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Bio-nanotechnology offers eco-friendly processes for the synthesis of stable nanoparticles (NPs). We hypothesized that microorganisms isolated from the root nodules of leguminous plants would biosynthesize silver (Ag) bio-nanoparticles. Clover root nodules enriched with nutrient broth (NB) produced four distinct colonies on NA plates. Microbial colonies were purified by repeated streaking and designated as SS6, SS7, SS8, and SS9 for identification using 16S rRNA sequencing. Four species of Pseudomonas were identified with a similarity score of over 99% using the EZ Taxon search engine, and tested for extracellular biosynthesis of AgNPs. Microorganism Pseudomonas taiwanensis-SS8 with alkaliphilic growth characteristics reduced the AgNO3 solution into AgNPs in the shortest time period. AgNPs were characterized using UV-Vis spectrophotometry and electron and transmission electron microscopy. A number of physical (i.e., temperature and time) and chemical (i.e., pH and growth media) parameters were optimized. An efficient polydispersal biosynthesis of AgNPs at pH 8–9 after 48 hrs in NB growth medium was observed. In addition, the AgNPs showed antimicrobial properties against 16 commonly occurring pathogenic microorganisms.

The synthesis of furano-rotenoid, pongarotene, by oxidative 1,2-aryl rearrangement of the sprirochromanone (11) using thallium(III) p-tosylate as key step has been described. Pongarotene (12) structure was confirmed by 2D NMR, HRMS and finally by X-ray crystallography. The sprirochromanones were synthesized by radical cyclization of chromone derivative (10). This methodology will be useful for the synthesis of naturally occurring rotenoids.

The emergence of multidrug-resistant (MDR) bacteria threatens humans in various health sectors, including medical devices. Since formal classifications for medical device sterilization and disinfection were established in the 1970's, microbial adaptation under adverse environmental conditions has evolved rapidly. MDR microbial biofilms that adhere to medical devices and recurrently infect patients pose a significant threat in hospitals. Therefore, it is essential to mitigate the risk associated with MDR outbreaks by establishing novel recommendations for medical device sterilization, in a world of MDR. MDR pathogens typically thrive on devices with flexible accessories, which are easily contaminated with biofilms due to previous patient use and faulty sterilization or reprocessing procedures. To prevent danger to immunocompromised individuals, there is a need to regulate the classification of reprocessed medical device sterilization. This article aims to assess the risks of improper sterilization of medical devices in the era of MDR when sterilization procedures for critical medical devices are not followed to standard. Further, we discuss key regulatory recommendations for consistent sterilization of critical medical devices in contrast to the risks of disinfection reusable medical devices.

Antibiotics are routinely used in intensive animal agriculture operations collectively known as Concentrated Animal Feed Operations (CAFO) which include dairy, poultry and swine farms. Wastewater generated by CAFOs often contains low levels of antibiotics and is typically managed in an anaerobic lagoon. The objective of this research is to investigate the uptake and fate of aqueous sulfamethazine (SMN) antibiotic by alfalfa ( Medicago sativa ) grass grown under hydroponic conditions. Uptake studies were conducted using hydroponically grown alfalfa in a commercially available nutrient solution supplemented with 10 mg/L of SMN antibiotic. Analysis of alfalfa sap, root zone, middle one-third, and top portion of the foliage showed varying uptake rate and translocation of SMN. The highest average amount of SMN (8.58 μg/kg) was detected in the root zone, followed by the top portion (1.89 μg/kg), middle one-third (1.30 μg/kg), and sap (0.38 μg/kg) samples, indicating a clear distribution of SMN within the sampled regions. The ultraviolet (UV) spectra of parent SMN and translocated SMN identified in different parts of the plant present the possibility of metabolization during the uptake process. Uptake of SMN using alfalfa grown under hydroponic conditions has potential as a promising remediation technology for removal of similar antibiotics from wastewater lagoons.

Bio-nanotechnology offers eco-friendly processes for the synthesis of stable nanoparticles (NPs). We hypothesized that microorganisms isolated from the root nodules of leguminous plants would biosynthesize silver (Ag) bio-nanoparticles. Clover root nodules enriched with nutrient broth (NB) produced four distinct colonies on NA plates. Microbial colonies were purified by repeated streaking and designated as SS6, SS7, SS8, and SS9 for identification using 16S rRNA sequencing. Four species of

As food safety advances, there is a great need to maintain, distribute, and provide high-quality food to a much broader consumer base. There is also an ever-growing "arms race" between pathogens and humans as food manufacturers. The human microbiome is a collective organ of microbes that have found community niches while associating with their host and other microorganisms. Humans play an important role in modifying the environment of these organisms through their life choices, especially through individual diet. The composition of an individual's diet influences the digestive system-an ecosystem with the greatest number and largest diversity of organisms currently known. Organisms living on and within food have the potential to be either friends or foes to the consumer. Maintenance of this system can have multiple benefits, but lack of maintenance can lead to a host of chronic and preventable diseases. Overall, this dynamic system is influenced by intense competition from food-borne pathogens, lifestyle, overall diet, and presiding host-associated microbiota.

Major shifts in intestinal commensal bacteria often result in changes in CD4+ T lymphocyte populations, leading to an influx of Th17 cells, chronic inflammation, and eventually cancer. Consequently, the inappropriate propagation of certain commensal species in the gut has been associated with mucosal inflammatory diseases and cancer development. Recent experiments investigating the relationships between food-borne pathogens, enteric bacteria, and cancer have exposed the ability of certain bacterial species to significantly reduce tumor size and tumor progression in mice. In similar studies, pro-inflammatory Th17 and Th1 cells were at times found present along with anti-inflammatory Treg populations in the intestinal mucosa. This antitumor response was mediated by a balanced production of pro- and anti-inflammatory cytokines, resulting in a controlled threshold of mucosal immunity largely moderated by CD4+ T lymphocyte populations, through a dendritic cell-dependent pathway. These findings provide new evidence that certain species of bacteria can help manage subcutaneous tumor development by calibrating mucosal and, in some instances, systemic thresholds of innate and adaptive immunity.

Foodborne pathogens, such as Escherichia coli, and Salmonella, are commonly prevalent in contaminated food products seen through annual food recalls. Excessive use of antibiotics through the past few decades has led to a multitude of antibiotic resistant bacteria, including foodborne pathogens. We investigated microbial occurrence and their antibiotics resistances in ready-to-go food items, i.e. canned food, bagged food, and baby food. A total of 112 isolates were isolated from varying food items, and 21 of these isolates were identified through 16S rRNA sequencing revealing Bacillus sp., Staphylococcus sp. and Micrococcus sp. Bagged food items showed the most microbial diversity as well as the largest colony forming unit (log 20–25 CFU/g). Isolates showed antibiotic resistance to ampicillin, streptomycin, chloramphenicol, and kanamycin at concentrations of 100, 500, and 1000 µg/mL. 57% isolates were ampicillin resistance followed by kanamycin (26%). A variety of microorganisms present in ready-to-go food items may not be pathogenic, however their occurrence and multiple antibiotic resistance (MAR) poses risk of transferring their genes to foodborne pathogens.

The worldwide increasing environmental issues owing to fossil fuels and their anticipated shortage in near future have fueled the research towards the search and development of alternative fuels from renewable sources. Recently, the biomass-based transport fuels have turn out to be strategic attention for counties with intention to enhance the sustainability in the terms of bioenergy. Interestingly, bioethanol is an oxygenated biofuel with 35% oxygen content, which can decrease the particulate matter and NOx emissions produced from fuel combustion. Therefore, gasoline blended with bioethanol can considerably decrease the petroleum consumption along with greenhouse gases emission. Though nearly all the present biofuel ethanol is produced from edible materials like sugars, starch etc., the lignocellulosic biomass has received considerable interest in recent years. Nevertheless, the transformation efficiency and ethanol yield of the biomass varies significantly mainly owing to the difference in lignocellulosic content. In lignocellulosic biomass, the complex lignocellulosic network of cellulose and hemicellulose with lignin is extremely resistant towards depolymerization. Thus, there still remain some obstacles that are to be addressed to make lignocellulosic biomass-based bioethanol a commercial reality. Further, the unmet need of cost reduction of lignocellulosic biomass-based bioethanol is progressing towards techno-economic improvements of overall transformation process through efficient biomass pretreatment process as well as recombinant genetic engineering for the microbial strain improvement. Overall, this chapter not only focuses on the current exploitation of different biomasses as substrates but also the biotechnological advances in various bioprocesses leading to improved bioethanol production.

Development and progress of cancer is a very complex disease process to comprehend because of the multiple changes in cellular physiology, pathology, and pathophysiology resulting from the numerous genetic changes from which cancer originates. As a result, most common treatments are not directed at the molecular level but rather at the tissue level. While personalized care is becoming an increasingly aim, the most common cancer treatments are restricted to chemotherapy, radiation, and surgery, each of which has a high likelihood of resulting in rather severe adverse side effects. For example, currently used radiation therapy does not discriminate between normal and cancerous cells and greatly relies on the external targeting of the radiation beams to specific cells and organs. Because of this, there is an immediate need for the development of new and innovative technologies that help to differentiate tumor cells and micrometastases from normal cells and facilitate the complete destruction of those cells. Recent advancements in nanoscience and nanotechnology have paved a way for the development of nanoparticles (NPs) as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery, and improve the therapeutic index of radiation and tumor response to the treatment. The application of NPs in radiation therapy has aimed to improve outcomes in radiation therapy by increasing therapeutic effect in tumors and reducing toxicity on normal tissues. Because NPs possess unique properties, such as preferential accumulation in tumors and minimal uptake in normal tissues, it makes them ideal for the delivery of radiotherapy. This review provides an overview of the recent development of NPs for carrying and delivering therapeutic radioisotopes for systemic radiation treatment for a variety of cancers in radiation oncology.

Moving charges due to electric current create electromagnetic waves, which generate electromagnetic fields (EMFs). The low frequency EMFs are unlikely to cause adverse effects on living organisms; however, health-related incidents have prompted researchers to investigate the biochemical characteristics in microorganisms. We hypothesized that a diverse variety of microorganisms, i.e., bacteria, will respond to EMF and bio-stimulate microbial metabolic products of commercial significance. An EMF generator that produces a 10-mT-strength magnetic field was built in-house to investigate the magnetic response of microbial communities from cave soil samples. 16S rRNA sequencing was employed to identify three EMF-responsive isolates: Streptomyces sp., Arthrobacter sp., and Lysinibacillus sphaericus, designated as EF1, EF2, and EF3, respectively. Streptomyces sp.-EF1 showed a dark brown pigment identified as melanin on nutrient agar plates supplemented with 0.4 % L-tyrosine and L-DOPA. We also investigated the bio-economics of melanin biosynthesis, which revealed that waste shredded paper ($33.29 /g melanin) followed by starch ($256.03 /g melanin) were among suitable substrates for melanin biosynthesis under non-EMF condition. The most time-efficient melanin formation was achieved by starch under submerged fermentation (3.52 h/μg/mL) conditions. Shredded, laser-printer paper was noticed to be a cost-efficient process ($33.29 /g melanin) for melanin biosynthesis.

Microorganisms with the ability to survive high doses of radiation are known as radiation-resistant extremophiles. This study attempts to demonstrate the diversity of microorganisms resistant to ultraviolet radiation (UVR) in the natural environment in order to investigate the molecular and physiological mechanisms by which these microorganisms survive under extreme radiation. We hypothesized that topsoil from elevated land (hills) would reveal a diverse variety of UVR-resistant extremophiles with modulated proteins/enzymes. A total of 10 different UV-C (UV subtype-C)-resistant extremophiles—UVP1, UVP3, UVP4, UVR1, UVR3, UVR4, UVR5a, UV20hr, YLP1, and BR2—were isolated and identified using 16S rRNA sequences for nearest homologues. All the isolates showed prolonged resistance against UV-C: 3.44 x 105 - 2.74 x 106 J/m2. Phylogenetic analysis between and within the UVR isolates revealed their relationship with other soil microorganisms using different outgroups. A unique pattern of protein expression at 25-50kDa was observed on SDS-PAGE under UVR and non-UVR from six prominent UVR isolates. Current studies are finding extreme UV-C-resistant in naturally occurring microorganisms found in stress-free environments.

