Judy Sng

Skin cancer trends among Asians living in Singapore from 1968 to 2006

BACKGROUND The incidence rates of skin cancers in Caucasian populations are increasing. There is little information on skin cancer trends in Asians, who have distinctly different skin types. OBJECTIVE We sought to study skin cancer incidence rates and time trends among the 3 Asian ethnic groups in Singapore. METHODS We analyzed skin cancer data from the Singapore Cancer Registry from 1968 to 2006 using the Poisson regression model. RESULTS There were 4044 reported cases of basal cell carcinoma, 2064 of squamous cell carcinoma, and 415 of melanoma. Overall skin cancer incidence rates increased from 2.9/100,000 in 1968 to 1972 to 8.4/100,000 in 1998 to 2002, declining to 7.4/100,000 in 2003 to 2006. Among older persons (> or = 60 years), basal cell carcinoma rates increased the most, by 18.9/100,000 in Chinese, 6.0/100,000 in Malays, and 4.1/100,000 in Indians from 1968 to 1972 to 2003 to 2006. Squamous cell carcinoma rates among those aged 60 years and older increased by 2.3/100,000 in Chinese and by 1/100,000 in Malays and Indians. Melanoma rates were constant for all 3 races. Skin cancer rates among the fairer-skinned Chinese were approximately 3 times higher than in Malays and Indians, who generally have darker complexions. LIMITATIONS Although appropriate population denominators were used, lack of data from 2007 could have affected the results for the last time period, which comprised 4 instead of 5 years. CONCLUSION Incidence rates of skin cancer in Singapore increased from 1968 to 2006, especially among older Chinese.

Comparative network-based recovery analysis and proteomic profiling of neurological changes in valproic acid-treated mice.

Despite its prominence for characterization of complex mixtures, LC–MS/MS frequently fails to identify many proteins. Network-based analysis methods, based on protein–protein interaction networks (PPINs), biological pathways, and protein complexes, are useful for recovering non-detected proteins, thereby enhancing analytical resolution. However, network-based analysis methods do come in varied flavors for which the respective efficacies are largely unknown. We compare the recovery performance and functional insights from three distinct instances of PPIN-based approaches, viz., Proteomics Expansion Pipeline (PEP), Functional Class Scoring (FCS), and Maxlink, in a test scenario of valproic acid (VPA)-treated mice. We find that the most comprehensive functional insights, as well as best non-detected protein recovery performance, are derived from FCS utilizing real biological complexes. This outstrips other network-based methods such as Maxlink or Proteomics Expansion Pipeline (PEP). From FCS, we identified known biological complexes involved in epigenetic modifications, neuronal system development, and cytoskeletal rearrangements. This is congruent with the observed phenotype where adult mice showed an increase in dendritic branching to allow the rewiring of visual cortical circuitry and an improvement in their visual acuity when tested behaviorally. In addition, PEP also identified a novel complex, comprising YWHAB, NR1, NR2B, ACTB, and TJP1, which is functionally related to the observed phenotype. Although our results suggest different network analysis methods can produce different results, on the whole, the findings are mutually supportive. More critically, the non-overlapping information each provides can provide greater holistic understanding of complex phenotypes.

The role of miRNAs in complex formation and control

UNLABELLED microRibonucleic acid (miRNAs) are small regulatory molecules that act by mRNA degradation or via translational repression. Although many miRNAs are ubiquitously expressed, a small subset have differential expression patterns that may give rise to tissue-specific complexes. MOTIVATION This work studies gene targeting patterns amongst miRNAs with differential expression profiles, and links this to control and regulation of protein complexes. RESULTS We find that, when a pair of miRNAs are not expressed in the same tissues, there is a higher tendency for them to target the direct partners of the same hub proteins. At the same time, they also avoid targeting the same set of hub-spokes. Moreover, the complexes corresponding to these hub-spokes tend to be specific and nonoverlapping. This suggests that the effect of miRNAs on the formation of complexes is specific.

Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice

Clinical symptoms may vary and not necessarily reflect serum thyroid hormone (TH) levels during acute and chronic hyperthyroidism as well as recovery from hyperthyroidism. We thus examined changes in hepatic gene expression and serum TH/TSH levels in adult male mice treated either with a single T3 (20 μg per 100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed by 10 days of withdrawal. Gene expression arrays from livers harvested at these time points showed that among positively-regulated target genes, 320 were stimulated acutely and 429 chronically by T3. Surprisingly, only 69 of 680 genes (10.1%) were induced during both periods, suggesting desensitization of the majority of acutely stimulated target genes. About 90% of positively regulated target genes returned to baseline expression levels after 10 days of withdrawal; however, 67 of 680 (9.9%) did not return to baseline despite normalization of serum TH/TSH levels. Similar findings also were observed for negatively regulated target genes. Chromatin immunoprecipitation analysis of representative positively regulated target genes suggested that acetylation of H3K9/K14 was associated with acute stimulation, whereas trimethylation of H3K4 was associated with chronic stimulation. In an in vivo model of chronic intrahepatic hyperthyroidism since birth, adult male monocarboxylate transporter-8 knockout mice also demonstrated desensitization of most acutely stimulated target genes that were examined. In summary, we have identified transcriptional desensitization and incomplete recovery of gene expression during chronic hyperthyroidism and recovery. Our findings may be a potential reason for discordance between clinical symptoms and serum TH levels observed in these conditions.

Influenza A (H1N1) infections among healthcare workers: a cause for cautious optimism

The 2009 swine flu (influenza A H1N1) pandemic defied predictions that the next influenza outbreak was likely to be due to avian influenza arising from H5N1-endemic countries in Southeast Asia. As the world struggled to cope with the global financial meltdown, a new unexpected influenza challenge emerged from the Americas, but with the public health community better prepared than before. Although the avian influenza predictions have not occurred yet, the dire warnings were not misplaced, as the pandemic planning that ensued greatly helped decision makers and healthcare professionals around the planet to deal with the current A(H1N1) outbreak. The numbers of A(H1N1) infections have increased rapidly. On 11 June 2009, after nearly 30 000 laboratory confirmed cases reported in 74 countries, the WHO declared the A(H1N1) outbreak the first pandemic of this century.1 Estimates of the reproduction number (defined as the “number of cases that one case generates on average over the course of their infectious period”) for A(H1N1) range from 1.4 to 1.6, which are higher than for the usual strains of seasonal influenza. However, compared to the 10% mortality rate seen with SARS, the case fatality ratio for A(H1N1) is lower and estimated to be from 0.2% to 0.4%.2 3 Although no official numbers have …

Contemporary Network Proteomics and Its Requirements

The integration of networks with genomics (network genomics) is a familiar field. Conventional network analysis takes advantage of the larger coverage and relative stability of gene expression measurements. Network proteomics on the other hand has to develop further on two critical factors: (1) expanded data coverage and consistency, and (2) suitable reference network libraries, and data mining from them. Concerning (1) we discuss several contemporary themes that can improve data quality, which in turn will boost the outcome of downstream network analysis. For (2), we focus on network analysis developments, specifically, the need for context-specific networks and essential considerations for localized network analysis.

Lessons From the Past: Perspectives on Severe Acute Respiratory Syndrome

On March 12, 2003, the World Health Organization issued a global health alert stating that a new, unrecognizable, flulike disease may spread to health care workers (HCWs). We now know this illness as severe acute respiratory syndrome (SARS). By August 2003, there were 8422 SARS cases and 916 deaths reported from 29 countries. SARS galvanized the world to the threat of emerging infectious diseases and provided a dress rehearsal for subsequent challenges such as H5N1 and H1N1 influenza. Among the insights gained were the following: SARS reminded us that health care work can be hazardous; the effects of SARS extended beyond the infection; general principles for prevention and control were effective against SARS; and SARS posed both a public health and an occupational health threat. Given these perspectives gained, we should be better prepared when faced with similar scenarios in the future.

HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience-dependent manner

During early postnatal development, neuronal circuits are sculpted by sensory experience provided by the external environment. This experience‐dependent regulation of circuitry development consolidates the balance of excitatory‐inhibitory (E/I) neurons in the brain. The cortical barrel‐column that innervates a single principal whisker is used to provide a clear reference frame for studying the consolidation of E/I circuitry. Sensory deprivation of S1 at birth disrupts the consolidation of excitatory‐inhibitory balance by decreasing inhibitory transmission of parvalbumin interneurons. The molecular mechanisms underlying this decrease in inhibition are not completely understood. Our findings show that epigenetic mechanisms, in particular histone deacetylation by histone deacetylases, negatively regulate the expression of brain‐derived neurotrophic factor (Bdnf) and parvalbumin (Pvalb) genes during development, which are required for the maturation of parvalbumin interneurons. After whisker deprivation, increased histone deacetylase 1 expression and activity led to increased histone deacetylase 1 binding and decreased histone acetylation at Bdnf promoters I–IV and Pvalb promoter, resulting in the repression of Bdnf and Pvalb gene transcription. The decrease in Bdnf expression further affected parvalbumin interneuron maturation at layer II/III in S1, demonstrated by decreased parvalbumin expression, a marker for parvalbumin interneuron maturation. Knockdown of HDAC1 recovered Bdnf and Pvalb gene transcription and also prevented the decrease of inhibitory synapses accompanying whisker deprivation.

All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation

Abstract. We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain.

Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation.

The brain adapts to dynamic environmental conditions by altering its epigenetic state, thereby influencing neuronal transcriptional programs. An example of an epigenetic modification is protein methylation, catalyzed by protein arginine methyltransferases (PRMT). One member, Prmt8, is selectively expressed in the central nervous system during a crucial phase of early development, but little else is known regarding its function. We hypothesize Prmt8 plays a role in synaptic maturation during development. To evaluate this, we used a proteome‐wide approach to characterize the synaptic proteome of Prmt8 knockout versus wild‐type mice. Through comparative network‐based analyses, proteins and functional clusters related to neurite development were identified to be differentially regulated between the two genotypes. One interesting protein that was differentially regulated was tenascin‐R (TNR). Chromatin immunoprecipitation demonstrated binding of PRMT8 to the tenascin‐r (Tnr) promoter. TNR, a component of perineuronal nets, preserves structural integrity of synaptic connections within neuronal networks during the development of visual‐somatosensory cortices. On closer inspection, Prmt8 removal increased net formation and decreased inhibitory parvalbumin‐positive (PV+) puncta on pyramidal neurons, thereby hindering the maturation of circuits. Consequently, visual acuity of the knockout mice was reduced. Our results demonstrated Prmt8′s involvement in synaptic maturation and its prospect as an epigenetic modulator of developmental neuroplasticity by regulating structural elements such as the perineuronal nets.