Plant defense signals: Players and pawns in plant-virus-vector interactions

Carr, John P.,Murphy, Alex M.,Tungadi, Trisna,Yoon, Ju-Yeon Elsevier 2019 Plant science Vol.279 No.-

<P><B>Abstract</B></P> <P>Plant viruses face an array of host defenses. Well-studied responses that protect against viruses include effector-triggered immunity, induced resistance (such as systemic acquired resistance mediated by salicylic acid), and RNA silencing. Recent work shows that viruses are also affected by non-host resistance mechanisms; previously thought to affect only bacteria, oomycetes and fungi. However, an enduring puzzle is how viruses are inhibited by several inducible host resistance mechanisms. Many viruses have been shown to encode factors that inhibit antiviral silencing. A number of these, including the cucumoviral 2b protein, the poytviral P1/HC-Pro and, respectively, geminivirus or satellite DNA-encoded proteins such as the C2 or βC1, also inhibit defensive signaling mediated by salicylic acid and jasmonic acid. This helps to explain how viruses can, in some cases, overcome host resistance. Additionally, interference with defensive signaling provides a means for viruses to manipulate plant-insect interactions. This is important because insects, particularly aphids and whiteflies, transmit many viruses. Indeed, there is now substantial evidence that viruses can enhance their own transmission through their effects on hosts. Even more surprisingly, it appears that viruses may be able to manipulate plant interactions with beneficial insects by, for example, ‘paying back’ their hosts by attracting pollinators.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Plants possess multiple antiviral defenses. </LI> <LI> Many of these depend on biosynthesis of signal chemicals. </LI> <LI> Plant viruses have evolved counter-defense factors. </LI> <LI> Viral proteins including counter-defense factors can affect host-insect interactions. </LI> <LI> Manipulation of host-insect interactions may facilitate virus transmission. </LI> </UL> </P>

Seasonal to multiannual marine ecosystem prediction with a global Earth system model

Park, Jong-Yeon,Stock, Charles A.,Dunne, John P.,Yang, Xiaosong,Rosati, Anthony American Association for the Advancement of Scienc 2019 Science Vol.365 No.6450

<P><B>Predicting marine futures</B></P><P>The ability to predict how climate variations will affect marine ecosystems would allow better economic and ecosystem planning and management. Park <I>et al.</I> found that a global Earth system model skillfully predicted seasonal to multiannual ocean chlorophyll fluctuations in many regions. This could allow annual fish catches in some regions to be forecast 2 to 3 years in advance.</P><P><I>Science</I>, this issue p. 284</P><P>Climate variations have a profound impact on marine ecosystems and the communities that depend upon them. Anticipating ecosystem shifts using global Earth system models (ESMs) could enable communities to adapt to climate fluctuations and contribute to long-term ecosystem resilience. We show that newly developed ESM-based marine biogeochemical predictions can skillfully predict satellite-derived seasonal to multiannual chlorophyll fluctuations in many regions. Prediction skill arises primarily from successfully simulating the chlorophyll response to the El Niño–Southern Oscillation and capturing the winter reemergence of subsurface nutrient anomalies in the extratropics, which subsequently affect spring and summer chlorophyll concentrations. Further investigations suggest that interannual fish-catch variations in selected large marine ecosystems can be anticipated from predicted chlorophyll and sea surface temperature anomalies. This result, together with high predictability for other marine-resource–relevant biogeochemical properties (e.g., oxygen, primary production), suggests a role for ESM-based marine biogeochemical predictions in dynamic marine resource management efforts.</P>

Preferential Binding to Elk-1 by SLE-Associated <i>IL10</i> Risk Allele Upregulates <i>IL10</i> Expression

Sakurai, Daisuke,Zhao, Jian,Deng, Yun,Kelly, Jennifer A.,Brown, Elizabeth E.,Harley, John B.,Bae, Sang-Cheol,Alarcό,n-Riquelme, Marta E.,Edberg, Jeffrey C.,Kimberly, Robert P.,Ramsey-Goldman, Ros Public Library of Science 2013 PLoS genetics Vol.9 No.10

