO. The core re-load design optimization has two parts, loading pattern (LP) optimization and burnable poison (BP) placement optimization. These parts depend on each other, but it is difficult to solve themore » combined problem due to its large size. Separating the problem into two parts provides a practical way to solve the problem. However, the result of this method does not reflect the real optimal solution. GARCO-PSU achieves to solve LP optimization and BP placement optimization simultaneously in an efficient manner. (authors)« less

Minimalism in fabrication of self-organized nanogels holding both anti-cancer drug and targeting moiety.

PubMed

Kim, Sungwon; Park, Kyong Mi; Ko, Jin Young; Kwon, Ick Chan; Cho, Hyeon Geun; Kang, Dongmin; Yu, In Tag; Kim, Kwangmeyung; Na, Kun

2008-05-01

Recent researches to develop nano-carrier systems in anti-cancer drug delivery have focused on more complicated design to improve therapeutic efficacy and to reduce side effects. Although such efforts have great impact to biomedical science and engineering, the complexity has been a huddle because of clinical and economic problems. In order to overcome the problems, a simplest strategy to fabricate nano-carriers to deliver doxorubicin (DOX) was proposed in the present study. Two significant subjects (i) formation of nanoparticles loading and releasing DOX and (ii) binding specificity of them to cells, were examined. Folic acid (FA) was directly coupled with pullulan (Pul) backbone by ester linkage (FA/Pul conjugate) and the degree of substitution (DS) was varied, which were confirmed by 1H NMR and UV spectrophotometry. Light scattering results revealed that the nanogels possessed two major size distributions around 70 and 270 nm in an aqueous solution. Their critical aggregation concentrations (CACs) were less than 10 microg/mL, which are lower than general critical micelle concentrations (CMCs) of low-molecular-weight surfactants. Transmission electron microscopy (TEM) images showed well-dispersed nanogel morphology in a dried state. Depending on the DS, the nanogels showed different DOX-loading and releasing profiles. The DOX release rate from FA8/Pul (with the highest DS) for 24h was slower than that from FA4/or FA6/Pul, indicating that the FA worked as a hydrophobic moiety for drug holding. Cellular uptake of the nanogels (KB cells) was also monitored by confocal microscopy. All nanogels were internalized regardless of the DS of FA. Based on the results, the objectives of this study, to suggest a new method overcoming the complications in the drug carrier design, were successfully verified.

1D quantum simulation using a solid state platform

NASA Astrophysics Data System (ADS)

Kirkendall, Megan; Irvin, Patrick; Huang, Mengchen; Levy, Jeremy; Lee, Hyungwoo; Eom, Chang-Beom

Understanding the properties of large quantum systems can be challenging both theoretically and numerically. One experimental approach-quantum simulation-involves mapping a quantum system of interest onto a physical system that is programmable and experimentally accessible. A tremendous amount of work has been performed with quantum simulators formed from optical lattices; by contrast, solid-state platforms have had only limited success. Our experimental approach to quantum simulation takes advantage of nanoscale control of a metal-insulator transition at the interface between two insulating complex oxide materials. This system naturally exhibits a wide variety of ground states (e.g., ferromagnetic, superconducting) and can be configured into a variety of complex geometries. We will describe initial experiments that explore the magnetotransport properties of one-dimensional superlattices with spatial periods as small as 4 nm, comparable to the Fermi wavelength. The results demonstrate the potential of this solid-state quantum simulation approach, and also provide empirical constraints for physical models that describe the underlying oxide material properties. We gratefully acknowledge financial support from AFOSR (FA9550-12-1- 0057 (JL), FA9550-10-1-0524 (JL) and FA9550-12-1-0342 (CBE)), ONR N00014-15-1-2847 (JL), and NSF DMR-1234096 (CBE).

Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene.

PubMed

Park, Jung-Young; Virts, Elizabeth L; Jankowska, Anna; Wiek, Constanze; Othman, Mohamed; Chakraborty, Sujata C; Vance, Gail H; Alkuraya, Fowzan S; Hanenberg, Helmut; Andreassen, Paul R

2016-10-01

Fanconi anaemia (FA) is a heterogeneous inherited disorder clinically characterised by progressive bone marrow failure, congenital anomalies and a predisposition to malignancies. Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Cells (900677A) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harboured by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677A cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677A cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677A cells to ionising radiation. These cells also share milder sensitivities towards olaparib and formaldehyde with certain other FA cells. XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

High prevalence of frequent attendance in the over 65s.

PubMed

McMahon, C Geraldine; Power Foley, Megan; Robinson, David; O'Donnell, Kate; Poulton, Miriam; Kenny, Rose A; Bennett, Kathleen

2018-02-01

Characteristics of older frequent users of Emergency Departments (EDs) are poorly understood. Our aim was to examine the characteristics of the ED frequent attenders (FAs) by age (under 65 and over 65 years). We examined the prevalence of FA attending the ED of an Urban Teaching Hospital in a cross-sectional study between 2009 and 2011. FA was defined as an individual who presented to the ED four or more times over a 12-month period. Randomly selected groups of FA and non-FA from two age groups (under 65 and over 65 years) were then examined to compare the characteristics between older FAs and non-FAs and older FAs and younger FAs. Logistic regression was used to calculate the odds ratio and 95% confidence intervals for 12-month mortality in FA compared with non-FA aged at least 65 years. Overall, 137 150 ED attendances were recorded between 2009 and 2011. A total of 21.6% were aged at least 65 years, 4.4% of whom were FAs, accounting for 18.4% of attendances by patients older than 65 years. There was a bimodal age distribution of FA (mean±SD; under 65 years 40±12.7; and over 65 years 76.9±7.4). Older FAs were five times more likely to present outside normal working hours and 5.5 times more likely to require admission. Cardiovascular emergencies were the most common complaint, in contrast with the younger FA group, where injury and psychosocial conditions dominated. The odds ratio for death at 12 months was 2.07 (95% confidence interval 0.93-4.63; P=0.07), adjusting for age and sex. One-in-five ED patients older than 65 years of age are FAs. Older FAs largely present with complex medical conditions. Enhanced access to expert gerontology assessment should be considered as part of effective intervention strategies for older ED users.

Adsorption of Eu(III) onto TiO2: effect of pH, concentration, ionic strength and soil fulvic acid.

PubMed

Tan, Xiaoli; Fang, Ming; Li, Jiaxing; Lu, Yi; Wang, Xiangke

2009-08-30

The effects of pH, initial Eu(III) concentration, ionic strength and fulvic acid (FA) on the adsorption of Eu(III) on TiO(2) are investigated by using batch techniques. The results indicate that the presence of FA strongly enhances the adsorption of Eu(III) on TiO(2) at low pH values. Besides, the adsorption of Eu(III) on TiO(2) is significantly dependent on pH values and independent of ionic strength. The adsorption of Eu(III) on TiO(2) is attributed to inner-sphere surface complexation. The diffuse layer model (DLM) is applied to simulate the adsorption data, and fits the experimental data well with the aid of FITEQL 3.2. X-ray photoelectron spectroscopy (XPS) is performed to study the species of Eu(III) adsorbed on the surfaces of TiO(2)/FA-TiO(2) hybrids at a molecular level, which suggest that FA act as "bridge" between Eu(III) and TiO(2) particles to enhance the ability to adsorb Eu(III) in solution.

A QM-MD simulation approach to the analysis of FRET processes in (bio)molecular systems. A case study: complexes of E. coli purine nucleoside phosphorylase and its mutants with formycin A.

PubMed

Sobieraj, M; Krzyśko, K A; Jarmuła, A; Kalinowski, M W; Lesyng, B; Prokopowicz, M; Cieśla, J; Gojdź, A; Kierdaszuk, B

2015-04-01

Predicting FRET pathways in proteins using computer simulation techniques is very important for reliable interpretation of experimental data. A novel and relatively simple methodology has been developed and applied to purine nucleoside phosphorylase (PNP) complexed with a fluorescent ligand - formycin A (FA). FRET occurs between an excited Tyr residue (D*) and FA (A). This study aims to interpret experimental data that, among others, suggests the absence of FRET for the PNPF159A mutant in complex with FA, based on novel theoretical methodology. MD simulations for the protein molecule containing D*, and complexed with A, are carried out. Interactions of D* with its molecular environment are accounted by including changes of the ESP charges in S1, compared to S0, and computed at the SCF-CI level. FRET probability W F depends on the inverse six-power of the D*-A distance, R da . The orientational factor 0 < k(2) < 4 between D* and A is computed and included in the analysis. Finally W F is time-averaged over the MD trajectories resulting in its mean value. The red-shift of the tyrosinate anion emission and thus lack of spectral overlap integral and thermal energy dissipation are the reasons for the FRET absence in the studied mutants at pH 7 and above. The presence of the tyrosinate anion results in a competitive energy dissipation channel and red-shifted emission, thus in consequence in the absence of FRET. These studies also indicate an important role of the phenyl ring of Phe159 for FRET in the wild-type PNP, which does not exist in the Ala159 mutant, and for the effective association of PNP with FA. In a more general context, our observations point out very interesting and biologically important properties of the tyrosine residue in its excited state, which may undergo spontaneous deprotonation in the biomolecular systems, resulting further in unexpected physical and/or biological phenomena. Until now, this observation has not been widely discussed in the literature.

JOMAR: Joint Operations with Mobile Autonomous Robots

DTIC Science & Technology

2015-12-21

AFRL-AFOSR-JP-TR-2015-0009 JOMAR: Joint Operations with Mobile Autonomous Robots Edwin Olson UNIVERSITY OF MICHIGAN Final Report 12/21/2015...SUBTITLE JOMAR: Joint Operations with Mobile Autonomous Robots 5a. CONTRACT NUMBER FA23861114024 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...14. ABSTRACT Under this grant, we formulated and implemented a variety of novel algorithms that address core problems in multi- robot systems. These

NIR stimulus-responsive core-shell type nanoparticles based on photothermal conversion for enhanced antitumor efficacy through chemo-photothermal therapy.

PubMed

Sun, Kai; You, Chaoqun; Wang, Senlin; Gao, Zhiguo; Wu, Hongshuai; Tao, W Andy; Zhu, Xiaoli; Sun, Baiwang

2018-07-13

A novel core-shell type nanoparticle (CSNP) was designed here to target co-delivery of doxorubicin (DOX) and photosensitizer indocyanine green (ICG) to tumor sites by the aid of NIR induced photothermal conversion effect for the purpose of synergistic chemo-photothermal cancer therapy. The electrostatically self-assembled CSNPs were prepared by amino-functionalized mesoporous silica nanoparticles (MSN-NH 2 ) as the positive inner core and DSPE-PEG 2000 -COOH and DSPE-PEG 2000 -FA modified lecithin as the negative outer shell. The obtained CSNPs were nanospheres with a uniform size of 47 nm, which were kept stable at 4 °C in PBS (pH = 7). Research on the release of NIR stimulus (808 nm, 1.54 W cm -2 , 6 min) manifested that the release property of the CSNPs was controllable under low pH conditions. In addition, specific concentration (40 μg ml -1 ) ICG-loaded CSNPs, achieving an appropriate temperature up to 45 °C, indicated a desired photothermal conversion efficiency. For targeting the folate receptor, the folate modified CSNPs enabled us to reach a higher cellular uptake by the mean fluorescence intensity. In vitro cell assay, the prepared CSNPs showed outstanding inhibitory efficiency (2.07% cell viability and 91.8% cell apoptosis) on MCF-7 cells for 24 h when irradiated by an 808 nm laser with a power of 1.54 W cm -2 for 6 min. Our research highlights that the prepared nanoparticles hold potential promise for cancer treatment based on photothermal conversion performance and FA-targeted delivery.

Closely related intertidal and deep-sea Halomonhystera species have distinct fatty acid compositions

NASA Astrophysics Data System (ADS)

Van Campenhout, Jelle; Vanreusel, Ann

2017-01-01

The deep-sea free-living nematode Halomonhystera hermesi, dominant in the sulphidic sediments of the Håkon Mosby mud volcano (1280 m, Barent sea slope), is part of the mainly estuarine Halomonhystera disjuncta species complex consisting of five cryptic species (GD1-GD5). Cryptic species have a very similar morphology raising questions on their specific environmental differences. This study analyzed total fatty acid (FA) compositions of H. hermesi and GD1, one of H. hermesi's closest relatives. Additionally, we experimentally investigated the effect of a temperature reduction, salinity increase and sulphide concentrations on GD1's FA composition. Because nematodes are expected to have low amounts of storage FA, total FA compositions most likely reflect FA contents of cellular membranes. The deep-sea nematode H. hermesi had significantly lower saturation levels and increased highly unsaturated fatty acid (HUFAs) proportions due to the presence of docosahexanoic acid (DHA—22:6ω3) and higher eicosapentaenoic acid (EPA—20:5ω3) proportions. HUFAs were absent in H. hermesi's food source indicating the ability and need for this nematode to synthesize HUFAs in a deep-sea environment. Our experimental data revealed that only a decrease in temperature resulted in lower saturated fatty acids proportions, indicating that the FA content of H. hermesi is most likely a response to temperature but not to sulphide concentrations or salinity differences. In experimental nematodes, EPA proportions were low and DHA was absent indicating that other factors than temperature, salinity and sulphides mediate the presence of these HUFAs in H. hermesi.

Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer.

PubMed

He, Zelai; Huang, Jingwen; Xu, Yuanyuan; Zhang, Xiangyu; Teng, Yanwei; Huang, Can; Wu, Yufeng; Zhang, Xi; Zhang, Huijun; Sun, Wenjie

2015-12-08

An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles (p < 0.05). In addition, more importantly, the enhanced anti-tumor efficacy of the CDDP+PTX-encapsulated nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with high FA receptor expression.

Spatio-Temporal Variation in Effects of Upwelling on the Fatty Acid Composition of Benthic Filter Feeders in the Southern Benguela Ecosystem: Not All Upwelling Is Equal

PubMed Central

McQuaid, Christopher David; Noyon, Margaux

2016-01-01

Variability in mesoscale nearshore oceanographic conditions plays an important role in the distribution of primary production and food availability for intertidal consumers. Advection of nutrient rich waters by upwelling usually allows the proliferation of diatoms, later replaced by dinoflagellates. We examined upwelling effects on the fatty acid (FA) signature of a benthic intertidal filter feeder to identify its response to pulsed variability in food availability. The study took place in two contrasting seasons and at two upwelling and two non-upwelling sites interspersed within the southern Benguela upwelling system of South Africa. We investigated the FA composition of the adductor muscles and gonads of the mussel Mytilus galloprovincialis to assess how FA are apportioned to the different tissues and whether this changes between upwelling and non-upwelling conditions. In situ temperature loggers used to identify upwelling conditions at the four sites indicated that such events occurred only at the upwelling centres and only in summer. Tissues differed strongly, with gonads presenting a higher proportion of essential FAs. This could reflect the faster turnover rate of gonad tissue or preferential retention of specific FA for reproductive purposes. FA composition did not vary as a direct function of upwelling, but there were strong dissimilarities among sites. Upwelling influenced mussel diets at one upwelling site while at the other, the expected signature of upwelling was displaced downstream of the core of upwelling. Condition Index (CI) and Gonad Index (GI) differed among sites and were not influenced by upwelling, with GI being comparable among sites. In addition, FA proportions were consistent among sites, indicating similar food quality and quantity over time and under upwelling and non-upwelling conditions. This suggests that the influence of upwelling on the west coast of South Africa is pervasive and diffuse, rather than discrete; while nearshore retention or advection of upwelled water is critical and site-specific so that the effects of upwelling differ even among sites categorised as upwelling centres. PMID:27570968

Super-quenched Molecular Probe Based on Aggregation-Induced Emission and Photoinduced Electron Transfer Mechanisms for Formaldehyde Detection in Human Serum.

PubMed

Yang, Haitao; Wang, Fujia; Zheng, Jilin; Lin, Hao; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

2018-06-04

Energy transfer between fluorescent dyes and quenchers is widely used in the design of light-up probes. Although dual quenchers are more effective in offering lower background signals and higher turn-on ratios than one quencher, such probes are less explored in practice as they require both quenchers to be within the proximity of the fluorescent core. In this contribution, we utilized intramolecular motion and photoinduced electron transfer (PET) as quenching mechanisms to build super-quenched light-up probes based on fluorogens with aggregation-induced emission. The optimized light-up probe possesses negligible background and is able to detect not only free formaldehyde (FA) but also polymeric FA, with an unprecedented turn-on ratio of >4900. We envision that this novel dual quenching strategy will help to develop various light-up probes for analyte sensing. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A 155-dB Dynamic Range Current Measurement Front End for Electrochemical Biosensing.

PubMed

Dai, Shanshan; Perera, Rukshan T; Yang, Zi; Rosenstein, Jacob K

2016-10-01

An integrated current measurement system with ultra wide dynamic range is presented and fabricated in a 180-nm CMOS technology. Its dual-mode design provides concurrent voltage and frequency outputs, without requiring an external clock source. An integrator-differentiator core provides a voltage output with a noise floor of 11.6 fA/ [Formula: see text] and a -3 dB cutoff frequency of 1.4 MHz. It is merged with an asynchronous current-to-frequency converter, which generates an output frequency linearly proportional to the input current. Together, the voltage and frequency outputs yield a current measurement range of 155 dB, spanning from 204 fA (100 Hz) or 1.25 pA (10 kHz) to 11.6 μA. The proposed architecture's low noise, wide bandwidth, and wide dynamic range make it ideal for measurements of highly nonlinear electrochemical and electrophysiological systems.

Impact of humic/fulvic acid on the removal of heavy metals from aqueous solutions using nanomaterials: a review.

PubMed

Tang, Wang-Wang; Zeng, Guang-Ming; Gong, Ji-Lai; Liang, Jie; Xu, Piao; Zhang, Chang; Huang, Bin-Bin

2014-01-15

Nowadays nanomaterials have been widely used to remove heavy metals from water/wastewater due to their large surface area and high reactivity. Humic acid (HA) and fulvic acid (FA) exist ubiquitously in aquatic environments and have a variety of functional groups which allow them to complex with metal ions and interact with nanomaterials. These interactions can not only alter the environmental behavior of nanomaterials, but also influence the removal and transportation of heavy metals by nanomaterials. Thus, the interactions and the underlying mechanisms involved warrant specific investigations. This review outlined the effects of HA/FA on the removal of heavy metals from aqueous solutions by various nanomaterials, mainly including carbon-based nanomaterials, iron-based nanomaterials and photocatalytic nanomaterials. Moreover, mechanisms involved in the interactions were discussed and potential environmental implications of HA/FA to nanomaterials and heavy metals were evaluated. © 2013.

Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

PubMed Central

Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

2015-01-01

Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

Epistatic effects between pairs of the growth hormone secretagogue receptor 1a, growth hormone, growth hormone receptor, non-SMC condensin I complex, subunit G and stearoyl-CoA desaturase genes on carcass, price-related and fatty acid composition traits in Japanese Black cattle.

PubMed

Komatsu, Masanori; Nishino, Kagetomo; Fujimori, Yuki; Haga, Yasutoshi; Iwama, Nagako; Arakawa, Aisaku; Aihara, Yoshito; Takeda, Hisato; Takahashi, Hideaki

2018-02-01

Growth hormone secretagogue receptor 1a (GHSR1a), growth hormone (GH), growth hormone receptor (GHR), non-SMC condensin I complex, subunit G (NCAPG) and stearoyl-CoA desaturase (SCD), are known to play important roles in growth and lipid metabolisms. Single and epistatic effects of the five genes on carcass, price-related and fatty acid (FA) composition traits were analyzed in a commercial Japanese Black cattle population of Ibaraki Prefecture. A total of 650 steers and 116 heifers for carcass and price-related traits, and 158 steers for FA composition traits were used in this study. Epistatic effects between pairs of the five genes were found in several traits. Alleles showing strain-specific differences in the five genes had significant single and epistatic effects in some traits. The data suggest that a TG-repeat polymorphism of the GHSR1a.5'UTR-(TG) n locus plays a central role in gene-gene epistatic interaction of FA composition traits in the adipose tissue of Japanese Black cattle. © 2017 Japanese Society of Animal Science.

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

PubMed

Sombolos, Kostas; Papaioannou, Anna; Christidou, Fotini; Natse, Taisir; Bamichas, Gerasimos; Gionanlis, Lazaros; Katsaris, George; Progia, Evagelia

2006-01-01

Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

Investigation of moisture-induced embrittlement of iron aluminides. Interim report

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

Castagna, A.; Stoloff, N.S.

Alloy FA-129 undergoes an increase in crack propagation rate and a loss of fracture toughness in moisture-bearing and hydrogen gas environments. A similar effect is seen on ductility of FA-129 in tensile tests. The embrittling effect in air is attributed to oxidation of aluminum in the alloy by water vapor to produce Al{sub 2}O{sub 3} and hydrogen gas. Alloy FAP-Y, which is disordered and contains only 16 a%Al is embrittled by hydrogen gas in a manner similar to that of FA-129. However, laboratory air had little effect on the crack growth rates, fracture toughness, or tensile ductility. The lower aluminummore » content apparently is insufficient to induce the Al-H{sub 2}O reaction. TEM and SEM analyses of microstructure and fracture surfaces were consistent with the change in fracture toughness with order and environment. Testing at elevated temperatures reduces crack growth rates in FA-129, and increases fracture toughness and ductility. This is consistent with the well documented peak in hydrogen embrittlement in structural alloys at or near room temperature. Elevated temperature affects the degree of embrittlement in a complex manner, possibly changing the rates of several of the processes involved.« less

International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

PubMed

Weis, Joachim; Tomaszewski, Krzysztof A; Hammerlid, Eva; Ignacio Arraras, Juan; Conroy, Thierry; Lanceley, Anne; Schmidt, Heike; Wirtz, Markus; Singer, Susanne; Pinto, Monica; Alm El-Din, Mohamed; Compter, Inge; Holzner, Bernhard; Hofmeister, Dirk; Chie, Wei-Chu; Czeladzki, Marek; Harle, Amelie; Jones, Louise; Ritter, Sabrina; Flechtner, Hans-Henning; Bottomley, Andrew

2017-05-01

The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Folic acid-conjugated GdPO4:Tb3+@SiO2 Nanoprobe for folate receptor-targeted optical and magnetic resonance bi-modal imaging

NASA Astrophysics Data System (ADS)

Xu, Xianzhu; Zhang, Xiaoying; Wu, Yanli

2016-11-01

Both fluorescent and magnetic nanoprobes have great potential applications for diagnostics and therapy. In the present work, a folic acid-conjugated and silica-modified GdPO4:Tb3+ (GdPO4:Tb3+@SiO2-FA) dual nanoprobe was strategically designed and synthesized for the targeted dual-modality optical and magnetic resonance (MR) imaging via a facile aqueous method. Their structural, optical, and magnetic properties were determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), ultraviolet-visible spectra (UV-Vis), photoluminescence (PL), and superconducting quantum interference device (SQUID). These results indicated that GdPO4:Tb3+@SiO2-FA were uniform monodisperse core-shell structured nanorods (NRs) with an average length of 200 nm and an average width of 25 nm. The paramagnetic property of the synthesized GdPO4:Tb3+@SiO2-FA NRs was confirmed with its linear hysteresis plot (M-H). In addition, the NRs displayed an obvious T1-weighted effect and thus it could potentially serve as a T1-positive contrast agent. The NRs emitted green lights due to the 5D4 → 7F5 transition of the Tb3+. The in vitro assays with NCI-H460 lung cancer cells and human embryonic kidney cell line 293T cells indicated that the GdPO4:Tb3+@SiO2-FA nanoprobe could specifically bind the cells bearing folate receptors (FR). The MTT assay of the NRs revealed that its cytotoxicity was very low. Further in vivo MRI experiments distinctively depict enhanced anatomical features in a xenograft tumor. These results suggest that the GdPO4:Tb3+@SiO2-FA NPs have excellent imaging and cell-targeting abilities for the folate receptor-targeted dual-modality optical and MR imaging and can be potentially used as the nanoprobe for bioimaging.

Robust Decision Making: The Cognitive and Computational Modeling of Team Problem Solving for Decision Making under Complex and Dynamic Conditions

DTIC Science & Technology

2015-07-14

AFRL-OSR-VA-TR-2015-0202 Robust Decision Making: The Cognitive and Computational Modeling of Team Problem Solving for Decision Making under Complex...Computational Modeling of Team Problem Solving for Decision Making Under Complex and Dynamic Conditions 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-12-1...functioning as they solve complex problems, and propose the means to improve the performance of teams, under changing or adversarial conditions. By

Assessment of Anatomical Knowledge and Core Trauma Competency Vascular Skills.

PubMed

Granite, Guinevere; Pugh, Kristy; Chen, Hegang; Longinaker, Nyaradzo; Garofalo, Evan; Shackelford, Stacy; Shalin, Valerie; Puche, Adam; Pasley, Jason; Sarani, Babak; Henry, Sharon; Bowyer, Mark; Mackenzie, Colin

2018-03-01

Surgical residents express confidence in performing specific vascular exposures before training, but such self-reported confidence did not correlate with co-located evaluator ratings. This study reports residents' self-confidence evaluated before and after Advanced Surgical Skills for Exposure in Trauma (ASSET) cadaver-based training, and 12-18 mo later. We hypothesize that residents will better judge their own skill after ASSET than before when compared with evaluator ratings. Forty PGY2-7 surgical residents performed four procedures: axillary artery (AA), brachial artery (BA), femoral artery exposure and control (FA), and lower extremity fasciotomy (FAS) at the three evaluations. Using 5-point Likert scales, surgeons self-assessed their confidence in anatomical understanding and procedure performance after each procedure and evaluators rated each surgeon accordingly. For all the three evaluations, residents consistently rated their anatomical understanding (p < 0.04) and surgical performance (p < 0.03) higher than evaluators for both FA and FAS. Residents rated their anatomical understanding and surgical performance higher (p < 0.005) than evaluators for BA after training and up to 18 mo later. Only for third AA evaluation were there no rating differences. Residents overrate their anatomical understanding and performance abilities for BA, FA, and FAS even after performing the procedures and being debriefed three times in 18 mo.

Environmental Assessment (EA): Proposed Emergency Power Unit Overhaul Complex at Little Mountain Test Annex, Utah

DTIC Science & Technology

2014-03-14

NUMBER FA8201-09-D-0002 Overhaul Complex at Little Mountain Test Annex, Utah 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Streamline Consulting, LLC 1713 N. Sweetwater Lane Farmington, Utah 84025...Hill Air Force Base (AFB) proposes to construct a new emergency power unit overhaul complex at Little Mountain Test Annex, Utah . Buildings 2005

AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

PubMed

Virts, Elizabeth L; Jankowska, Anna; Mackay, Craig; Glaas, Marcel F; Wiek, Constanze; Kelich, Stephanie L; Lottmann, Nadine; Kennedy, Felicia M; Marchal, Christophe; Lehnert, Erik; Scharf, Rüdiger E; Dufour, Carlo; Lanciotti, Marina; Farruggia, Piero; Santoro, Alessandra; Savasan, Süreyya; Scheckenbach, Kathrin; Schipper, Jörg; Wagenmann, Martin; Lewis, Todd; Leffak, Michael; Farlow, Janice L; Foroud, Tatiana M; Honisch, Ellen; Niederacher, Dieter; Chakraborty, Sujata C; Vance, Gail H; Pruss, Dmitry; Timms, Kirsten M; Lanchbury, Jerry S; Alpi, Arno F; Hanenberg, Helmut

2015-09-15

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene. © The Author 2015. Published by Oxford University Press.

Effect of fulvic and humic acids on iron and manganese homeostasis in rats.

PubMed

Szabó, József; Vucskits, András Valentin; Berta, Erzsébet; Andrásofszky, Emese; Bersényi, András; Hullár, István

2017-03-01

The objective of this study was to investigate the effects of fulvic acid (FA) and humic acid (HA) as the two main compounds of humic substances, separately on Fe and Mn homeostasis. Seventy-two male Wistar rats were randomly divided into 9 experimental groups. The control diet (AIN-93G formula) and diets supplemented with 0.1%, 0.2%, 0.4% and 0.8% HA or FA were fed for 26 days. Fe and Mn concentrations of the large intestinal content, liver, kidney, femur and hair were determined. No significant differences were observed in the production parameters. The effects of FA and HA on iron homeostasis were significantly different. FA proved to be a good iron source, and slightly increased the iron content of liver and kidney, but - up to a dietary iron level of 52.7 mg/kg - it did not influence the efficiency of iron absorption. Above a dietary iron level of 52.7 mg/kg down-regulation of Fe absorption can be assumed. HA significantly stimulated the iron uptake and there was no down-regulation of Fe absorption up to 0.8% dietary HA supplementation level (61.5 mg Fe/kg diet). In the HA groups the iron content of the liver and kidney decreased significantly, suggesting that in spite of the better Fe absorption, the HA-Fe complex does not provide iron to the investigated organs. Neither FA nor HA supplementation influenced the Fe content of the femur and hair and slightly decreased the Mn concentration in the large intestinal content. This effect was significant (with a 22.7% Mn concentration decrease) only at the HA supplementation rate of 0.8%. Neither FA nor HA influenced significantly the Mn concentrations of the liver, kidney and femur. The Mn concentration of the hair in rats receiving FA- or HA-supplemented diets was higher than in the control rats; however, this result needs further confirmation.

Investigating noncovalent squarylium dye-protein interactions by capillary electrophoresis-frontal analysis.

PubMed

Yan, Weiying; Colyer, Christa L

2006-11-24

Noncovalent interactions between fluorescent probe molecules and protein analyte molecules, which typically occur with great speed and minimal sample handling, form the basis of many high sensitivity analytical techniques. Understanding the nature of these interactions and the composition of the resulting complexes represents an important area of study that can be facilitated by capillary electrophoresis (CE). Specifically, we will present how frontal analysis (FA) and Hummel-Dreyer (HD) methods can be implemented with CE to determine association constants and stoichiometries of noncovalent complexes of the red luminescent squarylium dye Red-1c with bovine serum albumin (BSA) and beta-lactoglobulin A. By adjusting solution conditions, such as pH or ionic strength, it is possible to selectively modify the binding process. As such, conditions for optimal selectivity for labeling reactions can be established by capillary electrophoresis-frontal analysis (CE-FA) investigations.

Genetic Analysis of Strawberry Fruit Aroma and Identification of O-Methyltransferase FaOMT as the Locus Controlling Natural Variation in Mesifurane Content1[C][W][OA

PubMed Central

Zorrilla-Fontanesi, Yasmín; Rambla, José-Luis; Cabeza, Amalia; Medina, Juan J.; Sánchez-Sevilla, José F.; Valpuesta, Victoriano; Botella, Miguel A.; Granell, Antonio; Amaya, Iraida

2012-01-01

Improvement of strawberry (Fragaria × ananassa) fruit flavor is an important goal in breeding programs. To investigate genetic factors controlling this complex trait, a strawberry mapping population derived from genotype ‘1392’, selected for its superior flavor, and ‘232’ was profiled for volatile compounds over 4 years by headspace solid phase microextraction coupled to gas chromatography and mass spectrometry. More than 300 volatile compounds were detected, of which 87 were identified by comparison of mass spectrum and retention time to those of pure standards. Parental line ‘1392’ displayed higher volatile levels than ‘232’, and these and many other compounds with similar levels in both parents segregated in the progeny. Cluster analysis grouped the volatiles into distinct chemically related families and revealed a complex metabolic network underlying volatile production in strawberry fruit. Quantitative trait loci (QTL) detection was carried out over 3 years based on a double pseudo-testcross strategy. Seventy QTLs covering 48 different volatiles were detected, with several of them being stable over time and mapped as major QTLs. Loci controlling γ-decalactone and mesifurane content were mapped as qualitative traits. Using a candidate gene approach we have assigned genes that are likely responsible for several of the QTLs. As a proof of concept we show that one homoeolog of the O-methyltransferase gene (FaOMT) is the locus responsible for the natural variation of mesifurane content. Sequence analysis identified 30 bp in the promoter of this FaOMT homoeolog containing putative binding sites for basic/helix-loop-helix, MYB, and BZIP transcription factors. This polymorphism fully cosegregates with both the presence of mesifurane and the high expression of FaOMT during ripening. PMID:22474217

Total organic carbon and humus fractions in restored soils from limestone quarries in semiarid climate, SE Spain

NASA Astrophysics Data System (ADS)

Luna Ramos, Lourdes; Miralles Mellado, Isabel; Ángel Domene Ruiz, Miguel; Solé Benet, Albert

2016-04-01

Mining activities generate erosion and loss of plant cover and soil organic matter (SOM), especially in arid and semiarid Mediterranean regions. A precondition for ecosystem restoration in such highly disturbed areas is the development of functional soils with sufficient organic matter. But the SOM quality is also important to long-term C stabilization. The resistance to biodegradation of recalcitrant organic matter fractions has been reported to depend on some intrinsic structural factors of humic acid substances and formation of amorphous organo-mineral recalcitrant complexes. In an experimental soil restoration in limestone quarries in the Sierra de Gádor (Almería), SE Spain, several combinations of organic amendments (sewage sludge and compost from domestic organic waste) and mulches (gravel and woodchip) were added in experimental plots using a factorial design. In each plot, 75 native plants (Anthyllis cytisoides, A. terniflora and Macrochloa tenacissima) were planted and five years after the start of the experiment total organic carbon (TOC), physico-chemical soil properties and organic C fractions (particulate organic matter, H3PO4-fulvic fraction, fulvic acids (FA), humic acids (HA) and humin) were analyzed. We observed significant differences between treatments related to the TOC content and the HA/FA ratio. Compost amendments increased the TOC, HA content and HA/FA ratio, even higher than in natural undisturbed soils, indicating an effective clay humus-complex pointing to progressively increasing organic matter quality. Soils with sewage sludge showed the lowest TOC and HA/FA ratio and accumulated a lower HA proportion indicating poorer organic matter quality and comparatively lower resilience than in natural soils and soils amended with compost.

Identification of rare heterozygous missense mutations in FANCA in esophageal atresia patients using next-generation sequencing.

PubMed

Feng, Yu; Chen, Runsen; Da, Min; Qian, Bo; Mo, Xuming

2018-06-30

Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively common malformations in newborns, but the etiology of EA/TEF remains unknown. Fanconi anemia (FA) complementation group A (FANCA) is a key component of the FA core complex and is essential for the activation of the DNA repair pathway. The middle region (amino acids 674-1208) of FANCA is required for its interaction with FAAP20. We performed targeted sequencing of this binding region of FANCA (exons 23-36) in 40 EA/TEF patients. We also investigated the effect of the p.A958V mutation on the protein-protein interaction between FANCA and FAAP20 using an in vitro binding assay and co-immunoprecipitation. Immunolocalization analysis was performed to investigate the subcellular localization of FANCA, and tissue sections and immunohistochemistry were used to explore the expression of FANCA. We identified four rare missense variants in the FANCA binding region. FANCA mutations were significantly overrepresented in EA/TEF patients compared with 4300 control subjects from the NHLBI-ESP project (Fisher's exact p = 2.17 × 10 -5 , odds ratio = 31.75). p.A958V, a novel de novo mutation in the FANCA gene, was identified in one patient with EA/TEF. We provide further evidence that the p.A958V mutation reduces the binding affinity of FANCA for FAAP20. Interestingly, the p.A958V mutation impaired the nuclear localization of the FANCA protein expressed in HeLa cells. We found that FANCA was more highly expressed in stratified squamous epithelium than in smooth muscle. In conclusion, mutations in the FANCA gene are associated with EA/TEF in humans. Copyright © 2018. Published by Elsevier B.V.

Coordination of the recruitment of the FANCD2 and PALB2 Fanconi anemia proteins by an ubiquitin signaling network.

PubMed

Bick, Gregory; Zhang, Fan; Meetei, A Ruhikanta; Andreassen, Paul R

2017-06-01

Fanconi anemia (FA) is a chromosome instability syndrome and the 20 identified FA proteins are organized into two main arms which are thought to function at distinct steps in the repair of DNA interstrand crosslinks (ICLs). These two arms include the upstream FA pathway, which culminates in the monoubiquitination of FANCD2 and FANCI, and downstream breast cancer (BRCA)-associated proteins that interact in protein complexes. How, and whether, these two groups of FA proteins are integrated is unclear. Here, we show that FANCD2 and PALB2, as indicators of the upstream and downstream arms, respectively, colocalize independently of each other in response to DNA damage induced by mitomycin C (MMC). We also show that ubiquitin chains are induced by MMC and colocalize with both FANCD2 and PALB2. Our finding that the RNF8 E3 ligase has a role in recruiting FANCD2 and PALB2 also provides support for the hypothesis that the two branches of the FA-BRCA pathway are coordinated by ubiquitin signaling. Interestingly, we find that the RNF8 partner, MDC1, as well as the ubiquitin-binding protein, RAP80, specifically recruit PALB2, while a different ubiquitin-binding protein, FAAP20, functions only in the recruitment of FANCD2. Thus, FANCD2 and PALB2 are not recruited in a single linear pathway, rather we define how their localization is coordinated and integrated by a network of ubiquitin-related proteins. We propose that such regulation may enable upstream and downstream FA proteins to act at distinct steps in the repair of ICLs.

Sorption of Th (IV) to silica as a function of pH, humic/fulvic acid, ionic strength, electrolyte type.

PubMed

Chen, Changlun; Wang, Xiangke

2007-02-01

The removal behavior of thorium (Th(IV)) has been investigated in multicomponent systems containing silica (SiO2) as the model of inorganic particles because of its widespread presence in the earth's crust and soil humic acid (HA)/fulvic acid (FA) by batch experiments. The influence of pH from 2 to 12, ionic strength from 0.02 to 0.2 M KNO3, soil HA/FA concentration from 8.3 to 22.5 mg/L, and foreign cations (Li+, Na+, K+) and anions (NO3(-), Cl-) on the sorption of Th(IV) onto SiO2 was also tested. The sorption isotherms of Th(IV) at approximately constant pH (3.50+/-0.02) were determined and analyzed regressively with three kinds of sorption isotherm models, i.e., linear, Langmuir, and Freundlich models. The results demonstrated that the sorption of Th(IV) onto SiO2 increased steeply with increasing pH from 2 to 4. Generally, humic substances (HSs) were shown to enhance Th(IV) sorption at low pH, but to reduce Th(IV) sorption at intermediate and high pH. It was a hypothesis that the significantly positive influence of HA/FA at pH from 2 to 4 on the sorption of Th(IV) onto SiO2 was attributed to strong surface binding of HA/FA on SiO2 and subsequently the formation of ternary surface complexes such as [triple bond]MO-O-HA-Th or [triple bond]MO-O-FA-Th. The results also demonstrated that the sorption was strongly dependent on the concentration of HA/FA, and independent of ionic strength and foreign ions under our experimental conditions.

Loss of CHK1 function impedes DNA damage-induced FANCD2 monoubiquitination but normalizes the abnormal G2 arrest in Fanconi anemia.

PubMed

Guervilly, Jean-Hugues; Macé-Aimé, Gaëtane; Rosselli, Filippo

2008-03-01

Fanconi anemia (FA) is a cancer-prone hereditary disease resulting from mutations in one of the 13 genes defining the FANC/BRCA pathway. This pathway is involved in the cellular resistance to DNA-cross-linking agents. How the FANC/BRCA pathway is activated and why its deficiency leads to the accumulation of FA cells with a 4N DNA content are still poorly answered questions. We investigated the involvement of ATR pathway members in these processes. We show here that RAD9 and RAD17 are required for DNA interstrand cross-link (ICL) resistance and for the optimal activation of FANCD2. Moreover, we demonstrate that CHK1 and its interacting partner CLASPIN that act downstream in the ATR pathway are required for both FANCD2 monoubiquitination and assembling in subnuclear foci in response to DNA damage. Paradoxically, in the absence of any genotoxic stress, CHK1 or CLASPIN depletion results in an increased basal level of FANCD2 monoubiquitination and focalization. We also demonstrate that the ICL-induced accumulation of FA cells in late S/G2 phase is dependent on ATR and CHK1. In agreement with this, CHK1 phosphorylation is enhanced in FA cells, and chemical inhibition of the ATR/CHK1 axis in FA lymphoblasts decreases their sensitivity to mitomycin C. In conclusion, this work describes a complex crosstalk between CHK1 and the FANC/BRCA pathway: CHK1 activates this pathway through FANCD2 monoubiquitination, whereas FA deficiency leads to a CHK1-dependent G2 accumulation, raising the possibility that the FANC/BRCA pathway downregulates CHK1 activation.