Summary Radionuclides in the environment are a major human and environmental health concern. Like the Chernobyl disaster of 1986, the Fukushima Daiichi nuclear disaster in 2011 is once again causing damage to the environment: a large quantity of radioactive waste is being generated and dumped into the environment, and if the general population is exposed to it, may cause serious life-threatening disorders. Bioremediation has been viewed as the ecologically responsible alternative to environmentally destructive physical remediation. Microorganisms carry endogenous genetic, biochemical and physiological properties that make them ideal agents for pollutant remediation in soil and groundwater. Attempts have been made to develop native or genetically engineered (GE) microbes for the remediation of environmental contaminants including radionuclides. Microorganism-mediated bioremediation can affect the solubility, bioavailability and mobility of radionuclides. Therefore, we aim to unveil the microbial-mediated mechanisms for biotransformation of radionuclides under various environmental conditions as developing strategies for waste management of radionuclides. A discussion follows of ‘-omics’-integrated genomics and proteomics technologies, which can be used to trace the genes and proteins of interest in a given microorganism towards a cell-free bioremediation strategy.

Aims: To identify novel antibiotic-producing microbial strains with unprecedented pertinence. We hypothesize that site-specific soil samples will contain a variety of antibioticproducing species (APS) with diverse specificity of molecular elements. Place and Duration of Study: Laboratory of Microbiology, Division of Biological and Health Sciences, University of Pittsburgh, Bradford, PA-16701, USA, between August 2010 and May 2011. Methodology: The environmental soil samples were collected from residential and recreational sites in Southern, PA, USA at longitude: -76 42 21.7116, latitude: 39 56 35.7252; approximately 201 meters above sea level. Over 70 natural antibiotic-producing soil bacteria were screened against 19 pathogenic microorganisms. Agar-plug assay was established to identify the antibiotics’ potency and pathogenic inhibitory index calculations were employed to measure the inhibitory potential of each isolate; 16S rRNA sequencing was used for microbial classification. Results: A total of 71 microorganisms from residential soil demonstrated zones of inhibition (ZOI), followed by 9 organisms from recreational soil sample. A total of 15 bioactive strains demonstrated convincing growth inhibitory properties against 16 clinically relevant pathogens; 40% revealed pDNA presence, of which 67% exhibited stringent potencies against S. aureus. We observed a highly bioactive residential soil microbiota compared to recreational soil. Conclusion: 16S rRNA sequence analysis corroborated several of the species belonging to Enterobacteriaceae, Xanthomonadaceae, and Bacillaceae. These findings may indicate a co-evolutionary biosynthesis of novel antibiotics driven by the increase of bioactive microbiota in residential environments.

Industrial use of nanotechnology in daily life has produced an emphasis on the safe and efficient production of nanoparticles (NPs). Traditional chemical oxidation and reduction methods are seen as inefficient, environmentally unsound, and often dangerous to those exposed and involved in NP manufacturing. However, utilizing microorganisms for biosynthesis of NPs allows efficient green production of a range of inorganic NPs, while maintaining specific size, shape, stability, and dispersity. Microorganisms living under harsh environmental conditions, called "Extremophiles," are one group of microorganisms being utilized for this biosynthesis. Extremophiles' unique living conditions have endowed them with various processes that enable NP biosynthesis. This includes a range of extremophiles: thermophiles, acidophilus, halophiles, psychrophiles, anaerobes, and some others. Fungi, bacteria, yeasts, and archaea, i.e. Ureibacillus thermosphaericus, and Geobacillus stearothermophilus, among others, have been established for NP biosynthesis. This article highlights the extremophiles and methods found to be viable candidates for the production of varying types of NPs, as well as interpreting selective methods used by the organisms to synthesize NPs.

Among extremophiles, microorganisms resistant to ultraviolet radiation (UVR) have been known to produce a variety of metabolites (i.e., extremolytes). We hypothesized that natural microbial flora on elevated land (hills) would reveal a variety of UVR-resistant extremophiles and polyextremophiles with modulated proteins and enzymes that had biotechnological implications. Microorganisms Cellulosimicrobium cellulans UVP1 and Bacillus pumilus UVP4 were isolated and identified using 16S rRNA sequencing, and showed extreme UV resistance (1.03 × 10⁶ and 1.71 × 10⁵ J/m², respectively) from elevated land soil samples along with unique patterns of protein expression under UVR and non-UVR. A broad range of cellulolytic activity on carboxymethyl cellulose agar plates in C. cellulans UVP1 and B. pumilus UVP4 was revealed at varying pH, temperature, and inorganic salt concentration. Further, the microbial strain B. pumilus UVP4 showed the basic characteristics of a novel group: polyextremophiles with significance in bioenergy.

Chemical hydrolysis of lignocellulosic biomass (LB) produces a number of inhibitors in addition to sugars. These inhibitors include lignin-derived phenolics, carbohydrate-derived furans, and weak acids that have shown a marked effect on the productivities of various metabolites and the growth of biocatalysts in the fermentative reaction. In the past, a number of physicochemical and biological approaches have been proposed to overcome these fermentation inhibitors, including modified fermentative strategies. Additionally, the timely intervention of genetic engineering has provided an impetus to develop suitable technologies for the detoxification of lignocellulosics in biorefineries. However, the improvements in detoxification strategies for lignocellulose hydrolysates have resulted in significant loss of sugars after detoxification. Hydrolysis of myco-LB (LB after fungal pretreatment) has been recognized as a promising approach to avoid fermentation inhibitors and improve total sugar recovery. Biotechnological inventions have also made it possible to widen the range of suitable biocatalysts for biorefineries by microbial-routed induction of enzymatic expression for the elimination of inhibitors, eventually improving ethanol production from acid hydrolysates. This article aims to highlight the strategies that have been adopted to detoxify lignocellulosic hydrolysates and their effects on the chemical composition of the hydrolysates to improve the fermentability of lignocellulosics. In addition, genetic manipulation could widen the availability and variety of substrates and modify the metabolic routes to produce bioethanol or other value-added compounds in an efficient manner.

Sugarcane is among the principal agricultural crops cultivated in tropical countries. The annual world production of sugarcane is ∼1.6 billion tons, and it generates ∼279 million metric tons (MMT) of biomass residues (bagasse and leaves). Sugarcane residues, particularly sugarcane bagasse (SB) and leaves (SL) have been explored for both biotechnological and non-biotechnological applications. For the last three decades, SB and SL have been explored for use in lignocellulosic bioconversion, which offers opportunities for the economic utilization of residual substrates in the production of bioethanol and value-added commercial products such as xylitol, specialty enzymes, organic acids, single-cell protein, etc. However, there are still major technological and economic challenges to be addressed in the development of bio-based commercial processes utilizing SB and SL as raw substrates. This article aims to explore SB and SL as cheaper sources of carbohydrates in the developing world for their industrial implications, their use in commercial products including commercial evaluation, and their potential to advance sustainable bio-based fuel systems. Copyright © 2011 Society of Chemical Industry

The lignocellulosic biomass is a low-cost renewable resource for eco-benign liquid fuel ‘ethanol’. To resolve the hydrolysis of mixed sugars in lignocellulosic substrate Saccharum spontaneum, the microbial co-cultures of Pichia stipitis NCIM 3498 and thermotolerant Saccharomyces cerevisiae-VS3 were analyzed for efficient bioconversion of mixed sugars into ethanol. Among the hydrolysis conditions, the acid hydrolysis released maximum sugars along with furans, phenolics and acetic acid. The acidic hydrolysate was detoxified and fermented by monocultures of P. stipitis NCIM3498 (P.S.) and thermotolerant S. cerevisiae VS3 (S.C.), and co-culture of P.S. (7.5 mL) and S.C. (2.5 mL). Before the fermentation of hemicellulose acid hydrolysate, both the monocultures (P.S. and S.C.), and varying ratios of P.S. and S.C. microorganisms in co-cultures #1, #2 and #3 were grown on simulated synthetic medium. The ethanol yield from monocultures of P.S. (0.44 ± 0.021 g/g), S.C. (0.22 ± 0.01 g/g) and co-culture #3 (0.49 ± 0.02 g/g) revealed unique characteristics of each mono and co-culture technology. The fermentation of hemicellulose acid hydrolysate with monocultures of P.S., S.C. and co-culture #3 produced 12.08 ± 0.72 g/L, 1.40 ± 0.07 g/L, and 15.0 ± −0.92 g/L ethanol, respectively.

Micro-organisms with the ability to survive in extreme environmental conditions are known as 'extremophiles'. Currently, extremophiles have caused a sensation in the biotechnology/pharmaceutical industries with their novel compounds, known as 'extremolytes'. The potential applications of extremolytes are being investigated for human therapeutics including anticancer drugs, antioxidants, cell cycle-blocking agents, anticholesteric drugs, etc. It is hypothesized that the majority of ultraviolet radiation (UVR)-resistant micro-organisms can be used to develop anticancer drugs to prevent skin damage from UVR. The metabolites from UVR-resistant microbes are a great source of potential therapeutic applications in humans. This article aims to discuss the potentials of extremolytes along with their therapeutic implications of UVR extremophiles. The major challenges of therapeutic development using extremophiles are also discussed.

As the genomics era matures, the availability of complete microbial genome sequences is facilitating computational approaches to understand bacterial genomes and DNA structure/function relationships. From the genome of pathogens, we can derive invaluable information on potential targets for new antimicrobial agents. Advancements in high-throughput 'omics' technologies and the availability of multiple isolates of the same species have significantly changed the time frame and scope for identifying novel therapeutic targets. This article aims to discuss selected aspects of the bacterial genome, and advocates 'omics'-based techniques to advance the discovery of new therapeutic targets against extracellular bacterial pathogens.

Diallyl disulfide (DADS), an important component of garlic (Allium sativum) derivative, has been demonstrated to exert a potential molecular target against human cancers. We investigated DADS-induced expressions of Apaf1, cystatin B, caspase-3 and FADD (fas-associated protein with death domain) in breast, prostate and lung cancer cells. These showed coincident data when further examined by quantitative reverse transcription-polymerase chain reaction and Western blot analysis. Furthermore, DADS induced a marked amount of Bax translocation, cytochrome c release and activation of caspase-3 and caspase-9. DADS-treated tumor cells triggered mitochondria-mediated signaling pathways that led to a significant increase in apoptosis induction. Further studies with caspase-3 and caspase-9 inhibitors (zDEVD-fmk and zLEHD-fmk, respectively) proved that DADS induces apoptosis through a caspase-3-dependent pathway. DADS is only an agent used in the study. The molecular mechanism presented therefore provides strong additional support to the hypothesis that DADS is a strong inducer of apoptosis through a Bax-triggered mitochondria-mediated and caspase-3-dependent pathway. This study shows clearly that DADS causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. Therefore, the mitochondrial pathway might be the target for cancer chemoprevention and/or chemotherapy by DADS.

A new route for the synthesis of ipriflavone, an antiosteoporotic agent, is described that has four steps and 60% yields starting from resacetophenone (2). The key step of the present methodology is thallium(III) p-tosylate mediated oxidative 2,3-aryl rearrangement of flavanone to generate the isoflavone ring system of ipriflavone in a highly efficient manner.

In a previous study of sodium 4-phenylbutyrate (4-PBA)-responsive proteins in cystic fibrosis (CF) IB3-1 bronchial epithelial cells, we identified 85 differentially expressed high abundance proteins from whole cellular lysate (Singh, O. V., Vij, N., Mogayzel, P. J., Jr., Jozwik, C., Pollard, H. B., and Zeitlin, P. L. (2006) Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. J. Proteome Res. 5, 562–571). In the present work we hypothesize that a subset of heat shock proteins that interact with cystic fibrosis transmembrane conductance regulator (CFTR) in common during chemical rescue and genetic repair will identify therapeutic networks for targeted intervention. Immunocomplexes were generated from total cellular lysates, and three subcellular fractions (endoplasmic reticulum (ER), cytosol, and plasma membrane) with anti-CFTR polyclonal antibody from CF (IB3-1), chemically rescued CF (4-PBA-treated IB3-1), and genetically repaired CF (IB3-1/S9 daughter cells repaired by gene transfer with adeno-associated virus-(wild type) CFTR). CFTR-interacting proteins were analyzed on two-dimensional gels and identified by mass spectrometry. A set of 16 proteins known to act in ER-associated degradation were regulated in common and functionally connected to the protein processing, protein folding, and inflammatory response. Some of these proteins were modulated exclusively in ER, cytosol, or plasma membrane. A subset of 4-PBA-modulated ER-associated degradation chaperones (GRP94, HSP84, GRP78, GRP75, and GRP58) was observed to associate with the immature B form of CFTR in ER. HSP70 and HSC70 interacted with the C band (mature form) of CFTR at the cell surface. We conclude that chemically rescued CFTR associates with a specific set of HSP70 family proteins that mark therapeutic interactions and can be useful to correct both ion transport and inflammatory phenotypes in CF subjects.

A detailed chemical kinetic mechanism describing the thermal and catalytic cracking of methylcyclohexane over a 12CaO.7Al2O3 catalyst is presented. The model is based on balanced equations for both molecular and radical species describing an experimental fixed-bed reactor system. The mechanistic model is based on overall first-order decomposition kinetics, which satisfactorily describes experimental data. The simulated product distributions show a reasonably good agreement with the experimental results and confirm the hypothesis that the catalyst does not affect the pyrolysis mechanism and only increases the rate of the initiation steps. On presente un mecanisme cinetique chimique detaille decrivant le craquage thermique et catalytique du methylcyclohexane sur un catalyseur de 12CaO.7Al2O3. Le modele repose sur des equations equilibrees pour des especes moleculaires et radicales dans le cas d'un reacteur a lit fixe experimental. Le modele mecanistique s'appuie sur une cinetique de decomposition de premier ordre globale, qui decrit de maniere satisfaisante les donnees experimentales. Les distributions de produit simulees montrent un accord raisonnable avec les resultats experimentaux et confirment l'hypothese que le catalyseur n'influe pas sur le mecanisme de pyrolyse et ne fait qu'accroitre la vitesse des etapes initiales.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is the third leading cause of death from cancer. The diverse etiology, high morbidity/mortality, lack of diagnostic markers for early diagnosis and the highly variable clinical course of HCC have hindered advances in diagnosis and treatment. Microsatellite instability, chromosomal aberrations, mutations in key cell cycle genes and epigenetic changes have been reported in HCC. Availability of modern technologies advance 'high-dimensional biology' (HDB), a term that refers to the simultaneous study of the genetic variants (genome), transcription (mRNA; transcriptome), peptides and proteins (proteomics), and metabolites (metabolomics) for the intermediate products of metabolism of an organ, tissue or organism. The growing interest in omics-based research has enabled the simultaneous examination of thousands of genes, transcripts and proteins of interest, with high-throughput techniques and advanced analytical tools for data analysis. The use of each approach towards functional omics has lead to the classification of HCC into molecular subgroups. Here we review the use of HDB as a tool for the identification of markers for screening, diagnosis, molecular classification and the discovery of new therapeutic drug targets of HCC. With the extensive use of HDB, it may be possible in the near future, to have custom-made therapeutic regimens for HCC based on the molecular subtype, ultimately leading to an improved survival of HCC patients.

Penicillin G acylase (PGA; EC 3.5.1.11) is a hydrolytic enzyme that acts on the side chains of penicillin G, cephalosporin G and related antibiotics to produce the β-lactam antibiotic intermediates 6-amino penicillanic acid (6-APA) and 7-amino des-acetoxy cephalosporanic acid (7-ADCA), with phenyl acetic acid (PAA) as a common by-product. These antibiotic intermediates are among the potential building blocks of semi-synthetic antibiotics, such as ampicillin, amoxicillin, cloxacillin, cephalexin, and cefatoxime. Currently, β-lactam antibiotics have annual sales of ∼$15 billion and make up 65% of the total antibiotics market; the annual consumption of PGA is estimated to be in the range of 10–30 million tons. The high demand for PGA is being met through a submerged fermentation process that uses genetically manipulated Escherichia coli and Bacillus megaterium microorganisms. Advancements in biotechnology such as screening of microorganisms, manipulation of novel PGA-encoding traits, site-specific mutagenesis, immobilization techniques, and modifications to the fermentation process could enhance the production of PGA. Commercially, cheaper sources of carbohydrates and modified fermentation conditions could lead to more cost-effective production of PGA. These methodologies would open new markets and create new applications of PGA. This article describes the advancements made in PGA biotechnology and advocates its simulation for production of β-lactam antibiotics.

BACKGROUND: Gluconic acid (GA) production by immobilized cells of mutant Aspergillus niger ORS-4.410 on polyurethane sponge (PUS) and calcium-alginate (Ca-alginate) was evaluated in repeated batches of solid state surface fermentation (SSF) and submerged fermentation (SmF) conditions, respectively, utilizing rectified grape must as carbon source. RESULTS: The passive immobilization of cells in fermentation medium solid support of having 0.4 cm3 cube size, 4% spore suspension, 0.6 g inoculum of PUS immobilized cells at 32 °C and 2.0 L min−1 resulted in the maximum GA production (88.16 g L−1) with a 92.8% yield, while the Ca-alginate matrix with a 0.5 cm diameter bead size, 2–3% spore suspension, 15 g inoculum at 34 °C and 150 rpm agitation speed revealed 67.19 g L−1 GA with a 85.2% yield. Repeated use of PUS showed higher levels of GA (110.94 g L−1) in the third–fourth fermentation cycles with 95–98% yield and 22.50 g L−1 d−1 productivity under SSF that was 2.5-fold higher than the productivity obtained from a typical fermentation cycle, and 54% greater than the productivity obtained with repetitive use of Ca-alginate immobilized cells of A. niger under SmF. CONCLUSION: Using immobilized cells of A. niger in PUS, the rectified form of grape must can be utilized for GA production as an alternative source of carbohydrate by replacing the conventional fermentation conditions. Copyright © 2008 Society of Chemical Industry

The first asymmetric synthesis of (+)-iso-6-cassine is described. Lipase-catalyzed resolution, enantioselective Overman rearrangement, and diastereoselective intramolecular amidomercuration were used for the installation of the three stereocenters in (+)-iso-6-cassine, and cross-metathesis was employed for the attachment of the side-chain.

Manganese(III) acetate mediated oxidation of aporphines to oxoaporphines is described. The developed methodology was conveniently applied for the synthesis of naturally occurring oxoaporphine alkaloids, oxoglaucine, and atheroline, starting from commercially available boldine.

Ir(I)-catalyzed decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates has been shown to proceed with complete retention of enantiomeric purity and configuration. The transformation is stereospecific and appears to be quite general, accommodating a wide range of R groups.

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allylic carbonates with soft nitrogen nucleophiles under completely "salt-free" conditions is described. A combination of [Ir(COD)Cl](2), a chiral phosphoramidite ligand L*, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of Boc protected alpha- and beta-amino acids as well as (-)-cytoxazone.

The syntheses of a series of conformationally restricted 4-dimethylaminopyridine (DMAP) analogs 1-3 are described. Evaluations of catalyst effectiveness demonstrated that 1 was the best catalyst for the acetylation reaction of a tertiary alcohol, while 2 and 3 were roughly comparable to DMAP. The order of effectiveness of these catalysts roughly parallels their acetylation enthal- pies estimated from ab initio calculations. 2007 Elsevier Ltd. All rights reserved.