Refractory Status Epilepticus Associated With a Pathogenic Variant in TNFRSF13B.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic syndrome characterized by new-onset refractory status epilepticus preceded by a febrile illness. Limited literature exists regarding the relationship between primary immunodeficiencies and immune-mediated epilepsy, and the relationship between new-onset refractory status epilepticus and common variable immunodeficiency (CVID) is not well-understood. We present a case of a 21-year-old female with a history of recurrent sinus infections, asthma, thrombocytopenia, atrioventricular nodal reentrant tachycardia, and neonatal seizures who presented with fever and new-onset status epilepticus.

The role of the allergist in the management of eosinophilic esophagitis.

Purpose Of Review: The purpose of this review is to provide the current understanding of the role of allergens/antigens, the use of allergy testing, and to elucidate the role of the allergist in the management of eosinophilic esophagitis (EoE).

Recent Findings: EoE is a T2 immune disorder that is part of the atopic march. EoE patients commonly have multiple concurrent allergic disorders.

Spotlight on liposomal irinotecan for metastatic pancreatic cancer: patient selection and perspectives.

Pancreatic cancer is a highly lethal disease, where the mortality closely matches increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) is the most common histologic type that tends to metastasize early in tumor progression. For metastatic PDAC, gemcitabine had been the mainstay treatment for the past three decades.

Charge density influences C1 domain ligand affinity and membrane interactions.

The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids.

Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system.

Precise and accurate quantification of protein expression levels in a complex biological setting is challenging. Here, we describe a method for absolute quantitation of endogenous proteins in cell lysates using an automated capillary immunoassay system, the size-based Simple Western system (recently developed by ProteinSimple). The method was able to accurately measure the absolute amounts of target proteins at picogram or sub-picogram levels per nanogram of cell lysates.

Molecular basis for failure of "atypical" C1 domain of Vav1 to bind diacylglycerol/phorbol ester.

C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs.