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1.  Diaryl Hydrazones as Multifunctional Inhibitors of Amyloid Self-Assembly† 
Biochemistry  2013;52(7):1137-1148.
The design and application of an effective, new class of multifunctional small molecule inhibitors of amyloid self-assembly are described. Several compounds, based on the diaryl hydrazone scaffold were designed. Forty-four substituted derivatives of this core structure were synthesized using a variety of benzaldehydes and phenylhydrazines and were characterized. The inhibitor candidates were evaluated in multiple assays, including the inhibition of Aβ fibrillogenesis and oligomer formation and the reverse processes, the disassembly of preformed fibrils and oligomers. Since the structure of the hydrazone-based inhibitors mimic the redox features of the antioxidant resveratrol the radical scavenging effect of the compounds was evaluated by colorimetric assays against 2,2-diphenyl-lpicrylhydrazyl (DPPH) and superoxide radicals.
The hydrazone scaffold was active in all of the different assays. The structure-activity relationship revealed that the substituents on the aromatic rings had considerable effect on the overall activity of the compounds. The inhibitors showed strong activity in the fibrillogenesis inhibition and disassembly, and even greater potency in the inhibition of oligomer formation and oligomer disassembly. Supporting the quantitative fluorometric and colorimetric assays, size exclusion chromatographic studies indicated that the best compounds practically eliminated or substantially inhibited the formation of soluble, aggregated Aβ species, as well. Atomic Force Microscopy was also applied to monitor the morphology of Aβ deposits. The compounds also possessed the predicted antioxidant properties; approximately 30% of the synthesized compounds showed equal or better radical scavenging effect than resveratrol or ascorbic acid.
doi:10.1021/bi3012059
PMCID: PMC3608202  PMID: 23346953
2.  Under-reporting of birth registrations in New South Wales, Australia 
Background
To determine the rates of birth registration over a five-year period in New South Wales (NSW) and explore the factors associated with the rate of registration.
Methods
This is a cross-sectional study using linked population databases. The study population included all births of NSW residents in NSW between 2001 and 2005.
Results
Birth registration rates in NSW were 82.66% in the year of birth, 93.19% in the first year, 94.02% in the second, 94.56% in the third and 95.08% in the fourth year after birth. The non-registration of births was mainly associated with such factors as neonatal and postneonatal death (adjusted OR = 3.84, 95% CI: 3.23-4.57); being Indigenous (adjusted OR = 3.26, 95% CI: 3.10-3.43); maternal age <25 or >39 years (adjusted OR = 2.81, 95% CI: 2.72-2.90); low birthweight (<2,500 grams) (adjusted OR = 1.79, 95% CI: 1.69-1.90); living in remote areas (adjusted OR = 1.57, 95% CI: 1.52-1.63); being born after the first quarter of year (adjusted OR = 1.08-1.56, 95% CI between 1.03-1.12 and 1.49-1.64); mother having more pregnancies (adjusted OR = 1.85-7.29, 95% CI between1.78-1.93 and 6.87-7.73). Mothers who were born overseas were more likely to register their births than those born in Australia (adjusted OR = 0.72, 95% CI: 0.69-0.75). Multiple births were more likely to be registered than singleton births (adjusted OR = 0.84, 95% CI: 0.76-0.92). About one-third of the non-registrations of births in NSW were explained by the risk factors. The reasons for the remaining non-registrations need to be investigated.
Conclusion
Of birth in NSW, 4.92% were not registered by the fourth year after birth.
doi:10.1186/1471-2393-12-147
PMCID: PMC3562517  PMID: 23234578
Birth; Registration; Factor; Australia
3.  Enhanced reporting of deaths among Aboriginal and Torres Strait Islander peoples using linked administrative health datasets 
Background
Aboriginal and Torres Strait Islander peoples are under-reported in administrative health datasets in NSW, Australia. Correct reporting of Aboriginal and Torres Strait Islander peoples is essential to measure the effectiveness of policies and programmes aimed at reducing the health disadvantage experienced by Aboriginal and Torres Strait Islander peoples. This study investigates the potential of record linkage to enhance reporting of deaths among Aboriginal and Torres Strait Islander peoples in NSW, Australia.
Methods
Australian Bureau of Statistics death registration data for 2007 were linked with four population health datasets relating to hospitalisations, emergency department attendances and births. Reporting of deaths was enhanced from linked records using two methods, and effects on patterns of demographic characteristics and mortality indicators were examined.
Results
Reporting of deaths increased by 34.5% using an algorithm based on a weight of evidence of a person being Aboriginal or Torres Strait Islander, and by 56.6% using an approach based on 'at least one report' of a person being Aboriginal or Torres Strait Islander. The increase was relatively greater in older persons and those living in less geographically remote areas. Enhancement resulted in a reduction in the urban-remote differential in median age at death and increases in standardised mortality ratios particularly for chronic conditions.
