Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction.

Nectins are adhesion molecules that participate in the organization of epithelial and endothelial junctions and serve as receptors for herpes simplex virus entry. They belong to the immunoglobulin superfamily, are homologues of the poliovirus receptor (PVR/CD155), and were also named poliovirus receptor-related (PRR) proteins. We identify a new member of the nectin family named nectin4. Peptide sequences of human and murine nectin4 share 92% identity, and as for other members, the ectodomain is made of three immunoglobulin-like domains of V, C, C types. In contrast to other nectin molecules, detection of nectin4 transcripts is mainly restricted to placenta in human tissues. Expression is broader in mouse, and interestingly nectin4 is detected at days 11, 15, and 17 during murine embryogenesis. Nectin4 interacts with afadin, a F-actin-associated molecule, via its carboxyl-terminal cytoplasmic sequence. Both molecules co-localize at cadherin-based adherens junctions in the MDCKII epithelial cell line. Nectins are homophilic adhesion molecules, and recently heterophilic interactions have been described between nectin3/nectin1 and nectin3/nectin2. We confirmed these trans-interactions and also described nectin3 as the PVR/CD155 ligand. By means of several approaches, we report on the identification of nectin4 as a new ligand for nectin1. First, a soluble chimeric recombinant nectin4 ectodomain (nectin4-Fc) trans-interacts with cells expressing nectin1 but not with cells expressing nectin2, nectin3, or PVR/CD155. Conversely, nectin1-Fc binds to cells expressing nectin4. Second, nectin1-Fc precipitates nectin4 expressed in COS cells. Third, reciprocal in vitro physical interactions were detected between nectin4-Fc and nectin1-Fc. The nectin4-Fc/nectin4-Fc interaction was detected suggesting that nectin4 exhibits both homophilic and heterophilic properties. Using the same approaches we demonstrate, for the first time, that the V domain of nectin1 acts as a major functional region involved in trans-heterointeraction with nectin4 and also nectin3.

Cooperative reactivity of early-late heterodinuclear transition metal complexes with polar organic substrates

A comprehensive investigation into the cooperative reactivity of two chemically complementary metal-complex fragments in early-late heterodinuclear complexes has been carried out. Reaction of the partially fluorinated tripodal amidozirconium complexes [HC-(SiMe2NR)3Zr(mu-Cl)2Li(OEt2)2] (R = 2-FC6H4: 2a, 2,3,4-F3C6H4: 2b) with K[CpM(CO)2] (M=Fe, Ru) afforded the stable metal-metal bonded heterodinuclear complexes [HC[SiMe2NR]3-Zr-MCp(CO)2] (3-6). Reaction of the dinuclear complexes with methyl isonitrile as well as the heteroallenes CO2, CS2, RNCO and RNCS led to insertion into the polar metal-metal bond. Two of these complexes, [HC[SiMe2N(2-FC6-H4)]3Zr(S2C)Fe(CO)2Cp] (9a) and [HC-[SiMe2N(2-FC2H4)]3Zr-(SCNPh)Fe(CO)2-Cp] (12), have been structurally characterized by a single crystal X-ray structure analysis, proving the structural situation of the inserted substrate as a bridging ligand between the early and late transition metal centre. The reactivity towards organic carbonyl derivatives proved to be varied. Reaction of the heterobimetallic complexes with benzyl and ethylbenzoate led to the cleavage of the ester generating the respective alkoxozirconium complexes [HC[SiMe2N(2-FC6H4)]3ZrOR] (R = Ph-CH2: 13a, Et: 13b) along with [CpFe-[C(O)Ph](CO)2], whereas the analogous reaction with ethyl formate gave 13b along with [CpFeH(CO)2]; this latter complex results from the instability of the formyliron species initially formed. Aryl aldehydes were found to react with the Zr-M complexes according to a Cannizzaro disproportionation pattern yielding the aroyliron and ruthenium complexes along with the respective benzoxyzirconium species. The transfer of the aldehyde hydrogen atom in the course of the reaction was established in a deuteriation experiment. [HC[SiMe2-N(2-FC6H4)]3Zr-M(CO)2Cp] reacted with lactones to give the ring-opened species containing an alkoxozirconium and an acyliron or acylruthenium fragment; the latter binds to the early transition metal centre through the acyl oxygen atom, as evidenced from the unusuallly low-field shifted 13C NMR resonances of the RC(O)M units. Ketones containing a-CH units react with the Zr-Fe complexes cooperatively to yield the aldol coupling products coordinated to the zirconium complex fragment along with the hydridoiron compound [CpFeH(CO)2], whereas 1,2-diphenylcyclopropenone underwent an oxygen transfer from the keto group to a CO ligand to give a linking CO2 unit and a cyclopropenylidene ligand coordinated to the iron fragment in [HC-[Si(CH3)2N(2,3,4-F3C6H2)]3Zr(mu-O2C)-Fe(CO)[C3Ph2)Cp] (19). The atom transfer was established by 17O and 13C labelling studies. Similar oxygen-transfer processes were observed in the reactions with pyridine N-oxide, dimethylsulfoxide and methylphenylsulfoxide.

Hypocalcemia following thyroid surgery: incidence and prediction of outcome.

Postoperative hypocalcemia is a common and most often transient event after extensive thyroid surgery. It may reveal iatrogenic injury to the parathyroid glands and permanent hypoparathyroidism. We prospectively evaluated the incidence of hypocalcemia and permanent hypoparathyroidism following total or subtotal thyroidectomy in 1071 consecutive patients operated during 1990-1991. We then determined in a cross-sectional study which early clinical and biochemical characteristics of patients experiencing postoperative hypocalcemia correlated with the long-term outcome. Postoperative calcemia under 2 mmol/l was observed in 58 patients (5. 4%). In 40 patients hypocalcemia was considered severe (confirmed for more than 2 days, symptomatic or both). At 1 year after surgery five patients (0.5%) had persistent hypocalcemia. We found that patients carried a high risk for permanent hypoparathyroidism if fewer than three parathyroid glands were preserved in situ during surgery or the early serum parathyroid hormone level was /= 4 mg/dl under oral calcium therapy. When one or more of these criteria are present, long-term follow-up should be enforced to check for chronic hypocalcemia and to avoid its severe complications by appropriate supplement therapy.