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Novel one-pot reaction conditions have been developed for the preparation of glycosyl thiourea derivatives directly from glycosyl azides mediated by a combination of sulfamic acid and sodium iodide. The reaction conditions were clean, non-toxic and the products were isolated in good to excellent yield., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3'-(Arylmethylene)-bis-1H-indole (AMBI) derivative 3,3'-[(4-Methoxyphenyl) methylene]-bis-(5-bromo-1H-indole), named as Mephebrindole (MPB) as an effective anti-cancer agent in breast cancer cells. MPB disrupted calcium homeostasis in MCF7 cells which triggered ER stress development. Detailed evaluations revealed that mephebrindole by activating p38MAPK also regulated GRP78 and eIF2α/ATF4 downstream to promote apoptosis. Studies extended to in vivo allograft mice models revalidated its anti-carcinogenic property thus highlighting the role of MPB as an improved chemotherapeutic option.

Gout is a metabolic disorder that usually presents as recurrent episodes of acute arthritis due to deposition of crystals in joints and cartilages. Despite the availability of several drugs for gout, its management is still less than adequate. There is always a search for newer, safer, and more potent urate-lowering therapies for treating patients inadequately controlled with available drugs. Lesinurad in combination with a xanthine oxidase inhibitor provides an effective mode of therapy in the management of hyperuricemia associated with gout. Lesinurad is a selective uric acid transporter 1 (URAT1) inhibitor. URAT1 is responsible for the majority of uric acid absorption from kidneys to the circulation. Lesinurad was granted marketing approval based on three randomized, double-blind, placebo-controlled; phase III clinical trials. It is devoid of interaction with organic anion transporters (OATs) such as OAT1 and 3, responsible for drug-drug interactions, an undesirable property associated with probenecid. On-going research is more focused on reducing inflammation consequent to deposition of crystals rather than production and excretion of urate. Various targets are being explored, and interleukin-1 beta inhibition seems to be one of the most promising approaches., Competing Interests: There are no conflicts of interest.

Unlabelled: We developed a prototype instrument called the Standoff Biofinder, which can quickly locate biological material in a 500 cm(2) area from a 2 m standoff distance with a detection time of 0.1 s. All biogenic materials give strong fluorescence signals when excited with UV and visible lasers. In addition, the luminescence decay time of biogenic compounds is much shorter (<100 ns) than the micro- to millisecond decay time of transition metal ions and rare-earth ions in minerals and rocks. The Standoff Biofinder takes advantage of the short lifetime of biofluorescent materials to obtain real-time fluorescence images that show the locations of biological materials among luminescent minerals in a geological context. The Standoff Biofinder instrument will be useful for locating biological material during future NASA rover, lander, and crewed missions. Additionally, the instrument can be used for nondestructive detection of biological materials in unique samples, such as those obtained by sample return missions from the outer planets and asteroids. The Standoff Biofinder also has the capacity to detect microbes and bacteria on space instruments for planetary protection purposes., Key Words: Standoff Biofinder-Luminescence-Time-resolved fluorescence-Biofluorescence-Planetary exploration-Planetary protection-Noncontact nondestructive biodetection. Astrobiology 16, 715-729.

Background: Hill rices (Oryza sativa L.) are direct seeded rices grown on hill slopes of different gradients. These landraces have evolved under rainfed and harsh environmental conditions and may possess genes governing adaptation traits such as tolerance to cold and moisture stress. In this study, 64 hill rice landraces were collected from the state of Arunachal Pradesh of North-Eastern region of India, and assessed by agro-morphological variability and microsatellite markers polymorphism. Our aim was to use phenotypic and genetic diversity data to understand the basis of farmers' classification of hill rice landraces into two groups: umte and tening. Another goal was to understand the genetic differentiation of hill rices into Indica or japonica subspecies., Results: According to farmers' classification, hill rices were categorized into two groups: umte (large-grained, late maturing) and tening (small-grained, early maturing). We did not find significant difference in days to 50 % flowering between the groups. Principal component analysis revealed that two groups can be distinguished on the basis of kernel length-to-width ration (KLW), kernel length (KL), grain length (GrL), grain length-to-width ration (GrLW) and plant height (Ht). Stepwise canonical discriminant analysis identified KL and Ht as the main discriminatory characters between the cultivar groups. Genetic diversity analysis with 35 SSR markers revealed considerable genetic diversity in the hill rice germplasm (gene diversity: 0.66; polymorphism information content: 0.62). Pair-wise allelic difference between umte and tening groups was not statistically significant. The model-based population structure analysis showed that the hill rices were clustered into two broad groups corresponding to Indica and Japonica. The geographic distribution and cultivars grouping of hill rices were not congruent in genetic clusters. Both distance- and model-based approaches indicated that the hill rices were predominantly japonica or admixture among the groups within the subspecies. These findings were further supported by combined analysis hill rices with 150 reference rice accessions representing major genetic groups of rice., Conclusion: This study collected a valuable set of hill rice germplasm for rice breeding and for evolutionary studies. It also generated a new set of information on genetic and phenotypic diversity of hill rice landraces in North-Eastern region of India. The collected hill rices were mostly japonica or admixture among the subpopulations of Indica or Japonica. The findings are useful for utilization and conservation of hill rice germplasm.

Tea leaves are rich in plant secondary phenolics, especially flavonoids. Catechins are considered to be the most valuable flavonoids, and the catechin content in tea is an important trait for determining its quality. We have developed cleaved amplified polymorphic sequence (CAPS)-based markers for evaluating total catechin content that target two important secondary metabolite pathway genes, PAL (phenylalanine ammonia-lyase) and CHS (chalcone synthase). Catechin content levels in the tea samples tested ranged from 9 to 33 mg/mg. The CAPS technique identified clones with the homozygous profile PRc1, which has relatively lower catechin content than clones with the heterozygous profile PRc2. A significant difference (t = 16.85) in the level of catechin content was also detected between heterozygotes and homozygotes in the tea seed stock TS379. We found a polynomial relationship between the marker developed for CHS2 and catechin content in these tea samples with R2 = 0.9788. Moreover, PAL has less of a relationship with catechin content. Therefore, we recommend tea clones with heterozygous CAPS profiles for the gene CHS2+RcaI for the further improvement in these clones.

A series of C-cinnamoyl glycosides has been synthesized in good yield by the BF3·OEt2 catalyzed aldol condensation of C-glycosylated acetone derivative with a variety of aromatic aldehydes. The synthesized compounds were evaluated for their potential as anti-filarial agents against bovine filarial parasite Setaria cervi and human filariid Wuchereria bancrofti using a number of biological assays such as relative movability (RM) assessment and MTT reduction assay. Among twenty seven test compounds six compounds were found active in terms of MIC, IC50 and LC50 values. Further biological studies were carried out using three lead compounds because of their significantly low MIC values and IC50 values compared to the standard anti-filarial drug Ivermectin. In addition, structure activity relationship study of the test compounds has been carried out using 3D-QSAR analysis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Triple-negative breast cancer (TNBC), is a specific subtype of epithelial breast tumors that are immuno-histochemically negative for the protein expression of the estrogen receptor (ER), the progesterone receptor (PR) and lack over expression/gene amplification of HER2. This subtype of breast cancers is highly metastatic, shows poor prognosis and hence represents an important clinical challenge to researchers worldwide. Thus alternative approaches of drug development for TNBC have gained utmost importance in the present times. Dietary indole and its derivatives have gained prominence as anti-cancer agents and new therapeutic approaches are being developed to target them against TNBC. But a major drawback with 3, 3'di Indolyl methane (DIM) is their poor bioavailability and high effective concentration against TNBC. However, the Aryl methyl ring substituted analogs of DIM display interesting anti-cancer activity in breast cancer cells. In the current study we report the synthesis of a novel synthetic aryl methyl ring substituted analog of DIM, named as Phemindole as an effective anti-tumor agent against TNBC cells. Furthermore, we enumerated that Phemindole caused reactive oxygen species mediated mitochondrial-dependent apoptosis in MDAMB-231 cells. Furthermore, Phemindole mediated Store Operated Calcium Entry (SOCE) retardation favored inactivation of STIM1 and henceforth activated ER stress to induce apoptosis in TNBC cells. Simultaneously, Phemindole was also found to restrict the in vitro cell migration through its anti mitotic property and pFAK regulation. Studies extended to ex ovo and in vivo mice models further validated the efficacy of Phemindole. Thus our results cumulatively propose Phemindole as a new chemotherapeutic regime which might be effective to target the deadly aspects of the TNBC.