<▼1><P>Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of <I>IL10</I> with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the <I>IL10</I> gene cluster including <I>IL19</I>, <I>IL20</I> and <I>IL24</I>, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported <I>IL10</I> variant, rs3024505 located at 1 kb downstream of <I>IL10</I>, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (<I>P</I> = 2.7×10<SUP>−8</SUP>, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of <I>IL10</I>, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of <I>IL10</I> mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating <I>IL10</I> expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the <I>IL10</I> rs3122605-G allele upregulates <I>IL10</I> expression and confers increased risk for SLE in European Americans.</P></▼1><▼2><P><B>Author Summary</B></P><P>Systemic lupus erythematosus (SLE), a debilitating autoimmune disease characterized by the production of pathogenic autoantibodies, has a strong genetic basis. Variants of the <I>IL10</I> gene, which encodes cytokine interleukin-10 (IL-10) with known function of promoting B cell hyperactivity and autoantibody production, are associated with SLE and other autoimmune diseases, and serum IL-10 levels are elevated in SLE patients correlating with increased disease activity. In this study, to discover SLE-predisposing causal variant(s), we assessed variants within the genomic region containing <I>IL10</I> and its gene family member <I>IL19</I>, <I>IL20</I> and <I>IL24</I> for association with SLE in case and control subjects from diverse ancestries. We identified SLE-associated SNP rs3122605 located at 9.2 kb upstream of <I>IL10</I> as the most likely causal variant in subjects of European ancestry. The SLE-risk allele of rs3122605 was dose-dependently associated with elevated <I>IL10</I> expression at both mRNA and protein levels in peripheral blood samples from SLE patients and controls, which could be explained, at least in part, by its preferential binding to Elk-1, a transcription factor activated in B cells during active disease of SLE patients. Elk-1-mediated IL-10 overexpression could be downregulated by inhibiting activation of mitogen-activated protein kinases, suggesting a potential therapeutic target for SLE.</P></▼2>

The Potency of Immunomodulatory Herbs May Be Primarily Dependent upon Macrophage Activation

P. R. Oldfield,S. N. Groom,T. Johns 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

Standardized extracts of Echinacea, cat’s claw, and saw palmetto were each evaluated for ability to activatemacrophage and natural killer cells, in vitro, using two independent measures of activation for each immune cell population.A standard series of exposure concentrations were tested for each herbal extract in a panel of four assays that evaluatedmacrophage phagocytosis, macrophage synthesis of interleukin-12, natural killer (NK) cell cytocidal activity (synthesis ofgranzyme B), and NK cell synthesis of interferon-.. Macrophage phagocytosis was stimulated by all three herbs tested: sawpalmetto (up to 2.3-fold, P. .05), Echinacea P. .01), and cat’s claw (up to 4.7-fold, P. .01). Addition-ally, NK cell synthesis of interferon-. was stimulated by saw palmetto (up to 6.3-fold, P. .01) and Echinacea(up to 8.1-fold, P. .01) but not by exposure to cat’s claw. None of the three herbs stimulated macrophage synthesis of interleukin-12or NK cell synthesis of granzyme B. Comparison of the in vitrodata with our earlier observations that cat’s claw and Echi-naceagests macrophage activation is the primary means by which these herbs modulate the immune system. Thus, macrophage ac-tivation (phagocytosis) may provide a potentially higher throughput method to identify herbal extracts with in vivostimulatoryeffects.

The Influence of Iron on<i>Pseudomonas aeruginosa</i>Physiology : <i>A REGULATORY LINK BETWEEN IRON AND QUORUM SENSING</i>

Oglesby, Amanda G.,Farrow III, John M.,Lee, Joon-Hee,Tomaras, Andrew P.,Greenberg, E. P.,Pesci, Everett C.,Vasil, Michael L. American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.23

<P>In iron-replete environments, the Pseudomonas aeruginosa Fur (ferric uptake regulator) protein represses expression of two small regulatory RNAs encoded by prrF1 and prrF2. Here we describe the effects of iron and PrrF regulation on P. aeruginosa physiology. We show that PrrF represses genes encoding enzymes for the degradation of anthranilate (i.e. antABC), a precursor of the Pseudomonas quinolone signal (PQS). Under iron-limiting conditions, PQS production was greatly decreased in a DeltaprrF1,2 mutant as compared with wild type. The addition of anthranilate to the growth medium restored PQS production to the DeltaprrF1,2 mutant, indicating that its defect in PQS production is a consequence of anthranilate degradation. PA2511 was shown to encode an anthranilate-dependent activator of the ant genes and was subsequently renamed antR. AntR was not required for regulation of antA by PrrF but was required for optimal iron activation of antA. Furthermore, iron was capable of activating both antA and antR in a DeltaprrF1,2 mutant, indicating the presence of two distinct yet overlapping pathways for iron activation of antA (AntR-dependent and PrrF-dependent). Additionally, several quorum-sensing regulators, including PqsR, influenced antA expression, demonstrating that regulation of anthranilate metabolism is intimately woven into the quorum-sensing network of P. aeruginosa. Overall, our data illustrate the extensive control that both iron regulation and quorum sensing exercise in basic cellular physiology, underlining how intermediary metabolism can affect the regulation of virulence factors in P. aeruginosa.</P>

Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian Patients of Los Angeles: A Single Institution Analysis

( Courtney Duong ),( Thien Nguyen ),( John P. Sheppard ),( Vera Ong ),( Lawrance K. Chung ),( Daniel T. Nagasawa ),( Isaac Yang ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2017 Brain Tumor Research and Treatment Vol.5 No.2

Background Worldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood. Methods A retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS). Results A total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18-90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian pa-tients was 55.9 years (SD: 14.6 range: 26-89). Asian-only cohort tumor pathologies included glioblas-toma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (p= 0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048, respectively), or OS (p=0.3711 and p=0.8183, respectively). Conclusion Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consider-ation when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results.

