Required reading for any academic is Philip Roth’s “The Human Stain.” In the first few pages an older, tenured professor is “forced to retire.” Why? There were two students who never were present when he called roll. Even after roll … Continue reading →

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Q is for Queerlesque

Caryl Ann O'Reilly
Jul 1, 2005; 18:162-166
Articles

Beatrice K. Gandara
Nov 1, 2011; 24:199-205
From Research to Practice

Sarah S. Farabi
Feb 1, 2016; 29:10-13
From Research to Practice

Jimmy Doumit
Feb 1, 2016; 29:14-19
From Research to Practice

Erika Leung
Aug 1, 2018; 31:245-253
From Research to Practice

John R. White
May 1, 2014; 27:82-86
From Research to Practice

Brenna Cholerton
Nov 1, 2016; 29:210-219
From Research to Practice

Gretchen Benson
Feb 1, 2011; 24:36-40
Nutrition FYI

Ruban Dhaliwal
Feb 1, 2014; 27:9-20
Research to Practice

Priscilla Hollander
Jul 1, 2007; 20:159-165
Articles

Cathy Lloyd
Apr 1, 2005; 18:121-127
Feature Articles

Ryan A. Ristau
Nov 1, 2013; 26:211-215
From Research to Practice

Jeanette Ezzo
Oct 1, 2001; 14:
Articles

W. Guyton Hornsby
Apr 1, 2005; 18:102-107
Articles

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Ji Chun
May 1, 2019; 32:104-111
Feature Articles

Sue McLaughlin
Oct 1, 2010; 23:272-277
Special Report

Jennal L. Johnson
Jul 1, 2006; 19:148-153
Articles

Caroline Trapp
Feb 1, 2012; 25:38-44
Nutrition FYI

Pasquale Passarella
Aug 1, 2018; 31:218-224
From Research to Practice

Katherine S. O’Neal
Nov 1, 2016; 29:249-252
Pharmacy and Therapeutics

Deborah Hinnen
Aug 1, 2017; 30:202-210
Feature Articles

Jul 1, 2002; 15:
Patient Information

Amy P. Campbell
May 1, 2017; 30:76-81
From Research to Practice

Marion J. Franz
Jul 1, 2007; 20:133-136
Editorials

Samuel Dagogo-Jack
Jan 1, 2002; 15:
Articles

Shani V. Davis
Aug 1, 2011; 24:148-153
Feature Article/Vitamin D in African Americans

Maggie B. Covington
Aug 1, 2001; 14:
Articles

Teresa Martin
May 1, 2011; 24:113-118
Pharmacy and Therapeutics

Peggy Yarborough
Jan 1, 2003; 16:
Case Studies

Betsy B. Dokken
Jul 1, 2008; 21:160-165
From Research to Practice/Cardiovascular Disease and Diabetes

Curtis Triplitt
Oct 1, 2006; 19:202-211
Pharmacy Update

Guillermo E. Umpierrez
Jan 1, 2002; 15:
Articles

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

The linear ubiquitin assembly complex (LUBAC) is an essential component of the innate and adaptive immune system. Modification of cellular substrates with linear polyubiquitin chains is a key regulatory step in signal transduction that impacts cell death and inflammatory signaling downstream of various innate immunity receptors. Loss-of-function mutations in the LUBAC components HOIP and HOIL-1 yield a systemic autoinflammatory disease in humans, whereas their genetic ablation is embryonically lethal in mice. Deficiency of the LUBAC adaptor protein Sharpin results in a multi-organ inflammatory disease in mice characterized by chronic proliferative dermatitis (cpdm), which is propagated by TNFR1-induced and RIPK1-mediated keratinocyte cell death. We have previously shown that caspase-1 and -11 promoted the dermatitis pathology of cpdm mice and mediated cell death in the skin. Here, we describe a reciprocal regulation of caspase-1 and LUBAC activities in keratinocytes. We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death. HOIP processing impeded substrate ubiquitination in the NF-κB pathway and resulted in enhanced apoptosis. These results highlight a regulatory mechanism underlying efficient apoptosis in keratinocytes and provide further evidence of a cross-talk between inflammatory and cell death pathways.

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above.

(American Geriatrics Society) The American Geriatrics Society (AGS) today announced that John B. Murphy, MD, a clinician, educator, and administrator working to embed geriatrics education in the fabric of medical curricula and clinical operations will be honored with the 2020 Dennis W. Jahnigen Award celebrating work to train health professionals in the care we all need as we age.

(American Geriatrics Society) The American Geriatrics Society (AGS) and AGS Health in Aging Foundation today announced that Alexander K. Smith, MD, MPH, an associate professor of medicine at UCSF and one of geriatrics' most influential rising researchers and advocates, will be honored with the 2020/2021 Thomas and Catherine Yoshikawa Award for Outstanding Scientific Achievement in Clinical Investigation.