Human antibody response studies are largely restricted to periods of high immune activity (e.g. vaccination). To comprehensively understand the healthy B cell immune repertoire and how this changes over time and through natural infection, we conducted immune repertoire RNA sequencing on flow cytometry-sorted B cell subsets to profile a single individual's antibodies over 11 months through two periods of natural viral infection. We found that 1) a baseline of healthy variable (V) gene usage in antibodies exists and is stable over time, but antibodies in memory cells consistently have a different usage profile relative to earlier B cell stages; 2) a single complementarity-determining region 3 (CDR3) is potentially generated from more than one VJ gene combination; and 3) IgG and IgA antibody transcripts are found at low levels in early human B cell development, suggesting that class switching may occur earlier than previously realized. These findings provide insight into immune repertoire stability, response to natural infections, and human B cell development.

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 

After a pair of seasons -- and a World Series title -- with the Astros, Rays pitcher Charlie Morton is confident that his new team has what in takes to make a postseason run in 2019.

John Horton Conway died on April 11 of COVID-19. He was 82 years old. In the midst of social distancing measures to fight the coronavirus pandemic, a common refrain is “life goes on”.  But sometimes it doesn’t. Conway was an … Continue reading →

Katherine M Flegal
Jul 1, 1991; 14:628-638
Supplement 3: Diabetes in Hispanic Americans

The U.S.-based International Medical Relief is sponsoring outreach trips to Puerto Rico in response to the earthquakes that have devastated the region.

Dr. Robert M. Anderton, ADA president from 2000-01 and ADA trustee from 1995-99, died Feb. 14.

APPLICATION DEADLINE OCTOBER 15, 2019 The Operations, Information and Decisions Department at the Wharton School is seeking applicants for a full-time, tenure track, Assistant Professor faculty position in the area of decision-making. Our decision-making faculty is comprised of scholars with a diverse set of backgrounds and interests, and we encourage applicants with degrees in economics, […]

The post Professorship in decision making at Wharton, Operations, Information and Decisions (OID), University of Pennsylvania appeared first on Decision Science News.

SUBMISSION DEADLINE DECEMBER 13, 2019 In this conference, investigators present original research on a variety of topics related to judgment and decision making, including but not limited to: Decision making under risk, uncertainty, and ambiguity Intertemporal choice Cognitive models of judgment and decision making Mathematical and statistical methodology for analyzing behavioral data Applications of JDM […]

The post 57th Edwards Bayesian Research Conference, Feb 27-29, 2020, Fullerton, CA appeared first on Decision Science News.

Morton, Rick -- Childhood and youth.

Dogs -- Breeding -- Great Britain -- History -- 19th century.

Volcanoes.

Paris : Delahaye, 1873.

London : printed for B. and J. White, 1797.

Paris : J.-B. Bailliere ; Londres : H. Bailliere, 1852-1854.

Bruxelles : Etablissement Encyclographique, 1833-46.

Paris : G. Steinheil, 1895.

London (Poets Gallery Fleet Street) : Publish'd ... by Thos. Macklin, Novr. 30. 1799.

[London], [1827?]

London (in Cheapside) : Published according to Act of Parliament, by J Boydell engraver, 1763.

The Museo de la Massacre de Ponce and Casa Paoli were among the buildings affected by Saturday's tremors

Learn hip-hop dance or do citizen science without leaving home this week, thanks to the internet's many intrepid artists and educators

The following is a guest post by Martha H. Kennedy, Curator of Popular & Applied Graphic Art, Prints & Photographs Division. During Will Eisner Week, March 1-7, 2020, the Library of Congress joins art schools, libraries, universities, and museums in a global celebration of this legendary creator’s contributions to the world of comic art and […]

Gus has been captivating visitors to the Nova Scotia Museum of Natural History for more than seven decades.

Avid curler Dale Kohlenberg, 64, got a lucky break when he was seconded to Iqaluit — and was quickly scouted for Team Nunavut.

Fears that COVID-19 would spread at the Hamilton-Wentworth Detention Centre appear not to have materialized — at least not yet.

Dumbarton police station has temporarily closed after a member of staff showed symptoms of Covid-19.

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210.”

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210.”

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210