¹⁸F-BMS-986192, an adnectin-based human programmed cell death ligand 1 (PD-L1) tracer, was developed to non-invasively determine whole-body PD-L1 expression by positron emission tomography (PET). We evaluated usability of ¹⁸F-BMS-986192 PET to detect different PD-L1 expression levels and therapy-induced changes of PD-L1 expression in tumors. Methods: In vitro binding assays with ¹⁸F-BMS-986192 were performed in human tumor cell lines with different total cellular and membrane PD-L1 protein expression levels. Subsequently, PET imaging was executed in immunodeficient mice xenografted with these cell lines. Mice were treated with interferon gamma (IFN) intraperitoneally for 3 days or with the mitogen-activated protein kinase kinase (MEK1/2) inhibitor selumetinib by oral gavage for 24 hours. Thereafter ¹⁸F-BMS-986192 was administered intravenously, followed by a 60-minute dynamic PET scan. Tracer uptake was expressed as percentage injected dose per gram tissue (%ID/g). Tissues were collected to evaluate ex vivo tracer biodistribution and to perform flow cytometric, Western blot, and immunohistochemical tumor analyses. Results: ¹⁸F-BMS-986192 uptake reflected PD-L1 membrane levels in tumor cell lines, and tumor tracer uptake in mice was associated with PD-L1 expression measured immunohistochemically. In vitro IFN treatment increased PD-L1 expression in the tumor cell lines and caused up to 12-fold increase in tracer binding. In vivo, IFN did neither affect PD-L1 tumor expression measured immunohistochemically nor ¹⁸F-BMS-986192 tumor uptake. In vitro, selumetinib downregulated cellular and membrane levels of PD-L1 of tumor cells by 50% as measured by Western blotting and flow cytometry. In mice, selumetinib lowered cellular, but not membrane PD-L1 levels of tumors and consequently no treatment-induced change in ¹⁸F-BMS-986192 tumor uptake was observed. Conclusion: ¹⁸F-BMS-986192 PET imaging allows detection of membrane-expressed PD-L1, as soon as 60 minutes after tracer injection. The tracer can discriminate a range of tumor cell PD-L1 membrane expression levels.

Adenosine monophosphate-activated protein kinase (AMPK) is an obligate heterotrimer that consists of a catalytic subunit (α) and two regulatory subunits (β and ). AMPK is a key enzyme in the regulation of cellular energy homeostasis. It has been well studied and is known to function in many cellular pathways. However, the interactome of AMPK has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we used tandem-affinity purification, coupled with mass spectrometry (TAP-MS) analysis, to determine the interactome of AMPK and its functions. We conducted a TAP-MS analysis of all seven AMPK subunits. We identified 138 candidate high-confidence interacting proteins (HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complexes. Five candidate AMPK-binding proteins were experimentally validated, underlining the reliability of our data set. Furthermore, we demonstrated that AMPK acts with a strong AMPK-binding protein, Artemis, in non-homologous end joining. Collectively, our study established the first AMPK interactome and uncovered a new function of AMPK in DNA repair.

In this week's inexplicably klaxon-heavy and fish-themed APPLE SPECIAL episode, David Price praises Apple for rescuing us from the tyranny of wired headphones, and reveals a hitherto unsuspected penchant for former Everton strikers. Chris Martin (22:41) dazzles us with his knowledge of the Apple Watch Series Two, and display some unusual headphone usage, and Henry Burell (32:51) reveals that Berlin is big, and sheds some light on the tiny corner of tech that *isn't* Apple flavoured. Join us.  

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Host Matt Egan is in a sombre mood this week as the tech industry comes to terms with a Donald Trump US presidency. Staff writer at Macworld UK dives into what this could mean for Silicon Valley, Apple products and wether social media is at fault. Then producer Chris comes on to discuss the latest addition to the VR headset market with Google's Daydream. Will it be held back by a lack of applications though? (14:45) Finally, online editor at Computerworld UK talks about the biggest data breach at a UK bank, as Tesco Bank suffers a £2.5 million cyber theft and what this means for the banking industry as a whole (25:00).  

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21 April 2020

The cyclic GMP-AMP synthase (cGAS) protein is a pattern-recognition receptor of the mammalian innate immune system that is recognized as a main cytosolic sensor of pathogenic or damaged DNA. cGAS DNA binding initiates catalytic production of the second messenger, cyclic GMP-AMP, which activates the STING-TBK1-IRF3 signaling axis to induce cytokine expression. Post-translational modification (PTM) has started to be recognized as a critical component of cGAS regulation, yet the extent of these modifications remains unclear. Here, we report the identification and functional analysis of cGAS phosphorylations and acetylations in several cell types under basal and immune-stimulated conditions. cGAS was enriched by immunoaffinity purification from human primary fibroblasts prior to and after infection with herpes simplex virus type 1 (HSV-1), as well as from immune-stimulated STING-HEK293T cells. Six phosphorylations and eight acetylations were detected, of which eight PTMs were not previously documented. PTMs were validated by parallel reaction monitoring (PRM) mass spectrometry in fibroblasts, HEK293T cells, and THP-1 macrophage-like cells. Primary sequence and structural analysis of cGAS highlighted a subset of PTM sites with elevated surface accessibility and high evolutionary sequence conservation. To assess the functional relevance of each PTM, we generated a series of single-point cGAS mutations. Stable cell lines were constructed to express cGAS with amino acid substitutions that prevented phosphorylation (Ser-to-Ala) and acetylation (Lys-to-Arg) or that mimicked the modification state (Ser-to-Asp and Lys-to-Gln). cGAS-dependent apoptotic and immune signaling activities were then assessed for each mutation. Our results show that acetyl-mimic mutations at Lys384 and Lys414 inhibit the ability of cGAS to induce apoptosis. In contrast, the Lys198 acetyl-mimic mutation increased cGAS-dependent interferon signaling when compared to the unmodified charge-mimic. Moreover, targeted PRM quantification showed that Lys198 acetylation is decreased upon infections with two herpesviruses—HSV-1 and human cytomegalovirus (HCMV), highlighting this residue as a regulatory point during virus infection.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10^–6) with replication at Bonferroni-corrected P < 8.6 x 10^–4. Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10^–4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood–derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat–associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences.

21 April 2020

I hear God in cushion prints, Leopard pants, Ancestors, We Forget; What if it took place at midnight, would you Stack hay and win, Chicago with the broad shoulders, Hunt mosquitos, Midnight lover, the Ebullient wrestler in a, Pink Venetian mask, Would you, Be a brute, Pretending the contender was not God, Brisk breeze, Be […]

Since this week would have been carnival week in Jamaica, we are taking you back to the mecca, Trinidad and Tobago, where just a few months ago, before the pandemic, the region’s local designers, musicians and the revellers were on show. The...

The fourth in the series of the musical showcase Sunday Live, powered by Sagicor, was held on Sunday, April 19 at Pier One on the Waterfront and featured some of Jamaica’s top up-and-coming talents. The series, which is the brainchild of...

Sunday Live continues to showcase the musical prowess of some of Jamaica’s finest talent, and this past Sunday, April 26, the event featured songstress Shuga and reggae bands Earth Kry and TennShann Invasion. Now, with five episodes under its belt...

The Sunday Live stage continues to showcase some of Jamaica’s talented musicians, and on Sunday, May 3, up-and-coming singer Yeza; and singer, drummer and percussionist Roots Percussionist took centre stage and delivered powerful performances to...

As the Mets, Nationals and Phillies have made multiple upgrades, Braves GM Alex Anthopoulos has thus far limited his offseason activity to giving Josh Donaldson a record one-year deal and bringing to fruition the desires of Brian McCann and Nick Markakis to play for the Braves.

Direct-to-consumer genetic tests are sold online and in shops as a way to “find out what your DNA says". They insights into ancestry or disease risks; others claim to provide information on personality, athletic ability, and child talent. However, interpretation of genetic data is complex and context dependent, and DTC genetic tests may produce...

Reports from Italy, and more recently from the U.S. show the strain the healthcare system is under during this pandemic. We know that staff will step up in an emergency, but this isn’t a fire or a bombing, this is going to last for months. So how can organisations be proactive in supporting staff, and how can leaders try to mitigate the...

