All Papers

Amy H.Y. Tong, Marie Evangelista, Ainslie B. Parsons, Hong Xu et al.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Mirza Hasanuzzaman, Kamrun Nahar, Taufika Islam Anee, Masayuki Fujita

Glutathione (GSH; γ-glutamyl-cysteinyl-glycine) is a small intracellular thiol molecule which is considered as a strong non-enzymatic antioxidant. Glutathione regulates multiple metabolic functions; for example, it protects membranes by maintaining the reduced state of both α-tocopherol and zeaxanthin, it prevents the oxidative denaturation of proteins under stress conditions by protecting their thiol groups, and it serves as a substrate for both glutathione peroxidase and glutathione S -transferase. By acting as a precursor of phytochelatins, GSH helps in the chelating of toxic metals/metalloids which are then transported and sequestered in the vacuole. The glyoxalase pathway (consisting of glyoxalase I and glyoxalase II enzymes) for detoxification of methylglyoxal, a cytotoxic molecule, also requires GSH in the first reaction step. For these reasons, much attention has recently been directed to elucidation of the role of this molecule in conferring tolerance to abiotic stress. Recently, this molecule has drawn much attention because of its interaction with other signaling molecules and phytohormones. In this review, we have discussed the recent progress in GSH biosynthesis, metabolism and its role in abiotic stress tolerance.

Md. Abul Kalam Azad, Manobendro Sarker, Tiejun Li, Jie Yin

Probiotics are microbial strains that are beneficial to health, and their potential has recently led to a significant increase in research interest in their use to modulate the gut microbiota. The animal gut is a complex ecosystem of host cells, microbiota, and available nutrients, and the microbiota prevents several degenerative diseases in humans and animals via immunomodulation. The gut microbiota and its influence on human nutrition, metabolism, physiology, and immunity are addressed, and several probiotic species and strains are discussed to improve the understanding of modulation of gut microbiota. This paper provides a broad review of several Lactobacillus spp., Bifidobacterium spp., and other coliform bacteria as the most promising probiotic species and their role in the prevention of degenerative diseases, such as obesity, diabetes, cancer, cardiovascular diseases, malignancy, liver disease, and inflammatory bowel disease. This review also discusses a recent study of Saccharomyces spp. in which inflammation was prevented by promotion of proinflammatory immune function via the production of short-chain fatty acids. A summary of gut microbiota alteration with future perspectives is also provided.

Sarvajeet Singh Gill, Naser A. Anjum, Mirza Hasanuzzaman, Ritu Gill et al.

Abiotic stresses such as salinity, drought, clilling, heavy metal are the major limiting factors for crop productivity. These stresses induce the overproduction of reactive oxygen species (ROS) which are highly reactive and toxic, which must be minimized to protect the cell from oxidative damage. The cell organelles, particularly chloroplast and mitochondria are the major sites of ROS production in plants where excessive rate of electron flow takes place. Plant cells are well equipped to efficiently scavenge ROS and its reaction products by the coordinated and concerted action of antioxidant machinery constituted by vital enzymatic and non-enzymatic antioxidant components. Glutathione reductase (GR, EC 1.6.4.2) and tripeptide glutathione (GSH, γ-Glutamyl-Cysteinyl-Glycine) are two major components of ascorbate-glutathione (AsA-GSH) pathway which play significant role in protecting cells against ROS and its reaction products-accrued potential anomalies. Both GR and GSH are physiologically linked together where, GR is a NAD(P)H-dependent enzymatic antioxidant and efficiently maintains the reduced pool of GSH - a cellular thiol. The differential modulation of both GR and GSH in plants has been widely implicated for the significance of these two enigmatic antioxidants as major components of plant defense operations. Considering recent informations gained through molecular-genetic studies, the current paper presents an overview of the structure, localization, biosynthesis (for GSH only), discusses GSH and GR significance in abiotic stress (such as salinity, drought, clilling, heavy metal)-exposed crop plants and also points out unexplored aspects in the current context for future studies.

Harrison Specht, Edward Emmott, Aleksandra A. Petelski, R. Gray Huffman et al.

