Gene copy number analysis of granulin-epithelin precursor (GEP) and ATP-binding cassette subfamily F member 1 (ABCF1) in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in Hong Kong and Southeast Asian countries. Cancer progression is often symptomless, making the early diagnosis difficult, thus leading to a high mortality rate. Treatments against HCC were often found to be less effective than other cancers. Systemic chemotherapy, which is widely used in cancer treatments, has a low response rate in HCC. New treatment regimes, such as targeted therapy, have shown partial responses in clinical trials and therefore continuous effort in searching new drug targets is warranted. Granulin-epithelin Precursor (GEP) is a pluripotent growth factor, and has been shown to be overexpressed in HCC and various cancers. Our group has demonstrated that GEP promotes tumor growth, and regulates chemoresistance in HCC. It shares a highly similar expression pattern with one of the members of ATP-binding cassette (ABC) transporter family, ABCF1. Blocking GEP, both in vitro and in vivo, showed inhibition on HCC growth. These suggest that GEP is a potential target for HCC treatment. However, there is still little information on how GEP and ABCF1 is overexpressed in HCC. This project aims to investigate the mechanisms involved. GEP and ABCF1 genes are located on chromosomes 17q and 6p, respectively, which both are frequently amplified in HCC. We used quantitative microsatellite analysis (QuMA) to detect GEP and ABCF1 amplification in HCC samples. Both GEP and ABCF1 showed about 20% of HCC cases having amplification, and their copy numbers correlated to the mRNA expression levels. The copy numbers of GEP were also found to correlate to those of ABCF1 significantly. Clinico-pathological analysis showed that GEP copy numbers correlated with gender, serum AFP levels and HBV status, while ABCF1 did not associate with any of the clinico-pathological features. Fluorescence in situ hybridization (FISH) was performed to validate the results on DNA copy number by QuMA. The cases with highest DNA copy number on GEP and ABCF1, were examined. The average difference between FISH and QuMA results ranged ± 0.3 copies, indicating QuMA and FISH results were corroborated on DNA copy number. Furthermore, the FISH results indicated that there are different degrees of aneuploidy involved in chromosome 6p and 17q in 5 out of 6 cases investigated. These suggest that the copy number variations in GEP and ABCF1 were partly caused by the abnormal number of chromosomes. In summary, we observed that GEP and ABCF1 gene copy numbers were increased in subsets of HCC cases, and the increase correlated to their respective transcript expression levels. Furthermore, these copy number variations partly could be explained by aneuploidy as demonstrated by FISH analysis. The current study may help to understand the complex genomic aberrations in HCC and allow better treatment designs in the future.published_or_final_versionSurgeryMasterMaster of Philosoph

Drought Stress Priming Improved the Drought Tolerance of Soybean

The capability of a plant to protect itself from stress-related damages is termed “adaptability” and the phenomenon of showing better performance in subsequent stress is termed “stress memory”. While drought is one of the most serious disasters to result from climate change, the current understanding of drought stress priming in soybean is still inadequate for effective crop improvement. To fill this gap, in this study, the drought memory response was evaluated in cultivated soybean (Glycine max). To determine if a priming stress prior to a drought stress would be beneficial to the survival of soybean, plants were divided into three treatment groups: the unprimed group receiving one cycle of stress (1S), the primed group receiving two cycles of stress (2S), and the unstressed control group not subjected to any stress (US). When compared with the unprimed plants, priming led to a reduction of drought stress index (DSI) by 3, resulting in more than 14% increase in surviving leaves, more than 13% increase in leaf water content, slight increase in shoot water content and a slower rate of loss of water from the detached leaves. Primed plants had less than 60% the transpiration rate and stomatal conductance compared to the unprimed plants, accompanied by a slight drop in photosynthesis rate, and about a 30% increase in water usage efficiency (WUE). Priming also increased the root-to-shoot ratio, potentially improving water uptake. Selected genes encoding late embryogenesis abundant (LEA) proteins and MYB, NAC and PP2C domain-containing transcription factors were shown to be highly induced in primed plants compared to the unprimed group. In conclusion, priming significantly improved the drought stress response in soybean during recurrent drought, partially through the maintenance of water status and stronger expression of stress related genes. In sum, we have identified key physiological parameters for soybean which may be used as indicators for future genetic study to identify the genetic element controlling the drought stress priming

MATE-Type Proteins Are Responsible for Isoflavone Transportation and Accumulation in Soybean Seeds

Soybeans are nutritionally important as human food and animal feed. Apart from the macronutrients such as proteins and oils, soybeans are also high in health-beneficial secondary metabolites and are uniquely enriched in isoflavones among food crops. Isoflavone biosynthesis has been relatively well characterized, but the mechanism of their transportation in soybean cells is largely unknown. Using the yeast model, we showed that GmMATE1 and GmMATE2 promoted the accumulation of isoflavones, mainly in the aglycone forms. Using the tobacco BrightYellow-2 (BY-2) cell model, GmMATE1 and GmMATE2 were found to be localized in the vacuolar membrane. Such subcellular localization supports the notion that GmMATE1 and GmMATE2 function by compartmentalizing isoflavones in the vacuole. Expression analyses showed that GmMATE1 was mainly expressed in the developing soybean pod. Soybean mutants defective in GmMATE1 had significantly reduced total seed isoflavone contents, whereas the overexpression of GmMATE1 in transgenic soybean promoted the accumulation of seed isoflavones. Our results showed that GmMATE1, and possibly also GmMATE2, are bona fide isoflavone transporters that promote the accumulation of isoflavones in soybean seeds

Unintentional Injury Burden in Hong Kong: Results from a Representative Population-Based Survey.

Unintentional injuries are major causes of mortality and morbidity. Although generally perceived as accidents, it is possible to identify those at higher risk and implement appropriate prevention measures. This study aims to investigate the common causes of unintentional injuries and their associated risk factors among a large representative sample. Data of 12,022 individuals who completed the Hong Kong Population Health Survey 2014/15 were extracted. The primary outcome was the prevalence of having unintentional injury(-ies) in the previous 12 months that was severe enough to limit daily activities. Multivariable logistic regression analyses were conducted to identify associations between injuries and sociodemographic, clinical and lifestyle factors. 14.5% of respondents reported episode(s) of unintentional injury in the past 12 months in the population level. The main causes of top three most severe unintentional injuries were sprains (24.0%), falls (19.9%) and being hit/struck (19.6%). 13.2% injury episodes were work-related among the most severe episode. Factors independently associated with significantly higher risks of injury included currently employed, homemaker or student, born in Hong Kong (as compared with immigrants), doctor-diagnosed chronic conditions, harmful alcohol consumption, insufficient sleep, and disturbed sleep. To summarize, unintentional injuries are highly prevalent and associated with harmful drinking, insufficient sleep, and disturbed sleep, which are potential modifiable risk factors for prevention

Unintentional Injury Burden in Hong Kong: Results from a Representative Population-Based Survey

Unintentional injuries are major causes of mortality and morbidity. Although generally perceived as accidents, it is possible to identify those at higher risk and implement appropriate prevention measures. This study aims to investigate the common causes of unintentional injuries and their associated risk factors among a large representative sample. Data of 12,022 individuals who completed the Hong Kong Population Health Survey 2014/15 were extracted. The primary outcome was the prevalence of having unintentional injury(-ies) in the previous 12 months that was severe enough to limit daily activities. Multivariable logistic regression analyses were conducted to identify associations between injuries and sociodemographic, clinical and lifestyle factors. 14.5% of respondents reported episode(s) of unintentional injury in the past 12 months in the population level. The main causes of top three most severe unintentional injuries were sprains (24.0%), falls (19.9%) and being hit/struck (19.6%). 13.2% injury episodes were work-related among the most severe episode. Factors independently associated with significantly higher risks of injury included currently employed, homemaker or student, born in Hong Kong (as compared with immigrants), doctor-diagnosed chronic conditions, harmful alcohol consumption, insufficient sleep, and disturbed sleep. To summarize, unintentional injuries are highly prevalent and associated with harmful drinking, insufficient sleep, and disturbed sleep, which are potential modifiable risk factors for prevention

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present