Constraint-based probabilistic learning of metabolic pathways from tomato volatiles

Clustering and correlation analysis techniques have become popular tools for the analysis of data produced by metabolomics experiments. The results obtained from these approaches provide an overview of the interactions between objects of interest. Often in these experiments, one is more interested in information about the nature of these relationships, e.g., cause-effect relationships, than in the actual strength of the interactions. Finding such relationships is of crucial importance as most biological processes can only be understood in this way. Bayesian networks allow representation of these cause-effect relationships among variables of interest in terms of whether and how they influence each other given that a third, possibly empty, group of variables is known. This technique also allows the incorporation of prior knowledge as established from the literature or from biologists. The representation as a directed graph of these relationship is highly intuitive and helps to understand these processes. This paper describes how constraint-based Bayesian networks can be applied to metabolomics data and can be used to uncover the important pathways which play a significant role in the ripening of fresh tomatoes. We also show here how this methods of reconstructing pathways is intuitive and performs better than classical techniques. Methods for learning Bayesian network models are powerful tools for the analysis of data of the magnitude as generated by metabolomics experiments. It allows one to model cause-effect relationships and helps in understanding the underlying processes.     

Chemical diversity in the essential oil of Indian valerian (Valeriana jatamansi Jones)

To explore the diversity in the essential oil yield and composition of Valeriana jatamansi Jones (syn. V. wallichii DC) growing wild in Uttarakhand (Western Himalaya), 17 populations were collected from different locations and grown under similar conditions. Comparative results showed considerable variations in the essential oil yield and composition. The essential oil yield varied from 0.21 to 0.46% in the fresh roots and rhizomes of different populations of V. jatamansi. Analysis of the essential oils by GC (RI) and GC/MS and the subsequent classification by principal component analysis (PCA) resulted in six clusters with significant variations in their terpenoid composition. Major components in the essential oils of the different populations were patchouli alcohol (1; 13.4-66.7%), α-bulnesene (3; <0.05-23.5%), α-guaiene (4; 0.2-13.3%), guaiol (5; <0.05-12.2%), seychellene (6; 0.2-9.9%) viridiflorol (<0.05-7.3%), and β-gurjunene (7; 0.0-7.1%). V. jatamansi populations with contents of 1 higher than 60% may be utilized commercially in perfumery.     

S-nitrosylation of FLICE inhibitory protein determines its interaction with RIP1 and activation of NF-κB

Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-κB activation. However, the molecular mechanism that regulates FLIP within this complex is unknown. In this study, we provide new evidence for the regulation of NF-κB by FLIP through S-nitrosylation, which involves covalent modification of the protein’s cysteine thiol by nitric oxide to form S-nitrosothiol. Point mutations of FLIP at cysteine residues 254 and 259 prevent FLIP S-nitrosylation and its ability to activate NF-κB. The mechanism by which FLIP nitrosylation regulates NF-κB activity involves RIP1 binding and redistribution, whereas TRAF2 binding and distribution are unaffected. We further show that FLIP processing and cleavage is dependent on its nitrosylation status. Collectively, our study reveals a novel pathway for FLIP regulation of NF-κB through protein S-nitrosylation, which is a key posttranslational mechanism controlling DR-mediated cell death and survival. Since increased expression of FLIP and nitric oxide are frequently observed in chemotherapy-resistant tumors, S-nitrosylation of FLIP could be a key mechanism of chemoresistance and tumor growth.     

Host plant induced variation in gut bacteria of Helicoverpa armigera

Helicoverpa are important polyphagous agricultural insect pests and they have a worldwide distribution. In this study, we report the bacterial community structure in the midgut of fifth instar larvae of Helicoverpa armigera, a species prevalent in the India, China, South Asia, South East Asia, Southern & Eastern Africa and Australia. Using culturable techniques, we isolated and identified members of Bacillus firmus, Bacillus niabense, Paenibacillus jamilae, Cellulomonas variformis, Acinetobacter schindleri, Micrococcus yunnanesis, Enterobacter sp., and Enterococcus cassiliflavus in insect samples collected from host plants grown in different parts of India. Besides these the presence of Sphingomonas, Ralstonia, Delftia, Paracoccus and Bacteriodetes was determined by culture independent molecular analysis. We found that Enterobacter and Enterococcus were universally present in all our Helicoverpa samples collected from different crops and in different parts of India. The bacterial diversity varied greatly among insects that were from different host plants than those from the same host plant of different locations. This result suggested that the type of host plant greatly influences the midgut bacterial diversity of H. armigera, more than the location of the host plant. On further analyzing the leaf from which the larva was collected, it was found that the H. armigera midgut bacterial community was similar to that of the leaf phyllosphere. This finding indicates that the bacterial flora of the larval midgut is influenced by the leaf surface bacterial community of the crop on which it feeds. Additionally, we found that laboratory made media or the artificial diet is a poor bacterial source for these insects compared to a natural diet of crop plant.     

Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.     

Trimethylamine modulates dauer formation,neurodegeneration, and lifespan through tyra‐3/daf‐11 signaling in Caenorhabditis elegans

In the nematode Caenorhabditis elegans, signals derived from bacteria in the diet, the animal''s major nutrient source, can modulate both behavior and healthspan. Here we describe a dual role for trimethylamine (TMA), a human gut flora metabolite, which acts as a nutrient signal and a neurotoxin. TMA and its associated metabolites are produced by the human gut microbiome and have been suggested to serve as risk biomarkers for diabetes and cardiovascular diseases. We demonstrate that the tyramine receptor TYRA‐3, a conserved G protein‐coupled receptor (GPCR), is required to sense TMA and mediate its responses. TMA activates guanylyl cyclase DAF‐11 signaling through TYRA‐3 in amphid neurons (ASK) and ciliated neurons (BAG) to mediate food‐sensing behavior. Bacterial mutants deficient in TMA production enhance dauer formation, extend lifespan, and are less preferred as a food source. Increased levels of TMA lead to neural damage in models of Parkinson''s disease and shorten lifespan. Our results reveal conserved signaling pathways modulated by TMA in C. elegans that are likely to be relevant for its effects in mammalian systems.     

Marine Group-II archaea dominate particle-attached as well as free-living archaeal assemblages in the surface waters of Kongsfjorden,Svalbard, Arctic Ocean

Antonie van Leeuwenhoek - Marine archaea are a significant component of the global oceanic ecosystems, including the polar oceans. However, only a few attempts have been made to study archaea in...     

Antibody affinity versus dengue morphology influences neutralization

Different strains within a dengue serotype (DENV1-4) can have smooth, or “bumpy” surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes.