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Biomedical subjects

Andrew Berry

Publications and source records attributed to Andrew Berry.

9 recordsLinked to original sources

Genome variation and evolution of the malaria parasite Plasmodium falciparum.

Infections with the malaria parasite Plasmodium falciparum result in more than 1 million deaths each year worldwide. Deciphering the evolutionary history and genetic variation of P. falciparum is critical for understanding the evolution of drug resistance, identifying potential vaccine candidates and appreciating the effect of parasite variation on prevalence and severity of malaria in humans. Most studies of natural variation in P. falciparum have been either in depth over small genomic regions (up to the size of a small chromosome) or genome wide but only at low resolution. In an effort to complement these studies with genome-wide data, we undertook shotgun sequencing of a Ghanaian clinical isolate (with fivefold coverage), the IT laboratory isolate (with onefold coverage) and the chimpanzee parasite P. reichenowi (with twofold coverage). We compared these sequences with the fully sequenced P. falciparum 3D7 isolate genome. We describe the most salient features of P. falciparum polymorphism and adaptive evolution with relation to gene function, transcript and protein expression and cellular localization. This analysis uncovers the primary evolutionary changes that have occurred since the P. falciparum-P. reichenowi speciation and changes that are occurring within P. falciparum.

Animals↗

Improved outcomes of extremely premature outborn infants: effects of strategic changes in perinatal and retrieval services.

OBJECTIVE: The goal was to evaluate the impact of statewide coordinated changes in perinatal support and retrieval services on the outcomes of extremely premature births occurring outside perinatal centers in the state of New South Wales, Australia. METHODS: The intervention included additional, network-coordinated, perinatal telephone advice to optimize in utero transfers and centralization of the neonatal retrieval system, with preferential admission of retrieved infants (outborn infants) to perinatal centers instead of freestanding pediatric hospitals, from the middle of 1995. Population birth and NICU admission cohorts of infants of 23 to 28 weeks of gestation were studied. Outcomes of epoch 1 (1992 to the middle of 1995; 1778 births and 1100 NICU admissions) were compared with those of epoch 2 (1997-2002; 3099 births and 2100 NICU admissions), after an 18-month washout period. RESULTS: There were 25% fewer nontertiary hospital live births (19.7% vs 14.9%) and more prenatal steroid use. Despite an 11.4% average annual increase in NICU admissions between the 2 epochs, fewer infants were outborn (12.0% vs 9.3%) and outborn mortality rates decreased significantly (39.4% vs 25.1%), particularly for those between 27 and 28 weeks of gestation. The overall improvement was equivalent to 1 extra survivor per 16 New South Wales births. There were also significantly fewer serious outcome morbidities in outborn infants during epoch 2, over the improvements in inborn infants. CONCLUSIONS: Statewide coordinated strategies in reducing nontertiary hospital births and optimizing transport of outborn infants to perinatal centers have improved considerably the outcomes of extremely premature infants. These findings have vital implications for health outcomes and resource planning.

Child Health Services↗

Integration of tools and resources for display and analysis of genomic data for protozoan parasites.

Centralisation of tools for analysis of genomic data is paramount in ensuring that research is always carried out on the latest currently available data. As such, World Wide Web sites providing a range of online analyses and displays of data can play a crucial role in guaranteeing consistency of in silico work. In this respect, the protozoan parasite research community is served by several resources, either focussing on data and tools for one species or taking a broader view and providing tools for analysis of data from many species, thereby facilitating comparative studies. In this paper, we give a broad overview of the online resources available. We then focus on the GeneDB project, detailing the features and tools currently available through it. Finally, we discuss data curation and its importance in keeping genomic data 'relevant' to the research community.

Animals↗

An illness severity score and neonatal mortality in retrieved neonates.

UNLABELLED: The Clinical Risk Index for Babies (CRIB) score is a simple tool to measure clinical risk and illness severity in very low birth weight infants. The aim of this study was to determine if a modified CRIB score (MCRIB) used at first telephone contact with a transport service differentiated between retrieved infants who did or did not die in the neonatal period and hence might be a useful triage tool. A retrospective cohort study of 2504 infants, median gestational age 36 weeks and birth weight 2782 g, transported by the New South Wales Newborn and Paediatric Emergency Transport Service (NETS) was performed. MCRIB was calculated at four time points during the retrieval process. The MCRIB score at the time of the first call and the change in the MCRIB score over the retrieval process were related to outcome (neonatal death or survival). The mean MCRIB score at the time of first call was higher in those infants who died during the neonatal period (4.37) than in those who survived (2.63), (P < 0.0001). MCRIB performed better (area under the receiver operator characteristic curves of 0.72) with regard to predicting mortality than gestational age (0.56) or birth weight (0.52). The mean MCRIB score fell progressively from the time of first call to admission at the accepting NICU (P < 0.0001); infants whose MCRIB score increased were more likely to die (P < 0.0001). CONCLUSION: these results suggest an illness severity score, applied at the time of first call to a transport service would be helpful in setting priorities for retrievals.

