An approach to examining model dependence in EM reconstructions using cross-validation.

Reference bias refers to a common problem in fitting experimental data to an initial model. Given enough free parameters, a good fit of any experimental data to the model can be obtained, even if the experimental data contain only noise. Reference-based alignment methods used in electron microscopy (EM) are subject to this type of bias, in that images containing pure noise can regenerate the reference.

The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats.

We have demonstrated that the breakpoints of the constitutional t(11;22) are located at palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. As a mechanism for this recurrent translocation, we proposed that the PATRR forms a cruciform structure that induces the genomic instability leading to the rearrangement. A patient with neurofibromatosis type 1 (NF1) had previously been found to have a constitutional t(17;22) disrupting the NF1 gene on 17q11.

Subunit organization in a soluble complex of tar, CheW, and CheA by electron microscopy.

The Salmonella and Escherichia coli aspartate receptor, Tar, is representative of a large class of membrane receptors that generate chemotaxis responses by regulating the activity of an associated histidine protein kinase, CheA. Tar is composed of an NH(2)-terminal periplasmic ligand-binding domain linked through a transmembrane sequence to a COOH-terminal coiled-coil signaling domain in the cytoplasm. The isolated cytoplasmic domain of Tar fused to a leucine zipper sequence forms a soluble complex with CheA and the Src homology 3-like kinase activator, CheW.

Active copper- and zinc-containing superoxide dismutase in the cryptic genospecies of Haemophilus causing urogenital and neonatal infections discriminates them from Haemophilus influenzae sensu stricto.

The presence of active copper- and zinc-containing superoxide dismutase in isolates of the cryptic genospecies of Haemophilus, responsible for urogenital, neonatal, and mother-infant infections, can be used as a biochemical marker to discriminate them from H. influenzae sensu stricto strains.

Antithrombin and anti-Xa agents in the control of thrombogenesis.

Recent developments as well as future trends in the area of thrombin inhibitors and anti-Xa agents are reviewed.

Segmental duplications: an 'expanding' role in genomic instability and disease.

The knowledge that specific genetic diseases are caused by recurrent chromosomal aberrations has indicated that genomic instability might be directly related to the structure of the regions involved. The sequencing of the human genome has directed significant attention towards understanding the molecular basis of such recombination 'hot spots'. Segmental duplications have emerged as a significant factor in the aetiology of disorders that are caused by abnormal gene dosage.

Evolutionarily conserved low copy repeats (LCRs) in 22q11 mediate deletions, duplications, translocations, and genomic instability: an update and literature review.

Several constitutional rearrangements, including deletions, duplications, and translocations, are associated with 22q11.2. These rearrangements give rise to a variety of genomic disorders, including DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes (DGS/VCFS/CAFS), cat eye syndrome (CES), and the supernumerary der(22)t(11;22) syndrome associated with the recurrent t(11;22).

Cis-acting influences on Alu RNA levels.

The human short interspersed repeated element (SINE), Alu, amplifies through a poorly understood RNA-mediated mechanism, termed retroposition. There are over one million copies of Alu per haploid human genome. The copies show some internal variations in sequence and are very heterogeneous in chromosomal environment.

Alu-mediated PCR artifacts and the constitutional t(11;22) breakpoint.

The breakpoints of the recurrent t(11;22)(q23;q11) have recently been cloned. We identified palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11 as the mechanism responsible for the rearrangement. Contradictory to our results, A.

Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22).

Palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11 at the constitutional t(11;22) breakpoint are predicted to induce genomic instability, which mediates the translocation. A PCR-based translocation-detection system for the t(11;22) has been developed with PCR primers flanking the PATRRs of both chromosomes, to examine the involvement of the PATRRs in the recurrent rearrangement. Forty unrelated carriers of the t(11;22) balanced translocation, plus two additional, independent cases with the supernumerary-der(22) syndrome, were analyzed to compare their translocation breakpoints.

Regions of genomic instability on 22q11 and 11q23 as the etiology for the recurrent constitutional t(11;22).

The constitutional t(11;22)(q23;q11) is the only known recurrent, non-Robertsonian translocation. To analyze the genomic structure of the breakpoint, we have cloned the junction fragments from the der(11) and der(22) of a t(11;22) balanced carrier. On chromosome 11 the translocation occurs within a short, palindromic AT-rich region (ATRR).

Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.

The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial syndromes (DGS/VCFS), is the most common microdeletion syndrome. The majority of deleted patients share a common 3 Mb hemizygous deletion of 22q11.

Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families.

The t(11;22) is the only known recurrent, non-Robertsonian constitutional translocation. We have analyzed t(11;22) balanced-translocation carriers from multiple unrelated families by FISH, to localize the t(11;22) breakpoints on both chromosome 11 and chromosome 22. In 23 unrelated balanced-translocation carriers, the breakpoint was localized within a 400-kb interval between D22S788 (N41) and ZNF74, on 22q11.

Construction of a 780-kb PAC, BAC, and cosmid contig encompassing the minimal critical deletion involved in B cell chronic lymphocytic leukemia at 13q14.3.

A putative tumor suppressor gene involved in B cell chronic lymphocytic leukemia (B-CLL) was mapped to human chromosome 13q14.3 close to the genetic markers D13S25 and D13S319. We constructed a 780-kb-long contig composed of cosmids, bacterial artificial chromosomes, and bacteriophage P1-derived artificial chromosomes that provides essential information and tools for the positional cloning of this gene.

cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts.

We have isolated and sequenced twenty-six cDNAs derived from primary Alu transcripts. Most cDNAs (22/26) sequenced end in multiple T residues, known to be at the termination for RNA polymerase III-directed transcripts. We conclude that these cDNAs were derived from authentic, RNA polymerase III-directed primary Alu transcripts.

Interaction of Ca2(+)-activated K+ channels with refolded charybdotoxins mutated at a central interaction residue.

Charybdotoxin is a small peptide blocker of K+ channels, rigidly held in active conformation by three disulfide bonds. The toxin blocks K+ channels by binding to a receptor site located at the external "vestibule", and thus physically occluding the outer opening of the K+ conduction pore. In the blocked complex, K27, a residue on the toxin's molecular surface, projects its epsilon-amino group into the K(+)-selective pore.

The role and amplification of the HS Alu subfamily founder gene.

A recently identified Alu element (Leeflang et al. J. Mol.

Surveillance for fetal alcohol syndrome in Colorado.

The authors performed surveillance for fetal alcohol syndrome with an existing birth defects registry. Fetal alcohol syndrome cases were identified from multiple sources using passive surveillance and from two selected medical sites using enhanced surveillance. Between May 1992 and March 1994, a total of 173 cases were identified, and the medical records of the cases were reviewed to determine whether the cases met a surveillance case definition for fetal alcohol syndrome.

Sequence diversity and chromosomal distribution of "young" Alu repeats.

Members of the recently inserted human-specific (HS)/predicted variant (PV) subfamily of Alu elements were sequenced. A number of these Alu elements share greater than 98% sequence identity with the subfamily consensus sequence, and they are flanked by perfect 5' and 3' direct repeats ranging in size from 6 to 15 nucleotides (nt). Based on the low number of random mutations, the estimated average age of these elements was calculated to be 1.

Dispersion and insertion polymorphism in two small subfamilies of recently amplified human Alu repeats.

Newly isolated members of two recently propagated (young) Alu subfamilies were examined for sequence diversity and insertion polymorphism in primate genomes. The smaller subfamily (termed HS-2) is comprised of approximately 5 to 25 members, while the larger (termed Sb2) includes approximately 125 to 600 members. Individual members of these Alu subfamilies share distinguishing sets of diagnostic mutations, are well-conserved relative to each other, and have expanded in the human lineage.

Benefits of beta-blocker prophylaxis against supraventricular arrhythmias following aortocoronary bypass surgery in routine clinical practice.

Objective: To determine the effectiveness of beta-blocker therapy for suppression of supraventricular arrhythmias (SVA) following aortocoronary bypass surgery (ACBS) in routine clinical practice.

Design: Prospective data collection and retrospective assessment of the occurrence of SVA following ACBS.

Setting: Cardiovascular surgery intensive care unit and hospital patient ward with electrocardiogram (ECG) monitoring facilities.

African origin of human-specific polymorphic Alu insertions.

Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few "master" genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species; that is, not all chromosomes carry an Alu element at a particular locus. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay that uses primers that flank the insertion point to determine genotypes based on the presence or absence of the Alu element.