38 research outputs found
Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody
Multidrug-resistant Neisseria gonorrhoeae is a global health problem. Monoclonal antibody (mAb) 2C7 recognizes a gonococcal lipooligosaccharide epitope that is expressed by \u3e 95% of clinical isolates and hastens gonococcal vaginal clearance in mice. Chimeric mAb 2C7 (human immunoglobulin G1 [IgG1]) with an E430G Fc modification that enhances Fc:Fc interactions and hexamerization following surface-target binding and increases complement activation (HexaBody technology) showed significantly greater C1q engagement and C4 and C3 deposition compared to mAb 2C7 with wild-type Fc. Greater complement activation by 2C7-E430G Fc translated to increased bactericidal activity in vitro and, consequently, enhanced efficacy in mice, compared with Fc-unmodified chimeric 2C7. Gonococci bind the complement inhibitors factor H (FH) and C4b-binding protein (C4BP) in a human-specific manner, which dampens antibody (Ab)-mediated complement-dependent killing. The variant 2C7-E430G Fc overcame the barrier posed by these inhibitors in human FH/C4BP transgenic mice, for which a single 1 mug intravenous dose cleared established infection. Chlamydia frequently coexists with and exacerbates gonorrhea; 2C7-E430G Fc also proved effective against gonorrhea in gonorrhea/chlamydia-coinfected mice. Complement activation alone was necessary and sufficient for 2C7 function, evidenced by the fact that (1) complement-inactive Fc modifications that engaged Fc gamma receptor (FcgammaR) rendered 2C7 ineffective, nonetheless; (2) 2C7 was nonfunctional in C1q-/- mice, when C5 function was blocked, or in C9-/- mice; and (3) 2C7 remained effective in neutrophil-depleted mice and in mice treated with PMX205, a C5a receptor (C5aR1) inhibitor. We highlight the importance of complement activation for antigonococcal Ab function in the genital tract. Elucidating the correlates of protection against gonorrhea will inform the development of Ab-based gonococcal vaccines and immunotherapeutics
Non-surgical Management of Complex Refractory Pyoderma Gangrenosum With Negative Pressure Wound Therapy With Instillation
Pyoderma gangrenosum (PG) is a rare skin disorder primarily treated with immunosuppression medication. We report a case of a large, chronic PG wound treated with adjunct negative pressure wound therapy with instillation and dwell time (NPWTi-d) using nonadherent dressing (Mepitel) and reticular open-cell foam with through holes (ROCF-CC) with positive outcomes. The patient was a 62-year-old female with rheumatoid arthritis, Hashimoto\u27s thyroiditis, lymphedema, and morbid obesity who presented with a 19.5 cm x 13.2 cm x 2.1 cm wound of three years duration on the right posterolateral lower extremity that successfully responded to a multimodality approach of immunosuppression and wound vac therapy. We conclude in our case that NPWTi-d with Mepitel and ROCF-CC enhanced the wound healing process, and we discuss NPWTi-d\u27s potential role and benefit as an adjunctive therapy option for chronic and poorly controlled PG on patients taking concurrent immunosuppression
Place-Based Learning Communities on a Rural Campus: Turning Challenges into Assets
At Humboldt State University (HSU), location is everything. Students are as drawn to our spectacular natural setting as they are to the unique majors in the natural resource sciences that the university has to offer. However, the isolation that nurtures the pristine natural beauty of the area presents a difficult reality for students who are accustomed to more densely populated environments. With the large majority of our incoming students coming from distant cities, we set out to cultivate a “home away from home” by connecting first-year students majoring in science, technology, engineering and math (STEM) to the communities and local environment of Humboldt County. To achieve this, we designed first-year place-based learning communities (PBLCs) that integrate unique aspects and interdisciplinary themes of our location throughout multiple high impact practices, including a summer experience, blocked-enrolled courses, and a first-year experience course entitled Science 100: Becoming a STEM Professional in the 21st Century. Native American culture, traditional ways of knowing, and contemporary issues faced by tribal communities are central features of our place-based curriculum because HSU is located on the ancestral land of the Wiyot people and the university services nine federally recognized American Indian tribes. Our intention is that by providing a cross-cultural, validating environment, students will: feel and be better supported in their academic pursuits; cultivate values of personal, professional and social responsibility; and increase the likelihood that they will complete their HSU degree. As we complete the fourth year of implementation, we aim to harness our experience and reflection to improve our programming and enable promising early results to be sustained
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
Frank J. Shaughnessy Letter to J.G. Taylor Spink Regarding Congressional Sports Bills
Frank J. Shaughnessy Letter to J.G. Taylor Spink Regarding Congressional Sports Bill
Geese in Humboldt Help Eelgrass
On their annual northward migration, tens of thousands of brant geese descend on Humboldt Bay to feed on the long green ends of eelgrass. It might seem grazing could hurt eelgrass, which provides important vegetation and habitat for many marine species. However, this is not the case. California Sea Grant research shows that grazing by geese, at its current intensity level, stimulates eelgrass growth
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A Field Experimental Investigation of the Effects of Black Brant Geese Grazing on Eelgrass Growth and the Animals in an Eelgrass Bed
Eelgrass (Zostera marina) beds and other seagrass ecosystems around the world are recognized for their trophic support, nursery, refuge, water quality and recreational functions (Williams and Heck 2001)
Recommended from our members
A Field Experimental Investigation of the Effects of Black Brant Geese Grazing on Eelgrass Growth and the Animals in an Eelgrass Bed
Eelgrass (Zostera marina) beds and other seagrass ecosystems around the world are recognized for their trophic support, nursery, refuge, water quality and recreational functions (Williams and Heck 2001)