Natural History and Management of Fanconi Anemia Patients with Head and Neck Cancer: A 10-year Follow-up

PubMed Central

Kutler, David I.; Patel, Krupa R.; Auerbach, Arleen D.; Kennedy, Jennifer; Lach, Francis P.; Sanborn, Erica; Cohen, Marc A.; Kuhel, William I.; Smogorzewska, Agata

2015-01-01

Objective To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma. Study Design Cohort study. Methods Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry (IFAR) who developed head and neck squamous cell carcinoma (HNSCC) were analyzed. Results 35 FA patients were diagnosed with HNSCC at a mean age of 32 years. The most common site of primary cancer was the oral cavity (26/35, 74%). Thirty patients underwent surgical resection of the cancer. Sixteen patients received radiation therapy with an average radiation dose of 5050 cGy. The most common toxicities were high-grade mucositis (9/16, 56%), hematologic abnormalities (8/16, 50%), and dysphagia (8/16, 50%). Three patients received conventional chemotherapy and had significant complications while three patients who received targeted chemotherapy with cetuximab had fewer toxicities. The 5-year overall survival rate was 39% with a cause-specific survival rate of 47%. Conclusions Fanconi anemia patients have a high risk of developing aggressive HNSCC at an early age. FA patients can tolerate complex ablative and reconstructive surgeries, but careful post-operative care is required to reduce morbidity. The treatment of FA-associated HNSCC is difficult secondary to the poor tolerance of radiation and chemotherapy. However, radiation should be used for high-risk cancers because of the poor survival in these patients. PMID:26484938

Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

PubMed

Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

2018-01-01

Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

Biodiesel production by combined fatty acids separation and subsequently enzymatic esterification to improve the low temperature properties.

PubMed

Wang, Meng; Nie, Kaili; Cao, Hao; Deng, Li; Wang, Fang; Tan, Tianwei

2014-12-01

The poor low-temperature properties of biodiesel, which provokes easy crystallization at low temperature, can cause fuel line plugging and limits its blending amount with petro-diesel. This work aimed to study the production of biodiesel with a new process of improving the low temperature performance of biodiesel. Waste cooking oil was first hydrolyzed into fatty acids (FAs) by 60g immobilized lipase and 240g RO water in 15h. Then, urea complexation was used to divide the FAs into saturated and unsaturated components. The conditions for complexation were: FA-to-urea ratio 1:2 (w/w), methanol to FA ratio 5:1 (v/v), duration 2h. The saturated and unsaturated FAs were then converted to iso-propyl and methyl esters by lipase, respectively. Finally, the esters were mixed together. The CFPP of this mixture was decreased from 5°C to -3°C. Hydrolysis, urea complexation and enzymic catalyzed esterification processes are discussed in this paper. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Fanconi anemia: cellular and molecular features].

PubMed

Macé, G; Briot, D; Guervilly, J-H; Rosselli, F

2007-02-01

Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure. 11 among 12 FA gene have been isolated. The biochemical functions of the FANC proteins remain poorly understood. Anyhow, to cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the FANC proteins appear to be involved in cell protection against oxidative damage and in the control of TNF-alpha activity. In this review, we describe the current understanding of the FANC pathway and we present how it may be integrated in the complex networks of proteins involved in maintaining the cellular homeostasis.

Derivative Free Optimization of Complex Systems with the Use of Statistical Machine Learning Models

DTIC Science & Technology

2015-09-12

AFRL-AFOSR-VA-TR-2015-0278 DERIVATIVE FREE OPTIMIZATION OF COMPLEX SYSTEMS WITH THE USE OF STATISTICAL MACHINE LEARNING MODELS Katya Scheinberg...COMPLEX SYSTEMS WITH THE USE OF STATISTICAL MACHINE LEARNING MODELS 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-11-1-0239 5c.  PROGRAM ELEMENT...developed, which has been the focus of our research. 15. SUBJECT TERMS optimization, Derivative-Free Optimization, Statistical Machine Learning 16. SECURITY

Dual hydrogen-bonding motifs in complexes formed between tropolone and formic acid

NASA Astrophysics Data System (ADS)

Nemchick, Deacon J.; Cohen, Michael K.; Vaccaro, Patrick H.

2016-11-01

The near-ultraviolet π*←π absorption system of weakly bound complexes formed between tropolone (TrOH) and formic acid (FA) under cryogenic free-jet expansion conditions has been interrogated by exploiting a variety of fluorescence-based laser-spectroscopic probes, with synergistic quantum-chemical calculations built upon diverse model chemistries being enlisted to unravel the structural and dynamical properties of the pertinent ground [X˜ 1A'] and excited [A˜ 1A'(" separators="π*π )] electronic states. For binary TrOH ṡ FA adducts, the presence of dual hydrogen-bond linkages gives rise to three low-lying isomers designated (in relative energy order) as INT, EXT1, and EXT2 depending on whether docking of the FA ligand to the TrOH substrate takes place internal or external to the five-membered reaction cleft of tropolone. While the symmetric double-minimum topography predicted for the INT potential surface mediates an intermolecular double proton-transfer event, the EXT1 and EXT2 structures are interconverted by an asymmetric single proton-transfer process that is TrOH-centric in nature. The A ˜ -X ˜ origin of TrOH ṡ FA at ν˜ 00=27 484 .45 cm-1 is displaced by δ ν˜ 00=+466 .76 cm-1 with respect to the analogous feature for bare tropolone and displays a hybrid type - a/b rotational contour that reflects the configuration of binding. A comprehensive analysis of vibrational landscapes supported by the optically connected X˜ 1A' and A˜ 1A'(" separators="π*π ) manifolds, including the characteristic isotopic shifts incurred by partial deuteration of the labile TrOH and FA protons, has been performed leading to the uniform assignment of numerous intermolecular (viz., modulating hydrogen-bond linkages) and intramolecular (viz., localized on monomer subunits) degrees of freedom. The holistic interpretation of all experimental and computational findings affords compelling evidence that an external-binding motif (attributed to EXT1), rather than the thermodynamically more stable cleft-bound (INT) form, was the carrier of fluorescence signals observed during the present work.

Multimodal neuroimaging measures and intelligence influence pedophile child sexual offense behavior.

PubMed

Lett, Tristram A; Mohnke, Sebastian; Amelung, Till; Brandl, Eva J; Schiltz, Kolja; Pohl, Alexander; Gerwinn, Hannah; Kärgel, Christian; Massau, Claudia; Tenbergen, Gilian; Wittfoth, Matthias; Kneer, Jonas; Beier, Klaus M; Walter, Martin; Ponseti, Jorge; Krüger, Tillmann H C; Schiffer, Boris; Walter, Henrik

2018-06-04

Pedophilia is a heterogeneous disorder for which the neurobiological correlates are not well established. In particular, there are no biological markers identifying individuals with high risk to commit child sexual offense (CSO). Pedophiles with CSO (P+CSO; N = 73), pedophiles without CSO (P-CSO; N = 77), and non-pedophilic controls (NPC; N = 133) were assessed using multimodal structural neuroimaging measures including: cortical thickness (CT), surface area (SA), and white matter fractional anisotropy (FA), as well as full scale IQ (FSIQ) performance. Cortex-wise mediation analyses were used to assess the relationships among brain structure, FSIQ and CSO behavior. Lower FSIQ performance was strongly predict with P+CSO (Wald Chi 2 = 13.0, p = 3.1 × 10 -5 ). P+CSO had lower CT in the right motor cortex and pronounced reductions in SA spanning the bilateral frontal, temporal, cingulate, and insular regions (P FWE-corrected < 0.05). P+CSO also had lower FA particularly in the corpus callosum (P FWE-corrected < 0.05). The relationship between SA and P+CSO was significantly mediated by FSIQ, particularly in the prefrontal and anterior insular cortices (P FWE-corrected < 0.05). Within P+CSO, left prefrontal and right anterior cingulate SA negatively correlated with number of CSOs (P FWE-corrected < 0.05). This study demonstrates converging neurobiological findings in which P+CSO had lower FSIQ performance, reduced CT, reduced SA, and reduced FA, compared to P-CSO as well as NPC. Further, FSIQ potentially mediates abuse by pedophiles via aberrant SA, whereas the CT and FA associations were independent of FSIQ differences. These findings suggest aberrant neuroanatomy and lower intelligence as a potential core feature underlying child sexual abuse behavior by pedophiles. Copyright © 2018. Published by Elsevier B.V.

Evaluating psychological interventions in a novel experimental human model of anxiety

PubMed Central

Ainsworth, Ben; Marshall, Jemma E.; Meron, Daniel; Baldwin, David S.; Chadwick, Paul; Munafò, Marcus R.; Garner, Matthew

2015-01-01

Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and provides a novel experimental model of anxiety with which to evaluate pharmacological and psychological treatments for anxiety. To date several psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated using the 7.5% CO2 model; however, it has yet to be used to evaluate psychological interventions. We compared the effects of two core psychological components of mindfulness-meditation (open monitoring and focused attention) against general relaxation, on subjective, autonomic and neuropsychological outcomes in the 7.5% CO2 experimental model. 32 healthy screened adults were randomized to complete 10 min of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge participants completed an eye-tracking measure of attention control and selective attention. Measures of subjective anxiety, blood pressure and heart rate were taken at baseline and immediately following intervention and CO2-challenge. OM and FA practice reduced subjective feelings of anxiety during 20-min inhalation of 7.5% CO2 compared to relaxation control. OM practice produced a strong anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA effects occurred in the absence of group differences in autonomic arousal and eye-movement measures of attention. Our findings are consistent with neuropsychological models of mindfulness-meditation that propose OM and FA activate prefrontal mechanisms that support emotion regulation during periods of anxiety and physiological hyper-arousal. Our findings complement those from pharmacological treatment studies, further supporting the use of CO2 challenge to evaluate future therapeutic interventions for anxiety. PMID:25765144

Amplification of the major satellite DNA family (FA-SAT) in a cat fibrosarcoma might be related to chromosomal instability.

PubMed

Santos, Sara; Chaves, Raquel; Adega, Filomena; Bastos, Estela; Guedes-Pinto, Henrique

2006-01-01

Most mammalian chromosomes have satellite DNA sequences located at or near the centromeres, organized in arrays of variable size and higher order structure. The implications of these specific repetitive DNA sequences and their organization for centromere function are still quite cloudy. In contrast to most mammalian species, the domestic cat seems to have the major satellite DNA family (FA-SAT) localized primarily at the telomeres and secondarily at the centromeres of the chromosomes. In the present work, we analyzed chromosome preparations from a fibrosarcoma, in comparison with nontumor cells (epithelial tissue) from the same individual, by in situ hybridization of the FA-SAT cat satellite DNA family. This repetitive sequence was found to be amplified in the cat tumor chromosomes analyzed. The amplification of these satellite DNA sequences in the cat chromosomes with variable number and appearance (marker chromosomes) is discussed and might be related to mitotic instability, which could explain the exhibition of complex patterns of chromosome aberrations detected in the fibrosarcoma analyzed.

Metal-organic gel enhanced fluorescence anisotropy for sensitive detection of prostate specific antigen

NASA Astrophysics Data System (ADS)

Zhao, Ting Ting; Peng, Zhe Wei; Yuan, Dan; Zhen, Shu Jun; Huang, Cheng Zhi; Li, Yuan Fang

2018-03-01

In this contribution, we demonstrated that Cu-based metal-organic gel (Cu-MOG) was able to serve as a novel amplification platform for fluorescence anisotropy (FA) assay for the first time, which was confirmed by the sensitive detection of a common cancer biomarker, prostate specific antigen (PSA). The dye-labeled probe aptamer (PA) product was adsorbed onto the benzimidazole derivative-containing Cu-MOG via electrostatic incorporation and strong π-π stacking interactions, which significantly increased the FA value due to the enlargement of the molecular volume of the PA/Cu-MOG complex. With the introduction of target PSA, the FA value was obviously decreased on account of the specific recognition between PSA and PA which resulted in the detachment of PA from the surface of MOG. The linear range was from 0.5-8 ng/mL, with a detection limit of 0.33 ng/mL. Our work has thus helped to demonstrate promising application of MOG material in the fields of biomolecules analysis and disease diagnosis.

Pick a Color MARIA: Adaptive Sampling Enables the Rapid Identification of Complex Perovskite Nanocrystal Compositions with Defined Emission Characteristics.

PubMed

Bezinge, Leonard; Maceiczyk, Richard M; Lignos, Ioannis; Kovalenko, Maksym V; deMello, Andrew J

2018-06-06

Recent advances in the development of hybrid organic-inorganic lead halide perovskite (LHP) nanocrystals (NCs) have demonstrated their versatility and potential application in photovoltaics and as light sources through compositional tuning of optical properties. That said, due to their compositional complexity, the targeted synthesis of mixed-cation and/or mixed-halide LHP NCs still represents an immense challenge for traditional batch-scale chemistry. To address this limitation, we herein report the integration of a high-throughput segmented-flow microfluidic reactor and a self-optimizing algorithm for the synthesis of NCs with defined emission properties. The algorithm, named Multiparametric Automated Regression Kriging Interpolation and Adaptive Sampling (MARIA), iteratively computes optimal sampling points at each stage of an experimental sequence to reach a target emission peak wavelength based on spectroscopic measurements. We demonstrate the efficacy of the method through the synthesis of multinary LHP NCs, (Cs/FA)Pb(I/Br) 3 (FA = formamidinium) and (Rb/Cs/FA)Pb(I/Br) 3 NCs, using MARIA to rapidly identify reagent concentrations that yield user-defined photoluminescence peak wavelengths in the green-red spectral region. The procedure returns a robust model around a target output in far fewer measurements than systematic screening of parametric space and additionally enables the prediction of other spectral properties, such as, full-width at half-maximum and intensity, for conditions yielding NCs with similar emission peak wavelength.

Synthesis of customized petroleum-replica fuel molecules by targeted modification of free fatty acid pools in Escherichia coli

PubMed Central

Howard, Thomas P.; Middelhaufe, Sabine; Moore, Karen; Edner, Christoph; Kolak, Dagmara M.; Taylor, George N.; Parker, David A.; Lee, Rob; Smirnoff, Nicholas; Aves, Stephen J.; Love, John

2013-01-01

Biofuels are the most immediate, practical solution for mitigating dependence on fossil hydrocarbons, but current biofuels (alcohols and biodiesels) require significant downstream processing and are not fully compatible with modern, mass-market internal combustion engines. Rather, the ideal biofuels are structurally and chemically identical to the fossil fuels they seek to replace (i.e., aliphatic n- and iso-alkanes and -alkenes of various chain lengths). Here we report on production of such petroleum-replica hydrocarbons in Escherichia coli. The activity of the fatty acid (FA) reductase complex from Photorhabdus luminescens was coupled with aldehyde decarbonylase from Nostoc punctiforme to use free FAs as substrates for alkane biosynthesis. This combination of genes enabled rational alterations to hydrocarbon chain length (Cn) and the production of branched alkanes through upstream genetic and exogenous manipulations of the FA pool. Genetic components for targeted manipulation of the FA pool included expression of a thioesterase from Cinnamomum camphora (camphor) to alter alkane Cn and expression of the branched-chain α-keto acid dehydrogenase complex and β-keto acyl-acyl carrier protein synthase III from Bacillus subtilis to synthesize branched (iso-) alkanes. Rather than simply reconstituting existing metabolic routes to alkane production found in nature, these results demonstrate the ability to design and implement artificial molecular pathways for the production of renewable, industrially relevant fuel molecules. PMID:23610415

Genus-Specific Primers for Study of Fusarium Communities in Field Samples

PubMed Central

Edel-Hermann, Véronique; Gautheron, Nadine; Durling, Mikael Brandström; Kolseth, Anna-Karin; Steinberg, Christian; Persson, Paula; Friberg, Hanna

2015-01-01

Fusarium is a large and diverse genus of fungi of great agricultural and economic importance, containing many plant pathogens and mycotoxin producers. To date, high-throughput sequencing of Fusarium communities has been limited by the lack of genus-specific primers targeting regions with high discriminatory power at the species level. In the present study, we evaluated two Fusarium-specific primer pairs targeting translation elongation factor 1 (TEF1). We also present the new primer pair Fa+7/Ra+6. Mock Fusarium communities reflecting phylogenetic diversity were used to evaluate the accuracy of the primers in reflecting the relative abundance of the species. TEF1 amplicons were subjected to 454 high-throughput sequencing to characterize Fusarium communities. Field samples from soil and wheat kernels were included to test the method on more-complex material. For kernel samples, a single PCR was sufficient, while for soil samples, nested PCR was necessary. The newly developed primer pairs Fa+7/Ra+6 and Fa/Ra accurately reflected Fusarium species composition in mock DNA communities. In field samples, 47 Fusarium operational taxonomic units were identified, with the highest Fusarium diversity in soil. The Fusarium community in soil was dominated by members of the Fusarium incarnatum-Fusarium equiseti species complex, contradicting findings in previous studies. The method was successfully applied to analyze Fusarium communities in soil and plant material and can facilitate further studies of Fusarium ecology. PMID:26519387

Unsaturated Lipids Change in Olive Tree Drupe and Seed during Fruit Development and in Response to Cold-Stress and Acclimation

PubMed Central

D’Angeli, Simone; Altamura, Maria Maddalena

2016-01-01

The olive tree is a plant of economic value for the oil of its drupe. It is a cultigen complex composed of genotypes with differences in cold-hardiness. About 90% of the oil is stored in oil bodies (OBs) in the drupe during the oleogenic phase. Phenols and lipids contribute to oil quality, but the unsaturated fatty acid (FA) fraction is emerging as the most important for quality, because of the very high content in oleic acid, the presence of ω6-linoleic acid and ω3-linolenic acid, and the very low saturated FA content. Another 10% of oil is produced by the seed. Differences in unsaturated FA-enriched lipids exist among seed coat, endosperm, and embryo. Olive oil quality is also affected by the environmental conditions during fruit growth and genotype peculiarities. Production of linoleic and α-linolenic acids, fruit growth, fruit and leaf responses to low temperatures, including cuticle formation, and cold-acclimation are related processes. The levels of unsaturated FAs are changed by FA-desaturase (FAD) activities, involving the functioning of chloroplasts and endoplasmic reticulum. Cold induces lipid changes during drupe and seed development, affecting FADs, but its effect is related to the genotype capability to acclimate to the cold. PMID:27845749

Polynomial approximation of functions of matrices and its application to the solution of a general system of linear equations

NASA Technical Reports Server (NTRS)

Tal-Ezer, Hillel

1987-01-01

During the process of solving a mathematical model numerically, there is often a need to operate on a vector v by an operator which can be expressed as f(A) while A is NxN matrix (ex: exp(A), sin(A), A sup -1). Except for very simple matrices, it is impractical to construct the matrix f(A) explicitly. Usually an approximation to it is used. In the present research, an algorithm is developed which uses a polynomial approximation to f(A). It is reduced to a problem of approximating f(z) by a polynomial in z while z belongs to the domain D in the complex plane which includes all the eigenvalues of A. This problem of approximation is approached by interpolating the function f(z) in a certain set of points which is known to have some maximal properties. The approximation thus achieved is almost best. Implementing the algorithm to some practical problem is described. Since a solution to a linear system Ax = b is x= A sup -1 b, an iterative solution to it can be regarded as a polynomial approximation to f(A) = A sup -1. Implementing the algorithm in this case is also described.

The King is Dead: Regaining the Throne -- The Current State of the Field Artillery, Core Competency Atrophy, and the Way Ahead

DTIC Science & Technology

2011-03-17

with a built -in glass ceiling is not likely to retain or attract the best and the brightest. If it hasn’t happened already, FA accessions will begin...officer. This would also facilitate removing the glass ceiling currently atop the field 19 artillery with only six tactical command opportunities. This...missions excluding conventional warfare strategic failure can result. 71 In summer 2006 in southern Lebanon , the Israeli army suffered a significant

Generation of High Purity Photon-Pair in a Short Highly Non-Linear Fiber

DTIC Science & Technology

2013-01-01

Avalanche photodiode. A 10 m long HNLF fabricated by Sumitomo with a core diameter of 4 microns is fusion spliced to a single mode fiber for a...parametric down conversion (SPDC) was first observed in χ(2) nonlinear crystal [3]. However, the compatibility of a nonlinear crystal source with fiber and...PAIR IN A SHORT HIGHLY NON-LINEAR FIBER 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA8750-12-1-0136 5c. PROGRAM ELEMENT NUMBER N/A 6. AUTHOR(S

Conceptual Framework for Trait-Based Ecological Risk Assessment for Wildlife Populations Exposed to Pesticides

EPA Science Inventory

Between screening level risk assessments and complex ecological models, a need exists for practical identification of risk based on general information about species, chemicals, and exposure scenarios. Several studies have identified demographic, biological, and toxicological fa...

Development and Application of a Simple Hydrogeomorphic Model for Headwater Catchments

EPA Science Inventory

We developed a catchment model based on a hydrogeomorphic concept that simulates discharge from channel-riparian complexes, zero-order basins (ZOB, basins ZB and FA), and hillslopes. Multitank models simulate ZOB and hillslope hydrological response, while kinematic wave models pr...

Facilitated Bioaccumulation of Perfluorooctanesulfonate in Common Carp (Cyprinus carpio) by Graphene Oxide and Remission Mechanism of Fulvic Acid.

PubMed

Qiang, Liwen; Chen, Meng; Zhu, Lingyan; Wu, Wei; Wang, Qiang

2016-11-01

As one of the most popular carbon-based nanomaterials, graphene oxide (GO) has the potential to be released in aquatic environment and interact with some coexistent organic pollutants, such as perfluorooctanesulfonate (PFOS), which is an emerging persistent organic pollutant. In this study, the adsorption of PFOS on GO in the presence of fulvic acid (FA), the impacts of GO and FA on PFOS toxicokinetics in carp (Cyprinus carpio), and in vitro digestion behaviors were examined. The results indicated that PFOS could be strongly adsorbed on GO with a Freundlich affinity coefficient K F of 580 ± 205 (mg/g)/(mg/L) n , while the adsorption was suppressed by FA due to competitive adsorption. GO significantly enhanced the bioaccumulation of PFOS in blood, kidney, liver, gill, intestine, and muscle of carp, and the corresponding bioaccumulation factor (BAF) was in the range of 2026-53513 L/kg. The enhancement was greatest for liver and intestine, which was 10.3 and 9.33 times of that without GO, respectively. In vivo toxicokinetic and in vitro digestion-absorption experiments indicated that GO could carry PFOS to penetrate the intestine cells. There herein, PFOS absorption, especially via intestine, and the uptake rate coefficient (k u ) were greatly enhanced, leading to distinctly promoted bioaccumulation of PFOS in fish. However, FA could facilitate the flocculation of GO in the intestine and also accelerate excretion of GO-PFOS complex. Thus, in the presence of FA, PFOS absorption was reduced and the promotion effect of GO on PFOS accumulation was remitted.

[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension].

PubMed

Popova, E N; Bolevich, S B; Litvitskiĭ, P F; Arkhipova, D V; Osipenko, V I; Kogan, E A; Kornev, B M; Mukhin, N A

2004-01-01

To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

Silibinin Capsules improves high fat diet-induced nonalcoholic fatty liver disease in hamsters through modifying hepatic de novo lipogenesis and fatty acid oxidation.

PubMed

Cui, Chun-Xue; Deng, Jing-Na; Yan, Li; Liu, Yu-Ying; Fan, Jing-Yu; Mu, Hong-Na; Sun, Hao-Yu; Wang, Ying-Hong; Han, Jing-Yan

2017-08-17

Silibinin Capsules (SC) is a silybin-phospholipid complex with silybin as the bioactive component. Silybin accounts for 50-70% of the seed extract of Silybum marianum (L.) Gaertn.. As a traditional medicine, silybin has been used for treatment of liver diseases and is known to provide a wide range of hepatoprotective effects. High fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) is a worldwide health problem. This study was to investigate the role of SC in NAFLD with focusing on its underlying mechanism and likely target. Male hamsters (Cricetidae) received HFD for 10 weeks to establish NAFLD model. NAFLD was assessed by biochemical assays, histology and immunohistochemistry. Proton nuclear magnetic resonance spectroscopy and western blot were conducted to gain insight into the mechanism. Hamsters fed HFD for 10 weeks developed fatty liver accompanying with increased triglyceride (TG) accumulation, enhancing de novo lipogenesis, increase in fatty acid (FA) uptake and reducing FA oxidation and TG lipolysis, as well as a decrease in the expression of phospho-adenosine monophosphate activated protein kinase α (p-AMPKα) and Sirt 1. SC treatment at 50mg/kg silybin and 100mg/kg silybin for 8 weeks protected hamsters from development of fatty liver, reducing de novo lipogenesis and increasing FA oxidation and p-AMPKα expression, while having no effect on FA uptake and TG lipolysis. SC protected against NAFLD in hamsters by inhibition of de novo lipogenesis and promotion of FA oxidation, which was likely mediated by activation of AMPKα. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Probing 1D superlattices at the LaAlO3 / SrTiO3 interface

NASA Astrophysics Data System (ADS)

Briggeman, M.; Huang, M.; Tylan-Tyler, A.; Irvin, P.; Levy, J.; Lee, J.-W.; Lee, H.; Eom, C.-B.

Complex oxides and other quantum systems exhibit behavior that is currently too complex to be understood using analytic or computational methods. One approach is to use a configurable quantum system whose Hamiltonian can be mapped onto the system of interest. This approach, known as quantum simulation, requires a rich physical system whose quanta and interactions can be controlled precisely, at the level of single electrons and other degrees of freedom. Here we describe steps toward developing a quantum simulation platform, using the complex oxide heterostructure LaAlO3 / SrTiO3 , by creating quantum systems with features comparable to the mean spacing between electrons. This interface has strong, sign changing, gate-tunable electron-electron interactions that can strongly influence the quantum ground state. We explore the magnetotransport properties of 1D superlattices, where periodic modulation produces reproducible dispersive features not seen in control structures. The results of these experiments can be compared with effective 1D model Hamiltonians to bridge experiment and theory and enable quantum simulation of more complex systems. We gratefully acknowledge financial support from AFOSR (FA9550-12-1- 0057 (JL) and FA9550-12-1-0342 (CBE)), ONR N00014-15-1-2847 (JL), and NSF DMR-1234096 (CBE).

Coherent structures in a supersonic complex nozzle

NASA Astrophysics Data System (ADS)

Magstadt, Andrew; Berry, Matthew; Glauser, Mark

2016-11-01

The jet flow from a complex supersonic nozzle is studied through experimental measurements. The nozzle's geometry is motivated by future engine designs for high-performance civilian and military aircraft. This rectangular jet has a single plane of symmetry, an additional shear layer (referred to as a wall jet), and an aft deck representative of airframe integration. The core flow operates at a Mach number of Mj , c = 1 . 6 , and the wall jet is choked (Mj , w = 1 . 0). This high Reynolds number jet flow is comprised of intense turbulence levels, an intricate shock structure, shear and boundary layers, and powerful corner vortices. In the present study, stereo PIV measurements are simultaneously sampled with high-speed pressure measurements, which are embedded in the aft deck, and far-field acoustics in the anechoic chamber at Syracuse University. Time-resolved schlieren measurements have indicated the existence of strong flow events at high frequencies, at a Strouhal number of St = 3 . 4 . These appear to result from von Kàrmàn vortex shedding within the nozzle and pervade the entire flow and acoustic domain. Proper orthogonal decomposition is applied on the current data to identify coherent structures in the jet and study the influence of this vortex street. AFOSR Turbulence and Transition Program (Grant No. FA9550-15-1-0435) with program managers Dr. I. Leyva and Dr. R. Ponnappan.

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

Yang, Yanwu; Wang, Xiaoxia; Hawkins, Cheryl A.

The LIM-only adaptor PINCH (the particularly interesting cysteine- and histidine-rich protein) plays a pivotal role in the assembly of focal adhesions (FAs), supramolecular complexes that transmit mechanical and biochemical information between extracellular matrix and actin cytoskeleton, regulating diverse cell adhesive processes such as cell migration, cell spreading, and survival. A key step for the PINCH function is its localization to FAs, which depends critically on the tight binding of PINCH to integrin-linked kinase (ILK). Here we report the solution NMR structure of the core ILK {center_dot} PINCH complex (28 kDa, K{sub D} {approx} 68 nm) involving the N-terminal ankyrin repeatmore » domain (ARD) of ILK and the first LIM domain (LIM1) of PINCH. We show that the ILK ARD exhibits five sequentially stacked ankyrin repeat units, which provide a large concave surface to grip the two contiguous zinc fingers of the PINCH LIM1. The highly electrostatic interface is evolutionally conserved but differs drastically from those of known ARD and LIM bound to other types of protein domains. Consistently mutation of a hot spot in LIM1, which is not conserved in other LIM domains, disrupted the PINCH binding to ILK and abolished the PINCH targeting to FAs. These data provide atomic insight into a novel modular recognition and demonstrate how PINCH is specifically recruited by ILK to mediate the FA assembly and cell-extracellular matrix communication.« less

Structure characterization of lipocyclopeptide antibiotics, aspartocins A, B & C, by ESI-MSMS and ESI-nozzle-skimmer-MSMS.

PubMed

Siegel, Marshall M; Kong, Fangming; Feng, Xidong; Carter, Guy T

2009-12-01

Three lipocyclopeptide antibiotics, aspartocins A (1), B (2), and C (3), were obtained from the aspartocin complex by HPLC separation methodology. Their structures were elucidated using previously published chemical degradation results coupled with spectroscopic studies including ESI-MS, ESI-Nozzle Skimmer-MSMS and NMR. All three aspartocin compounds share the same cyclic decapeptide core of cyclo [Dab2 (Asp1-FA)-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11]. They differ only in the fatty acid side chain moiety (FA) corresponding to (Z)-13-methyltetradec-3-ene-carbonyl, (+,Z)-12-methyltetradec-3-ene-carbonyl and (Z)-12-methyltridec-3-ene-carbonyl for aspartocins A (1), B (2), and C (3), respectively. All of the sequence ions were observed by ESI-MSMS of the doubly charged parent ions. However, a number of the sequence ions observed were of low abundance. To fully sequence the lipocyclopeptide antibiotic structures, these low abundance sequence ions together with complementary sequence ions were confirmed by ESI-Nozzle-Skimmer-MSMS of the singly charged linear peptide parent fragment ions H-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-Dab2(1+)-Asp1-FA. Cyclization of the aspartocins was demonstrated to occur via the beta-amino group of Dab2 from ions of moderate intensity in the ESI-MSMS spectra. As the fatty acid moieties do not undergo internal fragmentations under the experimental ESI mass spectral conditions used, the 14 Da mass difference between the fatty acid moieties of aspartocins A (1) and B (2) versus aspartocin C (3) was used as an internal mass tag to differentiate fragment ions containing fatty acid moieties and those not containing the fatty acid moieties. The most numerous and abundant fragment ions observed in the tandem mass spectra are due to the cleavage of the tertiary nitrogen amide of the pipecolic acid residue-3 (16 fragment ions) and the proline residue-11 (7 fragment ions). In addition, the neutral loss of ethanimine from alpha,beta-diaminobutyric acid residue 9 was observed for the parent molecular ion and for 7 fragment ions. Copyright 2009 John Wiley & Sons, Ltd.

EC93-41094-4

NASA Image and Video Library

1993-05-18

A NASA F/A-18, specially modified to test the newest and most advanced system technologies, on its first research flight on May 21, 1993, at NASA's Dryden Flight Research Facility, Edwards, California. Flown by Dryden in a multi-year, joint NASA/DOD/industry program, the F/A-18 former Navy fighter was modified into a unique Systems Research Aircraft (SRA) to investigate a host of new technologies in the areas of flight controls, airdata sensing and advanced computing. The primary goal of the SRA program was to validate through flight research cutting-edge technologies which could benefit future aircraft and spacecraft by improving efficiency and performance, reducing weight and complexity, with a resultant reduction on development and operational costs.

Food allergy phenotypes: The key to personalized therapy.

PubMed

Deschildre, A; Lejeune, S; Cap, M; Flammarion, S; Jouannic, L; Amat, F; Just, J

2017-09-01

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies. © 2017 John Wiley & Sons Ltd.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

PubMed

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-09-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin.

PubMed

Jyonouchi, Soma; Abraham, Valsamma; Orange, Jordan S; Spergel, Jonathan M; Gober, Laura; Dudek, Emily; Saltzman, Rushani; Nichols, Kim E; Cianferoni, Antonella

2011-07-01

A key immunologic feature of food allergy (FA) is the presence of a T(h)2-type cytokine bias. Ligation of the invariant natural killer T cell (iNKT) T-cell receptor (TCR) by sphingolipids presented via the CD1d molecule leads to copious secretion of T(h)2-type cytokines. Major food allergens (eg, milk, egg) are the richest dietary source of sphingolipids (food-derived sphingolipids [food-SLs]). Nonetheless, the role of iNKTs in FA is unknown. To investigate the role of iNKTs in FA and to assess whether food-SL-CD1d complexes can engage the iNKT-TCR and induce iNKT functions. PBMCs from 15 children with cow's milk allergy (MA), 12 children tolerant to cow's milk but with allergy to egg, and 13 healthy controls were incubated with α-galactosylceramide (αGal), cow's milk-sphingomyelin, or hen's egg-ceramide. iNKTs were quantified, and their cytokine production and proliferation were assessed. Human CD1d tetramers loaded with milk-sphingomyelin or egg-ceramide were used to determine food-SL binding to the iNKT-TCR. Milk-sphingomyelin, but not egg-ceramide, can engage the iNKT-TCR and induce iNKT proliferation and T(h)2-type cytokine secretion. Children with FA, especially those with MA, had significantly fewer peripheral blood iNKTs and their iNKTs exhibited a greater T(h)2 response to αGal and milk-sphingomyelin than iNKTs of healthy controls. iNKTs from children with FA, especially those with MA, are reduced in number and exhibit a T(h)2 bias in response to αGal and milk-sphingomyelin. These data suggest a potential role for iNKTs in FA. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Is the onset of obesity in suckling fa/fa rats linked to a potentially larger milk intake?

PubMed

Buchberger, P; Schmidt, I

1996-08-01

We wanted to find out whether fatty (fa/fa) sucklings show abnormal intake when given access to an abundant milk reservoir. To do this, we gravimetrically determined the milk ingested by small groups (4-5 pups) of 5- to 15-day-old lean (+/fa) and fatty littermates allowed to suckle for 30 min after their mother had not been nursing for periods of between 1 and 7 h. The pups were grouped randomly and their phenotypes retrospectively identified. Within both genotypes, the intakes of simultaneously tested pups were significantly higher in pups deprived for longer periods. Deprived and undeprived fa/fa pups ingested, however, slightly but significantly less milk than +/fa littermates did in the same nursing bout. In the first 2 wk of life, when fa/fa pups deposit nearly twice as much body fat as their +/fa littermates do, fa/fa pups will thus suckle less rather than more milk. This extends previous findings showing that the onset of fa/fa obesity is independent of larger intakes and thus questions that fa impairs a receptor primarily controlling food intake.

Photoenergy Harvesting Organic PV Cells Using Modified Photosynthetic Light-Harvesting Complex for Energy Harvesting Materials

DTIC Science & Technology

2008-07-03

complex is still unclear even in the crystal structure of RC-LH1 core complex from Rhodopseudomonas (Rps.) palustris [1]. In this study, we use a...complex of R. palustris . 16 The NIR absorption spectra of these core complexes on the electrode indicate that these complexes are stable when...as the LH or the core complex. For example, the core complex, isolated from the photosynthetic bacterium, Rps. palustris , was successfully

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

PubMed Central

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB. PMID:28524868

ZnO@Gd2O3 core/shell nanoparticles for biomedical applications: Physicochemical, in vitro and in vivo characterization.

PubMed

Woźniak, Anna; Grześkowiak, Bartosz F; Babayevska, Nataliya; Zalewski, Tomasz; Drobna, Monika; Woźniak-Budych, Marta; Wiweger, Małgorzata; Słomski, Ryszard; Jurga, Stefan

2017-11-01

The chemical composition of nanoparticles (NPs) may be so designed as to provide measurability for numerous imaging techniques in order to achieve synergistic advantages. Innovative and unique structure of the core/shell ZnO@Gd 2 O 3 NPs possesses luminescent and magnetic properties, and is expected that they will become a new generation of contrast agents for Magnetic Resonance Imaging (MRI) and nanocarriers for theranostics. Thus, by surface biofunctionalization, it is possible to indicate particular nanoparticle compositions which provide efficient imaging, targeted drug delivery, and biocompatibility. Novel ZnO@Gd 2 O 3 NPs were synthesized and biofunctionalized by folic acid (FA) and doxorubicin (Doxo) to provide target and anticancer functions. Physicochemical analyses of the nanoparticles were performed. The biological study included a cytotoxicity in vitro, cellular distribution evaluation, as well as toxicity analyses, performed for the first time, on the in vivo zebrafish (Danio rerio) model. Nanoparticles were found to be effective double-function biomarkers (MRI T 2 contrast agents, fluorescent imaging). The biological study showed that ZnO@Gd 2 O 3 and ZnO@Gd 2 O 3 @OA-polySi@FA NPs are biocompatible in a particular concentration ranges. Conjugation with folic acid and/or doxorubicin resulted in effective drug delivery targeting. The in vivo results described the toxicology profile toward the zebrafish embryo/larvae, including new data concerning the survival, hatching ratio, and developmental malformations. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual Functional Core-Shell Fluorescent Ag2S@Carbon Nanostructure for Selective Assay of E. coli O157:H7 and Bactericidal Treatment.

PubMed

Wang, Ning; Wei, Xing; Zheng, An-Qi; Yang, Ting; Chen, Ming-Li; Wang, Jian-Hua

2017-03-24

A dual functional fluorescent core-shell Ag 2 S@Carbon nanostructure is prepared by a hydrothermally assisted multi-amino synthesis approach with folic acid (FA), polyethylenimine (PEI), and mannoses (Mans) as carbon and nitrogen sources (FA-PEI-Mans-Ag 2 S nanocomposite shortly as Ag 2 S@C). The nanostructure exhibits strong fluorescent emission at λ ex /λ em = 340/450 nm with a quantum yield of 12.57 ± 0.52%. Ag 2 S@C is bound to E. coli O157:H7 via strong interaction with the Mans moiety in Ag 2 S@C with FimH proteins on the fimbriae tip in E. coli O157:H7. Fluorescence emission from Ag 2 S@C/E. coli conjugate is closely related to the content of E. coli O157:H7. Thus, a novel procedure for fluorescence assay of E. coli O157:H7 is developed, offering a detection limit of 330 cfu mL -1 . Meanwhile, the Ag 2 S@C nanostructure exhibits excellent antibacterial performance against E. coli O157:H7. A 99.9% sterilization rate can be readily achieved for E. coli O157:H7 at a concentration of 10 6 -10 7 cfu mL -1 with 3.3 or 10 μg mL -1 of Ag 2 S@C with an interaction time of 5 or 0.5 min, respectively.

Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment

PubMed Central

Yin, Juan-Juan; Sharma, Sonali; Shumyak, Stepan P.; Wang, Zhi-Xin; Zhou, Zhi-Wei; Zhang, Yangde; Guo, Peixuan; Li, Chen-Zhong; Kanwar, Jagat R.; Yang, Tianxin; Mohapatra, Shyam S.; Liu, Wanqing; Duan, Wei; Wang, Jian-Cheng; Li, Qi; Zhang, Xueji; Tan, Jun; Jia, Lee; Liang, Jun; Wei, Ming Q.; Li, Xiaotian; Zhou, Shu-Feng

2013-01-01

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant K a was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer. PMID:23658721

CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

PubMed Central

Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

2016-01-01

CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

Digestion of fatty acids in ruminants: a meta-analysis of flows and variation factors. 1. Total fatty acids.