BACKGROUND: Macrophages are innate immune cells with diverse functional and molecular phenotypes. This diversity is largely unexplored at the level of single-cell proteomes because of the limitations of quantitative single-cell protein analysis. RESULTS: To overcome this limitation, we develop SCoPE2, which substantially increases quantitative accuracy and throughput while lowering cost and hands-on time by introducing automated and miniaturized sample preparation. These advances enable us to analyze the emergence of cellular heterogeneity as homogeneous monocytes differentiate into macrophage-like cells in the absence of polarizing cytokines. SCoPE2 quantifies over 3042 proteins in 1490 single monocytes and macrophages in 10 days of instrument time, and the quantified proteins allow us to discern single cells by cell type. Furthermore, the data uncover a continuous gradient of proteome states for the macrophages, suggesting that macrophage heterogeneity may emerge in the absence of polarizing cytokines. Parallel measurements of transcripts by 10× Genomics suggest that our measurements sample 20-fold more protein copies than RNA copies per gene, and thus, SCoPE2 supports quantification with improved count statistics. This allowed exploring regulatory interactions, such as interactions between the tumor suppressor p53, its transcript, and the transcripts of genes regulated by p53. CONCLUSIONS: Even in a homogeneous environment, macrophage proteomes are heterogeneous. This heterogeneity correlates to the inflammatory axis of classically and alternatively activated macrophages. Our methodology lays the foundation for automated and quantitative single-cell analysis of proteins by mass spectrometry and demonstrates the potential for inferring transcriptional and post-transcriptional regulation from variability across single cells.

Zubair Ahmed Ratan, Mohammad Faisal Haidere, Yo Han Hong, Sang Hee Park et al.

Ginseng has been used as a traditional herb in Asian countries for thousands of years. It contains a large number of active ingredients including steroidal saponins, protopanaxadiols, and protopanaxatriols, collectively known as ginsenosides. In the last few decades, the antioxidative and anticancer effects of ginseng, in addition to its effects on improving immunity, energy and sexuality, and combating cardiovascular diseases, diabetes mellitus, and neurological diseases, have been studied in both basic and clinical research. Ginseng could be a valuable resource for future drug development; however, further higher quality evidence is required. Moreover, ginseng may have drug interactions although the available evidence suggests it is a relatively safe product. This article reviews the bioactive compounds, global distribution, and therapeutic potential of plants in the genus Panax.

Ashok Kumar, Kartik Dhar, Shamsher S. Kanwar, Pankaj Kumar Arora

Lipases are industrial biocatalysts, which are involved in several novel reactions, occurring in aqueous medium as well as non-aqueous medium. Furthermore, they are well-known for their remarkable ability to carry out a wide variety of chemo-, regio- and enantio-selective transformations. Lipases have been gained attention worldwide by organic chemists due to their general ease of handling, broad substrate tolerance, high stability towards temperatures and solvents and convenient commercial availability. Most of the synthetic reactions on industrial scale are carried out in organic solvents because of the easy solubility of non-polar compounds. The effect of organic system on their stability and activity may determine the biocatalysis pace. Because of worldwide use of lipases, there is a need to understand the mechanisms behind the lipase-catalyzed reactions in organic solvents. The unique interfacial activation of lipases has always fascinated enzymologists and recently, biophysicists and crystallographers have made progress in understanding the structure-function relationships of these enzymes. The present review describes the advantages of lipase-catalyzed reactions in organic solvents and various effects of organic solvents on their activity.

Srujan Gandham, Xianyi Su, Jacqueline Wood, Angela L. Nocera et al.

Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component of a variety of physiological and pathological processes. Potential applications of EVs in novel diagnostic and therapeutic strategies have brought increasing attention. However, EV research remains highly challenging due to the inherently complex biogenesis of EVs and their vast heterogeneity in size, composition, and origin. There is a need for the establishment of standardized methods that address EV heterogeneity and sources of pre-analytical and analytical variability in EV studies. Here, we review technologies developed for EV isolation and characterization and discuss paths toward standardization in EV research.

Tofazzal Islam, Daniel Croll, Pierre Gladieux, Darren M. Soanes et al.

BACKGROUND: In February 2016, a new fungal disease was spotted in wheat fields across eight districts in Bangladesh. The epidemic spread to an estimated 15,000 hectares, about 16 % of the cultivated wheat area in Bangladesh, with yield losses reaching up to 100 %. Within weeks of the onset of the epidemic, we performed transcriptome sequencing of symptomatic leaf samples collected directly from Bangladeshi fields. RESULTS: Reinoculation of seedlings with strains isolated from infected wheat grains showed wheat blast symptoms on leaves of wheat but not rice. Our phylogenomic and population genomic analyses revealed that the wheat blast outbreak in Bangladesh was most likely caused by a wheat-infecting South American lineage of the blast fungus Magnaporthe oryzae. CONCLUSION: Our findings suggest that genomic surveillance can be rapidly applied to monitor plant disease outbreaks and provide valuable information regarding the identity and origin of the infectious agent.

Muhammad Torequl Islam, Eunüs S. Ali, Shaikh Jamal Uddin, Subrata Shaw et al.

Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.

Shengxiong Huang, Yongfeng Gao, Ji‐Kai Liu, Xiaoli Peng et al.

The WRKY transcription factors have been implicated in multiple biological processes in plants, especially in regulating defense against biotic and abiotic stresses. However, little information is available about the WRKYs in tomato (Solanum lycopersicum). The recent release of the whole-genome sequence of tomato allowed us to perform a genome-wide investigation for tomato WRKY proteins, and to compare these positively identified proteins with their orthologs in model plants, such as Arabidopsis and rice. In the present study, based on the recently released tomato whole-genome sequences, we identified 81 SlWRKY genes that were classified into three main groups, with the second group further divided into five subgroups. Depending on WRKY domains' sequences derived from tomato, Arabidopsis and rice, construction of a phylogenetic tree demonstrated distinct clustering and unique gene expansion of WRKY genes among the three species. Genome mapping analysis revealed that tomato WRKY genes were enriched on several chromosomes, especially on chromosome 5, and 16 % of the family members were tandemly duplicated genes. The tomato WRKYs from each group were shown to share similar motif compositions. Furthermore, tomato WRKY genes showed distinct temporal and spatial expression patterns in different developmental processes and in response to various biotic and abiotic stresses. The expression of 18 selected tomato WRKY genes in response to drought and salt stresses and Pseudomonas syringae invasion, respectively, was validated by quantitative RT-PCR. Our results will provide a platform for functional identification and molecular breeding study of WRKY genes in tomato and probably other Solanaceae plants.

Mufti Mahmud, M. Shamim Kaiser, T.M. McGinnity, Amir Hussain

Recent technological advancements in data acquisition tools allowed life scientists to acquire multimodal data from different biological application domains. Categorized in three broad types (i.e. images, signals, and sequences), these data are huge in amount and complex in nature. Mining such enormous amount of data for pattern recognition is a big challenge and requires sophisticated data-intensive machine learning techniques. Artificial neural network-based learning systems are well known for their pattern recognition capabilities, and lately their deep architectures—known as deep learning (DL)—have been successfully applied to solve many complex pattern recognition problems. To investigate how DL—especially its different architectures—has contributed and been utilized in the mining of biological data pertaining to those three types, a meta-analysis has been performed and the resulting resources have been critically analysed. Focusing on the use of DL to analyse patterns in data from diverse biological domains, this work investigates different DL architectures’ applications to these data. This is followed by an exploration of available open access data sources pertaining to the three data types along with popular open-source DL tools applicable to these data. Also, comparative investigations of these tools from qualitative, quantitative, and benchmarking perspectives are provided. Finally, some open research challenges in using DL to mine biological data are outlined and a number of possible future perspectives are put forward.

Baan Munim Twaij, Md. Nazmul Hasan

Plants are the source of various photochemicals; metabolites are used in medicinal and environmental sectors as well as being widely used in commercial and pharmaceutical products. Although they produce a number of medicinal products, either already on the market or under trial, the amounts obtained from plant sources are very minute or difficult to synthesize at an industrial level due to the complex chemical composition and chirality exhibited by these compounds. However, plant cell cultures offer a good alternative for the consistent production of desired secondary metabolites under the influence of precursors and elicitors. In this review, we discuss the various aspects of secondary metabolites, production synthesis, and sources of medical products from plant sources.

Mihai Pop, Alan W. Walker, Joseph N. Paulson, Brianna Lindsay et al.

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

Uta Erdbrügger, Charles J. Blijdorp, Irene V. Bijnsdorp, Francesc E. Borràs et al.

Abstract Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast‐growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV‐based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

Ying Bai, Yuan Zhang, Bing Han, Li Yang et al.

