Damaging insect pests and diseases and their threats to agarwood tree plantations

The cultivation of agarwood tree species such as Aquilaria has grown dramatically during the last ten years. This development is driven by the desire to produce sustainable agarwood to meet the high market demand. In the past, the main source of agarwood had been from natural forests, which resources are now declining. Although there are various examples of pests and diseases affecting early plantations, these damages were often overlooked. Recently, the emergence of new pests and diseases in large-scale Aquilaria tree plantations has raised concerns among planters and researchers, as the damage level to the trees may vary from unsubstantial to tree mortality. Lack of information on the types of pests and diseases in Aquilaria plantations makes it difficult to properly manage these threats, leading to economic losses. This review summarizes the insect pests and diseases known to damage cultivated agarwood trees in various countries including China, India, Indonesia, and Malaysia. As we learn from the cultivation practices of other monoculture crops, these insect pests and pathogens are a major challenge to the healthy growth of agarwood trees. The implementation of an integrated pest and disease management at an early stage of plantation establishment may hold the key to help control and contain these threats from turning into major outbreaks

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Abstract 733: Detection of HCC-derived major HBV integration junctions in urine and their implications for driver identification

Abstract Chronic Hepatitis B Virus (HBV) infection is a major etiology of hepatocellular carcinoma (HCC), a leading cause of cancer mortality worldwide. Integration of HBV DNA into the host genome occurs during the course of chronic infection. Integrated HBV DNA is observed in most of HBV-associated HCC. The integration junctions derived from the original tumor cell become abundant (referred to as major integration junctions) in the infected liver because of clonal expansion during tumor development. Detection of circulating DNA containing these tumor-derived integration junctions may therefore be useful for cancer detection. We have adapted a method known as Primer Extension Capture (PEC) to enrich integrated HBV DNA for next-generation sequencing (NGS). Our initial studies using this approach to enrich the HBV DR1-2 region (a common site for HBV integrated breakpoints) identified major integration junctions from HBV-HCC tissue samples and matched urine. Further analysis revealed that most recurrently targeted integrations from these HCC tumors have previously reported involvement in cancer. This suggested that identification of recurrently targeted genes is applicable for driver identification. Interestingly, we show how HBV targets the TERT promoter in a localized region even though no two TERT junctions examined are identical. We have further developed this PEC to enrich for the entire HBV genome and applied it to (i) liver tissue DNA from 20 matched HCC and adjacent non-HCC samples, and (ii) DNA from urine of 20 hepatitis, 20 cirrhosis and 20 HCC patients. The HBV enriched libraries were sequenced by NGS and the integration events were analyzed using the in-house developed software. The complexity of HBV junction sites in HCC and non-HCC tissue and urine derived circulating DNA is reported. Our approach has potential to be used for liquid biopsies to study the complexities of HBV integrations in chronic HBV infection and carcinogenesis, and to identify HCC-related DNA modifications for early detection and disease management. Citation Format: Selena Y. Lin, Jamin D. Steffen, Yih-Ping Su, Surbhi Jain, Ting-Tsung Chang, Wei Song, Ying-Hsiu Su. Detection of HCC-derived major HBV integration junctions in urine and their implications for driver identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 733. doi:10.1158/1538-7445.AM2017-733</jats:p

Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism

Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism.</jats:p

Abstract 5699: Detection of genetic and epigenetic DNA markers in urine for the early detection of liver cancer

Abstract The purpose of this study was to explore the potential of urine DNA biomarkers for the early detection of primary hepatocellular carcinoma (HCC). HCC is an aggressive disease with a 5-year survival rate of 26% in early-stage cancers, and a mere 2% in later stages. The most commonly used screening biomarker for HCC is serum alpha-fetoprotein (AFP), which detects only 40-60% of cases. We have previously shown that urine contains fragmented, circulation-derived, cell-free DNA that can be used for detection of cancer-related DNA markers, if a tumor is present. Given the molecular heterogeneity of HCC, we assembled a panel of frequently reported early detection DNA biomarkers for HCC that included genetic mutations (TERT -124 G to A, TP53 249 G to T and CTNNB1 hotspot at codon 32-45) and methylation markers (GSTP1, RASSF1A, CDKN2A, SFRP1, TFPI and MGMT). In this present study, we developed specialized short amplicon PCR assays optimized to detect these biomarkers from the urine of patients with cancer and tested the panel of biomarkers in urine of hepatitis, cirrhosis and HCC patients to demonstrate the feasibility of a breakthrough urine DNA test for HCC screening and early detection. Our evaluation indicated that the TP53 mutation, methylation of RASSF1A and GSTP1 urine DNA biomarkers were significantly higher in HCC than in non-HCC population. A correlation analysis indicated that these three markers do not correlate with each other and are suitable to be combined in a panel of biomarkers for the early detection of HCC. The 3-marker HCC urine DNA panel had an AUROC of 0.880 for distinguishing HCC from cirrhosis and hepatitis. By logistic regression, the sensitivity of the 3-DNA marker urine panel alone or in combination with AFP is 84.5% or 89.5% respectively, with a specificity of 90% for detecting HCC with AUROC of 0.951. Furthermore, these 3-DNA markers scored 43 of the 49 (87.8%) AFP-negative (less than 20 ng/mL) HCC urine samples "positive" in this study population. A novel statistic model was built by using Random Forest machine learning method as compared to full logistic regression in both open labeled urine samples and 242 blinded urine validation samples. A sensitivity of 92.3 % at a specificity of 87% was obtained by applying the random forest algorithm generated from the open labeled data (at 90% specificity cutoff) to the validation study, where as a sensitivity of 76.9% at a specificity of 84.7% was obtained from the full logistic regression derived from the open labeled data set. In conclusion, HCC DNA markers can be detected in urine of patients with HCC by short-amplicon, PCR-based assays and this urine test has the potential to become the first line of screening for HCC in high risk populations. Citation Format: Surbhi Jain, Jamin D. Steffen, Yih-Ping Su, Jeremy Wang, Ting-Tsung Chang, Chi-Tan Hu, Wei Song, Ying-Hsiu Su. Detection of genetic and epigenetic DNA markers in urine for the early detection of liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5699. doi:10.1158/1538-7445.AM2017-5699</jats:p