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Biomedical subjects

J M Berg

Publications and source records attributed to J M Berg.

At least 19 recordsLinked to original sources
PubMed2001

Down syndrome before Down: a retrospect.

We have attempted to identify published descriptions and reports of skeletal remains, figurines and paintings of suggested or supposed instances of Down syndrome predating John Langdon Haydon Down's initial account of the condition in 1866. A review of the ascertained material in each of these categories has not provided, in our opinion, convincing evidence of presence of the syndrome, although that possibility is not excluded. In the interests of historical authenticity readers are invited to point out perceived errors or omissions in this presentation.

Down Syndrome↗
PubMed2001

Spectroscopy of UO(2)Cl(4)(2)(-) in basic aluminum chloride-1-ethyl-3-methylimidazolium chloride.

The optical absorption, emission, FT Raman, one-photon excitation, two-photon excitation, and luminescence lifetime measurements are reported for UO(2)Cl(4)(2)(-) in 40:60 AlCl(3)-EMIC (where EMIC identical with 1-ethyl-3-methylimidazolium chloride), a room-temperature ionic liquid. Comparison of the spectra with previous results from single crystals containing UO(2)Cl(4)(2)(-) allowed the characterization of four ground-state vibrational frequencies, two excited-state vibrational frequencies, and the location of eight electronic excited-state energy levels. The vibrational frequencies and electronic energy levels are found to be consistent with the UO(2)Cl(4)(2)(-) ion. Comparison of the one-photon and two-photon excitation spectra, and the relative intensities of the transitions in the emission spectrum indicate that the center of symmetry is perturbed by an interaction with the solvent.

Journal Article↗
PubMed2001

Shakespeare as a geneticist.

There are frequent allusions in Shakespeare's plays to physical and mental characteristics and qualities of individuals that often reflect genetic and related insights, ideas and implications with a bearing on the determination of these phenotypes. Quotations from the plays with comments are presented here to indicate varied perceptions in these regards that Shakespeare brilliantly conveyed some 400 years ago through many of his 'dramatis personae'.

Drama↗
PubMed2000

Autologous blood collection and transfusion in cats undergoing partial craniectomy.

OBJECTIVE: To describe the procedure for autologous blood donation and associated complications in cats undergoing partial craniectomy for mass removal. DESIGN: Prospective case series. ANIMALS: 15 cats with intracranial mass confirmed by computed tomographic scan, no evidence of renal failure, and PCV > or = 22%. PROCEDURE: One unit (60 ml) of blood was collected and stored 7 to 17 days before surgery and transfused during the perioperative period if needed. The PCV was measured before donation, before surgery, during surgery, and after surgery to assess effect of donation on PCV before surgery and effect of transfusion on PCV after surgery. Cats were evaluated for donation complications, iatrogenic anemia, and adverse reactions associated with administration of autologous blood. RESULTS: Complications associated with phlebotomy were not detected. Fifteen cats underwent partial craniectomy 7 to 17 days after blood donation; all had histologic confirmation of meningioma by examination of tissue obtained at surgery. Eleven cats received autologous blood transfusions. None of the cats received allogeneic blood transfusions. Transfusion reactions were not observed. Subclinical iatrogenic anemia was detected in 3 cats. Two cats were considered to have received excessive transfusion, and 3 cats received inadequate transfusion. All cats undergoing partial craniectomy were discharged from the hospital and were alive > 6 months after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Autologous blood donation before surgery was considered safe for cats undergoing partial craniectomy for resection of meningioma. The only complication observed was iatrogenic anemia. The procedure contributed to blood conservation in our hospital.

Anemia↗
PubMed2000

A proposed model for the PEX5-peroxisomal targeting signal-1 recognition complex.

The three-dimensional structure of a protein can greatly illuminate the relationship between its sequence and its function. However, in the absence of a set of experimentally derived coordinates, one often seeks a model of the protein of interest to guide future study. We describe the combined utilization of orthologous sequence information along with knowledge of the related structural fold to model the interaction between PEX5 and its ligand, the peroxisomal targeting signal-1 (PTS1). With this model, we are able to identify residues within PEX5 that appear to be important for peptide recognition, as well as explain some of the sequence requirements of the PTS1. Specifically, our model highlights four asparagine residues as important for ligand backbone atom recognition, which, along with previously observed examples, suggests this as a general mechanism for the binding of extended polypeptides.