Circular RNAs (circRNAs) are highly expressed in the CNS and regulate physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, we show that the circRNA DLGAP4 (circDLGAP4) functions as an endogenous microRNA-143 (miR-143) sponge to inhibit miR-143 activity, resulting in the inhibition of homologous to the E6-AP C-terminal domain E3 ubiquitin protein ligase 1 expression. circDLGAP4 levels were significantly decreased in the plasma of acute ischemic stroke patients (13 females and 13 males) and in a mouse stroke model. Upregulation of circDLGAP4 expression significantly attenuated neurological deficits and decreased infarct areas and blood–brain barrier damage in the transient middle cerebral artery occlusion mouse stroke model. Endothelial-mesenchymal transition contributes to blood–brain barrier disruption and circDLGAP4 overexpression significantly inhibited endothelial-mesenchymal transition by regulating tight junction protein and mesenchymal cell marker expression. Together, the results of our study are illustrative of the involvement of circDLGAP4 and its coupling mechanism in cerebral ischemia, providing translational evidence that circDLGAP4 serves as a novel therapeutic target for acute cerebrovascular protection. SIGNIFICANCE STATEMENT Circular RNAs (circRNAs) are involved in the regulation of physiological and pathophysiological processes. However, whether circRNAs are involved in ischemic injury, particularly cerebrovascular disorders, remains largely unknown. Here, we demonstrate a critical role for circular RNA DLGAP4 (circDLGAP4), a novel circular RNA originally identified as a sponge for microRNA-143 (miR-143), in ischemic stroke outcomes. Overexpression of circDLGAP4 significantly attenuated neurological deficits and decreased infarct areas and blood–brain barrier damage in the transient middle cerebral artery occlusion mouse stroke model. To our knowledge, this is the first report describing the efficacy of circRNA injection in an ischemic stroke model. Our investigation suggests that circDLGAP4 may serve as a novel therapeutic target for acute ischemic injury.

Qing Li, Yong Ni, Liren Zhang, Runqiu Jiang et al.

N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC). In this study, specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown HCC cells, HCC organoids, and HCC patient-derived xenograft (PDX) murine models. YTHDF1 expression and hypoxia-induced autophagy were significantly correlated in vitro; significant overexpression of YTHDF1 in HCC tissues was associated with poor prognosis. Multivariate cox regression analysis identified YTHDF1 expression as an independent prognostic factor in patients with HCC. Multiple HCC models confirmed that YTHDF1 deficiency inhibited HCC autophagy, growth, and metastasis. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region under hypoxia. The results of methylated RNA immunoprecipitation sequencing, proteomics, and polysome profiling indicated that YTHDF1 contributed to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modified ATG2A and ATG14 mRNA, thus facilitating autophagy and autophagy-related malignancy of HCC. Taken together, HIF-1α-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner. Our findings suggest that YTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

Aida Shomali, Susmita Das, Namira Arif, Mohammad Sarraf et al.

Flavonoids are characterized as the low molecular weight polyphenolic compounds universally distributed in planta. They are a chemically varied group of secondary metabolites with a broad range of biological activity. The increasing amount of evidence has demonstrated the various physiological functions of flavonoids in stress response. In this paper, we provide a brief introduction to flavonoids’ biochemistry and biosynthesis. Then, we review the recent findings on the alternation of flavonoid content under different stress conditions to come up with an overall picture of the mechanism of involvement of flavonoids in plants’ response to various abiotic stresses. The participation of flavonoids in antioxidant systems, flavonoid-mediated response to different abiotic stresses, the involvement of flavonoids in stress signaling networks, and the physiological response of plants under stress conditions are discussed in this review. Moreover, molecular and genetic approaches to tailoring flavonoid biosynthesis and regulation under abiotic stress are addressed in this review.

Gous Miah, Mohd Y. Rafii, Mohd Razi Ismail, A. B. Puteh et al.

Blast disease caused by the fungal pathogen Magnaporthe oryzae is the most severe diseases of rice. Using classical plant breeding techniques, breeders have developed a number of blast resistant cultivars adapted to different rice growing regions worldwide. However, the rice industry remains threatened by blast disease due to the instability of blast fungus. Recent advances in rice genomics provide additional tools for plant breeders to improve rice production systems that would be environmentally friendly. This article outlines the application of conventional breeding, tissue culture and DNA-based markers that are used for accelerating the development of blast resistant rice cultivars. The best way for controlling the disease is to incorporate both qualitative and quantitative genes in resistant variety. Through conventional and molecular breeding many blast-resistant varieties have been developed. Conventional breeding for disease resistance is tedious, time consuming and mostly dependent on environment as compare to molecular breeding particularly marker assisted selection, which is easier, highly efficient and precise. For effective management of blast disease, breeding work should be focused on utilizing the broad spectrum of resistance genes and pyramiding genes and quantitative trait loci. Marker assisted selection provides potential solution to some of the problems that conventional breeding cannot resolve. In recent years, blast resistant genes have introgressed into Luhui 17, G46B, Zhenshan 97B, Jin 23B, CO39, IR50, Pusa1602 and Pusa1603 lines through marker assisted selection. Introduction of exotic genes for resistance induced the occurrence of new races of blast fungus, therefore breeding work should be concentrated in local resistance genes. This review focuses on the conventional breeding to the latest molecular progress in blast disease resistance in rice. This update information will be helpful guidance for rice breeders to develop durable blast resistant rice variety through marker assisted selection.