The dimerization of Δ1-piperidine-2-carboxylic acid

The l-amino acid oxidase of Mytilus edulis has been used to oxidize l-lysine on a large scale in the presence of catalase. The alpha-oxo acid derived from lysine cyclizes to a Schiff base, which readily dimerizes. The dimer undergoes spontaneous dehydration and decarboxylation to form 1,2,3,4,5,6,7,8-octahydropyrido[3,2-a]-indolizin-10(4bH)-one. This structure was established by a study of its molecular weight and infrared, nuclear-magnetic-resonance and mass spectra.     

Novel substratum-dependent dendritic morphology and motility in epithelial cells

NADPase activity has been localized in the exocrine pancreas of rat, by cytochemistry according to the procedure of Smith as modified by Clermont et al. With NADP or NADPH as substrate, an intense reaction was detected in one or two intermediary saccules of the Golgi stack. Reaction product was also present in lysosomes, dense bodies and the gland lumen. It was absent from condensing vacuoles and zymogen granules. A very intense reaction was found over a "snake-like" structure not previously reported. These are elongated tubules located in basal and central portions of the acinar cell where they are frequently seen close to the Golgi stack or the basolateral cell surface.     

Growth analysis of circular lichen thalli

A new model which describes the growth pattern of circular lichen thalli (foliose and placodioid) is developed. It is tested with published data and fits better than any previous models. A method is described for the calculation of the values of two constants, α and β which may be determined by the extent of lateral movement of carbohydrate and the rate of carbohydrate production respectively. It is believed that the model is sufficiently simple to be of general application in lichen ecology and physiology and in lichenometry.     

Sepharose 4B as a matrix for affinity chromatography. A spin-labelling investigation using nitroxides as model ligands

Nitroxide spin labels were attached to CNBr-activated Sepharose 4B directly and through oligoglycines and oo-amino-carboxylic acids of varying length. The homogeneity of the carbohydrate environments of directly attached labels was investigated by measuring dipolar interactions between nitroxides as a function of solvation and of spin dilution with a diamagnetic analogue, as well as by electron exchange between the nitroxides and paramagnetic metal ions in solution. Only the exchange experiment revealed any inhomogeneity, suggesting that a small proportion of sites may be less accessible than the majority. The distances between sites were sufficiently small to allow, in principle, multiple-site interactions between quite small proteins in solution and immobilized ligands. Reorientation of the label at the matrix, characterized by the correlation time t, became more rapid with increasing spacer length n. For n > 12, the decrease in t was less pronounced. The two types of spacer behaved similarly. Thus an ideal spacer length for affinity separations is 12 atoms; this is in good agreement with data from a variety of affinity separations. The results of electron spin resonance studies of the effect of non-aqueous solvent on directly and indirectly labelled Sepharose 4B were used to suggest reasons why enzymes immobilized on Sepharose may be stabilized to denaturing solvents.     

Spin-labelling studies of the agarose gelling-system

Rates of tumbling and exchange of free nitroxides in aqueous solution are unaffected by the presence of quite high concentrations of agarose gel. Low-level, covalent attachment of labels to the polysaccharide by means of stable, acetamido ether linkages, however, causes considerable diminution in their rate of reorientation. Dissolution of this material to form a gel and melting and setting of the gel cause further changes in the e.s.r. spectrum. Experimental correlation-times for reorientation of label may be decomposed into contributions from rotation about bonds in the linking group and from polysaccharide motions. This allows information to be obtained about the microscopic characteristics of the gel state, which is found to vary greatly depending on its history.     

Fascioloides magna (Bassi, 1875) in feral swine from southern Texas.

Between 1971 and 1975, Fascioloides magna was found in 46 of 67 (69%) feral swine (Sus scrofa) in southern Texas. Flukes were recovered from swine in areas where F. magna commonly has been recovered from white-tailed deer and cattle. One to 12 flukes were recovered from each infected animal. Their presence was indicated by black hematin pigment on the liver and various other internal organs. Eggs were not detected in the gallbladder or feces of infected animals although mature flukes and eggs were recovered in the livers suggesting that, like cattle, feral swine can be infected but are aberrant hosts for the parasite and do not disseminate eggs.     

The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma

Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Here, we found that phosphorylation of AMP-dependent kinase (AMPK) was elevated in BAP1-altered (or mutant) compared to BAP1-unaltered (or wild-type [WT]) UM tumors. As a readout of AMPK pathway activation, phosphorylation of an AMPK downstream effector, acetyl-CoA-carboxylase (ACC), was also elevated. BAP1 re-expression in BAP1-null UM cell lines decreased phospho-AMPK (pAMPK) and phospho-ACC (pACC) levels. AMPK phosphorylation is mediated by calcium/calmodulin dependent protein kinase kinase 2 (CaMKK2) and potentially liver kinase B1 (LKB1) in BAP1 mutant UM cells. Knockdown of AMPKα1/2 reduced the viability of BAP1 mutant UM cells, indicating a survival function of AMPK in BAP1 mutant UM. Our data suggest that the AMPK pathway is an important mechanism mediating the survival of BAP1 mutant UM. Targeting the AMPK pathway may be a novel therapeutic strategy for metastatic UM.     

Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton

It has become widely accepted that adhesion receptors can either directly activate, or significantly modulate, many of the signaling cascades initiated by circulating growth factors. An interesting recent development is the realization that adhesion receptors and their cytoskeletal partners can regulate the trafficking of signaling proteins between the cytoplasm and nucleus. Cell adhesion molecule control of nucleocytoplasmic trafficking allows adhesion to influence many cell decisions, and highlights the diversity of nuclear import and export mechanisms.