Amino Acid Sequence↗
PubMed2000

Toward ligand identification within a CCHHC zinc-binding domain from the NZF/MyT1 family.

A family of proteins that contain presumed zinc-binding domains with the consensus sequence Cys-X4-CysX4-His-X7-His-X5-Cys has recently been identified, but the metal binding and structural properties of these domains have not been investigated. This consensus is striking because of the presence of five conserved potential zinc-binding residues. A peptide corresponding to the third putative zinc-binding domain from the transcription factor NZF-1 (hereafter NZF-13) has been synthesized and characterized. The UV-visible absorption spectroscopic properties of the cobalt(H) complex of this peptide demonstrate that metal binding is tetrahedral, and the position of the visible absorption bands suggests coordination by three cysteinates and one histidine. To identify which of the two conserved histidine residues acts a metal-binding residue, two histidine to alanine variant peptides were also synthesized. Both variant peptides bound cobalt(II) in a tetrahedral fashion; replacement of the first of the two histidines has a somewhat larger effect on the detailed shape of the absorption spectral features than does replacement of the second histidine. These results suggest that the metal-coordinating residues (italicized) are Cys-X4-Cys-X4-His-X7-His-Xs-Cys. However, simultaneous substitution of both histidine residues with alanine generated a peptide with much more dramatically affected metal binding properties. These observations suggests that the relatively modest effects observed for the singly substituted peptides may be due to metal interactions involving the remaining histidine. Because of these phenomena, further studies will be required to establish more conclusively the roles of the two histidine residues in metal binding and the potential significance of the apparent alternative histidine coordination.

Ligands↗
PubMed2000

Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5.

Many proteins contain targeting signals within their sequences that specify their delivery to particular organelles. The peroxisomal targeting signal-1 (PTS1) is a C-terminal tripeptide that is sufficient to direct proteins into peroxisomes. The PTS1 sequence closely approximates Ser-Lys-Leu-COO-. PEX5, the receptor for PTS1, interacts with the signal via a series of tetratricopeptide repeats (TPRs) within its C-terminal half. Here we report the crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence. Two clusters of three TPRs almost completely surround the peptide, while a hinge region, previously identified as TPR4, forms a distinct structure that enables the two sets of TPRs to form a single binding site. This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction.

Amino Acid Motifs↗
PubMed1999

Metal and DNA binding properties of a two-domain fragment of neural zinc finger factor 1, a CCHC-type zinc binding protein.

Neural zinc finger factor 1 (NZF-1) is a member of a family of neural-specific transcription factors that contain multiple copies of a relatively uncharacterized zinc binding motif. We have studied the metal binding and DNA binding properties of a fragment of NZF-1 containing two adjacent zinc binding domains. Partial proteolysis with endoproteinase Lys-C identified metal-stabilized fragments containing either one or both of the zinc binding domains. Both domains were required for specific DNA binding to the beta-retinoic acid receptor element, producing a DNase I footprint covering predominantly one strand. The metal binding site was probed via cobalt(II) substitution. The visible absorption spectrum of the cobalt(II) complex is consistent with Cys-Cys-His-Cys coordination of the metal. The two domains appear to have similar affinities for metal and bind cobalt(II) and zinc(II) with dissociation constants of 4 (+/- 2) x 10(-)(7) M and 1.4 (+/- 0.8) x 10(-)(10) M, respectively. The domains fold upon the addition of zinc, as observed by (1)H NMR. However, an additional weak binding site causes line broadening in the presence of excess zinc, presumably due to aggregation.

Animals↗
PubMed1999

A detailed study of the substrate specificity of a chimeric restriction enzyme.

Recently, the crystal structure of the designed zinc finger protein, DeltaQNK, bound to a preferred DNA sequence was reported. We have converted DeltaQNK into a novel site-specific endonuclease by linking it to the Fok I cleavage domain (FN). The substrate specificity and DNA cleavage properties of the resulting chimeric restriction enzyme (DeltaQNK-FN) were investigated, and the binding affinities of DeltaQNK and DeltaQNK-FN for various DNA substrates were determined. Substrates that are bound by DeltaQNK with high affinity are the same as those that are cleaved efficiently by DeltaQNK-FN. Substrates bound by DeltaQNK with lower affinity are cleaved with very low efficiency or not at all by DeltaQNK-FN. The binding of DeltaQNK-FN to each substrate was approximately 2-fold weaker than that for DeltaQNK. Thus, the fusion of the Fok I cleavage domain to the zinc finger motif does not change the DNA sequence specificity of the zinc finger protein and does not change its binding affinity significantly.

