The Arabidopsis cellulose synthase complex: a proposed hexamer of CESA trimers in an equimolar stoichiometry.

Cellulose is the most abundant renewable polymer on Earth and a major component of the plant cell wall. In vascular plants, cellulose synthesis is catalyzed by a large, plasma membrane-localized cellulose synthase complex (CSC), visualized as a hexameric rosette structure. Three unique cellulose synthase (CESA) isoforms are required for CSC assembly and function. However, elucidation of either the number or stoichiometry of CESAs within the CSC has remained elusive. In this study, we show a 1:1:1 stoichiometry between the three Arabidopsis thaliana secondary cell wall isozymes: CESA4, CESA7, and CESA8. This ratio was determined utilizing a simple but elegant method of quantitative immunoblotting using isoform-specific antibodies and (35)S-labeled protein standards for each CESA. Additionally, the observed equimolar stoichiometry was found to be fixed along the axis of the stem, which represents a developmental gradient. Our results complement recent spectroscopic analyses pointing toward an 18-chain cellulose microfibril. Taken together, we propose that the CSC is composed of a hexamer of catalytically active CESA trimers, with each CESA in equimolar amounts. This finding is a crucial advance in understanding how CESAs integrate to form higher order complexes, which is a key determinate of cellulose microfibril and cell wall properties.

Disparities in Acute Lymphocytic Leukemia Outcomes Among Young Adults.

Background: Age is a strong prognostic factor in acute lymphocytic leukemia (ALL), with children doing better than adults with the same disease. One hypothesis for this age-based disparity is differences in treatment regimens. Optimizing care for adolescents and young adults (AYA) with ALL has not been well defined and disparities in care exist. We conducted a retrospective study of all veterans with ALL diagnosed between the ages of 18 and 45 since the year 2000 to evaluate disparities among prognostication methods, treatment regimens, and accrual to clinical trials with regard to age and race/ethnicity and how these factors influence overall survival. Methods: Electronic medical record data from the VA Informatics and Computing Infrastructure (VINCI) were used to identify 6,724 patients with an ICD-9 or 10 code for ALL. All patients were chart checked to confirm an ALL diagnosis between the ages of 18 and 45 and excluded if they were diagnosed before 2000, had childhood ALL, or if induction protocol was not recorded. A total of 252 patients were included in the final analysis. Multivariate analysis was performed with controls for age, ALL subtype (B, T, mixed phenotype), Ph status, cytogenetic risk (based on modified Medical Research Council-Eastern Cooperative Oncology Group (MRC-ECOG) study), obesity (body mass index (BMI) > 30), and race. Results: Patients treated with pediatric regimens, including pediatric-inspired regimens, have statistically significant (P = 0.009) survival gains, with a hazard ratio (HR) of 0.52 after controlling for age, obesity, ALL subtype, cytogenetic risk and race. White patients had significantly improved OS compared to people of color (HR 0.57, P = 0.02) after controlling for the aforementioned covariates. Black patients were far less likely (23%) to receive a transplant than non-Black patients (46%). Only 7% of patients were treated on a clinical trial. Conclusions: These data demonstrate that treatment with a pediatric regimen significantly improves overall survival in patients up to the age of 45 and suggests ongoing shortcomings in treatment for young adults with ALL, especially 30 to 45 years old, including persistently high use of adult induction regimens, low rates of referral to clinical trials, and significant racial disparities in bone marrow transplants for Black patients.

Management of Acute Episodes of Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome) With Intravenous Immunoglobulins.

Monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS, Clarkson disease) is a rare disorder defined by transient but recurrent bouts of hypotensive shock and anasarca resulting from plasma extravasation. Although prophylactic treatment with high-dose intravenous immunoglobulins (IVIG, 1-2 g/kg/mo) prevents most disease flares, its utility for acute episodes of ISCLS is unclear. Here, we report the results of a retrospective study of subjects with acute ISCLS treated at or near the onset of symptoms with IVIG. We found that administration of IVIG with minimal additional intravenous fluids was safe and associated with rapid clinical improvement. IVIG given close to the onset of ISCLS-related symptoms is associated with a favorable outcome.