Samanta S. Khora

Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer.

The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance.

An overview on the origin and production of tetrodotoxin, a potent neurotoxin.

Tetrodotoxin (TTX) is a deadly neurotoxin which selectively inhibits Na+ activation mechanism of nerve impulse, without affecting the permeability of K+ ions. Because of this sodium channel blocking action, it is majorly being studied for biomedical applications. TTX is present in taxonomically diverse groups of animals inhabiting terrestrial, marine, fresh water and brackish water environments, still its origin remains unclear. The extensive study of the toxin has revealed a few possibilities of its origin. This review reports on the aspects of the origin of TTX, where the primary focus is on its exogenous origin. The significance of bacterial, cellular and environmental factors in its biogenesis and accumulation is also discussed. The possible facets for engineering the bacterial genomics to modulate the gene expression for TTX production are also outlined.

Seafood-Associated Shellfish Allergy: A Comprehensive Review

ABSTRACT Shellfish are diverse, serve as main constituents of seafood, and are extensively consumed globally because of their nutritional values. Consequently, increase in reports of IgE-mediated seafood allergy is particularly food associated to shellfish. Seafood-associated shellfish consists of crustaceans (decapods, stomatopods, barnacles, and euphausiids) and molluskans (gastropods, bivalves, and cephalopods) and its products can start from mild local symptoms and lead to severe systemic anaphylactic reactions through ingestion, inhalation, or contact like most other food allergens. Globally, the most commonly causative shellfish are shrimps, crabs, lobsters, clams, oysters, and mussels. The prevalence of shellfish allergy is estimated to be 0.5–2.5% of the general population but higher in coastal Asian countries where shellfish constitute a large proportion of the diet. Diversity in allergens such as tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic binding protein are from crustaceans whereas tropomyosin, paramyosin, troponin, actine, amylase, and hemoyanin are reported from molluskans shellfish. Tropomyosin is the major allergen and is responsible for cross-reactivity between shellfish and other invertebrates, within crustaceans, within molluskans, between crustaceans vs. molluskans as well as between shellfish and fish. Allergenicity diagnosis requires clinical history, in vivo skin prick testing, in vitro quantification of IgE, immunoCAP, and confirmation by oral challenge testing unless the reactions borne by it are life-threatening. This comprehensive review provides the update and new findings in the area of shellfish allergy including demographic, diversity of allergens, allergenicity, their cross-reactivity, and innovative molecular genetics approaches in diagnosing and managing this life-threatening as well as life-long disease.

Molecular, Physiological and Phenotypic Characterization of Paracoccus denitrificans ATCC 19367 Mutant Strain P-87 Producing Improved Coenzyme Q10.

Coenzyme Q10 (CoQ10) is a blockbuster nutraceutical molecule which is often used as an oral supplement in the supportive therapy for cardiovascular diseases, cancer and neurodegenerative diseases. It is commercially produced by fermentation process, hence constructing the high yielding CoQ10 producing strains is a pre-requisite for cost effective production. Paracoccus denitrificans ATCC 19367, a biochemically versatile organism was selected to carry out the studies on CoQ10 yield improvement. The wild type strain was subjected to iterative rounds of mutagenesis using gamma rays and NTG, followed by selection on various inhibitors like CoQ10 structural analogues and antibiotics. The screening of mutants were carried out using cane molasses based optimized medium with feeding strategies at shake flask level. In the course of study, the mutant P-87 having marked resistance to gentamicin showed 1.25-fold improvements in specific CoQ10 content which was highest among all tested mutant strains. P-87 was phenotypically differentiated from the wild type strain on the basis of carbohydrate assimilation and FAME profile. Molecular differentiation technique based on AFLP profile showed intra specific polymorphism between wild type strain and P-87. This study demonstrated the beneficial outcome of induced mutations leading to gentamicin resistance for improvement of CoQ10 production in P. denitrificans mutant strain P-87. To investigate the cause of gentamicin resistance, rpIF gene from P-87 and wild type was sequenced. No mutations were detected on the rpIF partial sequence of P-87; hence gentamicin resistance in P-87 could not be conferred with rpIF gene. However, detecting the mutations responsible for gentamicin resistance in P-87 and correlating its role in CoQ10 overproduction is essential. Although only 1.25-fold improvement in specific CoQ10 content was achieved through mutant P-87, this mutant showed very interesting characteristic, differentiating it from its wild type parent strain P. denitrificans ATCC 19367, which are presented in this paper.

Risk From Viral Pathogens in Seafood

Abstract Viruses are stable in the environment and transmission occurs through ingestion of contaminated food or water or contact with a contaminated surface. Viral disease transmission to humans via consumption of seafood is described. Out of three types of illnesses associated with ingestion of seafood (i.e., allergic, toxic, and infectious), this review focuses on infectious viral illnesses. Seafood includes finfish, as well as shellfish, mostly from seawater. Viruses could be transmitted through shellfish that are at risk from contamination. The high risk results from two vectors: shellfish are filter feeders and many are ingested raw or in undercooked form. The risk is increasing because many species are cultivated near coastal waters, where contamination with human sewage, which may contain high levels of viral particles, can easily occur. Ingestion of pathogenic viruses through seafood can cause gastroenteritis, hepatitis, polio, and so on. Caliciviruses, such as Norovirus, have been recognized as the major cause of seafood-associated gastroenteritis. Human enteric viruses appear as the main diseases of shellfish origin and are principally responsible for non-A, non-B, enterically transmitted acute viral hepatitis in endemic regions. These are considered a major global health problem, causing significant morbidity worldwide.

Occurrence of Natural Toxins in Seafood

Abstract The possible presence of natural toxins in marine organisms has been known for centuries. At present, the effect of seafood toxins on the human health is of international concern as seafood toxicity is increasing on the global scale. Due to the desirable healthy nutrition that they provide and the novel bioactive compounds discovered in them, seafood has increased in popular demand, which has led to their expansion into newer and remote places. Seafood toxins have also gained attention as they make excellent tools to understand how biological systems function. With the increase of aquaculture/mariculture for seafood production, incidents involving their toxic trigger are also increasing. Further, the changing global environmental condition increases the chances of occurrence of harmful algal blooms. Many countries have set appropriate regulatory measures to cope with the economic extrication caused by rising toxic incidents. We discuss here the recent developments in the toxicology, pharmacology, detection, and regulations of various seafood toxins. The anticipated genesis of these toxins and the effect of climate change on the toxicity of seafood are also discussed to gather the knowledge required in the wake of the growing public health concerns.

Marine Dinoflagellates-Associated Human Poisoning

Seafood poisoning in humans is caused by consumption of toxin-containing seafood that is contaminated with marine dinoflagellates. This has been a concern for many years. There are a number of dinoflagellate species that produce strong neurotoxins, which are often associated with the phenomenon called red tide. Outbreaks of red tide are caused by harmful algal blooms (HAB s). HABs are not a new phenomenon, with written references dating back to biblical times. The most common type of HAB is referred to as a red tide because the bloom discolors the water, making it appear red. Humans eating seafood from infested areas during dinoflagellate bloom can become poisoned. With respect to the contaminants of toxic dinoflagellates in seafood, there are two main types of poisoning in humans. The terms fish and shellfish are associated with these illnesses because the toxins are concentrated in fish and shellfish that ingest the harmful dinoflagellates. According to the species of toxigenic dinoflagellates the poisoning syndromes have been given the names paralytic (PSP ), diarrhetic (DSP ), neurotoxic (NSP ), and azaspiracid shellfish poisoning (AZP ). Another human illness, ciguatera fish poisoning (CFP ) is caused by the ciguatoxins produced by dinoflagellates that attach to surfaces in many coral reef communities [1]. Besides these well-known poisoning types, several new poisoning syndromes resulting from newly appearing dinoflagellate toxins, such as yessotoxin (YTX ) and palytoxin (PTX ), have been reported and characterized recently, and this has increased global public concerns regarding dinoflagellates associated with humans poisoning.