Maximum likelihood estimation for a special type of grouped data with an application to a dose-response problem.

A short-cut method is given for calculating grouped maximum likelihood (ML) estimates when the data are relatively coarsely grouped in some directions, but more finely grouped in others. The algebraic details are then worked out for a dose-response problem that generates data of this kind. The situation envisaged is a variation on the usual quantal response problem in that dosage levels are taken to be random but grouped. Finally, the method is applied both to real and simulated response data conforming to this pattern and shown to work well in practice.     

Endothelial cell junctions

In the course of a freeze-cleave study on intercellular junctions in the regenerating rat liver, we observed an unusual array of intramembranous particles located in regions of contact between endothelial cells lining the hepatic sinusoids. These arrays were characterized by an accumulation of particles which resembled a zonula occludens in their linear deployment but differed in that the contact regions were composed of individual particles which remained separated from each other by regular particle-free intervals.     

Morphology and the classification of the so-called Cladocera

The validity as a monophyletic taxon of the group of branchiopod crustaceans long regarded as constituting the Cladocera is questioned. This seems in fact to be a heterogeneous assemblage whose members probably merit assignment to four separate orders. The Onychopoda and Haplopoda (the so-called Gymnomera) clearly stand apart from the Ctenopoda and Anomopoda (the so-called Calyptomera) and differ in important respects from each other. While sharing several characters, some doubtless indicative of distant ancestral similarities, others probably convergent, the Ctenopoda and Anomopoda differ in many respects, have clearly evolved along different lines, and are probably much less closely related than is generally assumed.     

Fish cell lines: establishment and characterization of nine cell lines from salmonids

Nine permanent cell lines have been established from five species of salmonids native to America's Pacific Northwest. With the exception of a hepatoma from an adult trout, the lines were derived from normal tissues of embryonic or juvenile fish. Cells were routinely grown in Eagle's minimum essential medium with 10% fetal bovine serum. Optimum growth temperatures for these lines ranged from 21 to 24 degrees C. All survived storage for at least 1 yr at -65 degrees C and at least 5 yr in liquid nitrogen. Six of the lines were demonstrably free of any microbial contamination but mycoplasmas were found in three. Eight of the lines were heteroploid. The morphology of only one was fibroblastic. All the lines effectively replicated one or more of the common salmonid viruses. Isozyme patterns were consistent with those of the species of origin. These cell lines have significant application in fish virology.     

Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)

Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Here, we report apolipoprotein E (apoE) as a novel ligand for TREM2. Using a biochemical assay, we demonstrated high-affinity binding of apoE to human TREM2. The functional significance of this binding was highlighted by increased phagocytosis of apoE-bound apoptotic N2a cells by primary microglia in a manner that depends on TREM2 expression. Moreover, when the AD-associated TREM2-R47H mutant was used in biochemical assays, apoE binding was vastly reduced. Our data demonstrate that apoE-TREM2 interaction in microglia plays critical roles in modulating phagocytosis of apoE-bound apoptotic neurons and establish a critical link between two proteins whose genes are strongly linked to the risk for AD.