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Protein complexes are key macromolecular machines of the cell, but their description remains incomplete. We and others previously reported an experimental strategy for global characterization of native protein assemblies based on chromatographic fractionation of biological extracts coupled to precision mass spectrometry analysis (chromatographic fractionation-mass spectrometry, CF-MS), but the resulting data are challenging to process and interpret. Here, we describe EPIC (elution profile-based inference of complexes), a software toolkit for automated scoring of large-scale CF-MS data to define high-confidence multi-component macromolecules from diverse biological specimens. As a case study, we used EPIC to map the global interactome of Caenorhabditis elegans, defining 612 putative worm protein complexes linked to diverse biological processes. These included novel subunits and assemblies unique to nematodes that we validated using orthogonal methods. The open source EPIC software is freely available as a Jupyter notebook packaged in a Docker container (https://hub.docker.com/r/baderlab/bio-epic/).

Treatment rates with intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (IS) remain low in Asian populations. Various logistic obstacles and higher anticipated bleeding risk in Asians are major concerns. We report on the feasibility and safety of IV-tPA therapy at our tertiary care center. Consecutive acute IS patients eligible for thrombolysis were treated with low-dose (maximum 50 mg) IV-tPA between January 2000 and September 2006 and with standard-dose (maximum 90 mg) IV-tPA between October 2006 and May 2008. The efficacy of IV-tPA was assessed by the modified Rankin Scale (mRS) score at 3 months and by absolute changes in the National Institute of Health Stroke Scale (NIHSS) score at hospital discharge and 3 months. The safety of IV-tPA was assessed by the rate of symptomatic intracranial hemorrhage (SICH). A total of 130 patients were included (mean age, 60±13 years; 60% males; median NIHSS score, 14). A total of 48 patients received low-dose IV-tPA, and 82 patients received standard-dose IV-tPA. The median onset to treatment time was 160 minutes. Some 59% of the patients achieved functional independence (mRS score 0-1) at 3 months with standard-dose tPA, compared with 35% in the low-dose group (P=.011). SICH occurred more frequently with the low dose (14.5%) than with the standard dose (1.2%; P=.004). In a multivariate logistic regression model, lower admission NIHSS score (odds ratio [OR]=0.78 per 1-point increase; 95% confidence interval [CI]=0.70-0.88), lower pretreatment blood glucose level (OR=0.76 per 1 mmol/L increase; 95% CI=0.60-0.95), shorter time from symptom onset to IV-tPA bolus (OR=0.97 per 1-minute increase; 95% CI=0.94-1.0), and standard-dose IV-tPA (OR=12.49; 95% CI=2.9-53.89) were associated with a higher likelihood for functional independence at 3 months. Our data indicate that standard-dose IV-tPA (0.9 mg/kg) was feasible and safe for treating acute IS in our multiethnic Asian population in Singapore.

Objective: To describe the patterns of early and delayed hypoxic damage to the brain parenchyma.Methods: This paper reports a case with interesting clinical course and MRI brain changes in a patient following a single hypoxic-anoxic exposure after an alcoholic binge.Results: Bilaterally symmetrical putaminal necrosis was noted in the initial MRI, but subsequent follow-up revealed extensive demyelination of the sub-cortical white matter, associated with the clinical deterioration.Conclusions: The brain, in general, and the neurons in caudate nucleus, putamen, globus pallidus and cerebral white matter, in particular, are susceptible to hypoxic injury. These changes may occur simultaneously and early or sequentially and late.

Background Prospective studies on lipids and risk of Parkinson9s disease (PD) in Asian populations are sparse. This study prospectively examined the associations between dietary cholesterol and major fatty acids, and risk of PD among the Chinese in Singapore. Methods This study used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 men and women aged 45–74 years in Singapore enrolled in 1993–1998. Dietary intakes of cholesterol and fatty acids were derived from a validated semiquantitative food frequency questionnaire and the Singapore Food Composition Table. Incident PD cases were identified either through follow-up interviews or record linkage analysis with hospital discharge and PD outpatient registries. Results After an average of 14.6 years, 218 men and 193 women in the cohort developed PD. Dietary cholesterol was associated with statistically significantly lower risk of PD in a dose–dependent manner among men after adjustment for established risk factors for PD and intakes of major fatty acids. Compared to the lowest quartile, HR (95% CI) for the highest quartile was 0.53 (95% CI 0.33 to 0.84) (P for trend=0.006). Among women, dietary monounsaturated fatty acid was inversely associated with PD risk (P for trend=0.033). Compared to the lowest quartile, HR for the highest quartile was 0.44 (95% CI 0.22 to 0.88). There was no statistically significant association between dietary saturated, n-3 and n-6 fatty acids and PD risk. Conclusions Higher intakes of cholesterol and monounsaturated fatty acids may reduce risk of PD in men and women, respectively.

Data from Asian populations on dietary and lifestyle factors associated with Parkinson's disease are sparse. In 1993-2005, the authors examined these factors in relation to Parkinson's disease in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women. Baseline data were collected through in-person interviews using structured questionnaires. All 157 incident Parkinson's disease cases were identified either through follow-up interviews or via linkage with hospital discharge databases and Parkinson's disease outpatient registries and were confirmed by review of medical records. Current versus never smokers exhibited a reduced risk of Parkinson's disease (relative risk = 0.29, 95% confidence interval: 0.16, 0.52). Total caffeine intake was inversely related to Parkinson's disease risk (p for trend = 0.002); the relative risk for the highest versus lowest quartile was 0.55 (95% confidence interval: 0.35, 0.88). Black tea, a caffeine-containing beverage, showed an inverse association with Parkinson's disease risk that was not confounded by total caffeine intake or tobacco smoking (p for trend = 0.0006; adjusted relative risk for the highest vs. lowest tertile of intake = 0.29, 95% confidence interval: 0.13, 0.67). Green tea drinking was unrelated to Parkinson's disease risk. Diet had no strong influence on risk. Ingredients of black tea other than caffeine appear to be responsible for the beverage's inverse association with Parkinson's disease.