PubMed

Schmidely, P; Glasser, F; Doreau, M; Sauvant, D

2008-05-01

A database built from 95 experiments with 303 treatments was used to quantify the ruminal biohydrogenation (BH) of fatty acids (FA), efficiency of microbial protein synthesis (EMPS), duodenal flow and intestinal absorption of total FA and of FA with 12 to 18 C units, in response to variations in dietary FA content, source or technological treatment of fat supplement. Flows of FA were expressed relative to dry matter intake (DMI) to compile data from bovine and ovine species. BH tended to increase curvilinearly with FA intake, whereas dietary FA did not affect EMPS. A linear relationship between FA intake and duodenal flow of total FA was obtained, with a coefficient of 0.75 ± 0.06 g duodenal FA/kg DMI for each g FA intake/kg DMI. Between experiments, positive balances of total FA (intake - duodenum) were related to low EMPS. Relationships between duodenal flows of FA with 12 to 18 C units and their respective intakes were linear, with a coefficient that increased with the number of C units. Duodenal flow of bacterial FA was linearly related to FA intake (coefficient 0.33 ± 0.13), whereas contribution of bacterial lipid to duodenal flow decreased as FA intake increased. For each FA with 12 to 16 C units, prediction of FA absorption from its respective duodenal flow was linear. For total FA and FA with 18 C units, apparent absorption levelled off at high duodenal flows. All these relationships were discussed according to current knowledge on microbial metabolism in the rumen and on the intestinal digestibility of FA in the intestine.

Fine Motor Skill Mediates Visual Memory Ability with Microstructural Neuro-correlates in Cerebellar Peduncles in Prematurely Born Adolescents.

PubMed

Thomas, Alyssa R; Lacadie, Cheryl; Vohr, Betty; Ment, Laura R; Scheinost, Dustin

2017-01-01

Adolescents born preterm (PT) with no evidence of neonatal brain injury are at risk of deficits in visual memory and fine motor skills that diminish academic performance. The association between these deficits and white matter microstructure is relatively unexplored. We studied 190 PTs with no brain injury and 92 term controls at age 16 years. The Rey-Osterrieth Complex Figure Test (ROCF), the Beery visual-motor integration (VMI), and the Grooved Pegboard Test (GPT) were collected for all participants, while a subset (40 PTs and 40 terms) underwent diffusion-weighted magnetic resonance imaging. PTs performed more poorly than terms on ROCF, VMI, and GPT (all P < 0.01). Mediation analysis showed fine motor skill (GPT score) significantly mediates group difference in ROCF and VMI (all P < 0.001). PTs showed a negative correlation (P < 0.05, corrected) between fractional anisotropy (FA) in the bilateral middle cerebellar peduncles and GPT score, with higher FA correlating to lower (faster task completion) GPT scores, and between FA in the right superior cerebellar peduncle and ROCF scores. PTs also had a positive correlation (P < 0.05, corrected) between VMI and left middle cerebellar peduncle FA. Novel strategies to target fine motor skills and the cerebellum may help PTs reach their full academic potential. © The Author 2017. Published by Oxford University Press.

Application of firefly algorithm to the dynamic model updating problem

NASA Astrophysics Data System (ADS)

Shabbir, Faisal; Omenzetter, Piotr

2015-04-01

Model updating can be considered as a branch of optimization problems in which calibration of the finite element (FE) model is undertaken by comparing the modal properties of the actual structure with these of the FE predictions. The attainment of a global solution in a multi dimensional search space is a challenging problem. The nature-inspired algorithms have gained increasing attention in the previous decade for solving such complex optimization problems. This study applies the novel Firefly Algorithm (FA), a global optimization search technique, to a dynamic model updating problem. This is to the authors' best knowledge the first time FA is applied to model updating. The working of FA is inspired by the flashing characteristics of fireflies. Each firefly represents a randomly generated solution which is assigned brightness according to the value of the objective function. The physical structure under consideration is a full scale cable stayed pedestrian bridge with composite bridge deck. Data from dynamic testing of the bridge was used to correlate and update the initial model by using FA. The algorithm aimed at minimizing the difference between the natural frequencies and mode shapes of the structure. The performance of the algorithm is analyzed in finding the optimal solution in a multi dimensional search space. The paper concludes with an investigation of the efficacy of the algorithm in obtaining a reference finite element model which correctly represents the as-built original structure.

Food addiction as a proxy for eating disorder and obesity severity, trauma history, PTSD symptoms, and comorbidity.

PubMed

Brewerton, Timothy D

2017-06-01

Food addiction (FA) is a newly defined yet still controversial condition that has important etiological, developmental, treatment, prevention, and social policy implications. In this review, the case is made that FA (or high scores on the Yale Food Addiction Scale) may be used as a proxy measure for a matrix of interrelated clinical features, including greater eating disorder severity, greater obesity severity, more severe trauma histories, greater symptoms of posttraumatic stress disorder (PTSD), greater psychiatric comorbidity, as well as greater medical morbidity and mortality. A Medline search was undertaken using the following terms: food addiction cross-referenced with eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder, and binge eating), obesity, trauma, posttraumatic stress disorder, and comorbidity. The thesis is that the identification and acknowledgment of the concept of FA, when integrated into an overall, trauma-focused and transdiagnostic treatment approach, are supported and can be useful in understanding clinically the "big picture." Food addiction (FA) may be used as a proxy for (1) bulimic eating disorder severity, (2) complex trauma histories, (3) severity of PTSD and PTSD symptoms, (4) intensity of psychiatric comorbidity, (5) severity of obesity, as well as (6) their combination. Implications for developing treatment strategies are discussed. The case for a comprehensive management that requires careful attention to medical and psychiatric assessment and integrated care that incorporates trauma-focused treatment is made.

Visible light photodegradation of phenanthrene catalyzed by Fe(III)-smectite: role of soil organic matter.

PubMed

Jia, Hanzhong; Li, Li; Fan, Xiaoyun; Liu, Mingdeng; Deng, Wenye; Wang, Chuanyi

2013-07-15

In the present study, phenanthrene is employed as a model to explore the roles played by three soil organic matter (SOM) fractions, i.e., dissolved organic matter (DOM), humic acid (HA), and fulvic acid (FA), in its photodegradation with assistance of Fe(III)-smectite under visible-light. Slight decrease in phenanthrene photodegradation rate was observed in the presence of DOM, which is explained in terms of oxidative-radical competition between DOM and target phenanthrene molecules due to the high electron-donor capacity of phenolic moieties in DOM. On the other hand, a critic content is observed with FA (0.70mg/g) and HA (0.65mg/g). Before reaching the critic content, the removal of phenanthrene is accelerated; while after that, the photodegradation rate is suppressed. The acceleration of phenanthrene degradation can be attributed to the photosensitization of FA and HA. Due to the strong interaction between phenanthrene and the phenyl rings, however, the retention of phenanthrene on SOM-Fe(III)-smectite in the presence of high content of HA or FA is enhanced, thus slowing down its photodegradation. Those observations provide valuable insights into the transformation and fate of PAHs in the natural soil environment and open a window for using clay-humic substances complexes for remediation of contaminated soil. Copyright © 2013 Elsevier B.V. All rights reserved.

Physiological adaptations to prolonged fasting in the overwintering striped skunk (Mephitis mephitis).

PubMed

Mustonen, Anne-Mari; Bowman, Jeff; Sadowski, Carrie; Nituch, Larissa A; Bruce, Laura; Halonen, Toivo; Puukka, Katri; Rouvinen-Watt, Kirsti; Aho, Jari; Nieminen, Petteri

2013-12-01

Wintertime physiology of captive striped skunks (Mephitis mephitis) in response to cold ambient temperature (Ta) and fasting was investigated with body temperature (Tb) and activity recordings and analyses of hematology, plasma biochemistry and tissue fatty acids (FA). After 105 days of food deprivation, the skunks were in phase II of fasting indicated by the elevated plasma nonesterified FA and glycerol but no accumulation of nitrogen end products. Shorter-chain saturated and monounsaturated FA together with C18-20 n-3 polyunsaturated FA were preferentially mobilized. Individual amino acids responded to fasting in a complex manner, while essential and nonessential amino acid sums remained stable. Increases in hemoglobin and hematocrit suggested dehydration. The activity levels were lower in mid-January-early March, and the activity bouts were mostly displayed between 17:00-23:00 h. Daily torpor was observed in two females with 29 and 46 bouts. The deepest torpor (Tb<31 °C) occurred between dawn and early afternoon and lasted for 3.3 ± 0.18 h. The average minimum Tb was 29.2 ± 0.15 °C and the lowest recorded Tb was 25.8 °C. There was significant relation between the average 24-h Tb and Ta. Increases in wintertime Ta, as predicted by climate change scenarios, could influence torpor patterns in the species. © 2013.

Muscle Damage After Total Hip Arthroplasty Through the Direct Anterior Approach for Developmental Dysplasia of the Hip.

PubMed

Kawasaki, Masashi; Hasegawa, Yukiharu; Okura, Toshiaki; Ochiai, Satoshi; Fujibayashi, Takayoshi

2017-08-01

Total hip arthroplasty (THA) through the direct anterior approach (DAA) is known to cause less muscle damage than other surgical approaches. However, more complex primary cases, such as developmental dysplasia of the hip (DDH), might often cause muscle damage. The objective of the present study was to clarify the muscle damage observed 1 year after THA through the DAA for DDH using magnetic resonance imaging. We prospectively compared the muscle cross-sectional area (M-CSA) and fatty atrophy (FA) in muscles by magnetic resonance imaging and the Harris hip score before and at 1-year follow-up after THA through the DAA in 3 groups: 37 patients with Crowe group 1 DDH (D1), 13 patients with Crowe group 2 and 3 DDH (D2 + 3), and 12 patients with osteonecrosis as a control. THA through the DAA for D1 displayed significantly decreased M-CSA and significantly increased FA in the gluteus minimus (Gmini), the tensor fasciae latae (TFL), and the obturator internus (OI). Patients with D2 + 3 group did not have decreased M-CSA in the TFL or increased FA in the Gmini. Postoperatively, a significant negative correlation was observed between the M-CSA and FA for the OI in patients with D1 and D2 + 3. THA through the DAA for DDH caused the damage in the Gmini, the TFL, and the OI; severe damage was observed in the OI, showing increased FA with decreased M-CSA in patients with both D1 and D2 + 3. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of LSPR and SPR sensor for the detection of an anti-cancer drug for chemotherapy

NASA Astrophysics Data System (ADS)

Zhao, Sandy Shuo; Bolduc, Olivier R.; Colin, Damien Y.; Pelletier, Joelle N.; Masson, Jean-François

2012-03-01

The anti-cancer drug, methotrexate (MTX) as a strong inhibitor of human dihydrofolate reductase (hDHFR) has been studied in localized surface plasmon resonance (LSPR) and surface plasmon resonance (SPR) competitive binding assays with folic acid stabilized gold nanoparticles (FA AuNP). The latter with a diameter of 15 nm were prepared in a simple step with sequential characterization using UV-Vis, FTIR, and Raman. A LSPR competitive binding assay between different concentrations of MTX and FA AuNP for hDHFR in solution was designed to quantify MTX by using UV-Vis spectroscopy. Sensitivity of the assay was optimized with respect to both concentrations of the enzyme and FA. The detection and quantification of spiked MTX was demonstrated in phosphate buffer saline and in fetal bovine serum accompanied by solid-phase extraction treatment of the serum. In addition, this assay could also provide as a screening tool for potential inhibitors of hDHFR. In another perspective, MTX was measured in a competitive binding assay with FA AuNP for histidine-tagged hDHFR immobilized on a SPR sensitive surface. In this case, FA AuNP offer a secondary amplification of the analytical response which is indirectly proportional to the concentration of MTX. This alternative approach could contribute to the realization of direct detection of MTX in complex biological fluids. A comparison of characteristics and analytical parameters such as sensitivity, dynamic range and limit of detection between the LSPR and SPR sensing platforms will also be presented. Both assays offer potential in tackling real biological samples for the purpose of monitoring and validating anti-cancer drug levels in human serum during chemotherapy.

Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway.

PubMed

Jing, Xingzhi; Ye, Yaping; Bao, Yuan; Zhang, Jinming; Huang, Junming; Wang, Rui; Guo, Jiachao; Guo, Fengjing

2018-05-15

Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling. Copyright © 2018. Published by Elsevier Inc.

Craniofacial structure alterations of foetuses from folic acid deficient pregnant mice.

PubMed

Maldonado, Estela; López, Yamila; Herrera, Manuel; Martínez-Sanz, Elena; Martínez-Álvarez, Concepción; Pérez-Miguelsanz, Juliana

2018-03-28

Craniofacial development in mammals is a complex process that involves a coordinated series of molecular and morphogenetic events. Folic acid (FA) deficiency has historically been associated with congenital spinal cord malformations, but the effect that a maternal diet deficient in FA has on the development of other structures has been poorly explored. In the present study, the objective was to describe and quantify the alterations of craniofacial structures presented in mouse foetuses from dams fed a FA deficient (FAD) diet compared with controls that were given a regular maternal diet. E17 mouse foetuses were removed from dams that were fed with a control diet or with a FAD diet for several weeks. Foetuses with maternal FAD diets were selected for the study when they showed an altered tongue or mandible. Histological sections were used to quantify the dimensions of the head, tongue, mandibular bone and masseter muscle areas using ImageJ software. The muscles of the tongue, suprahyoid muscles, lingual septum, submandibular ducts, and lingual arteries were also analysed. The heads of malformed foetuses were smaller than the heads of the controls, and they showed different types of malformations: microglossia with micrognathia (some of which were combined with cleft palate) and aglossia with either micrognathia or agnathia. Lingual and suprahyoid muscles were affected in different forms and degrees. We also found alterations in the lingual arteries and in the ducts of the submandibular glands. Summarised we can state that pharyngeal arches-derived structures were affected, and the main malformations observed corroborate the vulnerability of cranial neural crest cells to FA deficiency. The present study reveals alterations in the development of craniofacial structures in FAD foetuses. This study provides a new focus for the role of FA during embryological development. Copyright © 2018 Elsevier GmbH. All rights reserved.

Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex

PubMed Central

Coulthard, Rachel; Deans, Andrew J.; Swuec, Paolo; Bowles, Maureen; Costa, Alessandro; West, Stephen C.; McDonald, Neil Q.

2013-01-01

Summary Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling. PMID:23932590

Gas phase hydrolysis of formaldehyde to form methanediol: impact of formic acid catalysis.

PubMed

Hazra, Montu K; Francisco, Joseph S; Sinha, Amitabha

2013-11-21

We find that formic acid (FA) is very effective at facilitating diol formation through its ability to reduce the barrier for the formaldehyde (HCHO) hydrolysis reaction. The rate limiting step in the mechanism involves the isomerization of a prereactive collision complex formed through either the HCHO···H2O + FA and/or HCHO + FA···H2O pathways. The present study finds that the effective barrier height, defined as the difference between the zero-point vibrational energy (ZPE) corrected energy of the transition state (TS) and the HCHO···H2O + FA and HCHO + FA···H2O starting reagents, are respectively only ∼1 and ∼4 kcal/mol. These barriers are substantially lower than the ∼17 kcal/mol barrier associated with the corresponding step in the hydrolysis of HCHO catalyzed by a single water molecule (HCHO + H2O + H2O). The significantly lower barrier heights for the formic acid catalyzed pathway reveal a new important role that organic acids play in the gas phase hydrolysis of atmospheric carbonyl compounds.

Folic-Acid-Targeted Self-Assembling Supramolecular Carrier for Gene Delivery.

PubMed

Liao, Rongqiang; Yi, Shouhui; Liu, Manshuo; Jin, Wenling; Yang, Bo

2015-07-27

A targeting gene carrier for cancer-specific delivery was successfully developed through a "multilayer bricks-mortar" strategy. The gene carrier was composed of adamantane-functionalized folic acid (FA-AD), an adamantane-functionalized poly(ethylene glycol) derivative (PEG-AD), and β-cyclodextrin-grafted low-molecular-weight branched polyethylenimine (PEI-CD). Carriers produced by two different self-assembly schemes, involving either precomplexation of the PEI-CD with the FA-AD and PEG-AD before pDNA condensation (Method A) or pDNA condensation with the PEI-CD prior to addition of the FA-AD and PEG-AD to engage host-guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI-25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host-guest interactions, could be an effective, targeted, and low-toxicity carrier for delivering nucleic acid to target cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA.

PubMed

Takahashi, Daisuke; Sato, Koichi; Hirayama, Emiko; Takata, Minoru; Kurumizaka, Hitoshi

2015-09-01

Fanconi anaemia (FA) is a human infantile recessive disorder. Seventeen FA causal proteins cooperatively function in the DNA interstrand crosslink (ICL) repair pathway. Dual DNA strand incisions around the crosslink are critical steps in ICL repair. FA-associated nuclease 1 (FAN1) is a DNA structure-specific endonuclease that is considered to be involved in DNA incision at the stalled replication fork. Replication protein A (RPA) rapidly assembles on the single-stranded DNA region of the stalled fork. However, the effect of RPA on the FAN1-mediated DNA incision has not been determined. In this study, we purified human FAN1, as a bacterially expressed recombinant protein. FAN1 exhibited robust endonuclease activity with 5'-flapped DNA, which is formed at the stalled replication fork. We found that FAN1 efficiently promoted DNA incision at the proper site of RPA-coated 5'-flapped DNA. Therefore, FAN1 possesses the ability to promote the ICL repair of 5'-flapped DNA covered by RPA. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

DNA tests for strawberry: mesifurane "sherry" aroma - FaOMT-SI/NO

USDA-ARS?s Scientific Manuscript database

The amazing flavor and texture in strawberries is caused by a complex balance of numerous sugars and aromatic compounds. One of the most important aromatic compounds contributing to the flavor we have come to love in strawberries is mesifurane. Mesifurane produces a sweet sherry-like aroma and incre...

Macular Morphology and Visual Acuity in the Second Year of the Comparison of Age-Related Macular Degeneration Treatments Trials.

PubMed

Sharma, Sumit; Toth, Cynthia A; Daniel, Ebenezer; Grunwald, Juan E; Maguire, Maureen G; Ying, Gui-Shuang; Huang, Jiayan; Martin, Daniel F; Jaffe, Glenn J

2016-04-01

To describe the association between morphologic features on fundus photography (FP), fluorescein angiography (FA), and optical coherence tomography (OCT) and visual acuity (VA) in the second year of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Prospective cohort study within a randomized clinical trial. Participants in the CATT. Study eye eligibility required angiographic and OCT evidence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and VA between 20/25 and 20/320. Treatment was assigned randomly to ranibizumab or bevacizumab with 3 different dosing regimens over a 2-year period. Fluid type, location, and thickness; retina and subretinal tissue complex thickness on OCT; size and lesion composition on FP and FA; and VA. Among 1185 CATT participants, 993 (84%) had fluid on OCT at baseline and completed 2 years of follow-up. At 2 years, intraretinal fluid (IRF), subretinal fluid (SRF), sub-retinal pigment epithelium (RPE) fluid, and subretinal tissue complex thickness decreased in all treatment groups. Ranibizumab monthly was best able to resolve each type of fluid. Eyes with SRF in the foveal center on OCT had better mean VA than eyes with no SRF (72.8 vs. 66.6 letters; P = 0.006). Eyes with IRF in the foveal center had worse mean VA than eyes without IRF (59.9 vs. 70.9 letters; P < 0.0001). Eyes with retinal thickness <120 μm had worse VA compared with eyes with retinal thickness 120 to 212 and >212 μm (59.4 vs. 71.3 vs. 70.3 letters; P < 0.0001). At 2 years, the mean VA (letters) of eyes varied substantially by the type of subfoveal pathology on FP and FA: 70.6 for no pathology; 74.1 for fluid only; 73.3 for CNV or pigment epithelial (RPE) detachment; 68.4 for nongeographic atrophy; and 62.9 for geographic atrophy, hemorrhage, RPE tear, or scar (P < 0.0001). The associations between VA and morphologic features identified through year 1 were maintained or strengthened during year 2. Eyes with foveal IRF, abnormally thin retina, greater thickness of the subretinal tissue complex on OCT, and subfoveal geographic atrophy or scar on FP/FA had the worst VA. Subretinal fluid was associated with better VA. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Interactions between stepwise-eluted sub-fractions of fulvic acids and protons revealed by fluorescence titration combined with EEM-PARAFAC.

PubMed

Song, Fanhao; Wu, Fengchang; Guo, Fei; Wang, Hao; Feng, Weiying; Zhou, Min; Deng, Yanghui; Bai, Yingchen; Xing, Baoshan; Giesy, John P

2017-12-15

In aquatic environments, pH can control environmental behaviors of fulvic acid (FA) via regulating hydrolysis of functional groups. Sub-fractions of FA, eluted using pyrophosphate buffers with initial pHs of 3.0 (FA 3 ), 5.0 (FA 5 ), 7.0 (FA 7 ), 9.0 (FA 9 ) and 13.0 (FA 13 ), were used to explore interactions between the various, operationally defined, FA fractions and protons, by use of EEM-PARAFAC analysis. Splitting of peaks (FA 3 and FA 13 ), merging of peaks (FA 7 ), disappearance of peaks (FA 9 and FA 13 ), and red/blue-shifting of peaks were observed during fluorescence titration. Fulvic-like components were identified from FA 3 -FA 13 , and protein-like components were observed in fractions FA 9 and FA 13 . There primary compounds (carboxylic-like, phenolic-like, and protein-like chromophores) in PARAFAC components were distinguished based on acid-base properties. Dissociation constants (pK a ) for fulvic-like components with proton ranged from 2.43 to 4.13 in an acidic pH and from 9.95 to 11.27 at basic pH. These results might be due to protonation of di-carboxylate and phenolic functional groups. At basic pH, pK a values of protein-like components (9.77-10.13) were similar to those of amino acids. However, at acidic pH, pK a values of protein-like components, which ranged from 3.33 to 4.22, were 1-2units greater than those of amino acids. Results presented here, will benefit understanding of environmental behaviors of FA, as well as interactions of FA with environmental contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of combination treatment of S–amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats

PubMed Central

2014-01-01

Background Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats. Methods Following combination treatment for 14 days, blood pressure (BP), serum glucose, total cholesterol and triglycerides were measured. Aortic ring study was conducted to determine the effect of combination treatments on phenylephrine-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation. Results In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. Similar results were observed with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 ± 47.5 vs. 252.34 ± 27.86; BP, 184.4 ± 5.0 vs. 159.0 ± 8.0) except for serum glucose. ACh-induced vasorelaxation in aortic rings was also superior with both of the combinations compared to individual treatment. Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose tolerance test. Conclusions The results suggest that a combination of PPAR agonists and S-Amlodipine has partial benefits in improving the cardiovascular risk factors such as reduction in triglyceride levels, associated with chronic type 2 diabetes, and therefore may be utilized as an approach for addressing some of these devastating metabolic syndrome complications. PMID:24673913

Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., sp. nov., Starmerella opuntiae f.a., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a., sp. nov., isolated from flowers and bees, and transfer of related Candida species to the genus Starmerella as new combinations.

PubMed

Santos, Ana Raquel O; Leon, Marina P; Barros, Katharina O; Freitas, Larissa F D; Hughes, Alice F S; Morais, Paula B; Lachance, Marc-André; Rosa, Carlos A

2018-04-01

Six novel yeast species, Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., Starmerella opuntiae f.a., sp. nov., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a, sp. nov. are proposed to accommodate 19 isolates recovered from ephemeral flowers or bees in Brazil, Costa Rica and Belize. Sequence analysis of the ITS-5.8S region (when available) and the D1/D2 domains of the large subunit of the rRNA gene showed that the six novel yeasts are phylogenetically related to several species of the Starmerella clade. The type strains are Starmerella camargoi f.a., sp. nov. UFMG-CM-Y595 T (=CBS 14130 T ; Mycobank number MB 822640), Starmerella ilheusensis f.a., sp. nov. UFMG-CM-Y596 T (=CBS CBS14131 T ; MB 822641), Starmerella litoralis f.a., sp. nov. UFMG-CM-Y603 T (=CBS14104 T ; MB 822642), Starmerella opuntiae f.a., sp. nov. UFMG-CM-Y286 T (=CBS 13466 T ; MB 822643), Starmerella roubikii f.a., sp. nov. UWOPS 01-191.1 (=CBS 15148; MB 822645) and Starmerella vitae f.a., sp. nov. UWOPS 00-107.2 (=CBS 15147 T ; MB 822646). In addition, 25 species currently assigned to the genus Candida are reassigned formally to the genus Starmerella.

Liquid Crystals of Dendron-Like Pt Complexes Processable Into Nanofilms Dendrimers. Phase 2. Cholesteric Liquid Crystal Glass Platinum Acetylides

DTIC Science & Technology

2014-08-01

Std. Z39.18 Final Report Liquid Crystals of Dendron-Like Pt Complexes Processable Into Nanofilms. Dendrimers Eduardo Arias...to pack and also the presence of a polar group. Figure 4. Summary of phase behavior. DENDRIMERS New Denrimers. The synthesis...purification and some spectral characteristics of the new dendrimers shown in Fig 5 were reported in AFOSR FA9550-11-1-0169, May, 2013. Further

The adsorption behavior of U(VI) on granite.

PubMed

Fan, Q H; Hao, L M; Wang, C L; Zheng, Z; Liu, C L; Wu, W S

2014-03-01

The effects of pH, counter ions and temperature on the adsorption of U(VI) on Beishan granite (BsG) were investigated in the presence and absence of fulvic acid (FA) and humic acid (HA). The adsorption edge of U(VI) on BsG suggested that U(VI) adsorption was mainly controlled by ion exchange and outer-sphere complexation at low pH, whereas inner-sphere complex was the dominant adsorption species in the pH range of 4.0-9.0. Above pH 9.0, Na2U2O7 might play an important role in the rise of U(VI) adsorption again. Counter ions such as Cl(-), SO4(2-) and PO4(3-) can provoke U(VI) adsorption on BsG to some extent, which was directly correlated to the complexing ability of U(VI)-ligand. More noticeably, the large enhancement of U(VI) adsorption in the presence of phosphate can be attributed to the ternary complex formation (BsG-PO4-UO2), precipitation ((UO2)3(PO4)2(s)) and secondary phase (Na-autunite). Both FA and HA can slightly increase U(VI) adsorption at low pH, whereas they strongly inhibited U(VI) adsorption at high pH range. Artificial synthesized granite (AsG) prepared in the laboratory is impossible to use as an analogue of natural granite because of the large difference in the adsorption and surface properties.

An effective hybrid firefly algorithm with harmony search for global numerical optimization.

PubMed

Guo, Lihong; Wang, Gai-Ge; Wang, Heqi; Wang, Dinan

2013-01-01

A hybrid metaheuristic approach by hybridizing harmony search (HS) and firefly algorithm (FA), namely, HS/FA, is proposed to solve function optimization. In HS/FA, the exploration of HS and the exploitation of FA are fully exerted, so HS/FA has a faster convergence speed than HS and FA. Also, top fireflies scheme is introduced to reduce running time, and HS is utilized to mutate between fireflies when updating fireflies. The HS/FA method is verified by various benchmarks. From the experiments, the implementation of HS/FA is better than the standard FA and other eight optimization methods.

Assessment of workplace air concentrations of formaldehyde during and before working hours in medical facilities.

PubMed

Higashikubo, Ichiro; Miyauchi, Hiroyuki; Yoshida, Satoru; Tanaka, Shinsuke; Matsuoka, Mitsunori; Arito, Heihachiro; Araki, Akihiro; Shimizu, Hidesuke; Sakurai, Haruhiko

2017-04-07

Workplace air concentrations of formaldehyde (FA) in medical facilities where FA and FA-treated organs were stored and handled were measured before and during working hours and assessed by the official method specified by Work Environment Measurement Law. Sixty-percent of the total facilities examined were judged as inappropriately controlled work environment. The concentrations of FA before working hours by spot sampling were found to exceed 0.1 ppm in some facilities, and tended to increase with increasing volume of containers storing FA and FA-treated materials. Regression analysis revealed that logarithmic concentrations of FA during working hours by the Law-specified analytical method were highly correlated with those before working hours by spot sampling, suggesting the importance for appropriate storing methods of FA and FA-treated materials. The concentrations of FA during working hours are considered to be lowered by effective ventilation of FA-contaminated workplace air and appropriate storage of FA and FA-treated materials in plastic containers in the medical facilities. In particular, such improvement by a local exhaust ventilation system and tightly-sealed containment of FA-treated material were urgently needed for the dissecting room where FA-treated cadavers were prepared and handled for a gross anatomy course in a medical school.

Multifunctional Fe3O4@SiO2-Au Satellite Structured SERS Probe for Charge Selective Detection of Food Dyes.

PubMed

Sun, Zhenli; Du, Jingjing; Yan, Li; Chen, Shu; Yang, Zhilin; Jing, Chuanyong

2016-02-10

Nanofabrication of multifunctional surface-enhanced Raman scattering (SERS) substrates is strongly desirable but currently remains a challenge. The motivation of this study was to design such a substrate, a versatile core-satellite Fe3O4@SiO2-Au (FA) hetero-nanostructure, and demonstrate its use for charge-selective detection of food dye molecules as an exemplary application. Our experimental results and three-dimensional finite difference time domain (FDTD) simulation suggest that tuning the Au nanoparticle (NP) gap to sub-10 nm, which could be readily accomplished, substantially enhanced the Raman signals. Further layer-by-layer deposition of a charged polyelectrolyte on this magnetic SERS substrate induced active adsorption and selective detection of food dye molecules of opposite charge on the substrates. Molecular dynamics (MD) simulations suggest that the selective SERS enhancement could be attributed to the high affinity and close contact (within a 20 Å range) between the substrate and molecules. Density function theory (DFT) calculations confirm the charge transfer from food dye molecules to Au NPs via the polyelectrolytes. This multifunctional SERS platform provides easy separation and selective detection of charged molecules from complex chemical mixtures.

Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus

PubMed Central

Ericson, Megan E.; Subramanian, Chitra; Frank, Matthew W.

2017-01-01

ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. PMID:28765222

Sediment data collected in 2014 and 2015 from around Breton and Gosier Islands, Breton National Wildlife Refuge, Louisiana

USGS Publications Warehouse

Bernier, Julie C.; Kelso, Kyle W.; Tuten, Thomas M.; Stalk, Chelsea A.; Flocks, James G.

2017-03-08

Breton Island, located at the southern end of the Chandeleur Islands, supports one of Louisiana’s largest historical brown pelican (Pelecanus occidentalis) nesting colonies. Although the brown pelican was delisted as an endangered species in 2009, nesting areas are threatened by continued land loss and are extremely vulnerable to storm impacts. The U.S. Fish and Wildlife Service proposed to restore Breton Island to pre-Hurricane Katrina conditions through rebuilding the shoreface, dune, and back-barrier marsh environments. Prior to restoration, scientists from the U.S. Geological Survey’s (USGS) St. Petersburg Coastal and Marine Science Center Geologic and Morphologic Evolution of Coastal Margins project collected high-resolution geophysical (topography, bathymetry, and sub-bottom profiles) and sedimentologic data from around Breton Island to characterize the geologic framework of the island platform, nearshore, and shelf environments. These data will be used to characterize the geologic framework around Breton Island, identify potential borrow areas for restoration efforts, quantify seafloor change, and provide information for sediment transport and morphologic change models to assess island response to restoration and natural processes.This report, along with the accompanying USGS data release, serves as an archive of sediment data from vibracores, push cores, and submerged grab samples collected from around Breton and Gosier Islands, Louisiana, during two surveys conducted in July 2014 and January 2015 (USGS Field Activity Numbers 2014–314–FA and 2014–336–FA, respectively). Sedimentologic and stratigraphic metrics (for example, sediment texture or unit thicknesses) derived from these data can be used to ground-truth the geophysical data and characterize potential sand resources or can be incorporated into sediment transport or morphologic change models. Data products, including sample location tables, descriptive core logs, core photographs and x-radiographs, results of sediment grain-size analyses, and geographic information system data files with accompanying formal Federal Geographic Data Committee metadata can be downloaded from the accompanying data release.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

PubMed Central

Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

2017-01-01

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

An Effective Hybrid Firefly Algorithm with Harmony Search for Global Numerical Optimization

PubMed Central

Guo, Lihong; Wang, Gai-Ge; Wang, Heqi; Wang, Dinan

2013-01-01

A hybrid metaheuristic approach by hybridizing harmony search (HS) and firefly algorithm (FA), namely, HS/FA, is proposed to solve function optimization. In HS/FA, the exploration of HS and the exploitation of FA are fully exerted, so HS/FA has a faster convergence speed than HS and FA. Also, top fireflies scheme is introduced to reduce running time, and HS is utilized to mutate between fireflies when updating fireflies. The HS/FA method is verified by various benchmarks. From the experiments, the implementation of HS/FA is better than the standard FA and other eight optimization methods. PMID:24348137

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.

PubMed

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S; Poptani, Harish

2012-05-21

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

PubMed Central

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H.; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S.; Poptani, Harish

2012-01-01

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. PMID:22513103

The Plasticity of the Superior Longitudinal Fasciculus as a Function of Musical Expertise: A Diffusion Tensor Imaging Study

PubMed Central

Oechslin, Mathias S.; Imfeld, Adrian; Loenneker, Thomas; Meyer, Martin; Jäncke, Lutz

2009-01-01

Previous neuroimaging studies have demonstrated that musical expertise leads to functional alterations in language processing. We utilized diffusion tensor imaging (DTI) to investigate white matter plasticity in musicians with absolute pitch (AP), relative pitch and non-musicians. Using DTI, we analysed the fractional anisotropy (FA) of the superior longitudinal fasciculus (SLF), which is considered the most primary pathway for processing and production of speech and music. In association with different levels of musical expertise, we found that AP is characterized by a greater left than right asymmetry of FA in core fibres of the SLF. A voxel-based analysis revealed three clusters within the left hemisphere SLF that showed significant positive correlations with error rates only for AP-musicians in an AP-test, but not for musicians without AP. We therefore conclude that the SLF architecture in AP musicians is related to AP acuity. In order to reconcile our observations with general aspects of development of fibre bundles, we introduce the Pioneer Axon Thesis, a theoretical approach to formalize axonal arrangements of major white matter pathways. PMID:20161812

Laser Cooling for Heavy-Ion Fusion (HIF)

NASA Astrophysics Data System (ADS)

Ho, D. D.-M.; Brandon, S.; Lee, Y.

1997-05-01

A critical requirement for HIF is the ability to focus space-charge dominated beams onto a millimeter-size spot. However, chromatic aberration can result in a substantial fraction of the beam ions falling outside the spot radius. Because of the space-charge force, correcting the chromatic aberration using sextupoles is impractical. Success in laser cooling of low-current ion beams in storage rings leads us to explore the application of laser cooling to HIF. Basic scheme: After the beams have been accelerated to the desired energy by the recirculating induction linac, we let the beams coast around at constant energy. For efficient interaction between the laser and the beam ions, we use Ba+ beams. We use two lasers to pump the transitions in the Ba+ for generating the laser force FL. There is also an auxiliary force Fa, which is in the opposition direction of FL, provided by the induction cores. The momentum spread along the beam can be compressed by FL and Fa. We will present preliminary PIC simulations using the PIC code CONDOR. Potential difficulties caused by velocity space instabilities will be discussed.

A turn-on fluorescent probe for endogenous formaldehyde in the endoplasmic reticulum of living cells

NASA Astrophysics Data System (ADS)

Tang, Yonghe; Ma, Yanyan; Xu, An; Xu, Gaoping; Lin, Weiying

2017-06-01

As the simplest aldehyde compounds, formaldehyde (FA) is implicated in nervous system diseases and cancer. Endoplasmic reticulum is an organelle that plays important functions in living cells. Accordingly, the development of efficient methods for FA detection in the endoplasmic reticulum (ER) is of great biomedical importance. In this work, we developed the first ER-targeted fluorescent FA probe Na-FA-ER. The detection is based on the condensation reaction of the hydrazine group and FA to suppress the photo-induced electron transfer (PET) pathway, resulting in a fluorescence increase. The novel Na-FA-ER showed high sensitivity to FA. In addition, the Na-FA-ER enabled the bio-imaging of exogenous and endogenous FA in living HeLa cells. Most significantly, the new Na-FA-ER was employed to visualize the endogenous FA in the ER in living cells for the first time.

Epidemiologic and environmental risk factors of rift valley fever in southern Africa from 2008 to 2011

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Rift Valley fever outbreaks have been associated with periods of widespread and above average rainfall over several months which allows for the virus infected mosquito vector populations to emerge and propagate. This has provided basis to develop complex models based on environmental fa...

Mitochondrial Complex I Activity Suppresses Inflammation and Enhances Bone Resorption by Tipping the Balance of Macrophage-Osteoclast Polarization

PubMed Central

Jin, Zixue; Wei, Wei; Yang, Marie; Du, Yang; Wan, Yihong

2014-01-01

SUMMARY Mitochondrial complex I (CI) deficiency is associated with multiple neurological and metabolic disorders. However, its effect on innate immunity and bone remodeling is unclear. Using deletion of the essential CI subunit Ndufs4 as a model for mitochondrial dysfunction, we report that mitochondria suppress macrophage activation and inflammation while promoting osteoclast differentiation and bone resorption via both cell-autonomous and systemic regulation. Global Ndufs4 deletion causes systemic inflammation and osteopetrosis. Hematopoietic Ndufs4 deletion causes an intrinsic lineage shift from osteoclast to macrophage. Liver Ndufs4 deletion causes a metabolic shift from fatty acid oxidation to glycolysis, accumulating fatty acids and lactate (FA/LAC) in circulation. FA/LAC further activates Ndufs4−/− macrophages via ROS induction, and diminishes osteoclast lineage commitment in Ndufs4−/− progenitors; both inflammation and osteopetrosis in Ndufs4−/− mice are attenuated by TLR4/2 deletion. Together, these findings reveal mitochondrial CI as a critical rheostat of innate immunity and skeletal homeostasis. PMID:25130399

Natural history and management of Fanconi anemia patients with head and neck cancer: A 10-year follow-up.

PubMed

Kutler, David I; Patel, Krupa R; Auerbach, Arleen D; Kennedy, Jennifer; Lach, Francis P; Sanborn, Erica; Cohen, Marc A; Kuhel, William I; Smogorzewska, Agata

2016-04-01

To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma. Cohort study. Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry who developed head and neck squamous cell carcinoma (HNSCC) were analyzed. Thirty-five FA patients were diagnosed with HNSCC at a mean age of 32 years. The most common site of primary cancer was the oral cavity (26 of 35, 74%). Thirty patients underwent surgical resection of the cancer. Sixteen patients received radiation therapy with an average radiation dose of 5,050 cGy. The most common toxicities were high-grade mucositis (9 of 16, 56%), hematologic abnormalities (8 of 16, 50%), and dysphagia (8 of 16, 50%). Three patients received conventional chemotherapy and had significant complications, whereas three patients who received targeted chemotherapy with cetuximab had fewer toxicities. The 5-year overall survival rate was 39%, with a cause-specific survival rate of 47%. Fanconi anemia patients have a high risk of developing aggressive HNSCC at an early age. Fanconi anemia patients can tolerate complex ablative and reconstructive surgeries, but careful postoperative care is required to reduce morbidity. The treatment of FA-associated HNSCC is difficult secondary to the poor tolerance of radiation and chemotherapy. However, radiation should be used for high-risk cancers due to the poor survival in these patients. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Common Variable Immunodeficiency Caused by FANC Mutations.

