Parasitism of \u3ci\u3eCidia\u3c/i\u3e Spp. (Lepidoptera: Tortricidae) on \u3ci\u3eSophora Chrysophylla\u3c/i\u3e (Fabaceae) Along an Elevation Gradient of Dry Subalpine Forest on Mauna Kea, Hawaii

The biology and ecological importance of Hawaiian endemic Cydia spp. (Lepidoptera: Tortricidae) are poorly known. Cydia larvae arc an important food to palila, an endangered Hawaiian bird that inhabits Sophora woodlands on Mauna Kea, Hawaii. We quantified Cydia larval abundance in seeds of Sophora chrysophylla Salisbury (Fabaceae) and larval mortality caused by parasitism. Four new host plant associations are reported: C. crassicornis [Walsingham], C. fulsifalcella [Walsingham], C. obliqlla [Walsingham], and C. storeella [Walsingham]. Four parasitoid wasp species were consistently reared from larval Cydia: Calliephialtes grapholithae [Cresson], Diadegma blackburni [Cameron], Pristomerus hawaiiensis Perkins (Hymenoptera: Ichneumonidae), and Euderus metallicus [Ashmead] (Hymenoptera: Eulophidae). The three Ichneumonidae appear to be accidental introductions, while E. metallicus is likely to be native to Hawaii. Parasitism rates by all four wasps combined decreased with elevation from 94% at 1800 m to 20% at 2700 m

Parasitism of \u3ci\u3eCidia\u3c/i\u3e Spp. (Lepidoptera: Tortricidae) on \u3ci\u3eSophora Chrysophylla\u3c/i\u3e (Fabaceae) Along an Elevation Gradient of Dry Subalpine Forest on Mauna Kea, Hawaii

The biology and ecological importance of Hawaiian endemic Cydia spp. (Lepidoptera: Tortricidae) are poorly known. Cydia larvae arc an important food to palila, an endangered Hawaiian bird that inhabits Sophora woodlands on Mauna Kea, Hawaii. We quantified Cydia larval abundance in seeds of Sophora chrysophylla Salisbury (Fabaceae) and larval mortality caused by parasitism. Four new host plant associations are reported: C. crassicornis [Walsingham], C. fulsifalcella [Walsingham], C. obliqlla [Walsingham], and C. storeella [Walsingham]. Four parasitoid wasp species were consistently reared from larval Cydia: Calliephialtes grapholithae [Cresson], Diadegma blackburni [Cameron], Pristomerus hawaiiensis Perkins (Hymenoptera: Ichneumonidae), and Euderus metallicus [Ashmead] (Hymenoptera: Eulophidae). The three Ichneumonidae appear to be accidental introductions, while E. metallicus is likely to be native to Hawaii. Parasitism rates by all four wasps combined decreased with elevation from 94% at 1800 m to 20% at 2700 m

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single‐institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan‐Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive‐year overall survival (OS) was 49%. Five‐year disease‐free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation‐27 [ACE‐27] scale; HR 3.76; 95% confidence interval [CI] 1.56‐9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74‐4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/1/hed24918.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/2/hed24918_am.pd

Saposins utilize two strategies for lipid transfer and CD1 antigen presentation

Funding: We are grateful to A.N. Odyniec, M. Brigl, G.F.M. Watts, and T.Y. Cheng for suggestions and excellent technical assistance. This work was supported by National Institutes of Health (NIH) Grants AI028973 and AI063428 (to M.B.B.), DK36729 and NS36681 (to G.A.G.), and AR048632 and AI049313 (to D.B.M. and A.K.); a Howard Hughes Medical Institute Gilliam Fellowship (to L.L.); the Burroughs Wellcome Fund (D.B.M. and A.K.); a Personal Research Chair from Mr. James Bardrick (to V.B., N.V., and G.S.B.); a Royal Society Wolfson Research Merit Award (to V.B., N.V., and G.S.B.); the Medical Research Council (V.B., N.V., and G.S.B.); Wellcome Trust Grant 084923/B/08/Z (to V.B., N.V., and G.S.B.); and a Netherlands Organization for Scientific Research Grant (to A.J.M.Transferring lipid antigens from membranes into CD1 antigen-presenting proteins represents a major molecular hurdle necessary for T-cell recognition. Saposins facilitate this process, but the mechanisms used are not well understood. We found that saposin B forms soluble saposin protein-lipid complexes detected by native gel electrophoresis that can directly load CD1 proteins. Because saposin B must bind lipids directly to function, we found it could not accommodate long acyl chain containing lipids. In contrast, saposin C facilitates CD1 lipid loading in a different way. It uses a stable, membrane-associated topology and was capable of loading lipid antigens without forming soluble saposin-lipid antigen complexes. These findings reveal how saposins use different strategies to facilitate transfer of structurally diverse lipid antigens.publishersversionpublishe

IL-9 as a mediator of Th17-driven inflammatory disease

We report that like other T cells cultured in the presence of transforming growth factor (TGF) β, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-β as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6–producing macrophages in the central nervous system, as well as mast cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9 as a Th17-derived cytokine that can contribute to inflammatory disease

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd

Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions