Partial trisomy 4q in two unrelated cases

Summary Two unrelated cases of 4q trisomy are described with trisomic segment 4q254qter. The most conspicuous symptoms are psychomotor retardation, microcephaly, malformed ears, retrognathia, finger and toe malformations and cryptorchism in a male. Both cases are compared with 19 previously reported ones.To whon offprints requests should be sent     

Pressure dependence of side chain <Superscript>13</Superscript>C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH<Subscript>2</Subscript>

For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of ¹³C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH₂ (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B ₁ and B ₂ is dependent on the type of atom and amino acid studied. For H^N, N and C^α the first order pressure coefficient B ₁ is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically ¹³C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.     

Lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus infection

Cytomegalovirus (CMV) poses a threat to the therapy of hematopoietic malignancies by hematopoietic stem cell transplantation, but efficient reconstitution of antiviral immunity prevents CMV organ disease. Tumor relapse originating from a minimal residual leukemia poses another threat. Although a combination of risk factors was supposed to enhance the incidence and severity of transplantation-associated disease, a murine model of a liver-adapted B-cell lymphoma has previously shown a survival benefit and tumor growth inhibition by nonlethal subcutaneous infection with murine CMV. Here we have investigated the underlying antitumoral mechanism. Virus replication proved to be required, since inactivated virions or the highly attenuated enhancerless mutant mCMV-DeltaMIEenh did not impact the lymphoma in the liver. Surprisingly, the dissemination-deficient mutant mCMV-DeltaM36 inhibited tumor growth, even though this virus fails to infect the liver. On the other hand, various strains of herpes simplex viruses consistently failed to control the lymphoma, even though they infect the liver. A quantitative analysis of the tumor growth kinetics identified a transient tumor remission by apoptosis as the antitumoral effector mechanism. Tumor cell colonies with cells surviving the CMV-induced "apoptotic crisis" lead to tumor relapse even in the presence of full-blown tissue infection. Serial transfer of surviving tumor cells did not indicate a selection of apoptosis-resistant genetic variants. NK cell activity of CD49b-expressing cells failed to control the lymphoma upon adoptive transfer. We propose the existence of an innate antitumoral mechanism that is triggered by CMV infection and involves an apoptotic signal effective at a distant site of tumor growth.     

Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles

We have characterized the mechanisms of cargo selection into ER-derived vesicles by the COPII subunit Sec24p. We identified a site on Sec24p that recognizes the v-SNARE Bet1p and show that packaging of a number of cargo molecules is disrupted when mutations are introduced at this site. Surprisingly, cargo proteins affected by these mutations did not share a single common sorting signal, nor were proteins sharing a putative class of signal affected to the same degree. We show that the same site is conserved as a cargo-interaction domain on the Sec24p homolog Lst1p, which only packages a subset of the cargoes recognized by Sec24p. Finally, we identified an additional mutation that defines another cargo binding domain on Sec24p, which specifically interacts with the SNARE Sec22p. Together, our data support a model whereby Sec24p proteins contain multiple independent cargo binding domains that allow for recognition of a diverse set of sorting signals.     

Bipartite signals mediate subcellular targeting of tail-anchored membrane proteins in Saccharomyces cerevisiae

Tail-anchored proteins have an NH(2)-terminal cytosolic domain anchored to intracellular membranes by a single, COOH-terminal, transmembrane segment. Sequence analysis identified 55 tail-anchored proteins in Saccharomyces cerevisiae, with several novel proteins, including Prm3, which we find is required for karyogamy and is tail-anchored in the nuclear envelope. A total of six tail-anchored proteins are present in the mitochondrial outer membrane and have relatively hydrophilic transmembrane segments that serve as targeting signals. The rest, by far the majority, localize via a bipartite system of signals: uniformly hydrophobic tail anchors are first inserted into the endoplasmic reticulum, and additional segments within the cytosolic domain of each protein can dictate subsequent sorting to a precise destination within the cell.