Amino Acid Sequence↗
PubMed1998

Zinc fingers in Caenorhabditis elegans: finding families and probing pathways.

More than 3 percent of the protein sequences inferred from the Caenorhabditis elegans genome contain sequence motifs characteristic of zinc-binding structural domains, and of these more than half are believed to be sequence-specific DNA-binding proteins. The distribution of these zinc-binding domains among the genomes of various organisms offers insights into the role of zinc-binding proteins in evolution. In addition, the complete genome sequence of C. elegans provides an opportunity to analyze, and perhaps predict, pathways of transcriptional regulation.

Animals↗
PubMed1998

Lionel Sharples Penrose (1898-1972): aspects of the man and his works, with particular reference to his undertakings in the fields of intellectual disability and mental disorder.

The Penrose Club, named after Professor L. S. Penrose, is a society of academic psychiatrists in the UK with a particular focus on research in the sphere of intellectual disability. The inaugural lecture of the Club was delivered at the Institute of Psychiatry, London, on 29 November 1996. It is distinctly fitting that this lecture should appear in print in the Journal of Intellectual Disability Research in the centenary year of Professor Penrose's birth, both because of his major pioneering contributions to the field with which JIDR is concerned and because he played a crucial role in the founding of the Journal.

Female↗
PubMed1997

Site-specific cleavage of DNA-RNA hybrids by zinc finger/FokI cleavage domain fusions.

Zinc-finger proteins of the Cys2His2 type bind DNA-RNA hybrids with affinities comparable to those for DNA duplexes. Such zinc-finger proteins were converted into site-specific cleaving enzymes by fusing them to the FokI cleavage domain. The fusion proteins are active and under optimal conditions cleave DNA duplexes in a sequence-specific manner. These fusions also exhibit site-specific cleavage of the DNA strand within DNA-RNA hybrids albeit at a lower efficiency (approximately 50-fold) compared to the cleavage of the DNA duplexes. These engineered endonucleases represent the first of their kind in terms of their DNA-RNA cleavage properties, and they may have important biological applications.

Base Sequence↗
PubMed1997

Sequential metal binding by the RING finger domain of BRCA1.

Analysis of the amino acid sequence encoded by the familial breast and ovarian cancer susceptibility gene, BRCA1 [Miki et al. (1994) Science 266, 66-71], revealed the presence of an amino-terminal RING finger domain, a zinc binding motif found in a variety of proteins. Previously determined structures of two RING finger peptides from other proteins revealed that each RING finger sequence forms a single domain that includes two interleaved metal binding sites. One is a four-cysteine site comprised of metal binding residues 1, 2, 5, and 6 (in terms of position along the amino acid sequence) (site 1) and the other is a three-cysteine, one-histidine site involving metal binding residues 3, 4, 7, and 8 (site 2). We have characterized the metal binding and metal-dependent folding properties of peptides encompassing the BRCA1 RING finger. Using cobalt(II) as a spectroscopic probe, we have found that metal binding is sequential, with site 1 becoming nearly fully occupied prior to metal binding to site 2. More detailed thermodynamic analysis as well as studies of a variant peptide revealed that metal binding appears to be anticooperative with dissociation constants of 3 x 10(-8) M for site 1, 5 x 10(-7) M for site 2 with site 1 unoccupied, and 8 x 10(-6) M for site 2 when site 1 is occupied. Circular dichroism spectroscopic studies revealed that the BRCA1 RING finger peptide is somewhat structured at pH 7 in the absence of metal ions, with further structural changes occurring after the metal binding.

Amino Acid Sequence↗
PubMed1997

Electrostatic interactions across a beta-sheet.

The free energy consequences of electrostatic interactions across a model beta-sheet have been probed using a consensus zinc finger peptide. Relative folding free energies have been deduced from coupled peptide folding/metal binding reactions. The energies of the electrostatic interactions have been isolated via double mutant cycles performed at a series of NaCl concentrations. The observed favorable free energies associated with potential ion pairs are modest, less than 0.5 kcal/mol. Unfavorable interactions due to like-charge pairs of similar magnitude were also observed. The largest effects, both favorable and unfavorable, involved interactions with aspartic acid. These observations are consistent with electrostatic interactions occurring without contact ion pair formation with the larger interaction energies involving aspartic acid being due to the relative lack of flexibility of its side chain.

Models, Chemical↗