PubMed

Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Conjugating folate on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles using click chemistry

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

Shen, Xiaofang, E-mail: xfshen@jiangnan.edu.cn; Ge, Zhaoqiang; Pang, Yuehong

2015-02-15

Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe{sub 3}O{sub 4}@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenousmore » leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe{sub 3}O{sub 4}@Au–FA nanoparticles. - Graphical abstract: Self-assembled azide-terminated group on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles followed by click reaction with alkyne-functionalized folate, allowing the nanoparticles target folate receptor of cancer cells. - Highlights: • Azidoundecanethiol was coated on the superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles by forming self-assembled monolayers. • Alkyne-terminated folate was synthesized from a reaction between the amine and the carboxylic acid. • Conjugation of Fe{sub 3}O{sub 4}@Au nanoparticles with folate was made by copper-catalyzed azide-alkyne cycloaddition click chemistry.« less

High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution.

PubMed

Howard, E I; Guillot, B; Blakeley, M P; Haertlein, M; Moulin, M; Mitschler, A; Cousido-Siah, A; Fadel, F; Valsecchi, W M; Tomizaki, Takashi; Petrova, T; Claudot, J; Podjarny, A

2016-03-01

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H⋯H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

NASA Astrophysics Data System (ADS)

Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

2016-06-01

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation. Electronic supplementary information (ESI) available: (1) Molecular structure of Jeffamine-modified FA; (2) immunohistochemical analysis of FR expression in the colorectal tissue derived from mice treated with NaCl at different weeks; (3) biodistributions of probes of NP-FA and NP-IgG in the main organs of mice. See DOI: 10.1039/c5nr07858j

Multi-Enzyme Complexes in the Thermophilic Archaea: The Effects of Temperature on Stability, Catalysis and Enzyme Interactions in a Multi-Component System

DTIC Science & Technology

2012-01-01

COVERED (From - To) 4. TITLE AND SUBTITLE Multi- enzyme complexes in the thermophilic archaea: The effects of temperature on stability, catalysis and... enzyme interactions in a multi- component system 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-07-1-0058 5c. PROGRAM ELEMENT NUMBER 61102F 6...involves cloning of the genes for the relevant lipoylation enzymes , and characterisation of the protein products 15. SUBJECT TERMS 16. SECURITY

Ferulic acid-4-O-sulfate rather than ferulic acid relaxes arteries and lowers blood pressure in mice.

PubMed

Van Rymenant, Evelien; Van Camp, John; Pauwels, Bart; Boydens, Charlotte; Vanden Daele, Laura; Beerens, Katrijn; Brouckaert, Peter; Smagghe, Guy; Kerimi, Asimina; Williamson, Gary; Grootaert, Charlotte; Van de Voorde, Johan

2017-06-01

Consumption of foods rich in ferulic acid (FA) such as wholegrain cereals, or FA precursors such as chlorogenic acids in coffee, is inversely correlated with risk of cardiovascular disease and type 2 diabetes. As a result of digestion and phase II metabolism in the gut and liver, FA is converted predominantly into ferulic acid-4-O-sulfate (FA-sul), an abundant plasma metabolite. Although FA-sul is the main metabolite, very little has been reported regarding its bioactivities. We have compared the ex vivo vasorelaxing effect of FA and FA-sul (10 -7 -3.10 -5 M) on isolated mouse arteries mounted in tissue myographs. FA-sul, but not FA, elicited a concentration-dependent vasorelaxation of saphenous and femoral arteries and aortae. The FA-sul-mediated vasorelaxation was blunted by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylate cyclase (sGC) inhibitor. The role of sGC was confirmed in femoral arteries isolated from sGCα 1 (-/-) knockout mice. Furthermore, 4-aminopyridine, a specific inhibitor of voltage-dependent potassium channels, significantly decreased FA-sul-mediated effects. In anesthetized mice, intravenous injection of FA-sul decreased mean arterial pressure, whereas FA had no effect, confirming the results obtained ex vivo. FA-sul is probably one of the major metabolites accounting for the blood pressure-lowering effects associated with FA consumption. Copyright © 2017 Elsevier Inc. All rights reserved.

Ferulic Acid Administered at Various Time Points Protects against Cerebral Infarction by Activating p38 MAPK/p90RSK/CREB/Bcl-2 Anti-Apoptotic Signaling in the Subacute Phase of Cerebral Ischemia-Reperfusion Injury in Rats.

PubMed

Cheng, Chin-Yi; Tang, Nou-Ying; Kao, Shung-Te; Hsieh, Ching-Liang

2016-01-01

This study aimed to evaluate the effects of ferulic acid (FA) administered at various time points before or after 30 min of middle cerebral artery occlusion (MCAo) followed by 7 d of reperfusion and to examine the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in the cortical penumbra. FA was intravenously administered to rats at a dose of 100 mg/kg 24 h before ischemia (B-FA), 2 h before ischemia (P-FA), immediately after ischemic insult (I-FA), 2 h after reperfusion (R-FA), or 24 h after reperfusion (D-FA). Our study results indicated that P-FA, I-FA, and R-FA effectively reduced cerebral infarct areas and neurological deficits. P-FA, I-FA, and R-FA significantly downregulated glial fibrillary acidic protein (GFAP), mitochondrial Bax, cytochrome c, and cleaved caspase-3 expression, and effectively restored the phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK ratio, phospho-90 kDa ribosomal S6 kinase (p-p90RSK) expression, phospho-Bad (p-Bad) expression, the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio, the cytosolic and mitochondrial Bcl-2/Bax ratios, and the cytosolic Bcl-xL/Bax ratio in the cortical penumbra 7 d after reperfusion. SB203580, a specific inhibitor of p38 MAPK, administered 30 min prior to ischemia abrogated the downregulating effects of I-FA on cerebral infarction, and mitochondrial Bax and cleaved caspase-3 expression, and the upregulating effects of I-FA on the p-p38 MAPK/p38 MAPK ratio, p-p90RSK expression, p-Bad expression, and the p-CREB/CREB, and cytosolic and mitochondrial Bcl-2/Bax ratios. Our study results thus indicate that P-FA, I-FA, and R-FA effectively suppress reactive astrocytosis and exert neuroprotective effects against cerebral infarction by activating p38 MAPK signaling. The regulating effects of P-FA, I-FA, and R-FA on Bax-induced apoptosis result from activation of the p38 MAPK/p90RSK/CREB/Bcl-2 signaling pathway, and eventually contribute to inhibition of the cytochrome c-mediated caspase-3-dependent apoptotic pathway in the cortical penumbra 7 d after reperfusion.

Ferulic Acid Administered at Various Time Points Protects against Cerebral Infarction by Activating p38 MAPK/p90RSK/CREB/Bcl-2 Anti-Apoptotic Signaling in the Subacute Phase of Cerebral Ischemia-Reperfusion Injury in Rats

PubMed Central

Cheng, Chin-Yi; Tang, Nou-Ying; Kao, Shung-Te; Hsieh, Ching-Liang

2016-01-01

Objectives This study aimed to evaluate the effects of ferulic acid (FA) administered at various time points before or after 30 min of middle cerebral artery occlusion (MCAo) followed by 7 d of reperfusion and to examine the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in the cortical penumbra. Methods FA was intravenously administered to rats at a dose of 100 mg/kg 24 h before ischemia (B-FA), 2 h before ischemia (P-FA), immediately after ischemic insult (I-FA), 2 h after reperfusion (R-FA), or 24 h after reperfusion (D-FA). Results Our study results indicated that P-FA, I-FA, and R-FA effectively reduced cerebral infarct areas and neurological deficits. P-FA, I-FA, and R-FA significantly downregulated glial fibrillary acidic protein (GFAP), mitochondrial Bax, cytochrome c, and cleaved caspase-3 expression, and effectively restored the phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK ratio, phospho-90 kDa ribosomal S6 kinase (p-p90RSK) expression, phospho-Bad (p-Bad) expression, the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio, the cytosolic and mitochondrial Bcl-2/Bax ratios, and the cytosolic Bcl-xL/Bax ratio in the cortical penumbra 7 d after reperfusion. SB203580, a specific inhibitor of p38 MAPK, administered 30 min prior to ischemia abrogated the downregulating effects of I-FA on cerebral infarction, and mitochondrial Bax and cleaved caspase-3 expression, and the upregulating effects of I-FA on the p-p38 MAPK/p38 MAPK ratio, p-p90RSK expression, p-Bad expression, and the p-CREB/CREB, and cytosolic and mitochondrial Bcl-2/Bax ratios. Conclusions Our study results thus indicate that P-FA, I-FA, and R-FA effectively suppress reactive astrocytosis and exert neuroprotective effects against cerebral infarction by activating p38 MAPK signaling. The regulating effects of P-FA, I-FA, and R-FA on Bax-induced apoptosis result from activation of the p38 MAPK/p90RSK/CREB/Bcl-2 signaling pathway, and eventually contribute to inhibition of the cytochrome c-mediated caspase-3-dependent apoptotic pathway in the cortical penumbra 7 d after reperfusion. PMID:27187745

KSC-08pd3556

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – The U.S. Navy's Blue Angels F/A-18 jets fly in formation over the runway at NASA's Kennedy Space Center in Florida before landing. They are at Kennedy to perform in the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3558

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – The U.S. Navy's Blue Angels F/A-18 jet No. 1 lands on the runway at NASA's Kennedy Space Center in Florida. The Blue Angels are at Kennedy to perform in the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3559

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – Two F/A-18 jets fly over the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida. They will join the U.S. Navy's Blue Angels and other aircraft for demonstrations at the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3562

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – Three of the U.S. Navy's Blue Angels F/A-18 jets fly over the runway at NASA's Kennedy Space Center in Florida. The Blue Angels are at Kennedy to perform in the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3560

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – An F/A-18 jet lands at NASA's Kennedy Space Center in Florida. It will join the U.S. Navy's Blue Angels and other aircraft for demonstrations at the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

Rac1 Recruitment to the Archipelago Structure of the Focal Adhesion through the Fluid Membrane as Revealed by Single-Molecule Analysis

PubMed Central

Shibata, Akihiro C E; Chen, Limin H; Nagai, Rie; Ishidate, Fumiyoshi; Chadda, Rahul; Miwa, Yoshihiro; Naruse, Keiji; Shirai, Yuki M; Fujiwara, Takahiro K; Kusumi, Akihiro

2013-01-01

The focal adhesion (FA) is an integrin-based structure built in/on the plasma membrane (PM), linking the extracellular matrix to the actin stress-fibers, working as cell migration scaffolds. Previously, we proposed the archipelago architecture of the FA, in which FA largely consists of fluid membrane, dotted with small islands accumulating FA proteins: membrane molecules enter the inter-island channels in the FA zone rather freely, and the integrins in the FA-protein islands rapidly exchanges with those in the bulk membrane. Here, we examined how Rac1, a small G-protein regulating FA formation, and its activators αPIX and βPIX, are recruited to the FA zones. PIX molecules are recruited from the cytoplasm to the FA zones directly. In contrast, majorities of Rac1 molecules first arrive from the cytoplasm on the general inner PM surface, and then enter the FA zones via lateral diffusion on the PM, which is possible due to rapid Rac1 diffusion even within the FA zones, slowed only by a factor of two to four compared with that outside. The constitutively-active Rac1 mutant exhibited temporary and all-time immobilizations in the FA zone, suggesting that upon PIX-induced Rac1 activation at the FA-protein islands, Rac1 tends to be immobilized at the FA-protein islands. © 2013 Wiley Periodicals, Inc PMID:23341328

Strength characteristics of light weight concrete blocks using mineral admixtures

NASA Astrophysics Data System (ADS)

Bhuvaneshwari, P.; Priyadharshini, U.; Gurucharan, S.; Mithunram, B.

2017-07-01

This paper presents an experimental study to investigate the characteristics of light weight concrete blocks. Cement was partially replaced with mineral admixtures like Fly ash (FA), limestone powder waste (LPW), Rice husk ash (RHA), sugarcane fiber waste (SCW) and Chrysopogonzizanioides (CZ). The maximum replacement level achieved was 25% by weight of cement and sand. Total of 56 cubes (150 mm x 150 mm x150 mm) and 18 cylinders (100mmφ and 50mm depth) were cast. The specimens being (FA, RHA, SCW, LPW, CZ, (FA-RHA), (FA-LPW), (FA-CZ), (LPW-CZ), (FA-SCW), (RHA-SCW)).Among the different combination, FA,FA-SCW,CZ,FA-CZ showed enhanced strength and durability, apart from achieving less density.

Ringwoodite rim around olivine core in shock-induced melt veins of Antarctic chondrite : Mechanisms of transformation and Fe-Mg diffusion

NASA Astrophysics Data System (ADS)

Xie, Z.; Li, X.; Sharp, T. G.; de Carli, P. S.

2009-12-01

Introduction: High-pressure minerals, produced by shock metamorphism, are common in and around melt veins in highly shocked chondrites. The shock duration can be constrained by using transformation kinetics, such as the crystallization rate of the melt-vein matrix[1-2], or growth rate of the high-pressure minerals [3-4], or using elements diffusion rate between two minerals [5]. Using transformation kinetics to constrain shock duration de-pend on the details of the transformation mechanism. For example, growth of topotaxial ringwoodite in olivine with coherent interfaces is slower than growth of inclusions with incoherent interfaces [4-5]. Similarly, diffusion-controlled growth, where rates are determined by long-range diffusion, is generally much slower than interface-controlled growth, which is only dependent on diffusion across the interface [6-8]. The occurrences of the high-pressure mineral rims were recently reported in shock-induced melt veins in several heavily shocked (S6) chondrites, ALH78003, Peace River and GRV052049 [9-11]. Here we report EMAP and Raman results of the ringwoodite rims around olivine cores in shock veins of the Antarctic chondrites GRV 022321, and to elucidate the mechanisms of transformation and Mg-Fe diffusion of the olivine to ringwoodite. Results: GRV022321 has a network of black veins which enclose abundant host-rock fragments. The enclosed fragments have sizes ranging from 5 µm to 30 µm, with a brighter rim up to several µm wide and a dark core in reflected light and BSE image. The Raman data reveal that the rim mineral is ringwoodite signature, and the core minerals are dominated by olivine and mixed minor ringwoodite. EMAP data confirm that the ringwoodite in rim is richer in faylite (Fa) than the olivine core. The Fa values range from 50 to 10 with the outer rim having highest Fa value, and the inside darker area with a lower value. Discussion: The occurrence of the rounded shape grains with smooth edges embedded in the fine matrix in shock-induced melt veins suggest that they are enclosed host-rock fragments and that the ringwoodite in the rim was transformed by solid-state transformation from previous olivine. The variable extent of transformation is likely a result of temperature variations during shock, with the hottest outer olivine forming the ringwoodite rim. The outer hotter ringwoodite attract more Fe than inside cooler olivine, and Mg-Fe diffusion occurs in rapid transformation at high pressure and temperature over up to 10 µm distance. The sample is unique because we can test and double check different shock duration constraints in future work. References: [1] Langenhorst and Poirier (2000) EPSL 184, 37-55. [2] Xie, Z. et al. (2006) GCA, 70. 504-515. [3] Ohtani et al. (2004) EPSL 227(3-4), 505-515. [4] Xie and Sharp (2007), EPLS, 433-445. [5] Beck, et al. (2005) Nature 435, 1071-1074. [6] Kerschhofer et al. (1996) Science 274 (5284), 79-81. [7] Kerschhofer et al. (2000) PEPI 121, 59-76. [8] Sharp and DeCarli (2006) MESS II, 653-677. [9] Ohtani et al. (2006), Shock Waves, 16:45-52. [10] Miyahara et al. (2008) Proceedings. of NAS 105,8542-8547. [11] Feng et al. (2007), MAPS 42, A45.

Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus.

PubMed

Ericson, Megan E; Subramanian, Chitra; Frank, Matthew W; Rock, Charles O

2017-08-01

The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus , but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. IMPORTANCE The SaeRS two-component system is a master transcriptional activator of virulence factor production in response to the host environment in S. aureus , and strains lacking FA kinase have severely attenuated SaeRS-dependent virulence factor transcription. FA kinase is required for the activation of exogenous FAs, and it plays a role in cellular lipid homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway. Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain, and the FAs which accumulate in FA kinase knockout strains are potent inhibitors of SaeS-dependent signaling. This work identifies FAs as physiological effectors for the SaeRS system and reveals a connection between cellular lipid homeostasis and the regulation of virulence factor transcription. FA kinase is widely distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in these organisms. Copyright © 2017 Ericson et al.

Genetic analysis of predicted fatty acid profiles of milk from Danish Holstein and Danish Jersey cattle populations.

PubMed

Hein, L; Sørensen, L P; Kargo, M; Buitenhuis, A J

2018-03-01

The objective of this study was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

DTIC Science & Technology

2012-04-01

Appendix 1. Expansion of monoclonal populations of FA-A hTERT and FA-A + FANCA hTERT cells Appendix 2. Expansion of monoclonal populations of FA...marrow failure (BMF) and pronounced cancer susceptibility. The FA proteins and the major breast cancer susceptibility gene products BRCA1 and BRCA2...Correction of FA-A, FA-C, and FA-D2 hTERT cells with pLenti6.2/V5- FANCA , -FANCC, and FANCD2, respectively. Sub-task 1. Selection and expansion of clonal

De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

DTIC Science & Technology

2013-04-01

We have confirmed re-expression of FANCA , FANCD2, and FANCG in the FA-A + FANCA , FA-D2 + FANCD2, and FA-G + FANCG cells, respectively. We have also...confirmed restoration of FANCD2 and FANCI monoubiquitination and functional complementation of the FA-A + FANCA and FA-D2 + FANCD2 cells. In... gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have demonstrated that the FA-BRCA

Identification and quantification of fumonisin A1, A2, and A3 in corn by high-resolution liquid chromatography-orbitrap mass spectrometry.

PubMed

Tamura, Masayoshi; Mochizuki, Naoki; Nagatomi, Yasushi; Harayama, Koichi; Toriba, Akira; Hayakawa, Kazuichi

2015-02-16

Three compounds, hypothesized as fumonisin A1 (FA1), fumonisin A2 (FA2), and fumonisin A3 (FA3), were detected in a corn sample contaminated with mycotoxins by high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS). One of them has been identified as FA1 synthesized by the acetylation of fumonisin B1 (FB1), and established a method for its quantification. Herein, we identified the two remaining compounds as FA2 and FA3, which were acetylated fumonisin B2 (FB2) and fumonisin B3 (FB3), respectively. Moreover, we examined a method for the simultaneous analysis of FA1, FA2, FA3, FB1, FB2, and FB3. The corn samples were prepared by extraction using a QuEChERS kit and purification using a multifunctional cartridge. The linearity, recovery, repeatability, limit of detection, and limit of quantification of the method were >0.99, 82.9%-104.6%, 3.7%-9.5%, 0.02-0.60 μg/kg, and 0.05-1.98 μg/kg, respectively. The simultaneous analysis of the six fumonisins revealed that FA1, FA2, and FA3 were present in all corn samples contaminated with FB1, FB2, and FB3. The results suggested that corn marketed for consumption can be considered as being contaminated with both the fumonisin B-series and with fumonisin A-series. This report presents the first identification and quantification of FA1, FA2, and FA3 in corn samples.

Paclitaxel loaded magnetic nanocomposites with folate modified chitosan/carboxymethyl surface; a vehicle for imaging and targeted drug delivery.

PubMed

Bano, Shazia; Afzal, Muhammad; Waraich, Mustansar Mahmood; Alamgir, Khalid; Nazir, Samina

2016-11-20

In this study, Paclitaxel (PTX) containing, bovine serum albumin (BSA) nanoparticles were fabricated via a simple approach. Folic acid (FA) was conjugated to chitosan (CS)/carboxymethyl cellulose (CMC) through an esterification reaction to produce BSA-CS-FA or BSA-CMC-FA conjugates. NiFe 2 O 4 noncore (NFs) and PTX were loaded through a heat treatment and by a diffusion process. NFs-BSA-CS and NFs-BSA-CMC-FA with size of about 80nm, showed superior transversal R 2 relaxation rate of 349 (mM) -1 s -1 along with folate receptor-targeted and magnetically directed functions. NFs-BSA-CS-FA or NFs-BSA-CS-FA were found stable and biocompatible. Application of an external magnetic field effectively enhanced the PTX release from PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA and hence tumor inhibition rate. This study validate that NFs-BSA-CS-FA or NFs-BSA-CMC-FA and PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA are suitable systems for tumor diagnosis and therapy. Copyright © 2016. Published by Elsevier B.V.

Screening of the state of urban ecosystem with the use of bioindication method (on the example of Kazan city)

NASA Astrophysics Data System (ADS)

Minakova, E. A.; Shlychkov, A. P.; Arinina, A. V.

2018-01-01

The urban environment is a complex of natural, natural-anthropogenic and socioeconomic factors that exert a large and diverse impact on urban residents. In addition to traditional environmental monitoring, we propose to use a new bioindication method based on the evaluation of morphological changes in the leaves of Betula pendula Roth by fluctuating asymmetry (FA) to assess the quality of recreational areas. Such screening for the purpose of assessing of the environment state is very informative, since the bioindication assessment is an integral characteristic of the quality of the environment which is under the influence of all the abundance of chemical, physical and other factors. The two-sided symmetry of a leaf was calculated on the sites in the middle of the park zone, on the border of the park and on a roadside strip. The results of the study showed a connection between the FA values and the distance to the highway, and also revealed the absence of significant differences in FA indicators at the surveyed sites, which may indicate insufficient sizes of recreational areas and their insufficient potential to contribute to improving the quality of the environment.

Flectofold—a biomimetic compliant shading device for complex free form facades

NASA Astrophysics Data System (ADS)

Körner, A.; Born, L.; Mader, A.; Sachse, R.; Saffarian, S.; Westermeier, A. S.; Poppinga, S.; Bischoff, M.; Gresser, G. T.; Milwich, M.; Speck, T.; Knippers, J.

2018-01-01

Smart and adaptive outer façade shading systems are of high interest in modern architecture. For long lasting and reliable systems, the abandonment of hinges which often fail due to mechanical wear during repetitive use is of particular importance. Drawing inspiration from the hinge-less motion of the underwater snap-trap of the carnivorous waterwheel plant (Aldrovanda vesiculosa), the compliant façade shading device Flectofold was developed. Based on computational simulations of the biological role-model’s elastic and reversible motion, the actuation principle of the plant can be identified. The enclosed geometric motion principle is abstracted into a simplified curved-line folding geometry with distinct flexible hinge-zones. The kinematic behaviour is translated into a quantitative kinetic model, using finite element simulation which allows the detailed analyses of the influence of geometric parameters such as curved-fold line radius and various pneumatically driven actuation principles on the motion behaviour, stress concentrations within the hinge-zones, and actuation forces. The information regarding geometric relations and material gradients gained from those computational models are then used to develop novel material combinations for glass fibre reinforced plastics which enabled the fabrication of physical prototypes of the compliant façade shading device Flectofold.

Effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 on hepatic steatosis in Zucker rats.

PubMed

Plaza-Diaz, Julio; Gomez-Llorente, Carolina; Abadia-Molina, Francisco; Saez-Lara, Maria Jose; Campaña-Martin, Laura; Muñoz-Quezada, Sergio; Romero, Fernando; Gil, Angel; Fontana, Luis

2014-01-01

We have previously described the safety and immunomodulatory effects of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 in healthy volunteers. The scope of this work was to evaluate the effects of these probiotic strains on the hepatic steatosis of obese rats. We used the Zucker rat as a genetic model of obesity. Zucker-Lepr(fa/fa) rats received one of three probiotic strains, a mixture of L. paracasei CNCM I-4034 and B. breve CNCM I-4035, or a placebo for 30 days. An additional group of Zucker-lean+/fa rats received a placebo for 30 days. No alterations in intestinal histology, in the epithelial, lamina propria, muscular layers of the ileal or colonic mucosa, or the submucosae, were observed in any of the experimental groups. Triacylglycerol content decreased in the liver of Zucker-Lepr(fa/fa) rats that were fed L. rhamnosus, B. breve, or the mixture of B. breve and L. paracasei. Likewise, the area corresponding to neutral lipids was significantly smaller in the liver of all four groups of Zucker-Lepr(fa/fa) rats that received probiotics than in rats fed the placebo. Zucker-Lepr(fa/fa) rats exhibited significantly greater serum LPS levels than Zucker-lean+/fa rats upon administration of placebo for 30 days. In contrast, all four groups of obese Zucker-Lepr(fa/fa) rats that received LAB strains exhibited serum LPS concentrations similar to those of Zucker-lean+/fa rats. Serum TNF-α levels decreased in the Zucker-Lepr(fa/fa) rats that received B. breve, L. rhamnosus, or the mixture, whereas L. paracasei feeding decreased IL-6 levels in the serum of Zucker-Lepr(fa/fa) rats. In conclusion, the probiotic strains reduced hepatic steatosis in part by lowering serum LPS, and had an anti-inflammatory effect in obese Zucker rats.

Characterizing core-periphery structure of complex network by h-core and fingerprint curve

NASA Astrophysics Data System (ADS)

Li, Simon S.; Ye, Adam Y.; Qi, Eric P.; Stanley, H. Eugene; Ye, Fred Y.

2018-02-01

It is proposed that the core-periphery structure of complex networks can be simulated by h-cores and fingerprint curves. While the features of core structure are characterized by h-core, the features of periphery structure are visualized by rose or spiral curve as the fingerprint curve linking to entire-network parameters. It is suggested that a complex network can be approached by h-core and rose curves as the first-order Fourier-approach, where the core-periphery structure is characterized by five parameters: network h-index, network radius, degree power, network density and average clustering coefficient. The simulation looks Fourier-like analysis.

Influence of chitosan structure on the formation and stability of DNA-chitosan polyelectrolyte complexes.

PubMed

Strand, Sabina P; Danielsen, Signe; Christensen, Bjørn E; Vårum, Kjell M

2005-01-01

The interactions between DNA and chitosans varying in fractional content of acetylated units (FA), degree of polymerization (DP), and degree of ionization were investigated by several techniques, including an ethidium bromide (EtBr) fluorescence assay, gel retardation, atomic force microscopy, and dynamic and electrophoretic light scattering. The charge density of the chitosan and the number of charges per chain were found to be the dominating factors for the structure and stability of DNA-chitosan complexes. All high molecular weight chitosans condensed DNA into physically stable polyplexes; however, the properties of the complexes were strongly dependent on FA, and thereby the charge density of chitosan. By employing fully charged oligomers of constant charge density, it was shown that the complexation of DNA and stability of the polyplexes is governed by the number of cationic residues per chain. A minimum of 6-9 positive charges appeared necessary to provide interaction strength comparable to that of polycations. In contrast, further increase in the number of charges above 9 did not increase the apparent binding affinity as judged from the EtBr displacement assay. The chitosan oligomers exhibited a pH-dependent interaction with DNA, reflecting the number of ionized amino groups. The complexation of DNA and the stability of oligomer-based polyplexes became reduced above pH 7.4. Such pH-dependent dissociation of polyplexes around the physiological pH is highly relevant in gene delivery applications and might be one of the reasons for the high transfection activity of oligomer-based polyplexes observed.

Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation

PubMed Central

Zhang, Yi; Ng, Huck-Hui; Erdjument-Bromage, Hediye; Tempst, Paul; Bird, Adrian; Reinberg, Danny

1999-01-01

ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation. PMID:10444591

Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity

PubMed Central

Pepino, Marta Yanina; Stein, Richard I.; Eagon, J. Christopher; Klein, Samuel

2014-01-01

Objective To test the hypotheses that bariatric surgery-induced weight loss: 1) induces remission of food addiction (FA), and 2) normalizes other eating behaviors associated with FA. Design and Methods Forty-four obese subjects (BMI= 48±8 kg/m2) were studied before and after ~20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and 8 sleeve gastrectomy). We assessed: 1) FA (Yale Food Addiction Scale), 2) food cravings (Food Craving Inventory) and 3) restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire). Results FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values <0.01; all Cohen’s d >0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values <0.001; all Cohen’s d≥0.8). Restrictive eating behavior did not change in non-FA subjects but increased in FA subjects (P<0.01; Cohen’s d>1.1). Conclusion Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA. PMID:24852693

Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity.

PubMed

Pepino, Marta Yanina; Stein, Richard I; Eagon, J Christopher; Klein, Samuel

2014-08-01

To test the hypotheses that bariatric surgery-induced weight loss: induces remission of food addiction (FA), and normalizes other eating behaviors associated with FA. Forty-four obese subjects (BMI= 48 ± 8 kg/m(2) ) were studied before and after ∼20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and eight sleeve gastrectomy). We assessed: FA (Yale Food Addiction Scale), food cravings (Food Craving Inventory), and restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire). FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values <0.01; all Cohen's d >0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values < 0.001; all Cohen's d ≥ 0.8). Restrictive eating behavior did not change in non-FA subjects but increased in FA subjects (P < 0.01; Cohen's d>1.1). Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA. Copyright © 2014 The Obesity Society.

Interfacial reactions between humic-like substances and lateritic clay: application to the preparation of "geomimetic" materials.

PubMed

Goure-Doubi, Herve; Martias, Céline; Lecomte-Nana, Gisèle Laure; Nait-Ali, Benoît; Smith, Agnès; Thune, Elsa; Villandier, Nicolas; Gloaguen, Vincent; Soubrand, Marilyne; Konan, Léon koffi

2014-11-15

The aim of this study was to understand the mechanisms responsible for the strengthening of "geomimetic" materials, especially the chemical bonding between clay and humic substances. The mineral matter is lateritic clay which mainly consists in kaolinite, goethite, hematite and quartz. The other starting products are fulvic acid (FA) and lime. The preparation of these geomimetic materials is inspired from the natural stabilization of soils by humic substances occurring over thousands of years. The present process involves acidic and alkaline reactions followed by a curing period of 18days at 60°C under a water saturated atmosphere. The acceleration of the strengthening process usually observed in soils makes this an original process for treatment of soils. The consolidation of the "geomimetic" materials could result from two major phenomena: (i) chemical bonding at the interface between the clay particles and iron compounds and the functional groups of the fulvic acid, (ii) a partial dissolution of the clay grains followed by the precipitation of the cementitious phases, namely calcium silicate hydrates, calcium aluminate hydrates and mixed calcium silicum and aluminum hydrates. Indeed, the decrease of the BET specific area of the lateritic clay after 24 h of reaction with FA added to the structural reorganization observed between 900 and 1000°C in the "geomimetic" material, and to the results of adsorption measurements, confirm the formation of organo-ferric complexes. The presence of iron oxides in clay, in the form of goethite, appears to be another parameter in favor of a ligand exchange process and the creation of binding bridges between FA and the mineral matter. Indeed all faces of goethite are likely to be involved in complexation reactions whereas in lateritic clay only lateral faces could be involved. The results of the adsorption experiments realized at a local scale will improve our understandings about the process of adsorption of FA on lateritic clays and its involvement in the strengthening process of materials. Copyright © 2014 Elsevier Inc. All rights reserved.

Detailed fatty acid profile of milk, cheese, ricotta and by products, from cows grazing summer highland pastures.

PubMed

Bergamaschi, Matteo; Bittante, Giovanni

2017-08-01

In this research two-dimensional GC was used to analyse, for the first time, the detailed fatty acid (FA) profiles of 11 dairy matrices: raw milk (evening whole, evening partially skimmed, morning whole, and vat milk), cream, fresh cheese, whey, ricotta, scotta, 6- and 12-month-ripened cheeses, obtained across artisanal cheese- and ricotta-making trials carried out during the summer period while cows were on highland pastures. Samples were collected during 7 cheese- and ricotta-making procedures carried out at 2-week intervals from bulk milk to study possible differences in the transfer and modification of FA. Compared with morning milk, evening milk had fewer de novo synthetised FA. The detailed FA profile of partially skimmed milk differed little from that of evening whole milk before skimming, but the cream obtained differed from partially skimmed milk and from fresh cheese in about half the FA, due mainly to higher contents of all de novo FA, and lower contents of n-3 and n-6 FA. Fresh cheese and whey had similar FA profiles. The ricotta manufacturing process affected the partition of FA between ricotta and scotta, the FA profile of the latter differing in terms of groups and individual FA from the former, whereas ricotta and fresh cheese had similar composition of FA. In general, there was an increase in medium-chain saturated FA, and a decrease in many polyunsaturated FA during the first 6 months of ripening, but not during the second 6 months. Two-dimensional GC yielded a very detailed and informative FA profile on all the 11 dairy products and by-products analysed.

Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells

PubMed Central

Chen, Danqi; Fang, Lei; Mei, Shenglin; Li, Hongjie; Xu, Xia; Des Marais, Thomas L.; Lu, Kun; Liu, X. Shirley

2017-01-01

Background: Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies have shown that exogenous FA causes only a modest increase in DNA adduct formation compared with the amount of adducts formed by endogenous FA, raising the possibility that epigenetic mechanisms may contribute to FA-mediated carcinogenicity. Objectives: We investigated the effects of FA exposure on histone modifications and chromatin assembly. We also examined the role of defective chromatin assembly in FA-mediated transcription and cell transformation. Methods: Cellular fractionation and Western blot analysis were used to measure the levels of histone modifications in human bronchial epithelial BEAS-2B cells and human nasal RPMI2650 cells in the presence of FA. Chromatin immunoprecipitation (ChIP) and micrococcal nuclease (MNase) digest assays were performed to examine the changes in chromatin assembly and accessibility after FA exposure. RNA sequencing (RNA-seq) and real-time polymerase chain reaction (PCR) were used to examine transcriptional dysregulation. Finally, anchorage-independent cell growth ability was tested by soft agar assay following FA exposure. Results: Exposure to FA dramatically decreased the acetylation of the N-terminal tails of cytosolic histones. These modifications are important for histone nuclear import and subsequent chromatin assembly. Histone proteins were depleted in both the chromatin fraction and at most of the genomic loci tested following FA exposure, suggesting that FA compromises chromatin assembly. Moreover, FA increased chromatin accessibility and altered the expression of hundreds of cancer-related genes. Knockdown of the histone H3.3 gene (an H3 variant), which mimics inhibition of chromatin assembly, facilitated FA-mediated anchorage-independent cell growth. Conclusions: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by the environmental and occupational chemical carcinogen FA. https://doi.org/10.1289/EHP1275 PMID:28937961

Identification and Quantification of Fumonisin A1, A2, and A3 in Corn by High-Resolution Liquid Chromatography-Orbitrap Mass Spectrometry

PubMed Central

Tamura, Masayoshi; Mochizuki, Naoki; Nagatomi, Yasushi; Harayama, Koichi; Toriba, Akira; Hayakawa, Kazuichi

2015-01-01

Three compounds, hypothesized as fumonisin A1 (FA1), fumonisin A2 (FA2), and fumonisin A3 (FA3), were detected in a corn sample contaminated with mycotoxins by high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS). One of them has been identified as FA1 synthesized by the acetylation of fumonisin B1 (FB1), and established a method for its quantification. Herein, we identified the two remaining compounds as FA2 and FA3, which were acetylated fumonisin B2 (FB2) and fumonisin B3 (FB3), respectively. Moreover, we examined a method for the simultaneous analysis of FA1, FA2, FA3, FB1, FB2, and FB3. The corn samples were prepared by extraction using a QuEChERS kit and purification using a multifunctional cartridge. The linearity, recovery, repeatability, limit of detection, and limit of quantification of the method were >0.99, 82.9%–104.6%, 3.7%–9.5%, 0.02–0.60 μg/kg, and 0.05–1.98 μg/kg, respectively. The simultaneous analysis of the six fumonisins revealed that FA1, FA2, and FA3 were present in all corn samples contaminated with FB1, FB2, and FB3. The results suggested that corn marketed for consumption can be considered as being contaminated with both the fumonisin B-series and with fumonisin A-series. This report presents the first identification and quantification of FA1, FA2, and FA3 in corn samples. PMID:25690692

Synthesis and properties of feruloyl corn bran arabinoxylan esters.

PubMed

Li, Y; Yang, C

2016-06-01

To enhance the antioxidant activity and UV absorption coefficient of corn bran arabinoxylan (CAX), ferulic acid (FA) with this physiological activity is used to modify CAX. Corn bran arabinoxylan was extracted from corn bran according to alkaline hydrogen peroxide (AHP) method. FA was covalently linked to CAX by esterification in a two-step feasible synthesis to generate ferulic acid arabinoxylan esters (FA-CAX). The structure and molecular weight of FA-CAX were characterized by NMR and HPSEC, the degrees of substitution (DS) was determined by HPLC, and the ultraviolet (UV) coefficient of FA-CAX was tested by UV spectroscopy. The antioxidant activity of FA-CAX was investigated on the basis of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical assay, and protecting ability of FA-CAX to UV-induced oxidative damage was tested using linolenic acid dispersion as stratum corneum lipid model. The results demonstrated that FA was attached to CAX successfully, and the inherent structure of CAX would not be broken during the process of the synthesis. FA-CAX-1 and FA-CAX-2 contained different amount of FA, with DS at 0.33 and 1.25, respectively, can absorb UV both at UVA and UVB. Moreover, FA-CAX-2 exhibited better antioxidant activity than FA-CAX-1 based on the two test methods. Ferulic acid modified CAX had significant antioxidant ability and UV absorption coefficient. And higher amount of FA leads to higher antioxidant activity and stronger UV absorption and stability. With increasing amount of FA attached to CAX, the antioxidant activities were better and the UV absorption was stronger and more durable. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PubMed

Williams, Annabelle E; Croft, Julie; Napp, Vicky; Corrigan, Neil; Brown, Julia M; Hulme, Claire; Brown, Steven R; Lodge, Jen; Protheroe, David; Jayne, David G

2016-02-01

Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.

Cortical brain connectivity evaluated by graph theory in dementia: a correlation study between functional and structural data.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Curcio, Giuseppe; Altavilla, Riccardo; Scrascia, Federica; Giambattistelli, Federica; Quattrocchi, Carlo Cosimo; Bramanti, Placido; Vernieri, Fabrizio; Rossini, Paolo Maria

2015-01-01

A relatively new approach to brain function in neuroscience is the "functional connectivity", namely the synchrony in time of activity in anatomically-distinct but functionally-collaborating brain regions. On the other hand, diffusion tensor imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based technique with the capability to detect brain structural connection with fractional anisotropy (FA) identification. FA decrease has been observed in the corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI abnormalities are thought to be associated with functional disconnections among cortical areas. This study aimed to investigate possible correlations between structural damage, measured by MRI-DTI, and functional abnormalities of brain integration, measured by characteristic path length detected in resting state EEG source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11 moderate AD). For each subject, undirected and weighted brain network was built to evaluate graph core measures. eLORETA lagged linear connectivity values were used as weight of the edges of the network. Results showed that callosal FA reduction is associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha path length. These findings suggest that "global" (average network shortest path length representing an index of how efficient is the information transfer between two parts of the network) functional measure can reflect the reduction of fiber connecting the two hemispheres as revealed by DTI analysis and also anticipate in time this structural loss.

High payload nanostructured lipid carriers fabricated with alendronate/polyethyleneimine ion complexes.

PubMed

Abd El-Hamid, Basma N; Swarnakar, Nitin K; Soliman, Ghareb M; Attia, Mohamed A; Pauletti, Giovanni M

2018-01-15

Oral bioavailability of the anti-osteoporotic drug alendronate (AL) is limited to ≤ 1% due to unfavorable physicochemical properties. To augment absorption across the gastrointestinal mucosa, an ion pair complex between AL and polyethyleneimine (PEI) was formed and incorporated into nanostructured lipid carriers (NLCs) using a modified solvent injection method. When compared to free AL, ion pairing with PEI increased drug encapsulation efficiency in NLCs from 10% to 87%. Drug release from NLCs measured in vitro using fasted state simulated intestinal fluid, pH 6.5 (FaSSIF-V2) was significantly delayed after PEI complexation. Stability of AL/PEI was pH-dependent resulting in 10-fold faster dissociation of AL in FaSSIF-V2 than measured at pH 7.4. Intestinal permeation properties estimated in vitro across Caco-2 cell monolayers revealed a 3-fold greater flux of AL encapsulated as hydrophobic ion complex in NLCs when compared to AL solution (P app  = 8.43 ± 0.14 × 10 -6 cm/s and vs. 2.76 ± 0.42 × 10 -6 cm/s). Cellular safety of AL/PEI-containing NLCs was demonstrated up to an equivalent AL concentration of 2.5 mM. These results suggest that encapsulation of AL/PEI in NLCs appears a viable drug delivery strategy for augmenting oral bioavailability of this clinically relevant bisphosphonate drug and, simultaneously, increase gastrointestinal safety. Copyright © 2017 Elsevier B.V. All rights reserved.