Conclusions
Record linkage creates a statistical construct that helps to correct under-reporting of deaths and potential bias in mortality statistics for Aboriginal and Torres Strait Islander peoples.
doi:10.1186/1471-2288-12-91
PMCID: PMC3413579  PMID: 22747900
4.  Improvement of maternal Aboriginality in NSW birth data 
Background
The Indigenous population of Australia was estimated as 2.5% and under-reported. The aim of this study is to improve statistical ascertainment of Aboriginal women giving birth in New South Wales.
Methods
This study was based on linked birth data from the Midwives Data Collection (MDC) and the Registry of Births Deaths and Marriages (RBDM) of New South Wales (NSW). Data linkage was performed by the Centre for Health Record Linkage (CHeReL) for births in NSW for the period January 2001 to December 2005. The accuracy of maternal Aboriginal status in the MDC and RBDM was assessed by consistency, sensitivity and specificity. A new statistical variable, ASV, or Aboriginal Statistical Variable, was constructed based on Indigenous identification in both datasets. The ASV was assessed by comparing numbers and percentages of births to Aboriginal mothers with the estimates by capture-recapture analysis.
Results
Maternal Aboriginal status was under-ascertained in both the MDC and RBDM. The ASV significantly increased ascertainment of Aboriginal women giving birth and decreased the number of missing cases. The proportion of births to Aboriginal mothers in the non-registered birth group was significantly higher than in the registered group.
Conclusions
Linking birth data collections is a feasible method to improve the statistical ascertainment of Aboriginal women giving birth in NSW. This has ramifications for the ascertainment of babies of Aboriginal mothers and the targeting of appropriate services in pregnancy and early childhood.
doi:10.1186/1471-2288-12-8
PMCID: PMC3314542  PMID: 22289717
Birth; Aboriginality; data; Australia
5.  Intronic Binding Sites for hnRNP A/B and hnRNP F/H Proteins Stimulate Pre-mRNA Splicing 
PLoS Biology  2006;4(2):e21.
hnRNP A/B proteins modulate the alternative splicing of several mammalian and viral pre-mRNAs, and are typically viewed as proteins that enforce the activity of splicing silencers. Here we show that intronic hnRNP A/B–binding sites (ABS) can stimulate the in vitro splicing of pre-mRNAs containing artificially enlarged introns. Stimulation of in vitro splicing could also be obtained by providing intronic ABS in trans through the use of antisense oligonucleotides containing a non-hybridizing ABS-carrying tail. ABS-tailed oligonucleotides also improved the in vivo inclusion of an alternative exon flanked by an enlarged intron. Notably, binding sites for hnRNP F/H proteins (FBS) replicate the activity of ABS by improving the splicing of an enlarged intron and by modulating 5′ splice-site selection. One hypothesis formulated to explain these effects is that bound hnRNP proteins self-interact to bring in closer proximity the external pair of splice sites. Consistent with this model, positioning FBS or ABS at both ends of an intron was required to stimulate splicing of some pre-mRNAs. In addition, a computational analysis of the configuration of putative FBS and ABS located at the ends of introns supports the view that these motifs have evolved to support cooperative interactions. Our results document a positive role for the hnRNP A/B and hnRNP F/H proteins in generic splicing, and suggest that these proteins may modulate the conformation of mammalian pre-mRNAs.
Typically viewed as enforcing splicing silencers, hnRNP A/B proteins may facilitate splicing by modulating the conformation of mammalian pre-mRNAs.
doi:10.1371/journal.pbio.0040021
PMCID: PMC1326234  PMID: 16396608
6.  Aging and Death in an Organism That Reproduces by Morphologically Symmetric Division 
PLoS Biology  2005;3(2):e45.
In macroscopic organisms, aging is often obvious; in single-celled organisms, where there is the greatest potential to identify the molecular mechanisms involved, identifying and quantifying aging is harder. The primary results in this area have come from organisms that share the traits of a visibly asymmetric division and an identifiable juvenile phase. As reproductive aging must require a differential distribution of aged and young components between parent and offspring, it has been postulated that organisms without these traits do not age, thus exhibiting functional immortality. Through automated time-lapse microscopy, we followed repeated cycles of reproduction by individual cells of the model organism Escherichia coli, which reproduces without a juvenile phase and with an apparently symmetric division. We show that the cell that inherits the old pole exhibits a diminished growth rate, decreased offspring production, and an increased incidence of death. We conclude that the two supposedly identical cells produced during cell division are functionally asymmetric; the old pole cell should be considered an aging parent repeatedly producing rejuvenated offspring. These results suggest that no life strategy is immune to the effects of aging, and therefore immortality may be either too costly or mechanistically impossible in natural organisms.
Detailed time lapse photography reveals that organisms that divide symmetrically, such as the bacterium E. coli, can indeed age and consequently that no organism is immune to mortality
doi:10.1371/journal.pbio.0030045
PMCID: PMC546039  PMID: 15685293

Results 1-6 (6)