Analysis of Variance↗

The mortality index for neonatal transportation score: a new mortality prediction model for retrieved neonates.

OBJECTIVE: To develop a mortality prediction score for retrieved neonates based on the information given at the first telephone contact with a retrieval service. METHODS: Data from the New South Wales Newborn and Pediatric Emergency Transport Service database were examined. Analysis was performed with the results for 2504 infants (median gestational age: 36 weeks; range: 24-43 weeks) who were <72 hours of age at the time of referral and whose outcome (neonatal death or survival) was known. The study population was divided randomly into 2 halves, the derivation and validation cohorts. Univariate analysis was performed to identify variables in the derivation cohort related to neonatal death. The variables were entered into a multivariate logistic regression analysis with neonatal death as the outcome. Receiver operator characteristic (ROC) curves were constructed with the regression model and data from the derivation cohort and then the validation cohort. The results were used to generate an integer-based score, the Mortality Index for Neonatal Transportation (MINT) score. ROC curves were constructed to assess the ability of the MINT score to predict perinatal and neonatal death. RESULTS: A 7-variable (Apgar score at 1 minute, birth weight, presence of a congenital anomaly, and infant's age, pH, arterial partial pressure of oxygen, and heart rate at the time of the call) model was constructed that generated areas under ROC curves of 0.82 and 0.83 for the derivation and validation cohorts, respectively. The 7 variables were then used to generate the MINT score, which gave areas under ROC curves of 0.80 for both neonatal and perinatal death. CONCLUSION: Data collected at the first telephone contact by the referring hospital with a regionalized transport service can identify neonates at the greatest risk of dying.

Analysis of Variance↗

Dissociation of steroid receptor coactivator 1 and nuclear receptor corepressor recruitment to the human glucocorticoid receptor by modification of the ligand-receptor interface: the role of tyrosine 735.

Within the human glucocorticoid receptor (GR) steroid binding pocket, tyrosine 735 makes hydrophobic contact with the steroid D ring. Substitution of tyrosine735 selectively impairs glucocorticoid transactivation but not transrepression. We now show, using both mammalian two-hybrid and glutathione-S-transferase pull downs, that such substitutions reduce interaction with steroid receptor coactivator 1, both basally and in response to agonist binding. Using a yeast two-hybrid screen we identified one of the three nuclear receptor interacting domains (NCoR-N1) of nuclear receptor corepressor (NCoR) as interacting with the GR C terminus in an RU486-specific manner. This was confirmed in mammalian two-hybrid experiments, and so we used the NCoR-N1 peptide to probe the GR C-terminal conformation. Substitution of Tyr735phe, Tyr735val, and Tyr735 ser, which impaired steroid receptor coactivator 1 (SRC1) interaction, enhanced NCoR-N1 recruitment, basally and after RU486. RU486 did not direct SRC1 recruitment to any of the GR constructs, and dexamethasone did not allow NCoR-N1 recruitment. Using a glutathione-S-transferase pull-down approach, the NCoR-N1 peptide was found to bind the full-length GR constitutively, and no further induction was seen with RU486, but it was reduced by dexamethasone. As both SRC1 and NCoR are predicted to recognize a common hydrophobic cleft in the GR, it seems that changes favorable to one interaction are detrimental to the other, thus identifying a molecular switch.

Amino Acid Sequence↗

Resolving functional diversity in relation to microbial community structure in soil: exploiting genomics and stable isotope probing.

The microbial ecology of soil still presents a challenge to microbiologists attempting to establish the ways in which bacteria and fungi actively metabolise substrates, link into food webs and recycle plant and animal remains and provide essential nutrients for plants. Extraction and in situ analysis of rRNA has enabled identification of active taxa, and detection of mRNA has provided an insight into the expression of key functional genes in soil. Recent advances in genomic analysis and stable isotope probing are the first steps in resolving the linkage between structure and function in microbial communities.

Bacteria↗

Nucleotide variation along the Drosophila melanogaster fourth chromosome.

The Drosophila melanogaster fourth chromosome, believed to be nonrecombining and invariable, is a classic example of the effect of natural selection in eliminating genetic variation in linked loci. However, in a chromosome-wide assay of nucleotide variation in natural populations, we have observed a high level of polymorphism in a approximately 200-kilobase region and marked levels of polymorphism in several other fragments interspersed with regions of little variation, suggesting different evolutionary histories in different chromosomal domains. Statistical tests of neutral evolution showed that a few haplotypes predominate in the 200-kilobase polymorphic region. Finally, contrary to the expectation of no recombination, we identified six recombination events within the chromosome. Thus, positive Darwinian selection and recombination have affected the evolution of this chromosome.

Animals↗