The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors

YongYan Cui,Lauren G. Khanna,Anjali Saqi,John P. Crapanzano,James M. Mitchell,Amrita Sethi,Tamas A. Gonda,Michael D. Kluger,Beth A. Schrope,John Allendorf,John A. Chabot,John M. Poneros 대한소화기내시경학회 2020 Clinical Endoscopy Vol.53 No.2

Background/Aims: The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs)has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratifyPNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NF-PNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NF-PNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordancewas the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028)were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumorsize >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs withintermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUS-FNA can be monitored without surgical intervention, up to tumor size 20 mm.

Leadership Roles, Academic Appointments, and Scholarly Activity—Does a Fellowship after Plastic Surgery Training Make a Difference?

Christopher Adrienne N.,Patel Viren,Mellia Joseph A.,Morris Martin P.,Diatta Fortunay,Murphy Alexander I.,Fischer John P. 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.1

Background Fellowship training is becoming more popular in plastic surgery, with over half of residents pursuing advanced training. Here, we investigate how clinical and research fellowship training impacts career trajectory and scholastic achievement in academic plastic surgery.Methods Plastic surgery faculty members, from programs recognized by the American Council of Academic Plastic Surgeons, were identified using institutional Web sites. Data extracted included faculty demographics, training history, academic positions, and research productivity. Continuous and categorical variables were compared using t-tests and chi-square, respectively.Results In total, 949 faculty members were included, with 657 (69%) having completed fellowship training. Integrated program residents were more likely to complete a fellowship when compared with independent residents (p < 0.0001). Fellowship trained faculty were more likely to have graduated from a higher ranked residency program, in terms of both overall and research reputation (p = 0.005 and p = 0.016, respectively). When controlling for years in practice, there was no difference found in number of publications, Hirsch index (h-index), or National Institutes of Health funding between faculty between the two cohorts (p > 0.05). In a subanalysis comparing hand, craniofacial, microsurgery, and research fellowships, those who completed a research fellowship had higher h-indices and were more likely to reach full professor status (p < 0.001 and p = 0.001, respectively). Fellowship training had no effect on being promoted to Chief/Chair of departments (p = 0.16).Conclusion Fellowship training is common among academic plastic surgeons. In this study, both clinical and research fellowships were associated with various aspects of academic success. However, fellowship training alone did not affect attainment of leadership positions.

Leadership Roles, Academic Appointments, and Scholarly Activity—Does a Fellowship after Plastic Surgery Training Make a Difference?

Christopher Adrienne N.,Patel Viren,Mellia Joseph A.,Morris Martin P.,Diatta Fortunay,Murphy Alexander I.,Fischer John P. 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.2

Background Fellowship training is becoming more popular in plastic surgery, with over half of residents pursuing advanced training. Here, we investigate how clinical and research fellowship training impacts career trajectory and scholastic achievement in academic plastic surgery.Methods Plastic surgery faculty members, from programs recognized by the American Council of Academic Plastic Surgeons, were identified using institutional Web sites. Data extracted included faculty demographics, training history, academic positions, and research productivity. Continuous and categorical variables were compared using t-tests and chi-square, respectively.Results In total, 949 faculty members were included, with 657 (69%) having completed fellowship training. Integrated program residents were more likely to complete a fellowship when compared with independent residents (p < 0.0001). Fellowship trained faculty were more likely to have graduated from a higher ranked residency program, in terms of both overall and research reputation (p = 0.005 and p = 0.016, respectively). When controlling for years in practice, there was no difference found in number of publications, Hirsch index (h-index), or National Institutes of Health funding between faculty between the two cohorts (p > 0.05). In a subanalysis comparing hand, craniofacial, microsurgery, and research fellowships, those who completed a research fellowship had higher h-indices and were more likely to reach full professor status (p < 0.001 and p = 0.001, respectively). Fellowship training had no effect on being promoted to Chief/Chair of departments (p = 0.16).Conclusion Fellowship training is common among academic plastic surgeons. In this study, both clinical and research fellowships were associated with various aspects of academic success. However, fellowship training alone did not affect attainment of leadership positions.

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

Flannick, Jason,Thorleifsson, Gudmar,Beer, Nicola L,Jacobs, Suzanne B R,Grarup, Niels,Burtt, Noë,l P,Mahajan, Anubha,Fuchsberger, Christian,Atzmon, Gil,Benediktsson, Rafn,Blangero, John,Bowden, Do Nature Pub. Co 2014 Nature genetics Vol.46 No.4

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10<SUP>−6</SUP>), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (−0.17 s.d., P = 4.6 × 10<SUP>−4</SUP>). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.