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H₂O₂) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H₂O₂ by high glucose, and H₂O₂ reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a's natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA-RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA sequence. Our analysis further revealed robust nonspecific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

The action mechanisms revealed by the biochemical and structural analyses of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellular roles. In this regard, DNA polymerase θ differs from other Pols in that whereas purified Polθ misincorporates an A opposite 1,N6-ethenodeoxyadenosine (ϵdA) using an abasic-like mode, Polθ performs predominantly error-free TLS in human cells. To test the hypothesis that Polθ adopts a different mechanism for replicating through ϵdA in human cells than in the purified Pol, here we analyze the effects of mutations in the two highly conserved tyrosine residues, Tyr-2387 and Tyr-2391, in the Polθ active site. Our findings that these residues are indispensable for TLS by the purified Pol but are not required in human cells, as well as other findings, provide strong evidence that the Polθ active site is reconfigured in human cells to stabilize ϵdA in the syn conformation for Hoogsteen base pairing with the correct nucleotide. The evidence that a DNA polymerase can configure its active site entirely differently in human cells than in the purified Pol establishes a new paradigm for DNA polymerase function.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

Kerri L. Cavanaugh
Jul 1, 2007; 25:90-97
Feature Articles

Ian H. de Boer
Jan 1, 2014; 37:24-30
DCCT/EDIC 30th Anniversary Summary Findings

Muh Geot Wong
May 1, 2016; 39:694-700
Cardiovascular Disease and Diabetes

The U.S. Navy Flight Demonstration Squadron, also known as the Blue Angels, will fly over Dallas/Fort Worth, Houston and New Orleans Wednesday to honor frontline workers fighting the COVID-19 pandemic.

Paola Fioretto
Aug 1, 2016; 39:S165-S171
III. SGLT2 Therapy

OBJECTIVE

Telomere shortening and DNA oxidation are associated with premature vascular aging, which may be involved in lower-extremity amputation (LEA). We sought to investigate whether leukocyte telomere length (LTL) and plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation, were associated with LEA in subjects with type 1 diabetes at high vascular risk.

ADNOC sold a 20 percent state in its refinery operations to Italy's Eni and 15 percent to OMV, from Austria in one of the biggest refinery transactions ever.

OBJECTIVE

To compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function.

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

Cleveland police say they have used DNA research to solve the 33-year-old strangling of a teenage girl, and arrest her killer.

The perjury trial of I. Lewis "Scooter" Libby goes to the jury this week. The case speaks to several issues -- how the Bush administration deals with critics of the war in Iraq, and the games that Washington's reporters and politicians play with each other. As far as the jury is concerned, however,...

Kerri L. Cavanaugh
Jul 1, 2007; 25:90-97
Feature Articles

The June 2020 issue of History of Psychiatry is now online. Full details follow below: “Wild melancholy. On the historical plausibility of a black bile theory of blood madness, or hæmatomania,” Jan Verplaetse. Abstract: Nineteenth-century art historian John Addington Symonds coined the term hæmatomania (blood madness) for the extremely bloodthirsty behaviour of a number of … Continue reading New History of Psychiatry: Melancholy, Madness, Chinese Psychiatry, Psychedelic Therapy, and More →

ABSTRACT SUBMISSION DEADLINE JANUARY 15, 2020 The Foundations of Utility and Risk (FUR) Conference will, for the first time, take place in the Asia Pacific area in 2020. We invite all Economists and other Social Scientists interested in the study of Decision-making to submit papers to the conference. Since 1982, FUR gathers every two years […]

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DEADLINE FOR ORAL PRESENTATIONS: FEB 15, 2020 On June 5-6 2020, Temple University will host the 10th Annual Interdisciplinary Symposium on Decision Neuroscience (ISDN) in Philadelphia, PA. This symposium is unique in that it brings together a range of constituencies involved in the use of neuroscience techniques to understand consumer decision making – world renowned […]

The post Annual Interdisciplinary Symposium on Decision Neuroscience (ISDN), Philadelphia, June 5-6, 2020 appeared first on Decision Science News.

Thousands of teachers will head to the state capital on Wednesday to call for a nearly $10,000 raise over four years and an increase to per-pupil spending.