Background: Smoking, alcohol use, and depression are interrelated and highly prevalent in patients with head and neck cancer, adversely affecting quality of life and survival. Smoking, alcohol, and depression share common treatments, such as cognitive behavioral therapy and antidepressants. Consequently, we developed and tested a tailored smoking, alcohol, and depression intervention for patients with head and neck cancer. Methods: Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers. Subjects were randomized to usual care or nurseadministered intervention consisting of cognitive behavioral therapy and medications. Data collected included smoking, alcohol use, and depressive symptoms at baseline and at 6 months.

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MAp19 is an alternative splicing product of the MASP-2 gene comprising the N-terminal CUB1-epidermal growth factor (EGF) segment of MASP-2, plus four additional residues at its C-terminal end. Like fulllength MASP-2, it forms Ca 2؉ -dependent complexes with mannan-binding lectin (MBL) and L-ficolin. The x-ray structure of human MAp19 was solved to a resolution of 2.5 Å. It shows a head to tail homodimer held together by interactions between the CUB1 module of one monomer and the EGF module of its counterpart. A Ca 2؉ ion bound to each EGF module stabilizes the dimer interfaces. A second Ca 2؉ ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu 52 , Asp 60 , Asp 105 , Ser 107 , Asn 108 , and a water molecule. Compared with its counterpart in human C1s, the Nterminal end of the MAp19 CUB1 module contains a 7-residue extension that forms additional inter-monomer contacts. To identify the residues involved in the interaction of MAp19 with MBL and L-ficolin, point mutants were generated and their binding ability was determined using surface plasmon resonance spectroscopy. Six mutations at Tyr 59 , Asp 60 , Glu 83 , Asp 105 , Tyr 106 , and Glu 109 either strongly decreased or abolished interaction with both MBL and L-ficolin. These mutations map a common binding site for these proteins located at the distal end of each CUB1 module and stabilized by the Ca 2؉ ion.

Diamond–Blackfan anemia (DBA) is a rare congenital disease linked to mutations in the ribosomal protein genes rps19, rps24 and rps17. It belongs to the emerging class of ribosomal disorders. To understand the impact of DBA mutations on RPS19 function, we have solved the crystal structure of RPS19 from Pyrococcus abyssi. The protein forms a five α-helix bundle organized around a central amphipathic α-helix, which corresponds to the DBA mutation hot spot. From the structure, we classify DBA mutations relative to their respective impact on protein folding (class I) or on surface properties (class II). Class II mutations cluster into two conserved basic patches. In vivo analysis in yeast demonstrates an essential role for class II residues in the incorporation into pre-40S ribosomal particles. This data indicate that missense mutations in DBA primarily affect the capacity of the protein to be incorporated into pre-ribosomes, thus blocking maturation of the pre-40S particles.