FACTOR 9.2: A Comprehensive Program for Fitting Exploratory and Semiconfirmatory Factor Analysis and IRT Models

ERIC Educational Resources Information Center

Lorenzo-Seva, Urbano; Ferrando, Pere J.

2013-01-01

FACTOR 9.2 was developed for three reasons. First, exploratory factor analysis (FA) is still an active field of research although most recent developments have not been incorporated into available programs. Second, there is now renewed interest in semiconfirmatory (SC) solutions as suitable approaches to the complex structures are commonly found…

Stress and DNA repair biology of the Fanconi anemia pathway

PubMed Central

Longerich, Simonne; Li, Jian; Xiong, Yong; Sung, Patrick

2014-01-01

Fanconi anemia (FA) represents a paradigm of rare genetic diseases, where the quest for cause and cure has led to seminal discoveries in cancer biology. Although a total of 16 FA genes have been identified thus far, the biochemical function of many of the FA proteins remains to be elucidated. FA is rare, yet the fact that 5 FA genes are in fact familial breast cancer genes and FA gene mutations are found frequently in sporadic cancers suggest wider applicability in hematopoiesis and oncology. Establishing the interaction network involving the FA proteins and their associated partners has revealed an intersection of FA with several DNA repair pathways, including homologous recombination, DNA mismatch repair, nucleotide excision repair, and translesion DNA synthesis. Importantly, recent studies have shown a major involvement of the FA pathway in the tolerance of reactive aldehydes. Moreover, despite improved outcomes in stem cell transplantation in the treatment of FA, many challenges remain in patient care. PMID:25237197

Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics.

PubMed

Huang, Yinping; Mao, Kaili; Zhang, Baolin; Zhao, Yingzheng

2017-01-01

Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co-coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs). Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67nm, respectively, performed excellent colloidal stability in PBS. Confocal laser scanning microscope (CLSM) study implicates that the DOX@FA-SPIONs target MCF-7 cells efficiently through the FA receptor-mediated endocytosis. DOX@FA-SPIONs were tested in nude mice with xenograft MCF-7 breast tumor though tail intravenous injection and were found inhibiting tumor growth more efficiently. The application of a magnetic field (MF) greatly improved the growth inhibiting efficiencies of DOX@FA-SPIONs on MCF-7 cells in vitro and on xenograft MCF-7 breast tumor of nude mice in vivo. The aggregation of SPIONs in tumor was monitored by magnetic resonance imaging (MRI) as the DOX@FA-SPIONs exhibited high r 2 relaxivity (81.77mM -1 S -1 ). Histology on liver, Lung, kidney and heart in mice showed no significant toxicity of DOX@FA-SPIONs on mice organs after 35-day treatment. The FA-SPIONs are a high efficient drug delivery nanoplatform for advanced cancer theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of parent-reported immediate hypersensitivity food allergy in Chilean school-aged children.

PubMed

Hoyos-Bachiloglu, R; Ivanovic-Zuvic, D; Álvarez, J; Linn, K; Thöne, N; de los Ángeles Paul, M; Borzutzky, A

2014-01-01

Food allergies (FAs) affect 2-4% of school-aged children in developed countries and strongly impact their quality of life. The prevalence of FA in Chile remains unknown. Cross-sectional survey study of 488 parents of school-aged children from Santiago who were asked to complete a FA screening questionnaire. Parents who reported symptoms suggestive of FA were contacted to answer a second in-depth questionnaire to determine immediate hypersensitivity FA prevalence and clinical characteristics of school-aged Chilean children. A total of 455 parents answered the screening questionnaire: 13% reported recurrent symptoms to a particular food and 6% reported FA. Forty-three screening questionnaires (9%) were found to be suggestive of FA. Parents of 40 children answered the second questionnaire; 25 were considered by authors to have FA. FA rate was 5.5% (95% CI: 3.6-7.9). Foods reported to frequently cause FA included walnut, peanut, egg, chocolate, avocado, and banana. Children with FA had more asthma (20% vs. 7%, P<0.02) and atopic dermatitis (32% vs. 13%, P<0.01) by report. The parents of children with FA did not report anaphylaxis, but 48% had history compatible with anaphylaxis. Of 13 children who sought medical attention, 70% were diagnosed with FA; none were advised to acquire an epinephrine autoinjector. Up to 5.5% of school-aged Chilean children may suffer from FA, most frequently to walnut and peanut. It is critical to raise awareness in Chile regarding FA and recognition of anaphylaxis, and promote epinephrine autoinjectors in affected children. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Fatty Acid Profile of Sunshine Bass: II. Profile Change Differs Among Fillet Lipid Classes.

PubMed

Trushenski, Jesse T; Lewis, Heidi A; Kohler, Christopher C

2008-07-01

Fatty acid (FA) profile of fish tissue mirrors dietary FA profile and changes in a time-dependent manner following a change in dietary FA composition. To determine whether FA profile change varies among lipid classes, we evaluated the FA composition of fillet cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) of sunshine bass (SB, Morone chrysops x M. saxatilis) raised on feeds containing fish oil or 50:50 blend of fish oil and coconut, grapeseed, linseed, or poultry oil, with or without implementation of a finishing period (100% FO feed) prior to harvest. Each lipid class was associated with a generalized FA signature, irrespective of nutritional history: fillet PL was comprised largely of saturated FA (SFA), long-chain polyunsaturated FA (LC-PUFA), and total n-3 FA; fillet TAG was higher in MC-PUFA and total n-6 FA; and fillet CE was highest in monounsaturated FA (MUFA). Neutral lipids reflected dietary composition in a near-direct fashion; conversely, PL showed evidence of selectivity for MC- and LC-PUFA. Shorter-chain SFA were not strongly reflected within any lipid fraction, even when dietary availability was high, suggesting catabolism of these FA. FA metabolism in SB is apparently characterized by a division between saturated and unsaturated FA, whereby LC-PUFA are preferentially incorporated into tissues and SFA are preferentially oxidized for energy production. We demonstrated provision of SFA in grow-out feeds for SB, instead MC-PUFA which compete for tissue deposition, meets energy demands and allows for maximum inclusion of LC-PUFA within fillet lipids.

The concept and practice of Fanconi Anemia: from the clinical bedside to the laboratory bench

PubMed Central

2013-01-01

Fanconi Anemia (FA) is characterised with multiple gene mutations, multiple types of genetic abnormalities, multiple organ involvements and multiple types of cancer risks. It is a life threatening disease commonly at 5 years old children. Research on FA is one of the fastest areas in medical research field. The identification of 15 different FA genes and the elucidation of the FA molecular pathways have translated into the understanding of the pathogenic mechanism and practically provided the directions for therapies. Studies on FA rendered invaluable information for the studies on cancers because FA possesses the unique features in many different biological aspects. Studies revealed the genetic linking between FA and cancers that FA genes are in cancers and cancers genes are in FA. As a result, FA is named as a paradigmatic disease for the understanding of cancer and aging. In clinical practice, an early and accurate diagnosis of FA before the stage of bone marrow failure, cancer/leukemia is crucial for the adequate treatment, the prevention of serious medical complications and also for the properly management in the other caring areas including paediatric, hematology, immunology, endocrinology, reproductive/IVF, obstetrics and surgery. However, an early and accurate diagnosis for FA is often difficult because FA is genetically and phenotypically heterogeneous disease. Diagnosis in more or less cases can be delayed until bone marrow failure or cancer/leukemia occurs. As a result that delayed or misdiagnosis even wrong treatment received for patients with FA are not uncommon events clinically in some regions or countries due to the lack of recognition of FA from the clinicians and the limitation in testing resource in laboratory. In this review, the new concept, brief clinical characteristics, research advancing, diagnostic guidelines/differential diagnosis, laboratory testing issues and strategies on FA are discussed. PMID:26835301

FaPOD27 functions in the metabolism of polyphenols in strawberry fruit (Fragaria sp.)

PubMed Central

Yeh, Su-Ying; Huang, Fong-Chin; Hoffmann, Thomas; Mayershofer, Mechthild; Schwab, Wilfried

2014-01-01

The strawberry (Fragaria × ananassa) is one of the most preferred fresh fruit worldwide, accumulates numerous flavonoids but has limited shelf life due to excessive tissue softening caused by cell wall degradation. Since lignin is one of the polymers that strengthen plant cell walls and might contribute to some extent to fruit firmness monolignol biosynthesis was studied in strawberry fruit. Cinnamoyl-CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), and a peroxidase (POD27) gene were strongly expressed in red, ripe fruit whereas a second POD gene was primarily expressed in green, immature fruit. Moreover, FaPOD27 transcripts were strongly and constitutively induced in fruits exposed to Agrobacterium infection. Gene expression levels and enzymatic activities of FaCCR and FaCAD were efficiently suppressed through RNAi in FaCCR- and FaCAD-silenced strawberries. Besides, significantly elevated FaPOD transcript levels were detected after agroinfiltration of pBI-FaPOD constructs in fruits. At the same time, levels of G-monomers were considerably reduced in FaCCR-silenced fruits whereas the proportion of both G- and S-monomers decisively decreased in FaCAD-silenced and pBI-FaPOD fruits. Development, firmness, and lignin level of the treated fruits were similar to pBI-intron control fruits, presumably attributed to increased expression levels of FaPOD27 upon agroinfiltration. Additionally, enhanced firmness, accompanied with elevated lignin levels, was revealed in chalcone synthase-deficient fruits (CHS−), independent of down- or up-regulation of individual and combined FaCCR. FaCAD, and FaPOD genes by agroinfiltration, when compared to CHS−/pBI-intron control fruits. These approaches provide further insight into the genetic control of flavonoid and lignin synthesis in strawberries. The results suggest that FaPOD27 is a key gene for lignin biosynthesis in strawberry fruit and thus to improving the firmness of strawberries. PMID:25346738

The Tom Core Complex

PubMed Central

Ahting, Uwe; Thun, Clemens; Hegerl, Reiner; Typke, Dieter; Nargang, Frank E.; Neupert, Walter; Nussberger, Stephan

1999-01-01

Translocation of nuclear-encoded preproteins across the outer membrane of mitochondria is mediated by the multicomponent transmembrane TOM complex. We have isolated the TOM core complex of Neurospora crassa by removing the receptors Tom70 and Tom20 from the isolated TOM holo complex by treatment with the detergent dodecyl maltoside. It consists of Tom40, Tom22, and the small Tom components, Tom6 and Tom7. This core complex was also purified directly from mitochondria after solubilization with dodecyl maltoside. The TOM core complex has the characteristics of the general insertion pore; it contains high-conductance channels and binds preprotein in a targeting sequence-dependent manner. It forms a double ring structure that, in contrast to the holo complex, lacks the third density seen in the latter particles. Three-dimensional reconstruction by electron tomography exhibits two open pores traversing the complex with a diameter of ∼2.1 nm and a height of ∼7 nm. Tom40 is the key structural element of the TOM core complex. PMID:10579717

Enhancing oxidative stability in heated oils using core/shell structures of collagen and α-tocopherol complex.

PubMed

Gim, Seo Yeong; Hong, Seungmi; Kim, Jisu; Kwon, YongJun; Kim, Mi-Ja; Kim, GeunHyung; Lee, JaeHwan

2017-11-15

In this study, collagen mesh structure was prepared by carrying α-tocopherol in the form of core/shell complex. Antioxidant properties of α-tocopherol loaded carriers were tested in moisture added bulk oils at 140°C. From one gram of collagen core/shell complex, 138mg α-tocopherol was released in medium chain triacylglycerol (MCT). α-Tocopherol was substantially protected against heat treatment when α-tocopherol was complexed in collagen core/shell. Oxidative stability in bulk oil was significantly enhanced by added collagen mesh structure or collagen core/shell complex with α-tocopherol compared to that in control bulk oils (p<0.05), although no significant difference was observed between oils containing collagen mesh structure and collagen core/shell with α-tocopherol (p>0.05). Results of DPPH loss in methanol demonstrated that collagen core/shell with α-tocopherol had significantly (p<0.05) higher antioxidant properties than collagen mesh structure up to a certain period. Therefore, collagen core/shell complex is a promising way to enhance the stability of α-tocopherol and oxidative stability in oil-rich foods prepared at high temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer

PubMed Central

Luo, Xin; Peng, Xia; Hou, Jingying; Wu, Shuyun; Shen, Jun; Wang, Lingyun

2017-01-01

Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)–polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers. PMID:28794626

Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer.

PubMed

Luo, Xin; Peng, Xia; Hou, Jingying; Wu, Shuyun; Shen, Jun; Wang, Lingyun

2017-01-01

Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe 3 O 4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T 2 -weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers.

A survey. Financial accounting and internal control functions pursued by hospital boards.

PubMed

Gavin, T A

1984-09-01

Justification for a board committee's existence is its ability to devote time to issues judged to be important by the full board. This seems to have happened. Multiple committees pursue more functions than the other committee structures. Boards lacking an FA/IC committee pursue significantly fewer functions than their counterparts with committees. Substantial respondent agreement exists on those functions most and least frequently pursued, those perceived to be most and least important, and those perceived to be most and least effectively undertaken. Distinctions between committee structures and the full board, noted in the previous paragraph, hold true with respect to the importance of functions. All board structures identified reviewing the budget and comparing it to actual results as important. Committee structures are generally more inclined to address functions related to the work of the independent auditor and the effectiveness of the hospital's system and controls than are full board structures. Functions related to the internal auditor are pursued least frequently by all FA/IC board structures. The following suggestions are made to help boards pay adequate attention to and obtain objective information about the financial affairs of their hospitals. Those boards that do not have some form of an FA/IC committee should consider starting one. Evidence shows chief financial officers have been a moving force in establishing and strengthening such committees. Boards having a joint or single committee structure should consider upgrading their structure to either a single committee or multiple committees respectively. The complexity of the healthcare environment requires that more FA/IC functions be addressed by the board. The board or its FA/IC committee(s) should meet with their independent CPA's, fiscal intermediary auditors, and internal auditors. Where the hospital lacks an internal audit function a study should be undertaken to determine the feasibility of initiating such a function. In most cases, the benefits derived from an independent, properly staffed internal audit function far exceed the cost of such a function.

Effects of practice and experience on the arcuate fasciculus: comparing singers, instrumentalists, and non-musicians.

PubMed

Halwani, Gus F; Loui, Psyche; Rüber, Theodor; Schlaug, Gottfried

2011-01-01

Structure and function of the human brain are affected by training in both linguistic and musical domains. Individuals with intensive vocal musical training provide a useful model for investigating neural adaptations of learning in the vocal-motor domain and can be compared with learning in a more general musical domain. Here we confirm general differences in macrostructure (tract volume) and microstructure (fractional anisotropy, FA) of the arcuate fasciculus (AF), a prominent white-matter tract connecting temporal and frontal brain regions, between singers, instrumentalists, and non-musicians. Both groups of musicians differed from non-musicians in having larger tract volume and higher FA values of the right and left AF. The AF was then subdivided in a dorsal (superior) branch connecting the superior temporal gyrus and the inferior frontal gyrus (STG ↔ IFG), and ventral (inferior) branch connecting the middle temporal gyrus and the inferior frontal gyrus (MTG ↔ IFG). Relative to instrumental musicians, singers had a larger tract volume but lower FA values in the left dorsal AF (STG ↔ IFG), and a similar trend in the left ventral AF (MTG ↔ IFG). This between-group comparison controls for the general effects of musical training, although FA was still higher in singers compared to non-musicians. Both musician groups had higher tract volumes in the right dorsal and ventral tracts compared to non-musicians, but did not show a significant difference between each other. Furthermore, in the singers' group, FA in the left dorsal branch of the AF was inversely correlated with the number of years of participants' vocal training. Our findings suggest that long-term vocal-motor training might lead to an increase in volume and microstructural complexity of specific white-matter tracts connecting regions that are fundamental to sound perception, production, and its feedforward and feedback control which can be differentiated from a more general musician effect.

Alluvial to lacustrine sedimentation in an endorheic basin during the Mio-Pliocene: The Toro Negro Formation, Central Andes of Argentina

NASA Astrophysics Data System (ADS)

Ciccioli, Patricia L.; Marenssi, Sergio A.; Amidon, William H.; Limarino, Carlos O.; Kylander-Clark, Andrew

2018-07-01

A 2400 m-thick sedimentary column belonging to the Toro Negro Formation was recorded along the Quebrada del Yeso, Sierra de Los Colorados (Vinchina Basin), La Rioja province, NW Argentina. The Vinchina basin is a good example of a closed basin surrounded by the Precordillera fold and thrust belt to the west and basement-cored blocks to the north, south (Western Sierras Pampeanas) and east (Sierra de Famatina). Seven facies associations (FA) are described and interpreted to represent fluvial, lacustrine and alluvial environments developed in the southern part of the Vinchina basin from the Late Miocene until the earliest Pleistocene. The depositional evolution of the formation was divided in four phases. Phase I (∼7-6.6 Ma) represents sedimentation in medial (FA I) to distal (FA II) parts of a southward directed distributive fluvial system with a retrogradational pattern. During phase II (6.6-6.1Ma), the distributive fluvial system was replaced by a mixed clastic-evaporitic shallow lake (FA III) in a high aggradational basin. In phase III (∼6.1-5 Ma) the eastward progradation of a fluvial system (FA IV) was recorded as a distal clastic wedge. Finally, phase IV (∼5-2.4Ma) records two depositional cycles of proximal clastic wedge progradation of fluvial-dominated piedmonts (FAV, FAVII) from the southwest (Sierra de Umango) and/or the west (Precordillera) with an intervening playa lake (FA VI). Two new U-Pb ages obtained from zircons in volcanic ash layers confirm the Late Miocene age of the lower member of the Toro Negro Formation and permit a tight correlation with the central part of the basin (Quebrada de La Troya section). The sedimentation rate calculated for the dated lacustrine-fluvial interval is higher than the corresponding one in La Troya area suggesting a higher subsidence in the southern part of the basin. During the Late Miocene (∼7-6.6Ma) the ephemeral drainage was controlled by an arid to semiarid climate and initially dissipated mostly internally as terminal fan/distributive fluvial systems descending from the north. A thick lacustrine interval developed in the southern part of the basin between ∼6.6 and 6.1 Ma during a period of high subsidence and closed drainage. Besides, this interval coincides with increased aridity recorded in other basins in the Northwest of Argentina. By ∼6.1 Ma the area started to receive the first coarse-grained sediments heralding the progradation of a clastic wedge from the southwest-west (Sierra de Umango and Precordillera) which fully developed during the rest of the Pliocene to the earliest Pleistocene (∼5-2.4 Ma). The 6.1-2.4 Ma interval records ameliorating climate conditions.

Fatty acids and breast cancer: Make them on site or have them delivered

PubMed Central

Kinlaw, William B.; Baures, Paul W.; Lupien, Leslie E.; Davis, Wilson L.; Kuemmerle, Nancy B.

2016-01-01

Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a “lipogenic-lipolytic axis”, and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed. PMID:26844415

The effect of peculiar complex core balance training on isokinetic muscle functions of the knee and lumbus.

PubMed

Lee, Myungsun; Han, Gunsoo

2016-04-01

[Purpose] This study aimed to investigate the effect of peculiar complex core balance training on the isokinetic muscle function of the knee joint and lumbus to provide fundamental data for establishing a training program that focuses on improving the performance and prevention of injury by developing the core and low extremity muscles. [Subjects and Methods] The participants in this study included a total of ten high school athletes involved in a throwing event for over five years. The subjects were randomly divided into two groups: The experimental group (N=5) and the control group (N=5). The experimental group underwent peculiar complex core balance training. [Results] According to the analysis of covariance, there was a significant effect of peculiar complex core balance training. Therefore, the isokinetic muscle function of the knee joint and lumbus in the experimental group participating in peculiar complex core balance training was significantly increased compared to the control group. [Conclusion] It is concluded that peculiar complex core balance training had a positive effect on the isokinetic muscle function of the knee and lumbus in throwing event athletes.

Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults.

PubMed

Hall, Megan N; Howe, Caitlin G; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

2016-05-01

Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Choline decreased in the placebo group (-6.6%; 95% CI: -10.2%, -2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: -0.9%, 6.1%; FA800: 1.4%; 95% CI: -2.5%, 5.5%; P < 0.05). Betaine did not change in the placebo group (-3.5%; 95% CI: -9.3%, 2.6%) but increased in the FA groups (FA400: 14.1%; 95% CI: 9.4%, 19.0%; FA800: 13.0%; 95% CI: 7.2%, 19.1%; P < 0.01). The decrease in DMG was greater in the FA groups (FA400: -26.7%; 95% CI: -30.9%, -22.2%; FA800: -27.8%; 95% CI: -31.8%, -23.4%) than in the placebo group (-12.3%; 95% CI: -18.1%, -6.2%; P < 0.01). The percentage change in choline, betaine, and DMG did not differ between creatine treatment arms and their respective reference groups. Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. © 2016 American Society for Nutrition.

Supplementation with Folic Acid, but Not Creatine, Increases Plasma Betaine, Decreases Plasma Dimethylglycine, and Prevents a Decrease in Plasma Choline in Arsenic-Exposed Bangladeshi Adults123

PubMed Central

Hall, Megan N; Liu, Xinhua; Caudill, Marie A; Malysheva, Olga; Ilievski, Vesna; Lomax-Luu, Angela M; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad N; Islam, Tariqul; Graziano, Joseph H; Gamble, Mary V

2016-01-01

Background: Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. Objective: The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). Methods: We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n = 605, aged 24–55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC–tandem mass spectrometry at baseline and at week 12. Group comparisons were between 1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo, 2) creatine (3 g/d) compared with placebo, and 3) creatine plus FA400 compared with FA400. Results: Choline decreased in the placebo group (−6.6%; 95% CI: −10.2%, −2.9%) but did not change in the FA groups (FA400: 2.5%; 95% CI: −0.9%, 6.1%; FA800: 1.4%; 95% CI: −2.5%, 5.5%; P < 0.05). Betaine did not change in the placebo group (−3.5%; 95% CI: −9.3%, 2.6%) but increased in the FA groups (FA400: 14.1%; 95% CI: 9.4%, 19.0%; FA800: 13.0%; 95% CI: 7.2%, 19.1%; P < 0.01). The decrease in DMG was greater in the FA groups (FA400: −26.7%; 95% CI: −30.9%, −22.2%; FA800: −27.8%; 95% CI: −31.8%, −23.4%) than in the placebo group (−12.3%; 95% CI: −18.1%, −6.2%; P < 0.01). The percentage change in choline, betaine, and DMG did not differ between creatine treatment arms and their respective reference groups. Conclusion: Supplementation for 12 wk with FA, but not creatine, increases plasma betaine, decreases plasma DMG, and prevents a decrease in plasma choline in arsenic-exposed Bangladeshi adults. This trial was registered at clinicaltrials.gov as NCT01050556. PMID:27052531

Fatty acid patterns of dog erythrocyte membranes after feeding of a fish-oil based DHA-rich supplement with a base diet low in n-3 fatty acids versus a diet containing added n-3 fatty acids.

PubMed

Stoeckel, Katja; Nielsen, Leif Højvang; Fuhrmann, Herbert; Bachmann, Lisa

2011-10-24

In dogs, increasing the tissue n-3 fatty acid (FA) content is associated with potential benefit in some medical conditions, e.g. atopic dermatitis, cancer or heart disease. Therefore effectively and conveniently increasing tissue n-3 FA levels in dogs is of interest. Incorporation of dietary n-3 FA into cell membranes may be studied by FA analysis of erythrocyte membranes (EM), because of the correlation of its FA composition with the FA composition of other cells. Aim of the study was to determine whether an n-3 FA additive added to a control diet is as effective in increasing EM n-3 FA content as feeding an n-3 FA enriched diet. Furthermore the time course of the incorporation of dietary n-3 FA into canine EM was investigated. Thirty dogs were randomly divided into three dietary groups with ten dogs per group. CONT got a dry dog food diet which did not contain EPA or DHA. FO got a dry dog food diet with a high EPA and DHA content. ADD got the CONT diet combined with an n-3 FA additive rich in DHA and EPA. After a feeding period of 12 weeks the additive was discontinued in ADD and these dogs were fed CONT diet for another four weeks to observe washout effects. Erythrocyte lipids were extracted from venous blood samples and their FA composition was determined by gas chromatography. The Mann-Whitney-U-test was used to detect significant differences between the different groups and time points. After one week the proportions of n-3 FA, DHA and EPA were already significantly increased in ADD and FO, apparently reaching a plateau within eight weeks. In our study DHA and not EPA was preferably incorporated into the EM. After discontinuing the administration of the additive in ADD, the n-3 FA values declined slowly without reaching baseline levels within four weeks. In dogs, an increase of dietary n-3 FA content leads to a rapid inclusion of n-3 FA into EM, regardless of whether the n-3 FA are offered as an enriched diet or as a normal diet supplemented with an n-3 FA additive.

Fatty acid patterns of dog erythrocyte membranes after feeding of a fish-oil based DHA-rich supplement with a base diet low in n-3 fatty acids versus a diet containing added n-3 fatty acids

PubMed Central

2011-01-01

Background In dogs, increasing the tissue n-3 fatty acid (FA) content is associated with potential benefit in some medical conditions, e.g. atopic dermatitis, cancer or heart disease. Therefore effectively and conveniently increasing tissue n-3 FA levels in dogs is of interest. Incorporation of dietary n-3 FA into cell membranes may be studied by FA analysis of erythrocyte membranes (EM), because of the correlation of its FA composition with the FA composition of other cells. Aim of the study was to determine whether an n-3 FA additive added to a control diet is as effective in increasing EM n-3 FA content as feeding an n-3 FA enriched diet. Furthermore the time course of the incorporation of dietary n-3 FA into canine EM was investigated. Methods Thirty dogs were randomly divided into three dietary groups with ten dogs per group. CONT got a dry dog food diet which did not contain EPA or DHA. FO got a dry dog food diet with a high EPA and DHA content. ADD got the CONT diet combined with an n-3 FA additive rich in DHA and EPA. After a feeding period of 12 weeks the additive was discontinued in ADD and these dogs were fed CONT diet for another four weeks to observe washout effects. Erythrocyte lipids were extracted from venous blood samples and their FA composition was determined by gas chromatography. The Mann-Whitney-U-test was used to detect significant differences between the different groups and time points. Results After one week the proportions of n-3 FA, DHA and EPA were already significantly increased in ADD and FO, apparently reaching a plateau within eight weeks. In our study DHA and not EPA was preferably incorporated into the EM. After discontinuing the administration of the additive in ADD, the n-3 FA values declined slowly without reaching baseline levels within four weeks. Conclusions In dogs, an increase of dietary n-3 FA content leads to a rapid inclusion of n-3 FA into EM, regardless of whether the n-3 FA are offered as an enriched diet or as a normal diet supplemented with an n-3 FA additive. PMID:22024384

Cross-Hemispheric Collaboration and Segregation Associated with Task Difficulty as Revealed by Structural and Functional Connectivity

PubMed Central

Cabeza, Roberto

2015-01-01

Although it is known that brain regions in one hemisphere may interact very closely with their corresponding contralateral regions (collaboration) or operate relatively independent of them (segregation), the specific brain regions (where) and conditions (how) associated with collaboration or segregation are largely unknown. We investigated these issues using a split field-matching task in which participants matched the meaning of words or the visual features of faces presented to the same (unilateral) or to different (bilateral) visual fields. Matching difficulty was manipulated by varying the semantic similarity of words or the visual similarity of faces. We assessed the white matter using the fractional anisotropy (FA) measure provided by diffusion tensor imaging (DTI) and cross-hemispheric communication in terms of fMRI-based connectivity between homotopic pairs of cortical regions. For both perceptual and semantic matching, bilateral trials became faster than unilateral trials as difficulty increased (bilateral processing advantage, BPA). The study yielded three novel findings. First, whereas FA in anterior corpus callosum (genu) correlated with word-matching BPA, FA in posterior corpus callosum (splenium-occipital) correlated with face-matching BPA. Second, as matching difficulty intensified, cross-hemispheric functional connectivity (CFC) increased in domain-general frontopolar cortex (for both word and face matching) but decreased in domain-specific ventral temporal lobe regions (temporal pole for word matching and fusiform gyrus for face matching). Last, a mediation analysis linking DTI and fMRI data showed that CFC mediated the effect of callosal FA on BPA. These findings clarify the mechanisms by which the hemispheres interact to perform complex cognitive tasks. PMID:26019335

A new framework for the documentation and interpretation of oral food challenges in population-based and clinical research.

PubMed

Grabenhenrich, L B; Reich, A; Bellach, J; Trendelenburg, V; Sprikkelman, A B; Roberts, G; Grimshaw, K E C; Sigurdardottir, S; Kowalski, M L; Papadopoulos, N G; Quirce, S; Dubakiene, R; Niggemann, B; Fernández-Rivas, M; Ballmer-Weber, B; van Ree, R; Schnadt, S; Mills, E N C; Keil, T; Beyer, K

2017-03-01

The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC). A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods. A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making. The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

PubMed

Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J

2017-04-08

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cell proliferation and progesterone synthesis depend on lipid metabolism in bovine granulosa cells.

PubMed

Elis, Sebastien; Desmarchais, Alice; Maillard, Virginie; Uzbekova, Svetlana; Monget, Philippe; Dupont, Joëlle

2015-03-15

In dairy cows, lipids are essential to support energy supplies for all biological functions, especially during early lactation. Lipid metabolism is crucial for sustaining proper reproductive function. Alteration of lipid metabolism impacts follicular development and affects oocyte developmental competence. Indeed, nonesterified fatty acids are able to decrease granulosa cell (GC) proliferation and affect estradiol synthesis, thus potentially affecting follicular growth and viability. The objective of this study was to assess the impact of lipid metabolism on bovine GCs, through the use of the lipid metabolism inhibitors etomoxir, an inhibitor of fatty acid (FA) oxidation through inhibition of carnitine palmitoyl transferase 1 (CPT1), and C75, an inhibitor of FA synthesis through inhibition of fatty acid synthase. We showed that etomoxir and C75 significantly inhibited DNA synthesis in vitro; C75 also significantly decreased progesterone synthesis. Both inhibitors significantly reduced AMPK (5' adenosine monophosphate-activated protein kinase) and acetyl-CoA carboxylase phosphorylation. Etomoxir also affected the AKT (protein kinase B) signaling pathway. Combined, these data suggest that both FA oxidation and synthesis are important for the bovine GCs to express a proliferative and steroidogenic phenotype and, thus, for sustaining follicular growth. Despite these findings, it is important to note that the changes caused by the inhibitors of FA metabolism on GCs in vitro are globally mild, suggesting that lipid metabolism is not as critical in GCs as was observed in the oocyte-cumulus complex. Further studies are needed to investigate the detailed mechanisms by which lipid metabolism interacts with GC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

KSC-08pd3563

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – Three of the U.S. Navy's Blue Angels F/A-18 jets fly in formation over the runway before landing at NASA's Kennedy Space Center in Florida. The Blue Angels are at Kennedy to perform in the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3557

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – Storks seem to join the formation as the U.S. Navy's Blue Angels F/A-18 jets land on the runway at NASA's Kennedy Space Center in Florida. The Blue Angels are at Kennedy to perform in the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

KSC-08pd3551

NASA Image and Video Library

2008-11-06

CAPE CANAVERAL, Fla. – At the Shuttle Landing Facility at NASA's Kennedy Space Center in Florida, ground support personnel work on an F/A-18, one of the U.S. Navy's Blue Angels aircraft. The demonstration squadron will perform at the Kennedy Space Center Visitor Complex Space and Air Show Nov. 8-9. The Navy's elite flight demonstration squadron will take to the skies in military aircraft demonstrations by the F-16 Fighting Falcon and F/A-18 Super Hornet jets for the second annual Space & Air Show at Kennedy. This year’s show brings together the best in military aircraft, coupled with precision pilots and veteran astronauts to celebrate spaceflight and aviation. The event includes military aircraft demonstrations by the F-16 Fighting Falcon and a water rescue demonstration by the 920th Rescue Wing. Photo credit: NASA/Kim Shiflett

Exploration of interactions between bioactive solutes and vitamin B9 in aqueous medium by physico-chemical contrivances

NASA Astrophysics Data System (ADS)

Roy, Mahendra Nath; Chakraborti, Palash; Ekka, Deepak

2014-09-01

Molecular interaction prevailing in α-amino acids (glycine, L-alanine, L-valine) and aqueous solution of folic acid (FA) has been reported by physico-chemical properties as density (ρ), viscosity (η), refractive index (nD) and ultrasonic speed (u) at 298.15 K. The extent of interaction (solute-solvent interaction) is expressed in terms of the limiting apparent molar volume (φ0V), viscosity B-coefficient, molar refraction (RM) and limiting apparent molar adiabatic compressibility (φ0K). The trends in transfer volumes, Δφ0V, have been interpreted in terms of solute-cosolute interactions on the basis of a co-sphere overlap model. The role of the cosolute (FA), and the contribution of solute-solute and solute-solvent interactions to the solution complexes, has also been analysed through the derived properties.

Noble gases in gas shales : Implications for gas retention and circulating fluids.

NASA Astrophysics Data System (ADS)

Basu, Sudeshna; Jones, Adrian; Verchovsky, Alexander

2016-04-01

Gas shales from three cores of Haynesville-Bossier formation have been analysed simultaneously for carbon, nitrogen and noble gases (He, Ne, Ar, Xe) to constrain their source compositions and identify signatures associated with high gas retention. Ten samples from varying depths of 11785 to 12223 feet from each core, retrieved from their centres, have been combusted from 200-1200°C in incremental steps of 100°C, using 5 - 10 mg of each sample. Typically, Xe is released at 200°C and is largely adsorbed, observed in two of the three cores. The third core lacked any measureable Xe. High 40Ar/36Ar ratio up to 8000, is associated with peak release of nitrogen with distinctive isotopic signature, related to breakdown of clay minerals at 500°C. He and Ne are also mostly released at the same temperature step and predominantly hosted in the pore spaces of the organic matter associated with the clay. He may be produced from the uranium related to the organic matter. The enrichment factors of noble gases defined as (iX/36Ar)sample/(iX/36Ar)air where iX denotes any noble gas isotope, show Ne and Xe enrichment observed commonly in sedimentary rocks including shales (Podosek et al., 1980; Bernatowicz et al., 1984). This can be related to interaction of the shales with circulating fluids and diffusive separation of gases (Torgersen and Kennedy, 1999), implying the possibility of loss of gases from these shales. Interaction with circulating fluids (e.g. crustal fluids) have been further confirmed using 20Ne/N2, 36Ar/N2 and 4He/N2 ratios. Deviations of measured 4He/40Ar* (where 40Ar* represents radiogenic 40Ar after correcting for contribution from atmospheric Ar) from expected values has been used to monitor gas loss by degassing. Bernatowicz, T., Podosek, F.A., Honda, M., Kramer, F.E., 1984. The Atmospheric Inventory of Xenon and Noble Gases in Shales: The Plastic Bag Experiment. Journal of Geophysical Research 89, 4597-4611. Podosek, F.A., Honda, M., Ozima, M., 1980. Sedimentary noble gases. Geochimica Cosmochimica Acta 44, 1875-1884. Torgersen, T., Kennedy, B.M., 1999. Air-Xe enrichments in Oil Field Gases and the Influence of Water during Oil Migration and Storage. Earth and Planetary Science Letters167, 239-253.

Association between Plasma Nonesterified Fatty Acids Species and Adipose Tissue Fatty Acid Composition

PubMed Central

Hellmuth, Christian; Demmelmair, Hans; Schmitt, Isabel; Peissner, Wolfgang; Blüher, Matthias; Koletzko, Berthold

2013-01-01

Fatty acid composition of adipose tissue (AT) is an established long-term biomarker for fatty acid (FA) intake and status, but AT samples are not easily available. Nonesterified FA composition in plasma (pNEFA) may be a good indicator of AT FA composition, because pNEFA are mainly generated by AT lipolysis. We investigated the correlation of 42 pNEFA and subcutaneous as well as visceral AT FA in 27 non-diabetic women with a median BMI of 36 kg/m2 (Q0.25: 25 kg/m2; Q0.75: 49 kg/m2). Close correlations of pNEFA and AT FA were found for odd-chain FA (15∶0 r = 0.838 and 0.862 for subcutaneous and visceral AT, respectively) and omega-3 FA (22∶6 r = 0.719/0.535), while no significant or low correlations were found for other FA including 18∶1 (r = 0.384/0.325) and 20∶4 (r = 0.386/0.266). Close correlations of pNEFA and AT FA were found for essential fatty acids, like 18∶2 (r = 0.541/0.610) and 20∶5 (r = 0.561/0.543). The lower correlation for some pNEFA species with AT FA indicates that the variation of most pNEFA is significantly affected by other FA sources and flux of FA to tissue, in addition to release from AT. A relevant influence of BMI on the level of correlation was shown for saturated FA. NEFA analysis in fasted plasma can serve as a virtual AT biopsy for some FA, and as a biomarker for intake of dairy products and sea fish. PMID:24098359

Association between plasma nonesterified fatty acids species and adipose tissue fatty acid composition.

PubMed

Hellmuth, Christian; Demmelmair, Hans; Schmitt, Isabel; Peissner, Wolfgang; Blüher, Matthias; Koletzko, Berthold

2013-01-01

Fatty acid composition of adipose tissue (AT) is an established long-term biomarker for fatty acid (FA) intake and status, but AT samples are not easily available. Nonesterified FA composition in plasma (pNEFA) may be a good indicator of AT FA composition, because pNEFA are mainly generated by AT lipolysis. We investigated the correlation of 42 pNEFA and subcutaneous as well as visceral AT FA in 27 non-diabetic women with a median BMI of 36 kg/m(2) (Q0.25: 25 kg/m(2); Q0.75: 49 kg/m(2)). Close correlations of pNEFA and AT FA were found for odd-chain FA (15∶0 r = 0.838 and 0.862 for subcutaneous and visceral AT, respectively) and omega-3 FA (22∶6 r = 0.719/0.535), while no significant or low correlations were found for other FA including 18∶1 (r = 0.384/0.325) and 20∶4 (r = 0.386/0.266). Close correlations of pNEFA and AT FA were found for essential fatty acids, like 18∶2 (r = 0.541/0.610) and 20∶5 (r = 0.561/0.543). The lower correlation for some pNEFA species with AT FA indicates that the variation of most pNEFA is significantly affected by other FA sources and flux of FA to tissue, in addition to release from AT. A relevant influence of BMI on the level of correlation was shown for saturated FA. NEFA analysis in fasted plasma can serve as a virtual AT biopsy for some FA, and as a biomarker for intake of dairy products and sea fish.

Effects of whole flaxseed, raw soybeans, and calcium salts of fatty acids on measures of cellular immune function of transition dairy cows.

PubMed

Gandra, J R; Barletta, R V; Mingoti, R D; Verdurico, L C; Freitas, J E; Oliveira, L J; Takiya, C S; Kfoury, J R; Wiltbank, M C; Renno, F P

2016-06-01

The objective of the current study was to evaluate the effects of supplemental n-3 and n-6 fatty acid (FA) sources on cellular immune function of transition dairy cows. Animals were randomly assigned to receive 1 of 4 diets: control (n=11); whole flaxseed (n-3 FA source; n=11), 60 and 80g/kg of whole flaxseed [diet dry matter (DM) basis] during pre- and postpartum, respectively; whole raw soybeans (n-6 FA source; n=10), 120 and 160g/kg of whole raw soybeans (diet DM basis) during pre- and postpartum, respectively; and calcium salts of unsaturated FA (Megalac-E, n-6 FA source; n=10), 24 and 32g/kg of calcium salts of unsaturated FA (diet DM basis) during pre- and postpartum, respectively. Supplemental FA did not alter DM intake and milk yield but increased energy balance during the postpartum period. Diets containing n-3 and n-6 FA sources increased phagocytosis capacity of leukocytes and monocytes and phagocytosis activity of monocytes. Furthermore, n-3 FA source increased phagocytic capacity of leukocytes and neutrophils and increased phagocytic activity in monocytes and neutrophils when compared with n-6 FA sources. Supplemental FA effects on adaptive immune system included increased percentage of T-helper cells, T-cytotoxic cells, cells that expressed IL-2 receptors, and CD62 adhesion molecules. The results of this study suggest that unsaturated FA can modulate innate and adaptive cellular immunity and trigger a proinflammatory response. The n-3 FA seems to have a greater effect on phagocytic capacity and activity of leukocytes when compared with n-6 FA. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition.

