MLK3 promotes prooncogenic signaling in hepatocellular carcinoma via TGFß pathway.

Advanced hepatocellular carcinoma (HCC) is a lethal disease, with limited therapeutic options. Mixed Lineage Kinase 3 (MLK3) is a key regulator of liver diseases, although its role in HCC remains unclear. Analysis of TCGA databases suggested elevated MAP3K11 (MLK3 gene) expression, and TMA studies showed higher MLK3 activation in human HCCs. To understand MLK3's role in HCC, we utlized carcinogen-induced HCC model and compared between wild-type and MLK3 knockout (MLK3-/-) mice. Our studies showed that MLK3 kinase activity is upregulated in HCC, and MLK3 deficiency alleviates HCC progression. MLK3 deficiency reduced proliferation in vivo and MLK3 inhibition reduced proliferation and colony formation in vitro. To obtain further insight into the mechanism and identify newer targets mediating MLK3-induced HCCs, RNA-sequencing analysis was performed. These showed that MLK3 deficiency modulates various gene signatures, including EMT, and reduces TGFB1&2 expressions. HCC cells overexpressing MLK3 promoted EMT via autocrine TGFß signaling. Moreover, MLK3 deficiency attenuated activated hepatic stellate cell (HSC) signature, which is increased in wild-type. Interestingly, MLK3 promotes HSC activation via paracrine TGFß signaling. These findings reveal TGFß playing a key role at different steps of HCC, downstream of MLK3, implying MLK3-TGFß axis to be an ideal drug target for advanced HCC management.

Prospects of microgreens as budding living functional food: Breeding and biofortification through OMICS and other approaches for nutritional security.

Nutrient deficiency has resulted in impaired growth and development of the population globally. Microgreens are considered immature greens (required light for photosynthesis and growing medium) and developed from the seeds of vegetables, legumes, herbs, and cereals. These are considered "living superfood/functional food" due to the presence of chlorophyll, beta carotene, lutein, and minerals like magnesium (Mg), Potassium (K), Phosphorus (P), and Calcium (Ca). Microgreens are rich at the nutritional level and contain several phytoactive compounds (carotenoids, phenols, glucosinolates, polysterols) that are helpful for human health on Earth and in space due to their anti-microbial, anti-inflammatory, antioxidant, and anti-carcinogenic properties. Microgreens can be used as plant-based nutritive vegetarian foods that will be fruitful as a nourishing constituent in the food industryfor garnish purposes, complement flavor, texture, and color to salads, soups, flat-breads, pizzas, and sandwiches (substitute to lettuce in tacos, sandwich, burger). Good handling practices may enhance microgreens'stability, storage, and shelf-life under appropriate conditions, including light, temperature, nutrients, humidity, and substrate. Moreover, the substrate may be a nutritive liquid solution (hydroponic system) or solid medium (coco peat, coconut fiber, coir dust and husks, sand, vermicompost, sugarcane filter cake, etc.) based on a variety of microgreens. However integrated multiomics approaches alongwith nutriomics and foodomics may be explored and utilized to identify and breed most potential microgreen genotypes, biofortify including increasing the nutritional content (macro-elements:K, Ca and Mg; oligo-elements: Fe and Zn and antioxidant activity) and microgreens related other traits viz., fast growth, good nutritional values, high germination percentage, and appropriate shelf-life through the implementation of integrated approaches includes genomics, transcriptomics, sequencing-based approaches, molecular breeding, machine learning, nanoparticles, and seed priming strategiesetc.

Proteo-Molecular Investigation of Cultivated Rice, Wild Rice, and Barley Provides Clues of Defense Responses against Rhizoctonia solani Infection.

Rhizoctonia solani is a soil-borne fungus causing sheath blight disease in cereal crops including rice. Genetic resistance to sheath blight disease in cereal crops is not well understood in most of the host(s). Aside from this, a comparative study on the different hosts at the biochemical and proteomic level upon R. solani infection was not reported earlier. Here, we performed proteomic based analysis and studied defense pathways among cultivated rice (cv. Pusa Basmati-1), wild rice accession (Oryza grandiglumis), and barley (cv. NDB-1445) after inoculation with R. solani. Increased levels of phenol, peroxidase, and ß-1, 3-glucanase were observed in infected tissue as compared to the control in all of the hosts. Wild rice accession O. grandiglumis showed a higher level of biochemical signals than barley cv. NDB 1445 and cultivated rice cv. Pusa Basmati-1. Using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS), differently expressed proteins were also studied in control and after inoculation with R. solani. Wild rice accession O. grandiglumis induced a cysteine protease inhibitor and zinc finger proteins, which have defense functions and resistance against fungal pathogens. On the other hand, barley cv. NDB-1445 and cultivated rice cv. Pusa Basmati-1 mainly induce energy metabolism-related proteins/signals after inoculation with R. solani in comparison to wild rice accession O. grandiglumis. The present comprehensive study of R. solani interaction using three hosts, namely, Pusa Basmati-1 (cultivated rice), O. grandiglumis (wild rice), and NDB-1445 (barley) would interpret wider possibilities in the dissection of the protein(s) induced during the infection process. These proteins may further be correlated to the gene(s) and other related molecular tools that will help for the marker-assisted breeding and/or gene editing for this distressing disease among the major cereal crops.

Envisioning the immune interactome in Arabidopsis.

During plant-pathogen interaction, immune targets were regulated by protein-protein interaction events such as ligand-receptor/co-receptor, kinase-substrate, protein sequestration, activation or repression via post-translational modification and homo/oligo/hetro-dimerisation of proteins. A judicious use of molecular machinery requires coordinated protein interaction among defence components. Immune signalling in Arabidopsis can be broadly represented in successive or simultaneous steps; pathogen recognition at cell surface, Ca2+ and reactive oxygen species signalling, MAPK signalling, post-translational modification, transcriptional regulation and phyto-hormone signalling. Proteome wide interaction studies have shown the existence of interaction hubs associated with physiological function. So far, a number of protein interaction events regulating immune targets have been identified, but their understanding in an interactome view is lacking. We focussed specifically on the integration of protein interaction signalling in context to plant-pathogenesis and identified the key targets. The present review focuses towards a comprehensive view of the plant immune interactome including signal perception, progression, integration and physiological response during plant pathogen interaction.

Genetic diversity and population structure analysis of Asian and African aromatic rice (Oryza sativa L.) genotypes.

Rice germplasms collected from different regions could be used as valuable resources for the future breeding programme. For the utilization of such collections, knowledge about the level and distribution of genetic diversity among these collections will facilitate the breeder. In this study, we report the phenotypic correlation, biochemical quality parameters and population genetic analysis of 35 rice accessions including 34 aromatic rice from different countries and a nonaromatic, Nagina 22, a well-known drought resistance variety. Further biochemical quality analysis, gel consistency test, molecular diversity analysis with 55 simple sequence repeat markers, population structure analysis and pair wise FST analysis were also conducted to assess the genetic diversity. The collected rice genotypes showed significant variability in different agronomic traits, i.e. spikelet per panicle, branches per panicle etc. Results obtained from the above tests demonstrated the importance of regional genetic studies for understanding the diversification of aromatic rice in Asian and African rice.

High-density equation of state for a two-dimensional Lennard-Jones solid.

We present a new equation of state for a two-dimensional Lennard-Jones (2D LJ-EOS) solid at high densities, ρ2D*≥0.9. The new 2D LJ-EOS is of analytic form, consisting of a zero-temperature contribution and vibrational contributions up to and including the second anharmonic term. A detailed analysis of all contributing terms is performed. Comparisons between the 2D LJ-EOS and Monte Carlo simulation results show that the 2D LJ-EOS is very accurate over a wide range of temperatures in the high-density region. A criterion to find the temperature range over which the 2D LJ-EOS is applicable at a certain density is derived. We also demonstrate an application of the equation of state to predict an effective tangential pressure for the adsorbed contact layer near the wall in a slit-pore system. Tangential pressures predicted by this "2D-route" are found to be in qualitative agreement with those found by the more traditional virial route of Irving and Kirkwood.

The Nitric Oxide Dimer Reaction in Carbon Nanopores.

When confined within nanoporous carbons (activated carbon fibers or carbon nanotubes) having pore widths of about 1 nm, nitric oxide is found to react completely to form the dimer, (NO)2, even though almost no dimers are present in the bulk gas phase in equilibrium with the pore phase. Moreover, the yield of dimer is unchanged upon varying the temperature over the range studied in the experiments. Earlier molecular simulation studies showed a significant increase in dimer formation in carbon nanopores, but the dimer yield was considerably less than that found in the experiments, and decreased rapidly as the temperature was raised. Here, we report an ab initio and molecular simulation study of this reaction in both slit-shaped pores and single-walled carbon nanotubes. The ab initio calculations show that the nitric oxide dimer forms a weak chemical bond with the carbon, and the bonding energy is more than 20 times stronger than the van der Waals energy assumed in the previous studies. When this is accounted for, the predicted dimer yield is in good agreement with the experimental values, as is its temperature dependence. We also report results for the pressure tensor components for this confined reactive mixture. Local tangential pressures near the pore walls are as high as millions of bar, reflecting the strong nanoscale forces.

Pressure Enhancement in Confined Fluids: Effect of Molecular Shape and Fluid-Wall Interactions.

Recently, several experimental and simulation studies have found that phenomena that normally occur at extremely high pressures in a bulk phase can occur in nanophases confined within porous materials at much lower bulk phase pressures, thus providing an alternative route to study high-pressure phenomena. In this work, we examine the effect on the tangential pressure of varying the molecular shape, strength of the fluid-wall interactions, and pore width, for carbon slit-shaped pores. We find that, for multisite molecules, the presence of additional rotational degrees of freedom leads to unique changes in the shape of the tangential pressure profile, especially in larger pores. We show that, due to the direct relationship between the molecular density and the fluid-wall interactions, the latter have a large impact on the pressure tensor. The molecular shape and pore size have a notable impact on the layering of molecules in the pore, greatly influencing both the shape and scale of the tangential pressure profile.

Computationally Mapping pKa Shifts Due to the Presence of a Polyelectrolyte Chain around Whey Proteins.

Experimental studies have shown the formation of soluble complexes in the pure repulsive Coulombic regime even when the net charges of the protein and the polyelectrolyte have the same sign ( De Kruif et al. Curr. Opin. Colloid Interface Sci. 2004 , 9 , 340 ; De Vries et al. J. Chem. Phys. 2003 , 118 , 4649 ; Grymonpre et al. Biomacromolecules 2001 , 2 , 422 ; Hattori et al. Langmuir 2000 , 16 , 9738 ). This attractive phenomenon has often been described as "complexation on the wrong side of pI". While one theory assumes the existence of "charged patches" on the protein surface from ion-dipole interactions, thus allowing a polyelectrolyte to bind to an oppositely heterogeneous charged protein region, another theoretical view considers the induced-charge interactions to be the dominant factor in these complexations. This charge regulation mechanism can be described by proton fluctuations resulting from mutual rearrangements of the distributions of the charged groups, due to perturbations of the acid-base equilibrium. Using constant-pH Monte Carlo simulations and several quantitative and visual analysis tools, we investigate the significance of each of these interactions for two whey proteins, α-lactalbumin (α-LA) and lysozyme (LYZ). Through physical chemistry parameters, free energies of interactions, and the mapping of amino acid pKa shifts and polyelectrolyte trajectories, we show the charge regulation mechanism to be the most important contributor in protein-polyelectrolyte complexation regardless of pH, dipole moment, and protein capacitance in a low salt regime.

Neurilemmoma of Retromolar Region in the Oral Cavity.

Neurilemmoma also known as schwannoma is benign nerve sheath tumor rarely occurring in the oral cavity. Only 1% of all extracranial schwannomas show that intraoral occurrence with tongue is the commonest site and retromolar region is the least common site. It presents as encapsulated, slow growing, solitary, smooth-surfaced, usually asymptomatic tumor. We report a case of 70-year-old male with well-defined mass on left retromolar region which was painless and slow growing. Diagnosis is made by histological examination and immunohistochemistry analysis to confirm the neural tissue origin of the lesion. The treatment is complete surgical excision of the lesion without recurrence.

Serous adenofibroma of ovary: An eccentric presentation.

Surface epithelial tumors of the ovary comprise over fourth of the ovarian neoplasms. Serous adenofibromas are lesser known variants of serous surface epithelial tumors. Though these tumors have a benign fate, yet they can be misinterpreted clinically and radiologically due to their borderline or malignant gross morphological as well as clinical presentation. The cell of origin of surface epithelial tumors of the ovary is histological debated; however, it is now ascertained to have origins from the ovarian cortical and surface lining. Adenofibromas are known to progress in an indolent manner with metachronous behavior for years. The present case is of an ovarian serous adenofibroma in a young female masquerading as peritoneal carcinomatosis.

Concentrations of Volatile Organic Compound (Styrene) in an Industrial Area of Agra, India.

Volatile organic compounds (VOCs) are major group of air pollutants which play critical role in atmospheric chemistry. These contribute to toxic oxidants which are harmful to ecosystem, human health and atmosphere. A sampling program was conducted to determine the ambient VOC levels in the city of Agra (Uttar Pradesh), India during day time and overnight in 2010. Sampling sites were selected at three industrial area of Agra. Samples were analyzed for styrene. Concentration of Styrene was determined at different sampling points in the air of Agra in order to investigate their spatial distributions. The vertical motions of air masses also had a large impact on the variations of the level of VOC. The inter-species ratios exhibit clear seasonal variation indicating deferential reactivity of the VOCs species in different seasons.

Protective effects of selenium, calcium, and magnesium against arsenic-induced oxidative stress in male rats.

Inorganic arsenic is a potent carcinogen and environmental pollutant. More than one hundred million people are reported to be exposed to elevated concentrations of arsenic mainly via drinking water. Essential trace elements can affect toxicity of metals by interacting with metals at the primary site of action and can also modify the body's response to toxic metals by altering their metabolism and transport. This study investigates the effects of concomitant administration of selenium, magnesium, and calcium with arsenic on blood biochemistry and oxidative stress. Selenium was the most effective in reducing arsenic-induced inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity and liver oxidative stress. Calcium and magnesium also showed favourable effects on haematological and other biochemical parameters. Because selenium was the most effective, it should be added to chelation therapy to achieve the best protective effects against arsenic poisoning in humans.

Pentavalent arsenate reductase activity in cytosolic fractions of Pseudomonas sp., isolated from arsenic-contaminated sites of Tezpur, Assam.

Pentavalent arsenate reductase activity was localized and characterized in vitro in the cytosolic fraction of a newly isolated bacterial strain from arsenic-contaminated sites. The bacterium was gram negative, rod-shaped, nonmotile, non-spore-forming, and noncapsulated, and the strain was identified as Pseudomonas sp. DRBS1 following biochemical and molecular approaches. The strain Pseudomonas sp. DRBS1 exhibited enzymatic machinery for reduction of arsenate(V) to arsenite(III). The suspended culture of the bacterium reduced more than 97% of As(V) (40-100 mM) to As(III) in 48 h. The growth rate and total cellular yield decreased in the presence of higher concentration of arsenate. The suspended culture repeatedly reduced 10 mM As(V) within 5 h up to five consecutive inputs. The cell-free extracts reduced 86% of 100 microM As(V) in 40 min. The specific activity of arsenate reductase enzyme in the presence of 100 microM arsenate is 6.68 micromol/min per milligram protein. The arsenate reductase activity is maximum at 30 degrees C and at pH 5.2. The arsenate reductase activity increased in the presence of electron donors like citrate, glucose, and galactose and metal ions like Cd(+2), Cu(+2), Ca(+2), and Fe(+2). Selenate as an electron donor also supports the growth of strain DRBS1 and significantly increased the arsenate reduction.

Reserpine can confer stress tolerance and lifespan extension in the nematode C. elegans.

Though the lifespan extension mechanism is partly understood from C. elegans to mice, a viable pharmacological intervention is not yet feasible. Here, we report that reserpine largely known as an antipsychotic-antihypertensive drug, can extend C. elegans lifespan. Chronic reserpine treatment from embryo stage or young adults extends the C. elegans lifespan robustly at 25 degrees C. Most importantly, the reserpine treated long lived worms are active (locomotion and pharyngeal pumping) for a long time thereby conferring high quality throughout life. Reserpine mediated lifespan extension is independent of the daf-16 pathway and partly requires serotonin. Reserpine treatment makes the worms highly thermotolerant. Thus, in addition to its known function, reserpine is able to provide stress tolerance and lifespan extension in C. elegans.