Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis

Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis

Neuronal modulation of the immune response

The nervous and immune systems respond in distinct manners to diverse signals. Crosstalk between these systems has been known: microbial infections can result in infl ammation of nervous tissue and lead to conditions such as encephalitis and meningitis. Also, the immune response causes damage to nervous tissue during autoimmune diseases: extensive axonal damage is observed in multiple sclerosis due to demyelination and infi ltration by leukocytes (Mix et al 2007). To study the roles of immune molecules, researchers often use a mouse model of multiple sclerosis known as experimental autoimmune encephalomyelitis in which disease is induced upon injection of myelin oligodendrocyte glycoprotein in Complete Freund’s adjuvant. Here, infl ammatory cytokines, e.g. Interferon-γ (Tran et al 2000) and Tumour necrosis Factor-α (Liu et al 1998), or Toll-like receptors (TLR)-4 or TLR-9, which detect microbial constituents (Marta et al 2008), play regulatory roles to reduce disease severity. In cases like these, it is not too surprising that infl ammatory immune molecules affect nervous tissues. On the other hand, proper understanding is lacking on how neuronal products modulate immune reactions, especially with respect to anti-pathogen responses

Importance of non-conserved distal carboxyl terminal amino acids in two peptidases belonging to the M1 family: Thermoplasma acidophilum Tricorn interacting factor F2 and Escherichia coli Peptidase N

Enzymes belonging to the M1 family play important cellular roles and the key amino acids (aa) in the catalytic domain are conserved. However, C-terminal domain aa are highly variable and demonstrate distinct differences in organization. To address a functional role for the C-terminal domain, progressive deletions were generated in Tricorn interacting factor F2 from Thermoplasma acidophilum (F2) and Peptidase N from Escherichia coli (PepN). Catalytic activity was partially reduced in PepN lacking 4 C-terminal residues (PepNΔC4) whereas it was greatly reduced in F2 lacking 10 C-terminal residues (F2ΔC10) or PepN lacking eleven C-terminal residues (PepNΔC11). Notably, expression of PepNΔC4, but not PepNΔC11, in E. coliΔpepN increased its ability to resist nutritional and high temperature stress, demonstrating physiological significance. Purified C-terminal deleted proteins demonstrated greater sensitivity to trypsin and bound stronger to 8-amino 1-napthalene sulphonic acid (ANS), revealing greater numbers of surface exposed hydrophobic aa. Also, F2 or PepN containing large aa deletions in the C-termini, but not smaller deletions, were present in high amounts in the insoluble fraction of cell extracts probably due to reduced protein solubility. Modeling studies, using the crystal structure of E. coli PepN, demonstrated increase in hydrophobic surface area and change in accessibility of several aa from buried to exposed upon deletion of C-terminal aa. Together, these studies revealed that non-conserved distal C-terminal aa repress the surface exposure of apolar aa, enhance protein solubility, and catalytic activity in two soluble and distinct members of the M1 family

Importance of non-conserved distal carboxyl terminal amino acids in two peptidases belonging to the M1 family: thermoplasma acidophilum tricorn interacting factor F2 and Escherichia coli peptidase N

Enzymes belonging to the M1 family play important cellular roles and the key amino acids (aa) in the catalytic domain are conserved. However, C-terminal domain aa are highly variable and demonstrate distinct differences in organization. To address a functional role for the C-terminal domain, progressive deletions were generated in Tricorn interacting factor F2 from Thermoplasma acidophilum (F2) and Peptidase N from Escherichia coli (PepN). Catalytic activity was partially reduced in PepN lacking 4 C-terminal residues (PepNΔC4) whereas it was greatly reduced in F2 lacking 10 C-terminal residues (F2ΔC10) or PepN lacking eleven C-terminal residues (PepNΔC11). Notably, expression of PepNΔC4, but not PepNΔC11, in E. coliΔpepN increased its ability to resist nutritional and high temperature stress, demonstrating physiological significance. Purified C-terminal deleted proteins demonstrated greater sensitivity to trypsin and bound stronger to 8-amino 1-napthalene sulphonic acid (ANS), revealing greater numbers of surface exposed hydrophobic aa. Also, F2 or PepN containing large aa deletions in the C-termini, but not smaller deletions, were present in high amounts in the insoluble fraction of cell extracts probably due to reduced protein solubility. Modeling studies, using the crystal structure of E. coli PepN, demonstrated increase in hydrophobic surface area and change in accessibility of several aa from buried to exposed upon deletion of C-terminal aa. Together, these studies revealed that non-conserved distal C-terminal aa repress the surface exposure of apolar aa, enhance protein solubility, and catalytic activity in two soluble and distinct members of the M1 family