PubMed

Segura, Maria Teresa; Demmelmair, Hans; Krauss-Etschmann, Susanne; Nathan, Petra; Dehmel, Stefan; Padilla, Maria Carmen; Rueda, Ricardo; Koletzko, Berthold; Campoy, Cristina

2017-09-01

Placental fatty acid (FA) uptake and metabolism depend on maternal supply which may be altered when women have a high pre-pregnancy body mass index (BMI) or develop gestational diabetes (GDM). Consequently, an impaired FA transport to the fetus may negatively affect fetal development. While placental adaptation of maternal-fetal glucose transfer in mild GDM has been described, knowledge on placental FA acid metabolism and possible adaptations in response to maternal obesity or GDM is lacking. We aimed to analyze the FA composition and the expression of key genes involved in FA uptake and metabolism in placentas from women with pre-pregnancy normal weight (18.5 ≤ BMI<25 kg/m2), overweight (25 ≤ BMI<30 kg/m 2 ), obesity (BMI ≥ 30 kg/m 2 ), and lean pregnant women with GDM. Placental FA content was determined by gas liquid chromatography. Placental mRNA expression of FA transport proteins (FATP1, FATP4, FATP6), FA binding proteins (FABP3, FABP4, FABP7), FA translocase (FAT/CD36) and enzymes (Endothelial lipase (EL) and lipoprotein lipase (LPL)) were quantified by qRT-PCR. High pre-pregnancy BMI and GDM were associated with decreased placental FATP1, FATP4, EL and increased FAT/CD36 and FATP6 expressions. LPL mRNA levels and placental total FA content were similar among groups. Specific FA, including some long-chain polyunsaturated FA, were altered. Our results demonstrate that high pre-pregnancy BMI or GDM independently alter mRNA expression levels of genes involved in FA uptake and metabolism and the placental FA profile, which could affect fetal development and long-term health. Copyright © 2017. Published by Elsevier Ltd.

Metabolic fate of yolk fatty acids in the developing king penguin embryo.

PubMed

Groscolas, René; Fréchard, Françoise; Decrock, Frédéric; Speake, Brian K

2003-10-01

This study examines the metabolic fate of total and individual yolk fatty acids (FA) during the embryonic development of the king penguin, a seabird characterized by prolonged incubation (53 days) and hatching (3 days) periods, and a high n-3/n-6 polyunsaturated FA ratio in the egg. Of the approximately 15 g of total FA initially present in the egg lipid, 87% was transferred to the embryo by the time of hatching, the remaining 13% being present in the internalized yolk sac of the chick. During the whole incubation, 83% of the transferred FA was oxidized for energy, with only 17% incorporated into embryo lipids. Prehatching (days 0-49), the fat stores (triacylglycerol) accounted for 58% of the total FA incorporated into embryo lipid. During hatching (days 49-53), 40% of the FA of the fat stores was mobilized, the mobilization of individual FA being nonselective. At hatch, 53% of the arachidonic acid (20:4n-6) of the initial yolk had been incorporated into embryo lipid compared with only 15% of the total FA and 17-24% of the various n-3 polyunsaturated FA. Similarly, only 32% of the yolk's initial content of 20:4n-6 was oxidized for energy during development compared with 72% of the total FA and 58-66% of the n-3 polyunsaturated FA. The high partitioning of yolk FA toward oxidization and the intense mobilization of fat store FA during hatching most likely reflect the high energy cost of the long incubation and hatching periods of the king penguin. The preferential partitioning of 20:4n-6 into the structural lipid of the embryo in the face of its low content in the yolk may reflect the important roles of this FA in tissue function.

Identifying Dynamic Protein Complexes Based on Gene Expression Profiles and PPI Networks

PubMed Central

Li, Min; Chen, Weijie; Wang, Jianxin; Pan, Yi

2014-01-01

Identification of protein complexes from protein-protein interaction networks has become a key problem for understanding cellular life in postgenomic era. Many computational methods have been proposed for identifying protein complexes. Up to now, the existing computational methods are mostly applied on static PPI networks. However, proteins and their interactions are dynamic in reality. Identifying dynamic protein complexes is more meaningful and challenging. In this paper, a novel algorithm, named DPC, is proposed to identify dynamic protein complexes by integrating PPI data and gene expression profiles. According to Core-Attachment assumption, these proteins which are always active in the molecular cycle are regarded as core proteins. The protein-complex cores are identified from these always active proteins by detecting dense subgraphs. Final protein complexes are extended from the protein-complex cores by adding attachments based on a topological character of “closeness” and dynamic meaning. The protein complexes produced by our algorithm DPC contain two parts: static core expressed in all the molecular cycle and dynamic attachments short-lived. The proposed algorithm DPC was applied on the data of Saccharomyces cerevisiae and the experimental results show that DPC outperforms CMC, MCL, SPICi, HC-PIN, COACH, and Core-Attachment based on the validation of matching with known complexes and hF-measures. PMID:24963481

Impact of Moist Physics Complexity on Tropical Cyclone Simulations from the Hurricane Weather Research and Forecast System

NASA Astrophysics Data System (ADS)

Kalina, E. A.; Biswas, M.; Newman, K.; Grell, E. D.; Bernardet, L.; Frimel, J.; Carson, L.

2017-12-01

The parameterization of moist physics in numerical weather prediction models plays an important role in modulating tropical cyclone structure, intensity, and evolution. The Hurricane Weather Research and Forecast system (HWRF), the National Oceanic and Atmospheric Administration's operational model for tropical cyclone prediction, uses the Scale-Aware Simplified Arakawa-Schubert (SASAS) cumulus scheme and a modified version of the Ferrier-Aligo (FA) microphysics scheme to parameterize moist physics. The FA scheme contains a number of simplifications that allow it to run efficiently in an operational setting, which includes prescribing values for hydrometeor number concentrations (i.e., single-moment microphysics) and advecting the total condensate rather than the individual hydrometeor species. To investigate the impact of these simplifying assumptions on the HWRF forecast, the FA scheme was replaced with the more complex double-moment Thompson microphysics scheme, which individually advects cloud ice, cloud water, rain, snow, and graupel. Retrospective HWRF forecasts of tropical cyclones that occurred in the Atlantic and eastern Pacific ocean basins from 2015-2017 were then simulated and compared to those produced by the operational HWRF configuration. Both traditional model verification metrics (i.e., tropical cyclone track and intensity) and process-oriented metrics (e.g., storm size, precipitation structure, and heating rates from the microphysics scheme) will be presented and compared. The sensitivity of these results to the cumulus scheme used (i.e., the operational SASAS versus the Grell-Freitas scheme) also will be examined. Finally, the merits of replacing the moist physics schemes that are used operationally with the alternatives tested here will be discussed from a standpoint of forecast accuracy versus computational resources.

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

PubMed Central

Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

2008-01-01

Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

Time to Detection with BacT/Alert FA Plus Compared to BacT/Alert FA Blood Culture Media.

PubMed

Nutman, A; Fisher Even-Tsur, S; Shapiro, G; Braun, T; Schwartz, D; Carmeli, Y

2016-09-01

Rapid identification of the causative pathogen in patients with bacteremia allows adjustment of antibiotic therapy and improves patient outcomes. We compared in vitro and real-life time to detection (TTD) of two blood culture media, BacT/Alert FA (FA) and BacT/Alert FA Plus (FA Plus), for the nine most common species of bacterial pathogens recovered from blood samples. Experimental data from simulated cultures was compared with microbiology records of TTD for both culture media with growth of the species of interest in clinical blood cultures. In the experimental conditions, median TTD was 3.8 hours (23.9 %) shorter using FA Plus media. The magnitude of reduction differed between species. Similarly, in real life data, FA Plus had shorter TTD than FA media; however, the difference between culture media was smaller, and median TTD was only 1 hour (8.5 %) less. We found shorter TTD with BacT/Alert FA Plus culture media, both experimentally and in real-life conditions and unrelated to antibiotic neutralization, highlighting the importance of appropriate blood culture media selection.

Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients.

PubMed

An, W S; Lee, S M; Son, Y K; Kim, S E; Kim, K H; Han, J Y; Bae, H R; Park, Y

2012-01-01

Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double-blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pediatric Food Allergies and Psychosocial Functioning: Examining the Potential Moderating Roles of Maternal Distress and Overprotection

PubMed Central

Pincus, Donna B.; Comer, Jonathan S.

2015-01-01

Objectives Identify factors associated with maternal perceptions of health-related quality of life (QoL) among youth with food allergies (FA), and identify maternal factors that may moderate relationships between FA-related challenges and child QoL. Methods In all, 533 mothers of children with FA completed measures assessing characteristics of their child’s FA, maternal perceptions of child QoL, maternal psychological distress, and maternal overprotection. Results FA severity, maternal psychological distress, and overprotection were significantly associated with maternal reports of poorer child functioning and/or poorer QoL among youth with FA. Hierarchical linear regression analyses showed an FA severity by maternal distress interaction in the prediction of child FA-related anxiety; children of higher stress mothers showed a stronger link between auto-injector use and anxiety than children of lower stress mothers. Conclusions When identifying youth with FA who are at risk for low QoL, it is important to assess history of FA-related challenges, parental psychological distress, and overprotection. PMID:26089553

The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes

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

Liow, K.Y.; Chow, S.C., E-mail: chow.sek.chuen@monash.edu

The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-chloromethylketone (z-FA-CMK) was found to be toxic and readily induced cell death in the human T cell line, Jurkat, whereas two other analogs benzyloxycarbonyl-phenylalanine-alanine-fluoromethylketone (z-FA-FMK) and benzyloxycarbonyl-phenylalanine-alanine-diazomethylketone (z-FA-DMK) were not toxic. The toxicity of z-FA-CMK requires not only the CMK group, but also the presence of alanine in the P1 position and the benzyloxycarbonyl group at the N-terminal. Dose–response studies showed that lower concentrations of z-FA-CMK induced apoptosis in Jurkat T cells whereas higher concentrations induced necrosis. In z-FA-CMK-induced apoptosis, both initiator caspases (-8 and -9) and effector caspases (-3, -6 and -7) were processed tomore » their respective subunits in Jurkat T cells. However, only the pro-form of the initiator caspases were reduced in z-FA-CMK-induced necrosis and no respective subunits were apparent. The caspase inihibitor benzyloxycarbonyl-valine-alanine-aspartic acid-(O-methyl)-fluoromehylketone (z-VAD-FMK) inhibits apoptosis and caspase processing in Jurkat T cells treated with low concentration of z-FA-CMK but has no effect on z-FA-CMK-induced necrosis and the loss of initiator caspases. This suggests that the loss of initiator caspases in Jurkat T cells during z-FA-CMK-induced necrosis is not a caspase-dependent process. Taken together, we have demonstrated that z-FA-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. - Highlights: • z-FA-CMK is toxic and induce cell death in the human T cells. • z-FA-CMK toxicity requires the CMK group, alanine and the benzyloxycarbonyl group. • z-FA-CMK induced apoptosis at low concentration and necrosis at high concentration.« less

Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women.

PubMed

Page, Rachael; Robichaud, André; Arbuckle, Tye E; Fraser, William D; MacFarlane, Amanda J

2017-05-01

Background: Folate requirements increase during pregnancy and lactation. It is recommended that women who could become pregnant, are pregnant, or are lactating consume a folic acid (FA)-containing supplement. Objectives: We sought to determine breast-milk total folate and unmetabolized folic acid (UMFA) contents and their relation with FA-supplement use and doses in a cohort of Canadian mothers who were enrolled in the MIREC (Maternal-Infant Research on Environmental Chemicals) study. Design: Breast-milk tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and UMFA were measured with the use of liquid chromatography-tandem mass spectrometry ( n = 561). Total daily supplemental FA intake was based on self-reported FA-supplement use. Results: UMFA was detectable in the milk of 96.1% of the women. Total daily FA intake from supplements was associated with breast folate concentration and species. Breast-milk total folate was 18% higher ( P < 0.001) in supplement users ( n = 401) than in nonusers ( n = 160), a difference driven by women consuming >400 μg FA/d ( P ≤ 0.004). 5-Methyl-THF was 19% lower ( P < 0.001) and UMFA was 126% higher ( P < 0.001) in supplement users than in nonusers. Women who consumed >400 μg FA/d had proportionally lower 5-methyl-THF and higher UMFA than did women who consumed ≤400 μg FA/d. Conclusions: FA-supplement use was associated with modestly higher breast-milk total folate. Detectable breast-milk UMFA was nearly ubiquitous, including in women who did not consume an FA supplement. Breast-milk UMFA was proportionally higher than 5-methyl-THF in women who consumed >400 μg FA/d, thereby suggesting that higher doses exceed the physiologic capacity to metabolize FA and result in the preferential uptake of FA in breast milk. Therefore, FA-supplement doses >400 μg may not be warranted, especially in populations for whom FA fortification is mandatory. © 2017 American Society for Nutrition.

Novel femoral artery terminology: integrating anatomy and clinical procedures leading to standardized intuitive nomenclature.

PubMed

Benninger, Brion

2014-10-01

The objective of this study is to investigate the terminology of the femoral artery and recommended alternative terminology that satisfies both anatomy and clinical arenas.The femoral artery (FA) is often defined as the continuation of the external iliac artery. Specifically, when the external iliac artery reaches directly beneath the inguinal ligament, it becomes the FA. Currently, Terminologia Anatomica (TA) records the profunda femoris or deep femoral as a terminal branch. Clinicians often use superficial femoral artery (SFA) rather than FA and profunda or deep FA. SFA is actually very deep and well protected for most of its journey. On observation, the terminology in current use is not intuitive. The objective of this study was to investigate the terminology associated with the anatomical and clinical anatomical interpretations of the FA and its terminal branches and to suggest a more appropriate terminology that addresses the points of view of the macro anatomist, as well as that of the clinician. Literature search was conducted regarding the nomenclature of the FA and its terminal branches. Dissection of 89 embalmed cadavers (49F, 40M, ages 47-89) was conducted to analyze the morphology of the FA and its branches. Perusal of the literature revealed a difference in terminology between anatomical and clinical textbooks/atlases/journals regarding the FA and its terminal branch. Our dissections suggested that the FA may be better defined vis-à-vis its relationship to the anterior and posterior compartments of the thigh. A difference in terminology exists between the anatomical and clinical arenas. A need for a standardized terminology is necessary because clinicians and their publishers have not adopted TA. This study suggests that the current FA be considered the common FA and the continuation of the FA, the SFA be renamed the anterior FA and the current profunda (the deep FA) be renamed the posterior FA, respectively. The proposed terminology mirrors the lower limb anterior/posterior tibial artery terminology. © 2014 Wiley Periodicals, Inc.

Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

NASA Astrophysics Data System (ADS)

Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

2016-08-01

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

[Role of membrane lipids in myocardial cytoprotection

NASA Technical Reports Server (NTRS)

Grynberg, A.

2000-01-01

The cardiomyocyte capacity to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. This process is based on a balanced fatty acid (FA) metabolism, because FA is the main fuel of the heart, although the most expensive one in oxygen. The pathway is, however, weakly controlled by the cardiac myocyte which can well regulate FA mitochondrial entry but not cell FA uptake. For this reason, several pathological situations often result from either harmful accumulation of FA and derivatives or excess FA-oxidation. Control of the FA/glucose balance by decreased energy production from FA would thus offer an alternative strategy in the treatment of ischaemia, providing the cardiomyocytes weak ability in handling the non-metabolised FA is controlled. The initiation and the regulation of cardiac contraction both result from membrane activity; the other major role of lipids in the heart is their contribution to membrane homeostasis through phospholipid synthesis pathways and phospholipases. The anti-anginal activity of Trimetazidine, reported as a cytoprotective effect without a haemo-dynamic component; is associated with reduced use of FA for energy. However, accumulation of FA and derivatives has never been observed. Trimetazidine is reported to increase significantly the synthesis of phospholipids without influencing the other lipid classes, thus increasing the incorporation of FA in membrane structures. This cytoprotection appears to be based on the redirection of the use of FA to phospholipid synthesis, which would decrease their availability for energy production. This class of compounds, with the same properties as Trimetazidine, offers a metabolic approach to the treatment of ischaemia.

Expression Profiling of Regulatory and Biosynthetic Genes in Contrastingly Anthocyanin Rich Strawberry (Fragaria × ananassa) Cultivars Reveals Key Genetic Determinants of Fruit Color.

PubMed

Hossain, Mohammad Rashed; Kim, Hoy-Taek; Shanmugam, Ashokraj; Nath, Ujjal Kumar; Goswami, Gayatri; Song, Jae-Young; Park, Jong-In; Nou, Ill-Sup

2018-02-26

Anthocyanins are the resultant end-point metabolites of phenylapropanoid/flavonoid (F/P) pathway which is regulated at transcriptional level via a series of structural genes. Identifying the key genes and their potential interactions can provide us with the clue for novel points of intervention for improvement of the trait in strawberry. We profiled the expressions of putative regulatory and biosynthetic genes of cultivated strawberry in three developmental and characteristically colored stages of fruits of contrastingly anthocyanin rich cultivars: Tokun, Maehyang and Soelhyang. Besides FaMYB10, a well-characterized positive regulator, FaMYB5 , FabHLH3 and FabHLH3-delta might also act as potential positive regulators, while FaMYB11 , FaMYB9 , FabHLH33 and FaWD44-1 as potential negative regulators of anthocyanin biosynthesis in these high-anthocyanin cultivars. Among the early BGs, Fa4CL7 , FaF3H , FaCHI1 , FaCHI3 , and FaCHS, and among the late BGs, FaDFR4-3 , FaLDOX , and FaUFGT2 showed significantly higher expression in ripe fruits of high anthocyanin cultivars Maehyang and Soelhyang. Multivariate analysis revealed the association of these genes with total anthocyanins. Increasingly higher expressions of the key genes along the pathway indicates the progressive intensification of pathway flux leading to final higher accumulation of anthocyanins. Identification of these key genetic determinants of anthocyanin regulation and biosynthesis in Korean cultivars will be helpful in designing crop improvement programs.

Analysis of ATP-citrate lyase and malic enzyme mutants of Yarrowia lipolytica points out the importance of mannitol metabolism in fatty acid synthesis.

PubMed

Dulermo, Thierry; Lazar, Zbigniew; Dulermo, Rémi; Rakicka, Magdalena; Haddouche, Ramedane; Nicaud, Jean-Marc

2015-09-01

The role of the two key enzymes of fatty acid (FA) synthesis, ATP-citrate lyase (Acl) and malic enzyme (Mae), was analyzed in the oleaginous yeast Yarrowia lipolytica. In most oleaginous yeasts, Acl and Mae are proposed to provide, respectively, acetyl-CoA and NADPH for FA synthesis. Acl was mainly studied at the biochemical level but no strain depleted for this enzyme was analyzed in oleaginous microorganisms. On the other hand the role of Mae in FA synthesis in Y. lipolytica remains unclear since it was proposed to be a mitochondrial NAD(H)-dependent enzyme and not a cytosolic NADP(H)-dependent enzyme. In this study, we analyzed for the first time strains inactivated for corresponding genes. Inactivation of ACL1 decreases FA synthesis by 60 to 80%, confirming its essential role in FA synthesis in Y. lipolytica. Conversely, inactivation of MAE1 has no effects on FA synthesis, except in a FA overaccumulating strain where it improves FA synthesis by 35%. This result definitively excludes Mae as a major key enzyme for FA synthesis in Y. lipolytica. During the analysis of both mutants, we observed a negative correlation between FA and mannitol level. As mannitol and FA pathways may compete for carbon storage, we inactivated YlSDR, encoding a mannitol dehydrogenase converting fructose and NADPH into mannitol and NADP+. The FA content of the resulting mutant was improved by 60% during growth on fructose, demonstrating that mannitol metabolism may modulate FA synthesis in Y. lipolytica. Copyright © 2015. Published by Elsevier B.V.

Examining binge-eating disorder and food addiction in adults with overweight and obesity.

PubMed

Ivezaj, Valentina; White, Marney A; Grilo, Carlos M

2016-10-01

To compare four subgroups of adults with overweight/obesity: those with binge-eating disorder (BED) only, food addiction (FA) only, both BED + FA, and neither. For this study, 502 individuals with overweight/obesity (body mass index >25 kg/m(2) ) completed a Web-based survey with established measures of eating and health-related behaviors. Most were female (n = 415; 83.2%) and White (n = 404; 80.8%); mean age and body mass index were 38.0 (SD = 13.1) years and 33.6 (SD = 6.9) kg/m(2) , respectively. Among 502 participants with overweight/obesity, 43 (8.5%) met BED criteria, 84 (16.6%) met FA criteria, 51 (10.1%) met both BED + FA criteria, and 328 (64.8%) met neither (control). The three groups with eating pathology (BED, FA, and BED + FA) had significantly greater disturbances on most measures (eating disorder psychopathology, impulsivity, and self-control) than the control group, while the FA and BED + FA groups reported significantly higher depression scores relative to the control group. The three eating groups did not differ significantly from each other. In this online survey, of those with overweight/obesity, nearly one third met criteria for BED, FA, or BED + FA, and these forms of disordered eating were associated with greater pathology relative to individuals with overweight/obesity without BED and FA. Future research should examine whether the presence of BED, FA, or co-occurring BED + FA requires tailored interventions in individuals with overweight or obesity. © 2016 The Obesity Society.

Do constructed wetlands remove metals or increase metal bioavailability?

PubMed

Xu, Xiaoyu; Mills, Gary L

2018-07-15

The H-02 wetland was constructed to treat building process water and storm runoff water from the Tritium Processing Facility on the Department of Energy's Savannah River Site (Aiken, SC). Monthly monitoring of copper (Cu) and zinc (Zn) concentrations and water quality parameters in surface waters continued from 2014 to 2016. Metal speciation was modeled at each sampling occasion. Total Cu and Zn concentrations released to the effluent stream were below the NPDES limit, and the average removal efficiency was 65.9% for Cu and 71.1% for Zn. The metal-removal processes were found out to be seasonally regulated by sulfur cycling indicated by laboratory and model results. High temperature, adequate labile organic matter, and anaerobic conditions during the warm months (February to August) favored sulfate reduction that produced sulfide minerals to significantly remove metals. However, the dominant reaction in sulfur cycling shifted to sulfide oxidation during the cool months (September to next March). High concentrations of metal-organic complexes were observed, especially colloidal complexes of metal and fulvic acid (FA), demonstrating adsorption to organic matter became the primary process for metal removal. Meanwhile, the accumulation of metal-FA complexes in the wetland system will cause negative effects to the surrounding environment as they are biologically reactive, highly bioavailable, and can be easily taken up and transferred to ecosystems by trophic exchange. Copyright © 2018 Elsevier Ltd. All rights reserved.

Construction of hybrid photosynthetic units using peripheral and core antennae from two different species of photosynthetic bacteria: detection of the energy transfer from bacteriochlorophyll a in LH2 to bacteriochlorophyll b in LH1.

PubMed

Fujii, Ritsuko; Shimonaka, Shozo; Uchida, Naoko; Gardiner, Alastair T; Cogdell, Richard J; Sugisaki, Mitsuru; Hashimoto, Hideki

2008-01-01

Typical purple bacterial photosynthetic units consist of supra-molecular arrays of peripheral (LH2) and core (LH1-RC) antenna complexes. Recent atomic force microscopy pictures of photosynthetic units in intact membranes have revealed that the architecture of these units is variable (Scheuring et al. (2005) Biochim Bhiophys Acta 1712:109-127). In this study, we describe methods for the construction of heterologous photosynthetic units in lipid-bilayers from mixtures of purified LH2 (from Rhodopseudomonas acidophila) and LH1-RC (from Rhodopseudomonas viridis) core complexes. The architecture of these reconstituted photosynthetic units can be varied by controlling ratio of added LH2 to core complexes. The arrangement of the complexes was visualized by electron-microscopy in combination with Fourier analysis. The regular trigonal array of the core complexes seen in the native photosynthetic membrane could be regenerated in the reconstituted membranes by temperature cycling. In the presence of added LH2 complexes, this trigonal symmetry was replaced with orthorhombic symmetry. The small lattice lengths for the latter suggest that the constituent unit of the orthorhombic lattice is the LH2. Fluorescence and fluorescence-excitation spectroscopy was applied to the set of the reconstituted membranes prepared with various proportions of LH2 to core complexes. Remarkably, even though the LH2 complexes contain bacteriochlorophyll a, and the core complexes contain bacteriochlorophyll b, it was possible to demonstrate energy transfer from LH2 to the core complexes. These experiments provide a first step along the path toward investigating how changing the architecture of purple bacterial photosynthetic units affects the overall efficiency of light-harvesting.

pH sensitive core-shell magnetic nanoparticles for targeted drug delivery in cancer therapy.

PubMed

Lungu, Iulia Ioana; Rădulescu, Marius; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai

2016-01-01

In the last decade, nanobiotechnology has evolved rapidly with an extensive impact on biomedical area. In order to improve bioavailability and minimize adverse effects, drug delivery systems based on magnetic nanocomposites are under development mainly for cancer imaging and antitumor therapy. In this regard, pH sensitive core-shell magnetic nanoparticles (NPs) with accurate controlled size and shape are synthesized by various modern methods, such as homogeneous precipitation, coprecipitation, microemulsion or polyol approaches, high temperature and hydrothermal reactions, sol-gel reactions, aerosol÷vapor processes and sonolysis. Due to their unique combined physico-chemical and biological properties (such as higher dispensability, chemical and thermal stability, biocompatibility), pH responsive core-shell magnetic NPs are widely investigated for controlled release of cytostatic drugs into the tumor site by means of pH change: magnetite@silicon dioxide (Fe3O4@SiO2), Fe3O4@titanium dioxide (TiO2), β-thiopropionate-polyethylene glycol (PEG)-modified Fe3O4@mSiO2, Fe3O4 NPs core coated with SiO2 with an imidazole group modified PEG-polypeptide (mPEG-poly-L-Asparagine), polyacrylic acid (PAA) and folic acid (FA) coating of the iron oxide NP core, methoxy polyethylene glycol-block-polymethacrylic acid-block-polyglycerol monomethacrylate (MPEG-b-PMAA-b-PGMA) attached by a PGMA block to a Fe3O4 core, PEG-modified polyamidoamine (PAMAM) dendrimer shell with Fe3O4 core and mesoporous silica coated on Fe3O4, mostly coated with an anticancer drug. This review paper highlights the modern research directions currently employed to demonstrate the utility of the pH responsive core-shell magnetic NPs in diagnosis and treatment of oncological diseases.

Novel analytical method to measure formaldehyde release from heated hair straightening cosmetic products: Impact on risk assessment.

PubMed

Galli, Corrado Lodovico; Bettin, Federico; Metra, Pierre; Fidente, Paola; De Dominicis, Emiliano; Marinovich, Marina

2015-08-01

Hair straightening cosmetic products may contain formaldehyde (FA). In Europe, FA is permitted for use in personal care products at concentrations ⩽ 0.2g/100g. According to the Cosmetic Ingredient Review (CIR) Expert Panel products are safe when formalin (a 37% saturated solution of FA in water) concentration does not exceed 0.2g/100g (0.074 g/100g calculated as FA). The official method of reference does not discriminate between "free" FA and FA released into the air after heating FA donors. The method presented here captures and collects the FA released into the air from heated cosmetic products by derivatization with 2,4-dinitrophenylhydrazine and final analysis by UPLC/DAD instrument. Reliable data in terms of linearity, recovery, repeatability and sensitivity are obtained. On a total of 72 market cosmetic products analyzed, 42% showed FA concentrations very close to or above the threshold value (0.074 g/100g calculated as FA) suggested by the Cosmetic Ingredient Review committee, whereas 11 products, negative using the official method of reference, were close to or above the threshold value (0.074 g/100g calculated as FA). This may pose a health problem for occasional users and professional hair stylists. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum Levels of Fetal Antigen 1 in Extreme Nutritional States

PubMed Central

Andries, Alin; Niemeier, Andreas; Støving, Rene K.; Abdallah, Basem M.; Wolf, Anna-Maria; Hørder, Kirsten; Kassem, Moustapha

2012-01-01

Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover. PMID:22844611

Effect of copolymer latexes on physicomechanical properties of mortar containing high volume fly ash as a replacement material of cement.

PubMed

Negim, El-Sayed; Kozhamzharova, Latipa; Gulzhakhan, Yeligbayeva; Khatib, Jamal; Bekbayeva, Lyazzat; Williams, Craig

2014-01-01

This paper investigates the physicomechanical properties of mortar containing high volume of fly ash (FA) as partial replacement of cement in presence of copolymer latexes. Portland cement (PC) was partially replaced with 0, 10, 20, 30 50, and 60% FA. Copolymer latexes were used based on 2-hydroxyethyl acrylate (2-HEA) and 2-hydroxymethylacrylate (2-HEMA). Testing included workability, setting time, absorption, chemically combined water content, compressive strength, and scanning electron microscopy (SEM). The addition of FA to mortar as replacement of PC affected the physicomechanical properties of mortar. As the content of FA in the concrete increased, the setting times (initial and final) were elongated. The results obtained at 28 days of curing indicate that the maximum properties of mortar occur at around 30% FA. Beyond 30% FA the properties of mortar reduce and at 60% FA the properties of mortar are lower than those of the reference mortar without FA. However, the addition of polymer latexes into mortar containing FA improved most of the physicomechanical properties of mortar at all curing times. Compressive strength, combined water, and workability of mortar containing FA premixed with latexes are higher than those of mortar containing FA without latexes.

Effect of Copolymer Latexes on Physicomechanical Properties of Mortar Containing High Volume Fly Ash as a Replacement Material of Cement

PubMed Central

Kozhamzharova, Latipa; Gulzhakhan, Yeligbayeva; Bekbayeva, Lyazzat; Williams, Craig

2014-01-01

This paper investigates the physicomechanical properties of mortar containing high volume of fly ash (FA) as partial replacement of cement in presence of copolymer latexes. Portland cement (PC) was partially replaced with 0, 10, 20, 30 50, and 60% FA. Copolymer latexes were used based on 2-hydroxyethyl acrylate (2-HEA) and 2-hydroxymethylacrylate (2-HEMA). Testing included workability, setting time, absorption, chemically combined water content, compressive strength, and scanning electron microscopy (SEM). The addition of FA to mortar as replacement of PC affected the physicomechanical properties of mortar. As the content of FA in the concrete increased, the setting times (initial and final) were elongated. The results obtained at 28 days of curing indicate that the maximum properties of mortar occur at around 30% FA. Beyond 30% FA the properties of mortar reduce and at 60% FA the properties of mortar are lower than those of the reference mortar without FA. However, the addition of polymer latexes into mortar containing FA improved most of the physicomechanical properties of mortar at all curing times. Compressive strength, combined water, and workability of mortar containing FA premixed with latexes are higher than those of mortar containing FA without latexes. PMID:25254256

Plasma and erythrocyte phospholipid fatty acid profile in professional basketball and football players.

PubMed

Tepsic, Jasna; Vucic, Vesna; Arsic, Aleksandra; Blazencic-Mladenovic, Vera; Mazic, Sanja; Glibetic, Marija

2009-10-01

The effect of intensive long-term physical activity on phospholipid fatty acid (FA) composition has not been studied thoroughly. We determined plasma and erythrocyte phospholipid FA status of professional basketball and football players. Our results showed differences in plasma FA profile not only between sportsmen and sedentary subjects, but also between two groups of sportsmen. Plasma FA profile in basketball players showed significantly higher proportion of n-6 FA (20:3, 20:4, and 22:4) and total polyunsaturated FA (PUFA) than controls, while football players had higher palmitoleic acid (16:1) than basketball players and controls. Total PUFA and 22:4 were also higher in basketball than in football players. Erythrocyte FA profile showed no differences between football players and controls. However, basketball players had higher proportion of 18:0 than controls, higher saturated FA and lower 18:2 than two other groups, and higher 22:4 than football players. These findings suggest that long-term intensive exercise and type of sport influence FA profile.

Fly ash for soil amelioration: A review on the influence of ash blending with inorganic and organic amendments

NASA Astrophysics Data System (ADS)

Ram, L. C.; Masto, R. E.

2014-01-01

Globally, fly ash (FA), generated in huge quantities from coal fired power plants is a problematic solid waste. Utilization of FA as an ameliorant for improving soil quality has received a great deal of attention over the past four decades, and many studies have been carried out worldwide. The silt-sized particles, low bulk density (BD), higher water holding capacity (WHC), favorable pH, and significant presence of plant nutrients in FA, make it a potential amendment for soils. The studies suggest enormous potential for the use of FA to improve cultivable, degraded/waste land, mine soil, landfills, and also to reclaim abandoned ash ponds, for agriculture and forestry. FA application improves the physical, chemical and biological qualities of soils to which it is applied. However, in some cases, depending on the characteristics of FA, the release of trace elements and soluble salts from FA to a soil-plant-human system could be a constraint. The effect is minimal in the case of weathered FA. The findings reflected the heterogeneity of ash characteristics, soil types, and agro-climatic conditions, thus a generalized conclusion on the impact of FA on plant species and soil quality is difficult. It is very important that the application of FA to soil must be very specific depending on the properties of the FA and soil. A considerable amount of research has been carried out to blend FA with varieties of organic and inorganic materials, like lime, gypsum, red mud, animal manure, poultry manure, sewage sludge, composts, press mud, vermicompost, biochar, bioinoculants, etc. Co-application of FA with these materials has much advantage: enhanced nutrient availability, decreased bioavailability of toxic metals, pH buffering, organic matter addition, microbial stimulation, overall improvement in the general health of the soil, etc. The performance of FA blending with organic and inorganic materials is better than FA alone treatments. Farm manure was found to be the most promising amendment used along with FA. While using FA in agriculture as a soil ameliorant, it is better to seek the locally available fitting blend materials for exploiting the benefits from their synergistic interaction. However, continuous research in parallel for long durations to dispel apprehension, if any, is desirable under well defined regulatory measures.

Phenotypic and genetic variability of production traits and milk fatty acid contents across days in milk for Walloon Holstein first-parity cows.

PubMed

Bastin, C; Gengler, N; Soyeurt, H

2011-08-01

The objective of this study was to assess the phenotypic and genetic variability of production traits and milk fatty acid (FA) contents throughout lactation. Genetic parameters for milk, fat, and protein yields, fat and protein contents, and 19 groups and individual FA contents in milk were estimated for first-parity Holstein cows in the Walloon Region of Belgium using single-trait, test-day animal models and random regressions. Data included 130,285 records from 26,166 cows in 531 herds. Heritabilities indicated that de novo synthesized FA were under stronger genetic control than FA originating from the diet and from body fat mobilization. Estimates for saturated short- and medium-chain individual FA ranged from 0.35 for C4:0 to 0.44 for C8:0, whereas those for monounsaturated long-chain individual FA were lower (around 0.18). Moreover, de novo synthesized FA were more heritable in mid to late lactation. Approximate daily genetic correlations among traits were calculated as correlations between daily breeding values for days in milk between 5 and 305. Averaged daily genetic correlations between milk yield and FA contents did not vary strongly among FA (around -0.35) but they varied strongly across days in milk, especially in early lactation. Results indicate that cows selected for high milk yield in early lactation would have lower de novo synthesized FA contents in milk but a slightly higher content of C18:1 cis-9, indicating that such cows might mobilize body fat reserves. Genetic correlations among FA emphasized the combination of FA according to their origin: contents in milk of de novo FA were highly correlated with each other (from 0.64 to 0.99). Results also showed that genetic correlations between C18:1 cis-9 and other FA varied strongly during the first 100 d in milk and reinforced the statement that the release of long-chain FA inhibits FA synthesis in the mammary gland while the cow is in negative energy balance. Finally, results showed that the FA profile in milk changed during the lactation phenotypically and genetically, emphasizing the relationship between the physiological status of cow and milk composition. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Recycled asphalt pavement - fly ash geopolymers as a sustainable pavement base material: Strength and toxic leaching investigations.

PubMed

Hoy, Menglim; Horpibulsuk, Suksun; Rachan, Runglawan; Chinkulkijniwat, Avirut; Arulrajah, Arul

2016-12-15

In this research, a low-carbon stabilization method was studied using Recycled Asphalt Pavement (RAP) and Fly Ash (FA) geopolymers as a sustainable pavement material. The liquid alkaline activator (L) is a mixture of sodium silicate (Na 2 SiO 3 ) and sodium hydroxide (NaOH), and high calcium FA is used as a precursor to synthesize the FA-RAP geopolymers. Unconfined Compressive Strength (UCS) of RAP-FA blend and RAP-FA geopolymer are investigated and compared with the requirement of the national road authorities of Thailand. The leachability of the heavy metals is measured by Toxicity Characteristic Leaching Procedure (TCLP) and compared with international standards. The Scanning Electron Microscopy (SEM) analysis of RAP-FA blend indicates the Calcium Aluminate (Silicate) Hydrate (C-A-S-H) formation, which is due to a reaction between the high calcium in RAP and high silica and alumina in FA. The low geopolymerization products (N-A-S-H) of RAP-FA geopolymer at NaOH/Na 2 SiO 3 =100:0 are detected at the early 7days of curing, hence its UCS is lower than that of RAP-FA blend. The 28-day UCS of RAP-FA geopolymers at various NaOH/Na 2 SiO 3 ratios are significantly higher than that of the RAP-FA blend, which can be attributed to the development of geopolymerization reactions. With the input of Na 2 SiO 3 , the highly soluble silica from Na 2 SiO 3 reacted with leached silica and alumina from FA and RAP and with free calcium from FA and RAP; hence the coexistence of N-A-S-H gel and C-A-S-H products. Therefore, the 7-day UCS values of RAP-FA geopolymers increase with decreasing NaOH/Na 2 SiO 3 ratio. TCLP results demonstrated that there is no environmental risk for both RAP-FA blends and RAP-FA geopolymers in road construction. The geopolymer binder reduces the leaching of heavy metal in RAP-FA mixture. The outcomes from this research will promote the move toward increased applications of recycled materials in a sustainable manner in road construction. Copyright © 2016 Elsevier B.V. All rights reserved.

Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

PubMed

Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

1994-08-29

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

Influence of Fe content on the creep properties of olivine under anhydrous and hydrous conditions

NASA Astrophysics Data System (ADS)

Trimmer, M. B.; Zhao, Y.; Zimmerman, M. E.; Kohlstedt, D. L.

