Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen-the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen-the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies

Lessons Learned: Feasibility of a Discussion Prompting Tool to Increase Fertility Risk Discussion Among Adolescent Oncology Families

The purpose of this study was to explore the feasibility of distributing a prompting tool (stress egg) in order to increase discussions about fertility risk and preservation (FP) among female adolescent oncology patients, parents, and healthcare providers (HCP). 200 eggs were distributed to four pediatric oncology centers. Qualitative interviews were completed with healthcare staff (N=7) after 6 months of distribution to newly diagnosed female oncology patients ages 12-18. Interviews showed that the main barriers to distribution of the prompt were: forgetting to distribute the eggs; uncertainty about the significance of fertility; and uncertainty about fertility issues in general for female adolescent cancer patients. The scientific community must continually explore effective avenues of communication to ensure such information is received. The stress egg has potential to impact a cancer survivor’s outlook on future partnering, family life, and self-concept when used in conjunction with policy

Phosphorylation of eIF4GII and 4E-BP1 in response to nocodazole treatment: a reappraisal of translation initiation during mitosis

Translation mechanisms at different stages of the cell cycle have been studied for many years, resulting in the dogma that translation rates are slowed during mitosis, with cap-independent translation mechanisms favored to give expression of key regulatory proteins. However, such cell culture studies involve synchronization using harsh methods, which may in themselves stress cells and affect protein synthesis rates. One such commonly used chemical is the microtubule de-polymerization agent, nocodazole, which arrests cells in mitosis and has been used to demonstrate that translation rates are strongly reduced (down to 30% of that of asynchronous cells). Using synchronized HeLa cells released from a double thymidine block (G 1/S boundary) or the Cdk1 inhibitor, RO3306 (G 2/M boundary), we have systematically re-addressed this dogma. Using FACS analysis and pulse labeling of proteins with labeled methionine, we now show that translation rates do not slow as cells enter mitosis. This study is complemented by studies employing confocal microscopy, which show enrichment of translation initiation factors at the microtubule organizing centers, mitotic spindle, and midbody structure during the final steps of cytokinesis, suggesting that translation is maintained during mitosis. Furthermore, we show that inhibition of translation in response to extended times of exposure to nocodazole reflects increased eIF2α phosphorylation, disaggregation of polysomes, and hyperphosphorylation of selected initiation factors, including novel Cdk1-dependent N-terminal phosphorylation of eIF4GII. Our work suggests that effects on translation in nocodazole-arrested cells might be related to those of the treatment used to synchronize cells rather than cell cycle status

Defects in High Entropy Alloy HfNbTaTiZr Prepared by High Pressure Torsion

High entropy alloy HfNbTaTiZr was successfully processed by severe plastic deformation using high pressure torsion (HPT) and ultrafine grained microstructure was achieved. The microstructure of HPT-deformed HfNbTaTiZr alloy was characterized by X-ray diffraction and compared with conventionally cast ingots. The lattice defects introduced by HPT processing were characterized by positron annihilation spectroscopy. The X-ray diffraction profiles of HTP-deformed samples were extremely broadened due to small sizes of coherently diffracting domains and a high microstrain introduced by severe plastic deformation.11Ysciescopu

Notes on the natural history of \u3ci\u3eEnaphalodes archboldi\u3c/i\u3e Lingafelter and Chemsak, 2002 and E. bingkirki Lingafelter and Santos-Silva, 2018 (Coleoptera: Cerambycidae)

The life history of Enaphalodes archboldi Lingafelter and Chemsak (Coleoptera: Cerambycidae) is described in detail based on observations from Marion County, Florida. Notes on the life history of Enaphalodes bingkirki Lingafelter and Santos-Silva from Honduras are also provided. Enaphalodes bingkirki is reported from Honduras for the first time

Notes on the natural history of \u3ci\u3eEnaphalodes archboldi\u3c/i\u3e Lingafelter and Chemsak, 2002 and E. bingkirki Lingafelter and Santos-Silva, 2018 (Coleoptera: Cerambycidae)

The life history of Enaphalodes archboldi Lingafelter and Chemsak (Coleoptera: Cerambycidae) is described in detail based on observations from Marion County, Florida. Notes on the life history of Enaphalodes bingkirki Lingafelter and Santos-Silva from Honduras are also provided. Enaphalodes bingkirki is reported from Honduras for the first time

A new species of Ophtalmibidion Martins from French Guiana, and notes on O. luscum Martins (Coleoptera, Cerambycidae, Cerambycinae)

Ophtalmibidion gutta sp. nov. is described from French Guiana. The elytral color pattern of Ophtalmibidion luscum Martins, 1971 is commented on. A key to species of Ophtalmibidion is provided as well as photographs of all species

Observations on the natural history of \u3ci\u3eRomulus globosus\u3c/i\u3e Knull (Coleoptera: Cerambycidae)

Host plants of Romulus globosus Knull (Coleoptera: Cerambycidae) are described for the first time. Notes on its natural history are provided. The larvae of R. globosus feed in living roots of scrub oaks, including Quercus geminata Small, Quercus myrtifolia Willd., and Quercus laevis Walter. Field observations show that the beetle emerges below ground, and females may burrow to lay eggs on the roots

Description of two new species of Xenocona Gilmour (Coleoptera, Cerambycidae, Lamiinae) from Ecuador

Xenocona Gilmour, 1960 (Acanthocinini) includes seven species distributed through Central America and northern South America. Here we describe two new species from Ecuador: X. audureaui (differing from other species of the genus by the presence of large dark macula on dorsal surface of the basal ⅔ of the elytra combined with the absence of narrow white pubescent lines on other areas of the elytra) and X. uniformis (differing from the other species of the genus by the spiniform outer elytral angle)