Protein tagging, destruction and infection

Cells possess protein quality control mechanisms to maintain proper cellular homeostasis. In eukaryotes, the roles of the ubiquitination and proteasome-mediated degradation of cellular proteins is well established. Recent studies have elucidated protein tagging mechanisms in prokaryotes, involving transfer messenger RNA (tmRNA) and pupylation. In this review, newer insights and bioinformatics analysis of two distinct bacterial protein tagging machineries are discussed. The machinery for tmRNAmediated tagging is present in several eubacterial representatives, e.g. Escherichia coli, Mycobacterium tuberculosis, Bacillus subtilis etc., but not in two archaeal representatives, such as Thermoplasma acidophilum and Sulfolobus solfataricus. On the other hand, the machinery involving tagging with the prokaryotic ubiquitin-like protein (Pup) is absent in most bacteria but is encoded in some eubacterial representatives, e.g. Mycobacterium tuberculosis and Mycobacterium leprae. Furthermore, molecular details on the relationship between protein tagging and enzymes involved in protein degradation in bacteria during infection are emerging. Several pathogenic bacteria that do not express the major ATP-dependent proteases, Lon and Caseinolytic protease (ClpP), are avirulent. Also, some ATP-independent peptidases, such as PepA and PepN, modulate the infection process. The roles of bacterial proteins involved in tagging and degradation during infection are discussed. These aspects add a new dimension to better understanding of the peculiarities of host-pathogen interactions

DESIGN OF SOLAR DRYER FOR RICE AT KARJAT, RAIGAD, MAHARASHTRA

This paper deals with current practices of drying agricultural products in most of developing nations like India. It also try to coin the concept of utilization of Solar dryer at farm side. In a developing country like India, having the second largest population and agriculture as the source of income to nearly 60 % of the total population, post-harvest and storage loss is a major quandary, which needs to be addressed in due diligence. Many food preservation techniques like cold storage, drying, etc., have been evolved out over the years to tackle the above losses. The major constraint is that almost all the technologies are utilizing fossil fuel resources, which are depleting very fast and wise use of these precious resources are preferred for longterm energy sustainability. Therefore, sustainable methods for food preservation are the need of the hour. Solar drying is one of the best choices in this context. The effect of temperature to moisture contents against time and rate of drying are studied & discussed in this paper

Fruit based probiotic functional beverages: A review

Probiotics are living bacteria and yeasts that nourish the human body, particularly the digestive system. Fruit-based beverages are an excellent vehicle for delivering probiotics to the body since they are frequently taken in large quantities and include a number of nutrients that promote the growth of these beneficial microbes. When adding probiotics to a fruit-based drink, the probiotics must survive and remain viable in the drink until ingested. This may be accomplished by choosing probiotic strains that are known to be substantial, as well as keeping the drink at the appropriate temperatures. It's also worth noting that not all probiotics have the same characteristics, and different strains of bacteria and yeast may provide varied health advantages. Fruit-based probiotic drinks, fermented vegetables like sauerkraut and kimchi, kombucha, water kefir, and non-dairy yogurt prepared from plant-based milk are all prominent non-dairy sources of probiotics. These commodities are high in beneficial bacteria and can be used in a balanced diet to help with digestion. Individuals who are lactose intolerant or follow a vegan diet prefer these non-dairy probiotic alternatives. The purpose of this review to comprehensively cover the mechanism of fruit-based probiotics and sum-up the recent advances fruit-based probiotic beverages and value-added products from these probiotics. It covers the notion of probiotics, fruits as prebiotics, the comparative fermentation mechanism of dairy and non-dairy probiotics, and the physiochemical and sensory alterations that occur following fermentation

Catalytic activity of Peptidase N is required for adaptation of Escherichia coli to nutritional downshift and high temperature stress

Peptidase N (PepN), the sole M1 family member in Escherichia coli, displays broad substrate specificity and modulates stress responses: it lowers resistance to sodium salicylate (NaSal)-induced stress but is required during nutritional downshift and high temperature (NDHT) stress. The expression of PepN does not significantly change during different growth phases in LB or NaSal-induced stress; however, PepN amounts are lower during NDHT stress. To gain mechanistic insights on the roles of catalytic activity of PepN in modulating these two stress responses, alanine mutants of PepN replacing E264 (GAMEN motif) and E298 (HEXXH motif) were generated. There are no major structural changes between purified wild type (WT) and mutant proteins, which are catalytically inactive. Importantly, growth profiles of Delta pepN upon expression of WT or mutant proteins demonstrated the importance of catalytic activity during NDHT but not NaSal-induced stress. Further fluorescamine reactivity studies demonstrated that the catalytic activity of PepN is required to generate higher intracellular amounts of free N-terminal amino acids; consequently, the lower growth of Delta pepN during NDHT stress increases with high amounts of casamino acids. Together, this study sheds insights on the expression and functional roles of the catalytic activity of PepN during adaptation to NDHT stress. (C) 2012 Elsevier GmbH. All rights reserved

Bile Acids Activate YAP to Promote Liver Carcinogenesis

Elevated bile acid levels increase hepatocellular carcinoma by unknown mechanisms. Here, we show that mice with a severe defect in bile acid homeostasis due to the loss of the nuclear receptors FXR and SHP have enlarged livers, progenitor cell proliferation, and Yes-associated protein (YAP) activation and develop spontaneous liver tumorigenesis. This phenotype mirrors mice with loss of hippo kinases or overexpression of their downstream target, YAP. Bile acids act as upstream regulators of YAP via a pathway dependent on the induction of the scaffold protein IQGAP1. Patients with diverse biliary dysfunctions exhibit enhanced IQGAP1 and nuclear YAP expression. Our findings reveal an unexpected mechanism for bile acid regulation of liver growth and tumorigenesis via the Hippo pathway