2007-12-01

High-temperature, high-pressure compressive creep experiments were performed on both wet and dry aggregates of Fa75 in a gas-medium deformation apparatus. The results from these experiments are compared with those for San Carlos olivine, Fa10, and our previous results on Fa30 and Fa50 in order to provide a basis for comparing convection models for the mantle of Earth with those for the more iron-rich mantle of Mars. Samples were fabricated from powders of Fa75 that were synthesized from mixtures of Fe2O3 and SiO2 combined with San Carlos olivine. The Fa75 powders were cold-pressed into Fe capsules and then hot-pressed at 300 MPa, 1473 K for 3 h. The average grain size of the resultant hot-pressed samples was ~40 μm. For experiments under hydrous conditions, three drops of deionized water were added before sealing the sample within telescoping Fe cans for deformation. Water bubbles were present both within olivine grains and along grain boundaries, demonstrating that the samples were water-saturated. Triaxial compressive creep experiments were carried out in a servo-controlled, internally heated gas-medium apparatus at 50 K intervals between 1273 and 1423 K and a confining pressure of 300 MPa with differential stress of 10 to 300 MPa. For each sample, creep tests were performed at several differential stresses at a constant temperature to determine the stress exponent or at several temperatures to determine the activation energy for creep. Under anhydrous conditions the viscosity of samples of Fa75 is more than a factor of 10 lower than the viscosity of Fa50. Previous experiments showed a similar relationship between Fa50 and Fa30 and Fa30 and Fa10. Under hydrous conditions the viscosity of samples of Fa75 are about a factor of 5 lower than the viscosity of Fa50, which is less than that observed between Fa50 and Fa30 or Fa30 and Fa10. The viscosity of a sample of a specific Fe:Mg ratio deformed under hydrous conditions is a factor of 10 lower than its counterpart deformed under anhydrous conditions. Therefore, at the same thermodynamic conditions (e.g. P, T, water fugacity), the viscosity of the more Fe-rich mantle of Mars will be a factor of about 3 lower than the mantle of Earth.

Erythrocyte membrane fatty acids in multiple myeloma patients.

PubMed

Jurczyszyn, Artur; Czepiel, Jacek; Gdula-Argasińska, Joanna; Czapkiewicz, Anna; Biesiada, Grażyna; Dróżdż, Mirosław; Perucki, William; Castillo, Jorge J

2014-10-01

Mounting data show that fatty acids (FA) and fatty acid synthase (FAS) function could be potential targets for multiple myeloma (MM) therapy. Our study aimed at comparing the FA composition of erythrocyte membranes of MM patients and healthy controls. MM patients had higher saturated FA and n-6 polyunsaturated FA (PUFA) and lower monounsaturated, n-3 PUFA and trans-FA indices than controls. The n-3/n-6 PUFA ratio was lower in MM patients and there was distinct clustering of variants of individual FA in MM patients. The FA content of erythrocyte membrane could serve as a diagnostic and/or predictive biomarker in MM. Copyright © 2014. Published by Elsevier Ltd.

A never-ending story: the steadily growing family of the FA and FA-like genes

PubMed Central

Gueiderikh, Anna; Rosselli, Filippo; Neto, Januario B.C.

2017-01-01

Abstract Among the chromosome fragility-associated human syndromes that present cancer predisposition, Fanconi anemia (FA) is unique due to its large genetic heterogeneity. To date, mutations in 21 genes have been associated with an FA or an FA-like clinical and cellular phenotype, whose hallmarks are bone marrow failure, predisposition to acute myeloid leukemia and a cellular and chromosomal hypersensitivity to DNA crosslinking agents exposure. The goal of this review is to trace the history of the identification of FA genes, a history that started in the eighties and is not yet over, as indicated by the cloning of a twenty-first FA gene in 2016. PMID:28558075

The effect of peculiar complex core balance training on isokinetic muscle functions of the knee and lumbus

PubMed Central

Lee, Myungsun; Han, Gunsoo

2016-01-01

[Purpose] This study aimed to investigate the effect of peculiar complex core balance training on the isokinetic muscle function of the knee joint and lumbus to provide fundamental data for establishing a training program that focuses on improving the performance and prevention of injury by developing the core and low extremity muscles. [Subjects and Methods] The participants in this study included a total of ten high school athletes involved in a throwing event for over five years. The subjects were randomly divided into two groups: The experimental group (N=5) and the control group (N=5). The experimental group underwent peculiar complex core balance training. [Results] According to the analysis of covariance, there was a significant effect of peculiar complex core balance training. Therefore, the isokinetic muscle function of the knee joint and lumbus in the experimental group participating in peculiar complex core balance training was significantly increased compared to the control group. [Conclusion] It is concluded that peculiar complex core balance training had a positive effect on the isokinetic muscle function of the knee and lumbus in throwing event athletes. PMID:27190470

Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain

PubMed Central

Zhai, Rongwei; Zheng, Na; Rizak, Joshua; Hu, Xintian

2016-01-01

Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology. PMID:27066393

Pediatric Food Allergies and Psychosocial Functioning: Examining the Potential Moderating Roles of Maternal Distress and Overprotection.

PubMed

Chow, Candice; Pincus, Donna B; Comer, Jonathan S

2015-01-01

Identify factors associated with maternal perceptions of health-related quality of life (QoL) among youth with food allergies (FA), and identify maternal factors that may moderate relationships between FA-related challenges and child QoL. In all, 533 mothers of children with FA completed measures assessing characteristics of their child's FA, maternal perceptions of child QoL, maternal psychological distress, and maternal overprotection. FA severity, maternal psychological distress, and overprotection were significantly associated with maternal reports of poorer child functioning and/or poorer QoL among youth with FA. Hierarchical linear regression analyses showed an FA severity by maternal distress interaction in the prediction of child FA-related anxiety; children of higher stress mothers showed a stronger link between auto-injector use and anxiety than children of lower stress mothers. When identifying youth with FA who are at risk for low QoL, it is important to assess history of FA-related challenges, parental psychological distress, and overprotection. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Green synthesis of low-toxicity graphene-fulvic acid with an open band gap enhances demethylation of methylmercury.

PubMed

Hu, Xiangang; Mu, Li; Lu, Kaicheng; Kang, Jia; Zhou, Qixing

2014-06-25

The demethylation of methylmercury has received substantial attention. Here, a novel chemical method for the demethylation of methylmercury is proposed. The low-toxicity graphene-fulvic acid (FA, a ubiquitous material in the environment) was synthesized without the use of a chemical reagent. The hybridized graphene-FA presented an indirect open band gap of 2.25-2.87 eV as well as adequate aqueous dispersion. More importantly, the hybridized graphene-FA exhibited 6- and 10-fold higher photocatalytic efficiencies for the demethylation of methylmercury than FA and free FA with graphene, respectively. This result implies that immobilized, rather than free, FA accelerated the catalysis. Furthermore, inorganic mercuric ion, elemental mercury, and mercuric oxide were identified as the primary demethylation products. For free FA with graphene, graphene quenches the excited-state FA, inhibiting the demethylation by electron transfer. In contrast, the graphene of the self-assembled graphene-FA serves as an electron reservoir, causing electron-hole pair separation. Graphene-FA showed a negligible toxicity toward microalgae compared to graphene. The above results reveal that the green synthesis of graphene and organic molecules is a convenient strategy for obtaining effective cocatalysts.

Retention of first aid and basic life support skills in undergraduate medical students.

PubMed

de Ruijter, Pim A; Biersteker, Heleen A; Biert, Jan; van Goor, Harry; Tan, Edward C

2014-01-01

Undergraduate medical students follow a compulsory first aid (FA) and basic life support (BLS) course. Retention of BLS seems poor and only little information is provided on the retention of FA skills. This study aims at evaluating 1- and 2-year retention of FA and BLS training in undergraduate medical students. One hundred and twenty students were randomly selected from first year (n=349) medical students who successfully followed a compulsory FA and BLS course. From these 120 students, 94 (78%) and 69 (58%) participated in retention tests of FA and BLS skills after 1 and 2 years, respectively. The assessment consisted of two FA stations and one BLS station. After 1 year, only 2% passed both FA and BLS stations and 68% failed both FA and BLS stations. After 2 years, 5% passed and 50% failed both FA and BLS stations. Despite the high failure rate at the stations, 90% adequately checked vital signs and started cardiopulmonary resuscitation appropriately. The long-term retention of FA and BLS skills after a compulsory course in the first year is poor. Adequate check of vital signs and commencing cardiopulmonary resuscitation retained longer.

Retention of first aid and basic life support skills in undergraduate medical students.

PubMed

de Ruijter, Pim A; Biersteker, Heleen A; Biert, Jan; van Goor, Harry; Tan, Edward C

2014-01-01

Background Undergraduate medical students follow a compulsory first aid (FA) and basic life support (BLS) course. Retention of BLS seems poor and only little information is provided on the retention of FA skills. This study aims at evaluating 1- and 2-year retention of FA and BLS training in undergraduate medical students. Methods One hundred and twenty students were randomly selected from first year (n=349) medical students who successfully followed a compulsory FA and BLS course. From these 120 students, 94 (78%) and 69 (58%) participated in retention tests of FA and BLS skills after 1 and 2 years, respectively. The assessment consisted of two FA stations and one BLS station. Results After 1 year, only 2% passed both FA and BLS stations and 68% failed both FA and BLS stations. After 2 years, 5% passed and 50% failed both FA and BLS stations. Despite the high failure rate at the stations, 90% adequately checked vital signs and started cardiopulmonary resuscitation appropriately. Conclusions The long-term retention of FA and BLS skills after a compulsory course in the first year is poor. Adequate check of vital signs and commencing cardiopulmonary resuscitation retained longer.

Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models.

PubMed

Bakker, Sietske T; de Winter, Johan P; te Riele, Hein

2013-01-01

Fanconi anaemia (FA) is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF), haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL)-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.

Effects of intravenous gadolinium administration and flip angle on the assessment of liver fat signal fraction with opposed-phase and in-phase imaging.

PubMed

Yokoo, Takeshi; Collins, Julie M; Hanna, Robert F; Bydder, Mark; Middleton, Michael S; Sirlin, Claude B

2008-07-01

To assess the effects of intravenous gadolinium (Gd) and flip angle (FA) on liver fat quantification by opposed-phase (OP) and in-phase (IP) imaging. Our Institutional Review Board (IRB) approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant, retrospective, clinical study. We identified 79 patients in whom abdominal OP and IP gradient-echoes were obtained at 1.5T before and after Gd administration. All 79 patients were imaged at high FA (> or =70 degrees ); 57 were also imaged at low FA (< or =20 degrees ). Fat signal fraction (FSF) was calculated from pre- and post-Gd liver images for each subject and FA using the formula, FSF = (S(IP) - S(OP))/2S(IP), where S(IP) and S(OP) are the OP and IP signal intensities, respectively. The dataset pairs (pre-Gd vs. post-Gd; high-FA vs. low-FA) were compared using linear regression analysis. Before Gd, FSF was significantly greater at high FA than at low FA, with regression parameters (slope/intercept) of 1.27*/0.02*, where * indicates P value <0.01. After Gd, FSF was similar at high and low FA (0.99/-0.00). Gd administration caused an FA-dependent reduction in FSF, larger at high FA (0.68*/-0.03*) than at low FA (0.94, -0.01*). FSF by OP-IP imaging is highly dependent on FA before Gd, but this dependency is eliminated after administration of Gd. Gd appears to minimize the effect of T1-weighting and may improve the accuracy of liver fat quantification. (c) 2008 Wiley-Liss, Inc.

Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells.

PubMed

Zhao, Xueheng; Brusadelli, Marion G; Sauter, Sharon; Butsch Kovacic, Melinda; Zhang, Wujuan; Romick-Rosendale, Lindsey E; Lambert, Paul F; Setchell, Kenneth D R; Wells, Susanne I

2018-06-01

Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells. Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient-derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation. Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Lipid Partitioning, Incomplete Fatty Acid Oxidation, and Insulin Signal Transduction in Primary Human Muscle Cells: Effects of Severe Obesity, Fatty Acid Incubation, and Fatty Acid Translocase/CD36 Overexpression

PubMed Central

Bell, Jill A.; Reed, Melissa A.; Consitt, Leslie A.; Martin, Ola J.; Haynie, Kimberly R.; Hulver, Matthew W.; Muoio, Deborah M.; Dohm, G. Lynis

2010-01-01

Context: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. Objective: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes. Design, Setting, and Patients: Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology. Results: Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects. Conclusions: Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter. PMID:20427507

FANCD2 monoubiquitination and activation by hexavalent chromium [Cr(VI)] exposure

PubMed Central

Vilcheck, Susan K.; Ceryak, Susan; O’Brien, Travis J.; Patierno, Steven R.

2007-01-01

Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by congenital abnormalities, progressive bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA crosslinking agents. FA is a genetically heterogeneous disease with at least 11 complementation groups. The eight cloned FA proteins interact in a common pathway with established DNA-damage-response proteins, including BRCA1 and ATM. Six FA proteins (A, C, E, F, G, and L) regulate the monoubiquitination of FANCD2 after DNA damage by crosslinking agents, which targets FANCD2 to BRCA1 nuclear foci containing BRCA2 (FANCD1) and RAD51. Some forms of hexavalent chromium [Cr(VI)] are implicated as respiratory carcinogens and induce several types of DNA lesions, including DNA interstrand crosslinks. We have shown that FA-A fibroblasts are hypersensitive to both Cr(VI)-induced apoptosis and clonogenic lethality. Here we show that Cr(VI) treatment induced monoubiquitination of FANCD2 in normal human fibroblasts, providing the first molecular evidence of Cr(VI)-induced activation of the FA pathway. FA-A fibroblasts demonstrated no FANCD2 monoubiquitination, in keeping with the requirement of FA-A for this modification. We also found that Cr(VI) treatment induced significantly more S-phase-dependent DNA double strand breaks (DSBs), as measured by γ-H2AX expression, in FA-A fibroblasts compared to normal cells. However, and notably, DSBs were repaired equally in both normal and FA-A fibroblasts during recovery from Cr(VI) treatment. While previous research on FA has defined the genetic causes of this disease, it is critical in terms of individual risk assessment to address how cells from FA patients respond to genotoxic insult. PMID:16893675

Dietary fatty acid composition and the homeostatic regulation of mitochondrial phospholipid classes in red muscle of rainbow trout (Oncorhynchus mykiss).

PubMed

Martin, Nicolas; Kraffe, Edouard; Le Grand, Fabienne; Marty, Yanic; Bureau, Dominique P; Guderley, Helga

2015-01-01

Although dietary lipid quality markedly affects fatty acid (FA) composition of mitochondrial membranes from rainbow trout red muscle (Oncorhynchus mykiss), mitochondrial processes are relatively unchanged. As certain classes of phospholipids interact more intimately with membrane proteins than others, we examined whether specific phospholipid classes from these muscle mitochondria were more affected by dietary FA composition than others. To test this hypothesis, we fed trout with two diets differing only in their FA composition: Diet 1 had higher levels of 18:1n-9 and 18:2n-6 than Diet 2, while 22:6n-3 and 22:5n-6 were virtually absent from Diet 1 and high in Diet 2. After 5 months, trout fed Diet 2 had higher proportions of phosphatidylcholine (PC) and less phosphatidylethanolamine (PE) in mitochondrial membranes than those fed Diet 1. The FA composition of PC, PE and cardiolipin (CL) showed clear evidence of regulated incorporation of dietary FA. For trout fed Diet 2, 22:6n-3 was the most abundant FA in PC, PE and CL. The n-6 FA were consistently higher in all phospholipid classes of trout fed Diet 1, with shorter n-6 FA being favoured in CL than in PC and PE. Despite these marked changes in individual FA levels with diet, general characteristics such as total polyunsaturated FA, total monounsaturated FA and total saturated FA were conserved in PE and CL, confirming differential regulation of the FA composition of PC, PE and CL. The regulated changes of phospholipid classes presumably maintain critical membrane characteristics despite varying nutritional quality. We postulate that these changes aim to protect mitochondrial function. © 2014 Wiley Periodicals, Inc.

Delta-like 1/Fetal Antigen-1 (Dlk1/FA1) Is a Novel Regulator of Chondrogenic Cell Differentiation via Inhibition of the Akt Kinase-dependent Pathway*

PubMed Central

Chen, Li; Qanie, Diyako; Jafari, Abbas; Taipaleenmaki, Hanna; Jensen, Charlotte H.; Säämänen, Anna-Marja; Sanz, Maria Luisa Nueda; Laborda, Jorge; Abdallah, Basem M.; Kassem, Moustapha

2011-01-01

Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1 protein to the medium strongly inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation. Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1-mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways that leads to its inhibitory effects on chondrogenesis. PMID:21724852

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.

PubMed

Faivre, L; Guardiola, P; Lewis, C; Dokal, I; Ebell, W; Zatterale, A; Altay, C; Poole, J; Stones, D; Kwee, M L; van Weel-Sipman, M; Havenga, C; Morgan, N; de Winter, J; Digweed, M; Savoia, A; Pronk, J; de Ravel, T; Jansen, S; Joenje, H; Gluckman, E; Mathew, C G

2000-12-15

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (Blood. 2000;96:4064-4070)

The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL*

PubMed Central

Miles, Jennifer A.; Frost, Mark G.; Carroll, Eilis; Rowe, Michelle L.; Howard, Mark J.; Sidhu, Ateesh; Chaugule, Viduth K.; Alpi, Arno F.; Walden, Helen

2015-01-01

The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo. PMID:26149689

Immobilization free electrochemical biosensor for folate receptor in cancer cells based on terminal protection.

PubMed

Ni, Jiancong; Wang, Qingxiang; Yang, Weiqiang; Zhao, Mengmeng; Zhang, Ying; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Yang, Huang-Hao

2016-12-15

The determination of folate receptor (FR) that over expressed in vast quantity of cancerous cells frequently is significant for the clinical diagnosis and treatment of cancers. Many DNA-based electrochemical biosensors have been developed for FR detection with high selectivity and sensitivity, but most of them need complicated immobilization of DNA on the electrode surface firstly, which is tedious and therefore results in the poor reproducibility. In this study, a simple, sensitive, and selective electrochemical FR biosensor in cancer cells has been proposed, which combines the advantages of the convenient immobilization-free homogeneous indium tin oxide (ITO)-based electrochemical detection strategy and the high selectivity of the terminal protection of small molecule linked DNA. The small molecule of folic acid (FA) and an electroactive molecule of ferrocence (Fc) were tethered to 3'- and 5'-end of an arbitrary single-stranded DNA (ssDNA), respectively, forming the FA-ssDNA-Fc complex. In the absence of the target FR, the FA-ssDNA-Fc was degraded by exonuclease I (Exo I) from 3'-end and produced a free Fc, diffusing freely to the ITO electrode surface and resulting in strong electrochemical signal. When the target FR was present, the FA-ssDNA-Fc was bound to FR through specific interaction with FA anchored at the 3'-end, effectively protecting the ssDNA strand from hydrolysis by Exo I. The FR-FA-ssDNA-Fc could not diffuse easily to the negatively charged ITO electrode surface due to the electrostatic repulsion between the DNA strand and the negatively charged ITO electrode, so electrochemical signal reduced. The decreased electrochemical signal has a linear relationship with the logarithm of FR concentration in range of 10fM to 10nM with a detection limit of 3.8fM (S/N=3). The proposed biosensor has been applied to detect FR in HeLa cancer cells, and the decreased electrochemical signal has a linear relationship with the logarithm of cell concentration ranging from 100-10000cell/mL. Compared with the traditional heterogeneous electrochemical FR biosensors, the proposed biosensor owns the merits of the simplicity and high specificity, presenting the great potential application in the area of early diagnosis of cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of fulvic acids on bio-methanogenic treatment of municipal solid waste incineration leachate.

PubMed

Dang, Yan; Lei, Yuqing; Liu, Zhao; Xue, Yiting; Sun, Dezhi; Wang, Li-Ying; Holmes, Dawn E

2016-12-01

A considerable amount of leachate with high fulvic acid (FA) content is generated during the municipal solid waste (MSW) incineration process. This incineration leachate is usually processed by downstream bio-methanogenic treatment. However, few studies have examined the impact that these compounds have on methanogenesis and how they are degraded and transformed during the treatment process. In this study, a laboratory-scale expanded granular sludge bed (EGSB) reactor was operated with MSW incineration leachate containing various concentrations of FA (1500 mg/L to 8000 mg/L) provided as the influent. We found that FA degradation rates decreased from 86% to 72% when FA concentrations in the reactor were increased, and that molecular size, level of humification and aromatization of the residual FA macromolecules all increased after bio-methanogenic treatment. Increasing FA influent concentrations also inhibited growth of hydrogenotrophic methanogens from the genus Methanobacterium and syntrophic bacteria from the genus Syntrophomonas, which resulted in a decrease in methane production and a concomitant increase in CO 2 content in the biogas. Sequences most similar to species from the genus Anaerolinea went up as FA concentrations increased. Bacteria from this genus are capable of extracellular electron transfer and may be using FA as an electron acceptor for growth or as a shuttle for syntrophic exchange with other microorganisms in the reactor. In order to determine whether FA could serve as an electron shuttle to promote syntrophy in an anaerobic digester, co-cultures of Geobacter metallireducens and G. sulfurreducens were grown in the presence of FA from raw leachate or from residual bioreactor effluent. While raw FA stimulated electron transfer between these two bacteria, residual FA did not have any electron shuttling abilities, indicating that FA underwent a significant transformation during the bio-methanogenic treatment process. These results are significant and should be taken into consideration when optimizing anaerobic bioreactors used to treat MSW incineration leachate high in FA content. Copyright © 2016 Elsevier Ltd. All rights reserved.

131I-Traced PLGA-Lipid Nanoparticles as Drug Delivery Carriers for the Targeted Chemotherapeutic Treatment of Melanoma

NASA Astrophysics Data System (ADS)

Wang, Haiyan; Sheng, Weizhong

2017-05-01

Herein, folic acid (FA) conjugated Poly(d,l-lactide-co-glycolide) (PLGA)-lipid composites (FA-PL) were developed as nanocarriers for the targeted delivery of insoluble anti-cancer drug paclitaxel (PTX), resulting FA-PLP nanoparticles. Furthermore, 131I, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP-131I) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP-131I nanoparticles had a spherical morphology with great stability, a narrow size distribution (165.6 and 181.2 nm), and -22.1 mV in average zeta potential. Confocal laser scanning microscopy indicated that the targeting molecule FA promotes PLP-131I uptake by melanoma B16F10 cells, which was further confirmed by the cell incorporation rate via 131I activity detection as measured by a gamma counter. FA-PLP-131I without PTX (FA-PL-131I) shows minor cytotoxicity, good biocompatibility, while FA-PLP-131I was demonstrated to have efficient cell viability suppression compared to free PTX and PLP-131I. Following intravenous injection, the blood circulation half-life of free PTX ( t 1/2 = 5.4 ± 0.23 h) was prolonged to 18.5 ± 0.5 h by FA-PLP-131I. Through FA targeting, the tumor uptake of FA-PLP-131I was approximately 4.41- and 12.8-fold higher compared to that of PLP-131I and free PTX-131I, respectively. Moreover, following 40 days of treatment, FA-PLP-131I showed an improved tumor inhibition effect compared to free PTX and PLP-131I, with no relapse and no remarkable systemic in vivo toxicity. The results demonstrate that the 131I-labeled PLGA-lipid nanoparticle can be simultaneously applied for targeted drug delivery and reliable tracking of drugs in vivo.

Proteasome activity is important for replication recovery, CHK1 phosphorylation and prevention of G2 arrest after low-dose formaldehyde

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

Ortega-Atienza, Sara; Green, Samantha E.; Zhitkovich, Anatoly, E-mail: anatoly_zhitkovich@brown.edu

2015-07-15

Formaldehyde (FA) is a human carcinogen with numerous sources of environmental and occupational exposures. This reactive aldehyde is also produced endogenously during metabolism of drugs and other processes. DNA–protein crosslinks (DPCs) are considered to be the main genotoxic lesions for FA. Accumulating evidence suggests that DPC repair in high eukaryotes involves proteolysis of crosslinked proteins. Here, we examined a role of the main cellular proteolytic machinery proteasomes in toxic responses of human lung cells to low FA doses. We found that transient inhibition of proteasome activity increased cytotoxicity and diminished clonogenic viability of FA-treated cells. Proteasome inactivation exacerbated suppressive effectsmore » of FA on DNA replication and increased the levels of the genotoxic stress marker γ-H2AX in normal human cells. A transient loss of proteasome activity in FA-exposed cells also caused delayed perturbations of cell cycle, which included G2 arrest and a depletion of S-phase populations at FA doses that had no effects in control cells. Proteasome activity diminished p53-Ser15 phosphorylation but was important for FA-induced CHK1 phosphorylation, which is a biochemical marker of DPC proteolysis in replicating cells. Unlike FA, proteasome inhibition had no effect on cell survival and CHK1 phosphorylation by the non-DPC replication stressor hydroxyurea. Overall, we obtained evidence for the importance of proteasomes in protection of human cells against biologically relevant doses of FA. Biochemically, our findings indicate the involvement of proteasomes in proteolytic repair of DPC, which removes replication blockage by these highly bulky lesions. - Highlights: • Proteasome inhibition enhances cytotoxicity of low-dose FA in human lung cells. • Active proteasomes diminish replication-inhibiting effects of FA. • Proteasome activity prevents delayed G2 arrest in FA-treated cells. • Proteasome inhibition exacerbates replication stress by FA in normal human cells. • Protective role of proteasomes is linked to repair of DNA–protein crosslinks.« less

Curcumin-guided nanotherapy: a lipid-based nanomedicine for targeted drug delivery in breast cancer therapy.

PubMed

Lin, Mingzhen; Teng, Lili; Wang, Yang; Zhang, Jiaxin; Sun, Xianglian

2016-05-01

Delivery of anti-cancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment. In this study, folate (FA) decorated nanostructured lipid carriers (NLCs) were constructed as nanomedicine for the delivery of curcumin (CUR). CUR-loaded NLCs (CUR-NLCs) were prepared. FA containing polyethylene glycol (PEG)-distearoylphosphatidylethanolamine (DSPE) (FA-PEG-DSPE) was synthesized and used for the decoration of CUR-NLCs. Their particle size, zeta potential, and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study FA decorated CUR-NLCs (FA-CUR-NLCs) was tested in MCF-7 human breast cancer cells (MCF-7 cells). In vivo anti-tumor efficacies of the carriers were evaluated on mice bearing breast cancer model. The optimum FA-CUR-NLCs formulations with the particle size of 127 nm and with a +13 mV surface charge. The growth of MCF-7 cells in vitro was obviously inhibited. FA-CUR-NLCs also displayed the best anti-tumor activity than other formulations in vivo. The results demonstrated that FA-CUR-NLCs were efficient in selective delivery to cancer cells over-expressing FA receptors (FRs). Also FA-CUR-NLCs transfer CUR to the breast cancer cells, enhance the anti-tumor capacity. Thus, FA-CUR-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.

Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.

PubMed

Mantere, T; Haanpää, M; Hanenberg, H; Schleutker, J; Kallioniemi, A; Kähkönen, M; Parto, K; Avela, K; Aittomäki, K; von Koskull, H; Hartikainen, J M; Kosma, V-M; Laasanen, S-L; Mannermaa, A; Pylkäs, K; Winqvist, R

2015-07-01

Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recurrence of Neurological Deficits in an F/A-18D Pilot Following Loss of Cabin Pressure at Altitude.

PubMed

Robinson, Tom; Evangelista, Jose S; Latham, Emi; Mukherjee, Samir T; Pilmanis, Andrew

2016-08-01

Supersonic, high altitude aviation places its pilots and aircrew in complex environments, which may lead to injury that is not easily diagnosed or simply treated. Decompression illness (either venous or arterial) and environmental conditions (e.g., abnormal gases and pressure) are the most likely adverse effects aircrew often face. Though symptomatic aircrew personnel may occasionally require hyperbaric oxygen treatment, it is rare to require more than one treatment before returning to baseline function. This challenging aviation case details the clinical course and discusses the salient physiological factors of an F/A-18D pilot who presented with neurological symptoms following loss of cabin pressure at altitude. Most crucial to this discussion was the requirement for multiple hyperbaric oxygen treatments over several days due to recurrence of symptoms. The likelihood of recurrence during and after future flights cannot be estimated with accuracy. This case illustrates a degree of recurrences for neurological symptoms in aviation (hypobaric exposure to hyperbaric baseline environment) that has not previously been described. Robinson T, Evangelista JS III, Latham E, Mukherjee ST, Pilmanis A. Recurrence of neurological deficits in an F/A-18D pilot following loss of cabin pressure at altitude. Aerosp Med Hum Perform. 2016; 87(8):740-744.

Effect of FA/O complexing agents and H2O2 on chemical mechanical polishing of ruthenium in weakly alkaline slurry

NASA Astrophysics Data System (ADS)

Bo, Duan; Weijing, An; Jianwei, Zhou; Shuai, Wang

2015-07-01

This paper investigated the effect of FA/O and hydrogen peroxide (H2O2) on ruthenium (Ru) removal rate (RR) and static etching rate (SER). It was revealed that Ru RR and SER first linearly increased then slowly decreaseed with the increasing H2O2 probably due to the formation of uniform Ru oxides on the surface during polishing. Their corrosion behaviors and states of surface oxidation were analyzed. In addition, FA/O could chelate Ru oxides (such as (RuO4)2- and RuO4- changed into soluble amine salts [R(NH3)4] (RuO4)2) and enhance Ru RR. The non-ionic surfactant AD was used to improve the Ru CMP performance. In particular, the addition of AD can lead to significant improvement of the surface roughness. Project supported by the Special Project Items No. 2 in National Long-Term Technology Development Plan (No. 2009ZX02308), the Natural Science Foundation of Hebei Province (No. E2013202247), the Science and Technology Plan Project of Hebei Province (Nos. Z2010112, 10213936), the Hebei Provincial Department of Education Fund (No. 2011128), and the Scientific Research Fund of Hebei Provincial Education (No. QN2014208).

Sex differences in white matter development during adolescence: a DTI study.

PubMed

Wang, Yingying; Adamson, Chris; Yuan, Weihong; Altaye, Mekibib; Rajagopal, Akila; Byars, Anna W; Holland, Scott K

2012-10-10

Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure. Copyright © 2012 Elsevier B.V. All rights reserved.

Seasonal variation and mixing behaviour of glutathione, thioacetamide and fulvic acids in a temperate macrotidal estuary (Aulne, NW France)

NASA Astrophysics Data System (ADS)

Marie, Lauriane; Pernet-Coudrier, Benoît; Waeles, Matthieu; Riso, Ricardo

2017-01-01

Fulvic acids and two dissolved reduced sulphur substances (RSS) were analysed for one year along the whole salinity gradient in the Aulne estuary (north-western France) using differential pulse cathodic stripping voltammetry. Concentrations of glutathione-like (GSH-like), thioacetamide-like (TA-like) and fulvic acid-like (FA-like) compounds ranged from 0.2 to 38 nmol L-1, from 0.02 to 6.6 μmol L-1 and from 0.1 to 4 mgC L-1, respectively. Our results indicated primarily allochthonous-continental sources for all three compounds. The behaviour of GSH-like compounds along the salinity gradient was globally conservative, with minor losses (<25%), possibly limited due to metal complexation. TA-like compounds generally displayed non-conservative behaviour with important removals. In terms of the TA-like budget, losses were counterbalanced by exceptional inputs occurring in the flood period (February). FA-like compounds were intensely degraded (∼50%) in the last section of the river and then behaved conservatively in the estuary. The annual flux of FA-like compounds to coastal waters was 2800 ± 600 tC. This flux was mainly (74%) delivered during the high discharge period, in accordance with its known pedogenic origin.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

PubMed

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

What is an Oceanic Core Complex?

NASA Astrophysics Data System (ADS)

Schroeder, T.; Cheadle, M. J.

2007-12-01

The Mid-Atlantic Ridge (MAR) 75km north and south of the 15-20 Fracture Zone (FZ) has produced upper oceanic lithosphere composed dominantly of mantle peridotite with gabbro intrusions. In the absence of diapirism, mantle peridotite can only be exposed on the seafloor by extensional faulting, thus the sea floor geology and bathymetry provide widespread evidence for extensive low-angle faulting. However, only 3% of the seafloor in this region has the domal morphology characteristic of features that have been termed oceanic core complexes; suggesting that other processes, in addition to low-angle faulting, are responsible for the generation of domal core complexes. Most low-angle faults near the 15-20 FZ form gently dipping (10-15°), 10-15km-wide dip slopes on the flanks of 2000m relief bathymetric ridges that are up to 15-40km long (parallel to the MAR). Core recovered from ODP Leg 209 drill holes in these ridges is dominantly peridotite with small (<50m thick) gabbro intrusions. The peridotite is cut by a very high density of brittle faults dipping at both steep and gentle angles. Several holes also contain long-lived shear zones/faults in their upper reaches in which strain was localized at granulite facies, indicated by mylonitic olivine and cpx, and remained active during cooling to sub-greenschist grade, indicated by cross-cutting of progressively lower-grade syn-deformation mineral assemblages. These observations suggest that seafloor spreading is largely accommodated here by slip on low-angle faults, and that these faults are correctly termed detachment faults. Holes drilled into a domal oceanic core complex north of the 15-20 FZ during Leg 209 (ODP Site 1275) recovered dominantly gabbro and not mantle peridotite. This hole is cut by significantly fewer brittle and ductile faults than the peridotite drilled at the non-core-complex detachment fault sites. The detachment fault in the upper reaches (50m) of Site 1275 was localized at temperatures near feldspar's ductile-to-brittle transition, indicated by cataclasis with minor crystal plastic flow in plagioclase, and a lack of pervasive pure-ductile deformation. Amphibole-plagioclase thermometry in the fault yields equilibrium temperatures from 600-650°C, compared to equilibrium temperatures of 750-850°C for the gabbro outside the fault. The presence of talc- chlorite schists and cataclasites cutting the higher-temperature deformation textures indicate fault activity down- temperature from amphibolite through greenschist facies. This core-complex-bounding fault contrasts with the fault that bounds the Atlantis Bank Core Complex on the Southwest Indian Ridge (SWIR). There, the fault is 100m thick and strain was initially localized at granulite grade (>800°C) (Mehl & Hirth, 2007); significantly hotter than the Site 1275 fault. Therefore, the formation of core-complex morphology does not seem to depend on the initial faulting conditions. Both oceanic core complexes that have been drilled besides Site 1275, Atlantis Massif at 30°N (IODP Hole 1309D) on the MAR and Atlantis Bank on the SWIR (ODP Hole 735B), are also comprised dominantly of gabbro. This suggests that magma supply may be an essential requirement for core complex formation and raises the question whether all domal oceanic core complexes are cored by gabbro? We also ask whether the term 'oceanic core complex' should be restricted to these domal features and not applied to detachment-bound, non- domal, peridotite-cored ridges; or if these should be considered two sub-classes of oceanic core complexes.

Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging.

PubMed

Kevadiya, Bhavesh D; Bade, Aditya N; Woldstad, Christopher; Edagwa, Benson J; McMillan, JoEllyn M; Sajja, Balasrinivasa R; Boska, Michael D; Gendelman, Howard E

2017-02-01

The size, shape and chemical composition of europium (Eu 3+ ) cobalt ferrite (CFEu) nanoparticles were optimized for use as a "multimodal imaging nanoprobe" for combined fluorescence and magnetic resonance bioimaging. Doping Eu 3+ ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ∼7.2nm) were prepared by solvothermal techniques and encapsulated into poloxamer 407-coated mesoporous silica (Si-P407) to form superparamagnetic monodisperse Si-CFEu nanoparticles with a size of ∼140nm. Folic acid (FA) nanoparticle decoration (FA-Si-CFEu, size ∼140nm) facilitated monocyte-derived macrophage (MDM) targeting. FA-Si-CFEu MDM uptake and retention was higher than seen with Si-CFEu nanoparticles. The transverse relaxivity of both Si-CFEu and FA-Si-CFEu particles were r 2 =433.42mM -1 s -1 and r 2 =419.52mM -1 s -1 (in saline) and r 2 =736.57mM -1 s -1 and r 2 =814.41mM -1 s -1 (in MDM), respectively. The results were greater than a log order-of-magnitude than what was observed at replicate iron concentrations for ultrasmall superparamagnetic iron oxide (USPIO) particles (r 2 =31.15mM -1 s -1 in saline) and paralleled data sets obtained for T 2 magnetic resonance imaging. We now provide a developmental opportunity to employ these novel particles for theranostic drug distribution and efficacy evaluations. A novel europium (Eu 3+ ) doped cobalt ferrite (Si-CFEu) nanoparticle was produced for use as a bioimaging probe. Its notable multifunctional, fluorescence and imaging properties, allows rapid screening of future drug biodistribution. Decoration of the Si-CFEu particles with folic acid increased its sensitivity and specificity for magnetic resonance imaging over a more conventional ultrasmall superparamagnetic iron oxide particles. The future use of these particles in theranostic tests will serve as a platform for designing improved drug delivery strategies to combat inflammatory and infectious diseases. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

[Modifications in myocardial energy metabolism in diabetic patients

NASA Technical Reports Server (NTRS)

Grynberg, A.

2001-01-01

The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by a different metabolic "status" with similarities to that of myocardium in coronary disease. Diabetes and other chronic cardiac diseases share common FA metabolism disorders leading to an altered energy balance, a decrease in long chain polyunsaturated Fas, and altered FA profiles in cardiac membranes. These disturbances, however, do not represent independent therapeutic targets, and should be considered as a whole.

Pre-operative declining proportion of fractional anisotropy of trigeminal nerve is correlated with the outcome of micro-vascular decompression surgery.

PubMed

Chen, Fanfan; Chen, Lei; Li, Wei; Li, Ling; Xu, Xiangdong; Li, Weimin; Le, Wuhua; Xie, Wei; He, Hua; Li, Peng

2016-07-16

Type 2 trigeminal neuralgia (TN) is an intractable neuropathic pain syndrome compared with type 1 TN because of the difficulty of diagnosis as well as the unsatisfactory prognosis. Neurovascular compression (NVC) is considered the major pathology of TN. Routine magnetic resonance imaging (MRI) sequences are inadequate for revealing the effect of NVC which is related to the surgical decision and outcome. The decreasing of fractional anisotropy (FA), one of the MRI diffusion tensor imaging (DTI) metrics, is correlated with the demyelination of trigeminal nerve (TGN) that reveal the severity of NVC. A retrospective review of patients treated with micro-vascular decompression (MVD) surgery was undertaken. All the patients were diagnosed as type 2 TN. FA of TGN of both sides were measured. The FA declining proportion = ((the mean FA value of healthy lateral)-(the mean FA value of the symptomatic lateral))/(the mean FA value of healthy lateral). Declining proportion of FA value, discovery of surgery and outcome of MVD were recorded and analyzed. Logistic regression analysis and linear regression analysis were employed to analyze the risk factors of declining proportion of FA value and MVD outcome. Nineteen patients were assessed in our study. The average declining proportion of FA value for all patients was 0.25 ± 0.12. The average declining proportion of FA value of "success" and "failure" group was 0.32 ± 0.09 to 0.14 ± 0.10 (P = 0.002 < 0.05). The declining proportion of FA value of artery (including the artery plus vein situation) was 0.34 ± 0.06 in contrast to 0.15 ± 0.08 of vein (P = 0.000 < 0.05). MVD outcome was correlated with declining proportion of FA value (AUC = 0.900). Furthermore, declining proportion of FA value was higher in arterial compression situation. FA value quantitatively showed the alteration of TGN caused by NVC. It provided direct evidence about the effect of NVC which facilitated the diagnosis and surgical decision of type 2 TN. Besides, significant reduction of FA value may predict an optimistic outcome of MVD.

Acquisition of relative interstrand crosslinker resistance and PARP inhibitor sensitivity in Fanconi anemia head and neck cancers

PubMed Central

Lombardi, Anne J.; Hoskins, Elizabeth E.; Foglesong, Grant D.; Wikenheiser-Brokamp, Kathryn A.; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R.; Jacobs, Allison J.; Olson, Susan B.; Keeble, Winifred W.; Hays, Laura E.; Wells, Susanne I.

2015-01-01

Purpose Fanconi anemia (FA) is an inherited disorder associated with a constitutional defect in the FA DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with FA are predisposed to formation of head and neck squamous cell carcinomas (HNSCCs) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Experimental Design Using HNSCC cell lines derived from the tumors of FA patients, and murine HNSCC cell lines derived from the tumors of wild type and Fancc−/− mice, we sought to define FA-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of FA HNSCC cells for non-homologous end joining (NHEJ). Results Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily FA-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in FA cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by poly(ADP-ribose) polymerase (PARP) in FA-deficient cells. Moreover, human and murine FA HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by FA gene complementation. Conclusions The observed reliance upon PARP-mediated mechanisms reveals a means by which FA HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. PMID:25609062

Recycled asphalt pavement - fly ash geopolymer as a sustainable stabilized pavement material

NASA Astrophysics Data System (ADS)

Horpibulsuk, S.; Hoy, M.; Witchayaphong, P.; Rachan, R.; Arulrajah, A.

2017-11-01

Strength, durability, microstructure and leachate characteristics of Recycled Asphalt Pavement and Fly Ash (RAP-FA) geopolymers and RAP-FA blends as a sustainable pavement material are evaluated in this paper. The strength development of the stabilized materials with and without effect wetting-drying (w-d) cycles was determined by Unconfined Compression Strength (UCS) test. The mineralogical and microstructural changes of the stabilized material were analyzed by X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The leachability of the heavy metals were measured by Toxicity Characteristic Leaching Procedure (TCLP) and compared with international standard. The results show that both RAP-FA blend and RAP-FA geopolymer increase with increasing the number of w-d cycles (C), reaching its peak at 6 w-d cycles. The XRD and SEM analyses indicate that the strength development of RAP-FA blend occurs due to stimulation of the chemical reaction between the high amount to Calcium in RAP and the high amount of Silica and Alumina in FA leaching to production of Calcium Aluminium (Silicate) Hydrate, while the geopolymerization reaction is observed in RAP-FA geopolymer. For C> 6, the significant macro- and micro-cracks developed during w-d cycles cause strength reduction for both RAP-FA blend and geopolymer. The TCLP results demonstrate that there is no environmental risk for these stabilized materials. Furthermore, FA-geopolymer can reduce the leachability of heavy metal in RAP-FA blend. The outcome from this research confirms the viability of using RAP-FA blend and RAP-FA geopolymer as alternative sustainable pavement materials.

Food Addiction in Gambling Disorder: Frequency and Clinical Outcomes.

PubMed

Jiménez-Murcia, Susana; Granero, Roser; Wolz, Ines; Baño, Marta; Mestre-Bach, Gemma; Steward, Trevor; Agüera, Zaida; Hinney, Anke; Diéguez, Carlos; Casanueva, Felipe F; Gearhardt, Ashley N; Hakansson, Anders; Menchón, José M; Fernández-Aranda, Fernando

2017-01-01

Background: The food addiction (FA) model is receiving increasing interest from the scientific community. Available empirical evidence suggests that this condition may play an important role in the development and course of physical and mental health conditions such as obesity, eating disorders, and other addictive behaviors. However, no epidemiological data exist on the comorbidity of FA and gambling disorder (GD), or on the phenotype for the co-occurrence of GD+FA. Objectives: To determine the frequency of the comorbid condition GD+FA, to assess whether this comorbidity features a unique clinical profile compared to GD without FA, and to generate predictive models for the presence of FA in a GD sample. Method: Data correspond to N = 458 treatment-seeking patients who met criteria for GD in a hospital unit specialized in behavioral addictions. Results: Point prevalence for FA diagnosis was 9.2%. A higher ratio of FA was found in women (30.5%) compared to men (6.0%). Lower FA prevalence was associated with older age. Patients with high FA scores were characterized by worse psychological state, and the risk of a FA diagnosis was increased in patients with high scores in the personality traits harm avoidance and self-transcendence, and low scores in cooperativeness ( R 2 = 0.18). Conclusion: The co-occurrence of FA in treatment-seeking GD patients is related to poorer emotional and psychological states. GD treatment interventions and related behavioral addictions should consider potential associations with problematic eating behavior and aim to include techniques that aid patients in better managing this behavior.

Food Addiction in Gambling Disorder: Frequency and Clinical Outcomes

PubMed Central

Jiménez-Murcia, Susana; Granero, Roser; Wolz, Ines; Baño, Marta; Mestre-Bach, Gemma; Steward, Trevor; Agüera, Zaida; Hinney, Anke; Diéguez, Carlos; Casanueva, Felipe F.; Gearhardt, Ashley N.; Hakansson, Anders; Menchón, José M.; Fernández-Aranda, Fernando

2017-01-01

Background: The food addiction (FA) model is receiving increasing interest from the scientific community. Available empirical evidence suggests that this condition may play an important role in the development and course of physical and mental health conditions such as obesity, eating disorders, and other addictive behaviors. However, no epidemiological data exist on the comorbidity of FA and gambling disorder (GD), or on the phenotype for the co-occurrence of GD+FA. Objectives: To determine the frequency of the comorbid condition GD+FA, to assess whether this comorbidity features a unique clinical profile compared to GD without FA, and to generate predictive models for the presence of FA in a GD sample. Method: Data correspond to N = 458 treatment-seeking patients who met criteria for GD in a hospital unit specialized in behavioral addictions. Results: Point prevalence for FA diagnosis was 9.2%. A higher ratio of FA was found in women (30.5%) compared to men (6.0%). Lower FA prevalence was associated with older age. Patients with high FA scores were characterized by worse psychological state, and the risk of a FA diagnosis was increased in patients with high scores in the personality traits harm avoidance and self-transcendence, and low scores in cooperativeness (R2 = 0.18). Conclusion: The co-occurrence of FA in treatment-seeking GD patients is related to poorer emotional and psychological states. GD treatment interventions and related behavioral addictions should consider potential associations with problematic eating behavior and aim to include techniques that aid patients in better managing this behavior. PMID:28421009

Dual Targeting Biomimetic Liposomes for Paclitaxel/DNA Combination Cancer Treatment

PubMed Central

Liu, Guo-Xia; Fang, Gui-Qing; Xu, Wei

2014-01-01

Combinations of chemotherapeutic drugs with nucleic acid has shown great promise in cancer therapy. In the present study, paclitaxel (PTX) and DNA were co-loaded in the hyaluronic acid (HA) and folate (FA)-modified liposomes (HA/FA/PPD), to obtain the dual targeting biomimetic nanovector. The prepared HA/FA/PPD exhibited nanosized structure and narrow size distributions (247.4 ± 4.2 nm) with appropriate negative charge of −25.40 ± 2.7 mV. HA/FA/PD (PTX free HA/FA/PPD) showed almost no toxicity on murine malignant melanoma cell line (B16) and human hepatocellular carcinoma cell line (HepG2) (higher than 80% cell viability), demonstrating the safety of the blank nanovector. In comparison with the FA-modified PTX/DNA co-loaded liposomes (FA/PPD), HA/FA/PPD showed significant superiority in protecting the nanoparticles from aggregation in the presence of plasma and degradation by DNase I. Moreover, HA/FA/PPD could also significantly improve the transfection efficiency and cellular internalization rates on B16 cells comparing to that of FA/PPD (p < 0.05) and PPD (p < 0.01), demonstrating the great advantages of dual targeting properties. Furthermore, fluorescence microscope and flow cytometry results showed that PTX and DNA could be effectively co-delivered into the same tumor cell via HA/FA/PPD, contributing to PTX/DNA combination cancer treatment. In conclusion, the obtained HA/FA/PPD in the study could effectively target tumor cells, enhance transfection efficiency and subsequently achieve the co-delivery of PTX and DNA, displaying great potential for optimal combination therapy. PMID:25177862

Mixed-ligand Cu II complexes with Me 5dien and heterocyclic acids. Synthesis, antioxidant and anti-inflammatory activity. Crystal structure of [Cu(Me 5dien)(tpaa)(H 2O)](ClO 4)

NASA Astrophysics Data System (ADS)

Christidis, Panayiotis C.; Georgousis, Zacharias D.; Hadjipavlou-Litina, Dimitra; Bolos, Christos A.

2008-01-01

The reaction of sodium salt of 2-thiophenecarboxylic acid (tpca), 2-thiopheneacetic acid (tpaa), 2-furoic acid (fa) and picolinic acid (pica), with [Cu(Me 5dien)(ClO 4) 2] ( 1) (Me 5dien = N, N, N', N″ N″-pentamethyldiethylenetriamine) in a 1:1 molar ratio, afforded new mixed-ligand compounds of the type [Cu(Me 5dien)(tpca)(H 2O)](ClO 4) ( 2), [Cu(Me 5dien)(tpaa)(H 2O)](ClO 4) ( 3), [Cu(Me 5dien)(fa)](BPh 4) ( 4) and [Cu(Me 5dien)(pica)](ClO 4) ( 5). The new mixed-ligand complexes are mononuclear, paramagnetic, conductive compounds with a distorted square pyramidal geometry. The square pyramidal stereochemistry proposed by spectroscopic (IR, UV-vis) data was further confirmed by the X-ray structure analysis of the compound ( 3) in which the Cu atom is coordinated by the three N atoms from the Me 5dien ligand, one O atom from the mono-carboxylate anion, lying on the equatorial square plane, and one O atom from the water molecule, occupying the axial position. The two Cu sbnd O bond distances are 1.955(2) and 2.212(2) Ǻ, respectively. The complexes were tested for antioxidant/anti-inflammatory activity. Complex 4 is the most active against soybean lipoxygenase with IC 50 = 100 μM. The presence of a furoic ring leads to higher lipoxygenase inhibition, whereas the picolinyl-ring supports scavenging activity.

Survey of the total fatty acid and triacylglycerol composition and content of 30 duckweed species and cloning of a Δ6-desaturase responsible for the production of γ-linolenic and stearidonic acids in Lemna gibba

PubMed Central

2013-01-01

Background Duckweeds, i.e., members of the Lemnoideae family, are amongst the smallest aquatic flowering plants. Their high growth rate, aquatic habit and suitability for bio-remediation make them strong candidates for biomass production. Duckweeds have been studied for their potential as feedstocks for bioethanol production; however, less is known about their ability to accumulate reduced carbon as fatty acids (FA) and oil. Results Total FA profiles of thirty duckweed species were analysed to assess the natural diversity within the Lemnoideae. Total FA content varied between 4.6% and 14.2% of dry weight whereas triacylglycerol (TAG) levels varied between 0.02% and 0.15% of dry weight. Three FA, 16:0 (palmitic), 18:2Δ9,12 (Linoleic acid, or LN) and 18:3Δ9,12,15 (α-linolenic acid, or ALA) comprise more than 80% of total duckweed FA. Seven Lemna and two Wolffiela species also accumulate polyunsaturated FA containing Δ6-double bonds, i.e., GLA and SDA. Relative to total FA, TAG is enriched in saturated FA and deficient in polyunsaturated FA, and only five Lemna species accumulate Δ6-FA in their TAG. A putative Δ6-desaturase designated LgDes, with homology to a family of front-end Δ6-FA and Δ8-spingolipid desaturases, was identified in the assembled DNA sequence of Lemna gibba. Expression of a synthetic LgDes gene in Nicotiana benthamiana resulted in the accumulation of GLA and SDA, confirming it specifies a Δ6-desaturase. Conclusions Total accumulation of FA varies three-fold across the 30 species of Lemnoideae surveyed. Nine species contain GLA and SDA which are synthesized by a Δ6 front-end desaturase, but FA composition is otherwise similar. TAG accumulates up to 0.15% of total dry weight, comparable to levels found in the leaves of terrestrial plants. Polyunsaturated FA is underrepresented in TAG, and the Δ6-FA GLA and SDA are found in the TAG of only five of the nine Lemna species that produce them. When present, GLA is enriched and SDA diminished relative to their abundance in the total FA pool. PMID:24308551

FA-SAT Is an Old Satellite DNA Frozen in Several Bilateria Genomes

PubMed Central

Chaves, Raquel; Ferreira, Daniela; Mendes-da-Silva, Ana; Meles, Susana; Adega, Filomena

2017-01-01

Abstract In recent years, a growing body of evidence has recognized the tandem repeat sequences, and specifically satellite DNA, as a functional class of sequences in the genomic “dark matter.” Using an original, complementary, and thus an eclectic experimental design, we show that the cat archetypal satellite DNA sequence, FA-SAT, is “frozen” conservatively in several Bilateria genomes. We found different genomic FA-SAT architectures, and the interspersion pattern was conserved. In Carnivora genomes, the FA-SAT-related sequences are also amplified, with the predominance of a specific FA-SAT variant, at the heterochromatic regions. We inspected the cat genome project to locate FA-SAT array flanking regions and revealed an intensive intermingling with transposable elements. Our results also show that FA-SAT-related sequences are transcribed and that the most abundant FA-SAT variant is not always the most transcribed. We thus conclude that the DNA sequences of FA-SAT and their transcripts are “frozen” in these genomes. Future work is needed to disclose any putative function that these sequences may play in these genomes. PMID:29608678

FANCA safeguards interphase and mitosis during hematopoiesis in vivo

PubMed Central

Abdul-Sater, Zahi; Cerabona, Donna; Sierra Potchanant, Elizabeth; Sun, Zejin; Enzor, Rikki; He, Ying; Robertson, Kent; Goebel, W. Scott; Nalepa, Grzegorz

2015-01-01

Fanconi anemia (FA/BRCA) signaling network controls multiple genome-housekeeping checkpoints, from interphase DNA repair to mitosis. The in vivo role of abnormal cell division in FA remains unknown. Here, we quantified the origins of genomic instability in FA patients and mice in vivo and ex vivo. We found that both mitotic errors and interphase DNA damage significantly contribute to genomic instability during FA-deficient hematopoiesis and in non-hematopoietic human and murine FA primary cells. Super-resolution microscopy coupled with functional assays revealed that FANCA shuttles to the pericentriolar material (PCM) to regulate spindle assembly at mitotic entry. Loss of FA signaling rendered cells hypersensitive to spindle chemotherapeutics and allowed escape from the chemotherapy-induced spindle assembly checkpoint. In support of these findings, direct comparison of DNA cross-linking and antimitotic chemotherapeutics in primary FANCA−/− cells revealed genomic instability originating through divergent cell cycle checkpoint aberrations. Our data indicate that the FA/BRCA signaling functions as an in vivo gatekeeper of genomic integrity throughout interphase and mitosis, which may have implications for future targeted therapies in FA and FA-deficient cancers. PMID:26366677

Children's Food Allergies: Development of the Food Allergy Management and Adaptation Scale.

PubMed

Klinnert, Mary D; McQuaid, Elizabeth L; Fedele, David A; Faino, Anna; Strand, Matthew; Robinson, Jane; Atkins, Dan; Fleischer, David M; Hourihane, Jonathan O'B; Cohen, Sophia; Fransen, Hannah

2015-07-01

Develop a measure that evaluates effective pediatric food allergy (FA) management, child and parent FA anxiety, and integration of FA into family life. A semistructured family interview was developed to evaluate FA management using a pilot sample (n = 27). Rating scales evaluated eight dimensions of FA management (FAMComposite), child anxiety, parent anxiety, and overall balanced integration (BI). Families of children with IgE-mediated food allergies (n = 60, child age: 6-12) were recruited for interview and rating scale validation. FAMComposite was correlated with physician ratings for families' food avoidance and reaction response readiness. FA anxiety was correlated with general anxiety measures for children, but not parents. Parents' FA anxiety was correlated with expectations of negative outcomes from FA. Low BI was associated with poor quality of life and negative impact on family functioning. Preliminary analyses support Food Allergy Management and Adaptation Scale validity as a measure of family adaptation to pediatric FA. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ferulic acid ameliorates memory impairment in d-galactose-induced aging mouse model.

PubMed

Yang, Honggai; Qu, Zhuo; Zhang, Jingze; Huo, Liqin; Gao, Jing; Gao, Wenyuan

2016-11-01

Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1β by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.

Effect of unsaturated fatty acids and triglycerides from soybeans on milk fat synthesis and biohydrogenation intermediates in dairy cattle.

PubMed

Boerman, J P; Lock, A L

2014-11-01

Increased rumen unsaturated fatty acid (FA) load is a risk factor for milk fat depression. This study evaluated if increasing the amount of unsaturated FA in the diet as triglycerides or free FA affected feed intake, yield of milk and milk components, and feed efficiency. Eighteen Holstein cows (132 ± 75 d in milk) were used in a replicated 3 × 3 Latin square design. Treatments were a control (CON) diet, or 1 of 2 unsaturated FA (UFA) treatments supplemented with either soybean oil (FA present as triglycerides; TAG treatment) or soybean FA distillate (FA present as free FA; FFA treatment). The soybean oil contained a higher concentration of cis-9 C18:1 (26.0 vs. 11.8 g/100g of FA) and lower concentrations of C16:0 (9.6 vs. 15.0 g/100g of FA) and cis-9,cis-12 C18:2 (50.5 vs. 59.1g/100g of FA) than the soybean FA distillate. The soybean oil and soybean FA distillate were included in the diet at 2% dry matter (DM) to replace soyhulls in the CON diet. Treatment periods were 21 d, with the final 4 d used for sample and data collection. The corn silage- and alfalfa silage-based diets contained 23% forage neutral detergent fiber and 17% crude protein. Total dietary FA were 2.6, 4.2, and 4.3% of diet DM for CON, FFA, and TAG treatments, respectively. Total FA intake was increased 57% for UFA treatments and was similar between FFA and TAG. The intakes of individual FA were similar, with the exception of a 24 g/d lower intake of C16:0 and a 64 g/d greater intake of cis-9 C18:1 for the TAG compared with the FFA treatment. Compared with CON, the UFA treatments decreased DM intake (1.0 kg/d) but increased milk yield (2.2 kg/d) and milk lactose concentration and yield. The UFA treatments reduced milk fat concentration, averaging 3.30, 3.18, and 3.11% for CON, FFA, and TAG treatments, respectively. Yield of milk fat, milk protein, and 3.5% fat-corrected milk remained unchanged when comparing CON with the UFA treatments. No differences existed in the yield of milk or milk components between the FFA and TAG treatments. The UFA treatments increased feed efficiency (energy-corrected milk/DM intake), averaging 1.42, 1.53, and 1.48 for CON, FFA, and TAG treatments, respectively. Although milk fat yield was not affected, the UFA treatments decreased the yield of de novo (<16-carbon) synthesized FA (40 g/d) and increased the yield of preformed (>16-carbon) FA (134 g/d). Yield of FA from both sources (16-carbon FA) was reduced by the UFA treatments but to a different extent for FFA versus TAG (72 vs. 100g/d). An increase was detected in the concentration of trans-10 C18:1 and a trend for an increase in trans-10,cis-12 C18:2 and trans-9,cis-11 C18:2 for the UFA treatments compared with CON. Under the dietary conditions tested, UFA treatments supplemented at 2% diet DM as either soybean FA distillate or soybean oil increased milk yield but did not effectively cause a reduction in milk fat yield, with preformed FA replacing de novo synthesized FA in milk fat. Further research is required to determine if the response to changes in dietary free and esterified FA concentrations is different in diets that differ in their risk for milk fat depression. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Magnetoencephalographic alpha band connectivity reveals differential default mode network interactions during focused attention and open monitoring meditation

PubMed Central

Marzetti, Laura; Di Lanzo, Claudia; Zappasodi, Filippo; Chella, Federico; Raffone, Antonino; Pizzella, Vittorio

2014-01-01

According to several conceptualizations of meditation, the interplay between brain systems associated to self-related processing, attention and executive control is crucial for meditative states and related traits. We used magnetoencephalography (MEG) to investigate such interplay in a highly selected group of “virtuoso” meditators (Theravada Buddhist monks), with long-term training in the two main meditation styles: focused attention (FA) and open monitoring (OM) meditation. Specifically, we investigated the differences between FA meditation, OM meditation and resting state in the coupling between the posterior cingulate cortex, core node of the Default Mode Network (DMN) implicated in mind wandering and self-related processing, and the whole brain, with a recently developed phase coherence approach. Our findings showed a state dependent coupling of posterior cingulate cortex (PCC) to nodes of the DMN and of the executive control brain network in the alpha frequency band (8–12 Hz), related to different attentional and cognitive control processes in FA and OM meditation, consistently with the putative role of alpha band synchronization in the functional mechanisms for attention and consciousness. The coupling of PCC with left medial prefrontal cortex (lmPFC) and superior frontal gyrus characterized the contrast between the two meditation styles in a way that correlated with meditation expertise. These correlations may be related to a higher mindful observing ability and a reduced identification with ongoing mental activity in more expert meditators. Notably, different styles of meditation and different meditation expertise appeared to modulate the dynamic balance between fronto-parietal (FP) and DMN networks. Our results support the idea that the interplay between the DMN and the FP network in the alpha band is crucial for the transition from resting state to different meditative states. PMID:25360102

Identification of a New cry1I-Type Gene as a Candidate for Gene Pyramiding in Corn To Control Ostrinia Species Larvae

PubMed Central

Zhao, Can; Abdelgaffar, Heba M.; Pan, Hongyu; Song, Fuping

2015-01-01

Pyramiding of diverse cry toxin genes from Bacillus thuringiensis with different modes of action is a desirable strategy to delay the evolution of resistance in the European corn borer (Ostrinia nubilalis). Considering the dependency of susceptibility to Cry toxins on toxin binding to receptors in the midgut of target pests, a diverse mode of action is commonly defined as recognition of unique binding sites in the target insect. In this study, we present a novel cry1Ie toxin gene (cry1Ie2) as a candidate for pyramiding with Cry1Ab or Cry1Fa in corn to control Ostrinia species larvae. The new toxin gene encodes an 81-kDa protein that is processed to a protease-resistant core form of approximately 55 kDa by trypsin digestion. The purified protoxin displayed high toxicity to Ostrinia furnacalis and O. nubilalis larvae but low to no activity against Spodoptera or heliothine species or the coleopteran Tenebrio molitor. Results of binding assays with 125I-labeled Cry1Ab toxin and brush border membrane vesicles from O. nubilalis larvae demonstrated that Cry1Ie2 does not recognize the Cry1Ab binding sites in that insect. Reciprocal competition binding assays with biotin-labeled Cry1Ie2 confirmed the lack of shared sites with Cry1Ab or Cry1Fa in O. nubilalis brush border membrane vesicles. These data support Cry1Ie2 as a good candidate for pyramiding with Cry1Ab or Cry1Fa in corn to increase the control of O. nubilalis and reduce the risk of resistance evolution. PMID:25795679

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

PubMed

Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

2018-03-01

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Identification of a New cry1I-Type Gene as a Candidate for Gene Pyramiding in Corn To Control Ostrinia Species Larvae.

PubMed

Zhao, Can; Jurat-Fuentes, Juan Luis; Abdelgaffar, Heba M; Pan, Hongyu; Song, Fuping; Zhang, Jie

2015-06-01

Pyramiding of diverse cry toxin genes from Bacillus thuringiensis with different modes of action is a desirable strategy to delay the evolution of resistance in the European corn borer (Ostrinia nubilalis). Considering the dependency of susceptibility to Cry toxins on toxin binding to receptors in the midgut of target pests, a diverse mode of action is commonly defined as recognition of unique binding sites in the target insect. In this study, we present a novel cry1Ie toxin gene (cry1Ie2) as a candidate for pyramiding with Cry1Ab or Cry1Fa in corn to control Ostrinia species larvae. The new toxin gene encodes an 81-kDa protein that is processed to a protease-resistant core form of approximately 55 kDa by trypsin digestion. The purified protoxin displayed high toxicity to Ostrinia furnacalis and O. nubilalis larvae but low to no activity against Spodoptera or heliothine species or the coleopteran Tenebrio molitor. Results of binding assays with (125)I-labeled Cry1Ab toxin and brush border membrane vesicles from O. nubilalis larvae demonstrated that Cry1Ie2 does not recognize the Cry1Ab binding sites in that insect. Reciprocal competition binding assays with biotin-labeled Cry1Ie2 confirmed the lack of shared sites with Cry1Ab or Cry1Fa in O. nubilalis brush border membrane vesicles. These data support Cry1Ie2 as a good candidate for pyramiding with Cry1Ab or Cry1Fa in corn to increase the control of O. nubilalis and reduce the risk of resistance evolution. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Formaldehyde and co-exposure with benzene induce compensation of bone marrow and hematopoietic stem/progenitor cells in BALB/c mice during post-exposure period

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

Wei, Chenxi

Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m{sup 3} FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrowmore » cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. - Highlights: • Nucleated bone marrow cell count recovered after 7 days post-FA and/or BZ exposure. • CFU-GM showed an increase in colonies and 8-OHdG after 7 days post-FA + BZ exposure. • Levels of ROS in CFU-GM and BFU-E were increased by FA or FA + BZ during recovery. • Levels of GM-CSF and EPOR were suppressed after 7 days post-FA or FA + BZ exposure. • Co-exposure was more potent for some endpoints and may pose a greater leukemia risk.« less

Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates

NASA Astrophysics Data System (ADS)

Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

2015-03-01

Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications. Electronic supplementary information (ESI) available: 1H NMR assay, synthetic route of Ad-FA, AFM images and cellular internalization rate can be found in ESI. See DOI: 10.1039/c4nr07515c

Development of nanofluorapatite polymer-based composite for bioactive orthopedic implants and prostheses

PubMed Central

Hu, Gangfeng; Wang, Hui; Yao, Xiaocong; Bi, Dawei; Zhu, Gang; Tang, Songchao; Wei, Jie; Yang, Lili; Tong, Peijian; Xiao, Luwei

2014-01-01

Fluorapatite with low solubility is a promising biomaterial due to its structure, which is similar to hydroxyapatite. In this study a bioactive composite of nanofluorapatite (n-FA) and polyamide 12 (PA12) was fabricated. The results revealed that the mechanical properties (such as compressive strength and elastic modulus), hydrophilicity, and antibacterial properties of n-FA/PA12 composite were obviously improved by adding n-FA into PA12 as compared with PA12. In addition, cell proliferation of MC3T3-E1 cells cultured on n-FA/PA12 composite was significantly higher than with PA12, and alkaline phosphatase activity of MC3T3-E1 cells on the n-FA/PA12 composite was expressed at obviously higher levels as compared with PA12. The results suggest that n-FA/PA12 composite could support cell proliferation and differentiation, showing good cytocompatibility. Histological evaluation indicates that n-FA/PA12 composite enhances the efficiency of new bone formation with the introduction of n-FA into PA12, and the quantity of the newly formed bone for n-FA/PA12 composite is significantly higher than with PA12. In conclusion, n-FA/PA12 composite exhibits good biocompatibility and osteogenesis, which might be used for various orthopedic prostheses and dental implants. PMID:25143735

Personal formaldehyde exposure level in the gross anatomy dissecting room at College of Medicine King Saud University Riyadh.

PubMed

Vohra, Muhammad Saeed

2011-03-01

This study was conducted to correlate the personal formaldehyde (FA) exposure levels of instructors and students with the indoor FA concentrations in gross anatomy laboratory at King Saud University. The personal FA levels of instructors and students are higher than the indoor FA concentration in the gross anatomy laboratory. The gross anatomy laboratory at college of medicine, King Saud University Riyadh, was observed for indoor FA concentration and the personal exposure levels of instructors and the medical students during the 4th, 10th and 14th weeks of the dissection sessions. All air samples were collected by the diffusive sampling device and analyzed by using high performance liquid chromatography (HPLC). The personal exposure level of FA was higher than the indoor concentration, and the personal exposure levels of instructors were higher than that of the students. The concentration of FA was also higher in the center of the room than the corners and near the doors. Both the indoor FA concentrations and personal FA exposure levels are higher near the dissecting table than at locations away from it during the gross anatomy laboratory sessions. Thus, the instructors and students are exposed to the higher concentration of FA than the general population.

Formaldehyde exposure impairs the function and differentiation of NK cells.

PubMed

Kim, Eun-Mi; Lee, Hwa-Youn; Lee, Eun-Hee; Lee, Ki-Mo; Park, Min; Ji, Kon-Young; Jang, Ji-Hun; Jeong, Yun-Hwa; Lee, Kwang-Ho; Yoon, Il-Joo; Kim, Su-Man; Jeong, Moon-Jin; Kim, Kwang Dong; Kang, Hyung-Sik

2013-11-25

We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure also induced decreases in NK cytolytic activity and in the expression of NK cell-associated genes, such as IFN-γ, perforin and CD122. To determine the effect of FA on tumorigenicity, C57BL/6 mice were subcutaneously injected with B16F10 melanoma cells after FA exposure. The mass of the B16F10 tumor and the concentration of extravascular polymorphonuclear leukocytes were greater than those in unexposed tumor-bearing control mice. The number and cytolytic activity of NK cells were also reduced in B16F10 tumor-bearing mice exposed to FA. To determine how FA reduces the NK cell number, NK precursor (pNK) cells were treated with FA, and the differentiation status of the NK cells was analyzed. NK cell differentiation was impaired by FA treatment in a concentration-dependent manner. These findings indicate that FA exposure may promote tumor progression by impairing NK cell function and differentiation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Molecular structure of the pyruvate dehydrogenase complex from Escherichia coli K-12.

PubMed

Vogel, O; Hoehn, B; Henning, U

1972-06-01

The pyruvate dehydrogenase core complex from E. coli K-12, defined as the multienzyme complex that can be obtained with a unique polypeptide chain composition, has a molecular weight of 3.75 x 10(6). All results obtained agree with the following numerology. The core complex consists of 48 polypeptide chains. There are 16 chains (molecular weight = 100,000) of the pyruvate dehydrogenase component, 16 chains (molecular weight = 80,000) of the dihydrolipoamide dehydrogenase component, and 16 chains (molecular weight = 56,000) of the dihydrolipoamide dehydrogenase component. Usually, but not always, pyruvate dehydrogenase complex is produced in vivo containing at least 2-3 mol more of dimers of the pyruvate dehydrogenase component than the stoichiometric ratio with respect to the core complex. This "excess" component is bound differently than are the eight dimers in the core complex.

Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method.

PubMed

Zu, Yuangang; Zhao, Qi; Zhao, Xiuhua; Zu, Shuchong; Meng, Li

2011-01-01

Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.

Monitoring fractional anisotropy in developing rabbit brain using MR diffusion tensor imaging at 3T

NASA Astrophysics Data System (ADS)

Jao, Jo-Chi; Yang, Yu-Ting; Hsiao, Chia-Chi; Chen, Po-Chou

2016-03-01

The aim of this study was to investigate the factional anisotropy (FA) in various regions of developing rabbit brain using magnetic resonance diffusion tensor imaging (MR DTI) at 3 T. A whole-body clinical MR imaging (MRI) scanner with a 15-channel high resolution knee coil was used. An echo-planar-imaging (EPI)-DTI pulse sequence was performed. Five 5 week-old New Zealand white (NZW) rabbits underwent MRI once per week for 24 weeks. After scanning, FA maps were obtained. ROIs (regions of interests) in the frontal lobe, parietal & temporal lobe, and occipital lobe were measured. FA changes with time were evaluated with a linear regression analysis. The results show that the FA values in all lobes of the brain increased linearly with age. The ranking of FA values was FA(frontal lobe) < FA(parietal & temporal lobe) > FA(occipital lobe). There was significant difference (p < 0.05) among these lobes. FA values are associated with the nerve development and brain functions. The FA change rate could be a biomarker to monitor the brain development. Understanding the FA values of various lobes during development could provide helpful information to diagnosis the abnormal syndrome earlier and have a better treatment and prognosis. This study established a brain MR-DTI protocol for rabbits to investigate the brain anatomy during development using clinical MRI. This technique can be further applied to the pre-clinical diagnosis, treatment, prognosis and follow-up of brain lesions.

Estrogen Inhibits Dlk1/FA1 Production: A Potential Mechanism for Estrogen Effects on Bone Turnover

PubMed Central

Abdallah, B. M.; Bay-Jensen, A.; Srinivasan, B.; Tabassi, N. C.; Garnero, P.; Delaissé, J.; Khosla, S.; Kassem, M.

2011-01-01

We have recently identified Dlk1/FA1 (Delta-like 1/FA1) as a novel regulator of bone mass that functions to mediate bone loss, under estrogen deficiency, in mice. In this report, we investigated the effects of estrogen (E)-deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (s-CTx and s-osteocalcin), were measured in two cohorts: a group of pre- and postmenopausal women (n=100) and a group of postmenopausal women, where half had received estrogen replacement therapy (ERT) (n=166). s-Dlk1/FA1, and s-CTX were elevated in postmenopausal E-deficient compared to premenopausal E-replete women (both; P<0.001). s-Dlk1/FA1 was correlated with s-CTX (r=0.30, P<0.01). ERT, in postmenopausal women, decreased s-Dlk1/FA1, as well as s-CTX and s-osteoclacin (all; P<0.0001). Changes in s-Dlk1 were significantly correlated with those observed in s-CTx (r=0.18, P<0.05) and s-osteocalcin (r=0.28, P<0.001). In conclusion, s-Dlk1/FA1 is influenced by E-deficiency and is correlated with bone turnover. Increased levels of s-Dlk1/FA1 in post-menopausal women may be a mechanism mediating the effects estrogen deficiency on bone turnover. PMID:21681814

Roux-en Y gastric bypass is superior to duodeno-jejunal bypass in improving glycaemic control in Zucker diabetic fatty rats.

PubMed

Seyfried, Florian; Bueter, Marco; Spliethoff, Kerstin; Miras, Alexander D; Abegg, Kathrin; Lutz, Thomas A; le Roux, Carel W

2014-11-01

Whilst weight loss results in many beneficial metabolic consequences, the immediate improvement in glycaemia after Roux-en-Y Gastric bypass (RYGB) remains intriguing. Duodenal jejunal bypass (DJB) induces similar glycaemic effects, while not affecting calorie intake or weight loss. We studied diabetic ZDF(fa/fa) rats to compare the effects of DJB and RYGB operations on glycaemia. Male ZDF(fa/fa) rats, aged 12 weeks underwent RYGB, DJB or sham operations. Unoperated ZDF(fa/fa) and ZDF(fa/+w)ere used as controls. Body weight, food intake, fasting glucose, insulin and gut hormones were measured at baseline and on postoperative days 2, 10 and 35. An oral glucose tolerance test (OGTT) was performed on days 12 and 26. DJB had similar food intake and body weight to sham-operated and unoperated control ZDF(fa/fa) rats (p = NS), but had lower fasting glucose (p < 0.05). RYGB had lower food intake, body weight and fasting glucose compared to all groups (p < 0.001). DJB prevented the progressive decline in fasting insulin observed in the sham-operated or unoperated ZDF(fa/fa) rats, while RYGB with normalized glycaemia reduced the physiological requirement for raised fasting insulin. Bypassing the proximal small bowel with the DJB has mild to moderate body weight independent effects on glucose homeostasis and preservation of fasting insulin levels in the medium term. These effects might be further amplified by the additional anatomical and physiological changes after RYGB.

Towards understanding the E. coli PNP binding mechanism and FRET absence between E. coli PNP and formycin A.

PubMed

Prokopowicz, Małgorzata; Greń, Bartosz; Cieśla, Joanna; Kierdaszuk, Borys

2017-11-01

The aim of this study is threefold: (1) augmentation of the knowledge of the E. coli PNP binding mechanism; (2) explanation of the previously observed 'lack of FRET' phenomenon and (3) an introduction of the correction (modified method) for FRET efficiency calculation in the PNP-FA complexes. We present fluorescence studies of the two E. coli PNP mutants (F159Y and F159A) with formycin A (FA), that indicate that the aromatic amino acid is indispensable in the nucleotide binding, additional hydroxyl group at position 159 probably enhances the strength of binding and that the amino acids pair 159-160 has a great impact on the spectroscopic properties of the enzyme. The experiments were carried out in hepes and phosphate buffers, at pH7 and 8.3. Two methods, a conventional and a modified one, that utilizes the dissociation constant, for calculations of the energy transfer efficiency (E) and the acceptor-to-donor distance (r) between FA and the Tyr (energy donor) were employed. Total difference spectra were calculated for emission spectra (λ ex 280nm, 295nm, 305nm and 313nm) for all studied systems. Time-resolved techniques allowed to conclude the existence of a specific structure formed by amino acids at positions 159 and 160. The results showed an unexpected pattern change of FRET in the mutants, when compared to the wild type enzyme and a probable presence of a structure created between 159 and 160 residue, that might influence the binding efficiency. Additionally, we confirmed the indispensable role of the modification of the FRET efficiency (E) calculation on the fraction of enzyme saturation in PNP-FA systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Connecting Core Percolation and Controllability of Complex Networks

PubMed Central

Jia, Tao; Pósfai, Márton

2014-01-01

Core percolation is a fundamental structural transition in complex networks related to a wide range of important problems. Recent advances have provided us an analytical framework of core percolation in uncorrelated random networks with arbitrary degree distributions. Here we apply the tools in analysis of network controllability. We confirm analytically that the emergence of the bifurcation in control coincides with the formation of the core and the structure of the core determines the control mode of the network. We also derive the analytical expression related to the controllability robustness by extending the deduction in core percolation. These findings help us better understand the interesting interplay between the structural and dynamical properties of complex networks. PMID:24946797

Evidence that the assembly of the yeast cytochrome bc1 complex involves the formation of a large core structure in the inner mitochondrial membrane.

PubMed

Zara, Vincenzo; Conte, Laura; Trumpower, Bernard L

2009-04-01

The assembly status of the cytochrome bc(1) complex has been analyzed in distinct yeast deletion strains in which genes for one or more of the bc(1) subunits were deleted. In all the yeast strains tested, a bc(1) sub-complex of approximately 500 kDa was found when the mitochondrial membranes were analyzed by blue native electrophoresis. The subsequent molecular characterization of this sub-complex, carried out in the second dimension by SDS/PAGE and immunodecoration, revealed the presence of the two catalytic subunits, cytochrome b and cytochrome c(1), associated with the noncatalytic subunits core protein 1, core protein 2, Qcr7p and Qcr8p. Together, these bc(1) subunits build up the core structure of the cytochrome bc(1) complex, which is then able to sequentially bind the remaining subunits, such as Qcr6p, Qcr9p, the Rieske iron-sulfur protein and Qcr10p. This bc(1) core structure may represent a true assembly intermediate during the maturation of the bc(1) complex; first, because of its wide distribution in distinct yeast deletion strains and, second, for its characteristics of stability, which resemble those of the intact homodimeric bc(1) complex. By contrast, the bc(1) core structure is unable to interact with the cytochrome c oxidase complex to form respiratory supercomplexes. The characterization of this novel core structure of the bc(1) complex provides a number of new elements clarifying the molecular events leading to the maturation of the yeast cytochrome bc(1) complex in the inner mitochondrial membrane.

Evidence that assembly of the yeast cytochrome bc1 complex involves formation of a large core structure in the inner mitochondrial membrane

PubMed Central

Zara, Vincenzo; Conte, Laura; Trumpower, Bernard L.

2009-01-01

The assembly status of the cytochrome bc1 complex has been analyzed in distinct yeast deletion strains in which genes for one or more of the bc1 subunits had been deleted. In all the yeast strains tested a bc1 sub-complex of about 500 kDa was found when the mitochondrial membranes were analyzed by blue native electrophoresis. The subsequent molecular characterization of this sub-complex, carried out in the second dimension by SDS-PAGE and immunodecoration, revealed the presence of the two catalytic subunits cytochrome b and cytochrome c1, associated with the non catalytic subunits core protein 1, core protein 2, Qcr7p and Qcr8p. Altogether these bc1 subunits build up the core structure of the cytochrome bc1 complex which is then able to sequentially bind the remaining subunits, such as Qcr6p, Qcr9p, the Rieske iron-sulfur protein and Qcr10p. This bc1 core structure may represent a true assembly intermediate during the maturation of the bc1 complex, first because of its wide distribution in distinct yeast deletion strains and second for its characteristics of stability which resemble those of the intact homodimeric bc1 complex. Differently from this latter, however, the bc1 core structure is not able to interact with the cytochrome c oxidase complex to form respiratory supercomplexes. The characterization of this novel core structure of the bc1 complex provides a number of new elements for clarification of the molecular events leading to the maturation of the yeast cytochrome bc1 complex in the inner mitochondrial membrane. PMID:19236481

An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles1

PubMed Central

Medina-Puche, Laura; Molina-Hidalgo, Francisco Javier; Boersma, Maaike; Schuurink, Robert C.; López-Vidriero, Irene; Solano, Roberto; Franco-Zorrilla, José-Manuel; Caballero, José Luis; Blanco-Portales, Rosario; Muñoz-Blanco, Juan

2015-01-01

Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (EMISSION OF BENZENOID II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of CINNAMYL ALCOHOL DEHYDROGENASE1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles. PMID:25931522