Crystal structural analysis of human serum albumin complexed with hemin and fatty acid

BACKGROUND: Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. RESULTS: We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. CONCLUSION: The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties

Changing the Custody of Children Whose Parents Have Been Divorced: A General View of the Process

The purpose of this project was to obtain a preliminary description, through study of the legal files, of that group of persons who appear before the Court of Domestic Relations for a reconsideration of the custody decision made initially, at the time of divorce. A sample of 92 cases heard in Multnomah County in 1965 was obtained. A survey of the literature revealed that much of what has been written on the subject of divorce and custody is primarily from a statistical or legalistic standpoint and very little bears directly on the granting or obtaining of custody or the problems encountered by the custodial or non-custodial parents and the children. A reading schedule was developed for the purpose of recording the information in the legal files maintained by the court. The characteristics of the sample group were tallied in an effort to obtain a statistical profile of that group requiring additional court appearances to settle the matter of custody. A number of hypotheses were developed and tested by means of Chi Square. Though this study was limited by the fact that no control group was used and no personal interviews were obtained, it clearly indicates the need for additional research in the area of divorce and custody and suggestions are made for future projects

Insights into Cleavage Specificity from the Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease Complexed with a Peptide Substrate.

Accepted versio

Miscellany

Art Writings I Believe Roy F. Powell Awardshttps://digitalcommons.georgiasouthern.edu/miscell/1002/thumbnail.jp

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd

110 Years of Avipoxvirus in the Galapagos Islands

The role of disease in regulating populations is controversial, partly owing to the absence of good disease records in historic wildlife populations. We examined birds collected in the Galapagos Islands between 1891 and 1906 that are currently held at the California Academy of Sciences and the Zoologisches Staatssammlung Muenchen, including 3973 specimens representing species from two well-studied families of endemic passerine birds: finches and mockingbirds. Beginning with samples collected in 1899, we observed cutaneous lesions consistent with Avipoxvirus on 226 (6.3%) specimens. Histopathology and viral genotyping of 59 candidate tissue samples from six islands showed that 21 (35.6%) were positive for Avipoxvirus, while alternative diagnoses for some of those testing negative by both methods were feather follicle cysts, non-specific dermatitis, or post mortem fungal colonization. Positive specimens were significantly nonrandomly distributed among islands both for mockingbirds (San Cristobal vs. Espanola, Santa Fe and Santa Cruz) and for finches (San Cristobal and Isabela vs. Santa Cruz and Floreana), and overall highly significantly distributed toward islands that were inhabited by humans (San Cristobal, Isabela, Floreana) vs. uninhabited at the time of collection (Santa Cruz, Santa Fe, Espanola), with only one positive individual on an uninhabited island. Eleven of the positive specimens sequenced successfully were identical at four diagnostic sites to the two canarypox variants previously described in contemporary Galapagos passerines. We conclude that this virus was introduced late in 1890′s and was dispersed among islands by a variety of mechanisms, including regular human movements among colonized islands. At present, this disease represents an ongoing threat to the birds on the Galapagos Islands