Lymphatic filariasis, affecting around 120 million people in 80 countries worldwide, is an extremely painful disease and caused permanent and long term disability. Owing to its alarming prevalence there is immediate need for development of new therapeutics. A series of trans-stilbene derivatives were synthesized using aqueous reaction condition showing potential as antifilarial agents demonstrated in vitro. MTT reduction assay and dye exclusion test were performed to evaluate the micro and macrofilaricidal potential of these compounds. Amid 20 trans-stilbene derivatives together with Resveratrol (RSV), a multifunctional natural product was screened; nine compounds (28, 29, 33, 35, 36, 38, 39, 41 and 42) have showed promising micro and macrofilaricidal activities and four of them (28, 39, 41 and 42) showed better effectiveness than RSV. In the treated parasites apoptosis was established by DNA laddering, in situ DNA fragmentation and FACS analysis. The generation of ROS in the treated parasites was indicated by the depletion in the level of GSH, GR and GST activity and elevation of SOD, catalase, GPx activity and superoxide anion and H2O2 level. Along with the ROS generation and oxidative stress, the decreased expression of anti-apoptotic ced-9 gene and increased expression of nematode specific pro-apoptotic genes, egl-1, ced-4 and ced-3 at the level of transcription and translation level; the up-regulation of caspase-3 activity and involvement of caspase-8,9,3, cytochrome-c and PARP were also observed and which denotes the probable existence of both extrinsic and intrinsic pathways apoptosis in parasitic nematodes. This observation is reported first time and thus it confirmed the mode of action and effectiveness of the compounds. Further, the comparative bioavailability-pharmacokinetics studies showed that compound 28 possesses comparable properties with Ivermectin. This study will certainly intensify our understanding of the pharmacological importance of trans-stilbenes as an anti-filarial agent., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Exploration of the aquatic microbiota of several circum-neutral (6.0-8.5 pH) mid-temperature (55-85°C) springs revealed rich diversities of phylogenetic relatives of mesophilic bacteria, which surpassed the diversity of the truly-thermophilic taxa. To gain insight into the potentially-thermophilic adaptations of the phylogenetic relatives of Gram-negative mesophilic bacteria detected in culture-independent investigations we attempted pure-culture isolation by supplementing the enrichment media with 50 μg ml(-1) vancomycin. Surprisingly, this Gram-positive-specific antibiotic eliminated the entire culturable-diversity of chemoorganotrophic and sulfur-chemolithotrophic bacteria present in the tested hot water inocula. Moreover, it also killed all the Gram-negative hot-spring isolates that were obtained in vancomycin-free media. Concurrent literature search for the description of Gram-negative thermophilic bacteria revealed that at least 16 of them were reportedly vancomycin-susceptible. While these data suggested that vancomycin-susceptibility could be a global trait of thermophilic bacteria (irrespective of their taxonomy, biogeography and Gram-character), MALDI Mass Spectroscopy of the peptidoglycans of a few Gram-negative thermophilic bacteria revealed that tandem alanines were present in the fourth and fifth positions of their muropeptide precursors (MPPs). Subsequent phylogenetic analyses revealed a close affinity between the D-alanine-D-alanine ligases (Ddl) of taxonomically-diverse Gram-negative thermophiles and the thermostable Ddl protein of Thermotoga maritima, which is well-known for its high specificity for alanine over other amino acids. The Ddl tree further illustrated a divergence between the homologs of Gram-negative thermophiles and mesophiles, which broadly coincided with vancomycin-susceptibility and vancomycin-resistance respectively. It was thus hypothesized that thermophilic Ddls have been evolutionarily selected to favor a D-ala-D-ala bonding. However, preference for D-ala-D-ala-terminated MPPs does not singlehandedly guarantee vancomycin susceptibility of thermophilic bacteria as the large and relatively-hydrophilic vancomycin molecule has to cross the outer membrane before it can inhibit peptidoglycan biosynthesis. Literature shows that many mesophilic Gram-negative bacteria also have D-ala-D-ala-terminated MPPs, but they still remain resistant to vancomycin due to the relative impermeability of their membranes. But the global vancomycin-susceptibility phenotype of thermophilic bacteria itself testifies that the drug crosses the membrane in all these cases. As a corollary, it seems quite likely that the outer membranes of thermophilic bacteria have some yet-unknown characteristic feature(s) that invariably ensures the entry of vancomycin.

The proliferation of algal bloom in water bodies due to the enhanced concentration of nutrient inflow is becoming a global issue. A prime reason behind this aquatic catastrophe is agricultural runoff, which carries a large amount of nutrients that make the lakes more fertile and cause algal blooms. The only solution to this problem is curtailing the nutrient loading through agricultural runoff. This could be achieved by raising awareness among farmers to minimize the use of fertilizers in their farms. In view of this, in this paper, we propose a mathematical model to study the effect of awareness among the farmers of the mitigation of algal bloom in a lake. The growth rate of awareness among the farmers is assumed to be proportional to the density of algae in the lake. It is further assumed that the presence of awareness among the farmers reduces the inflow rate of nutrients through agricultural runoff and helps to remove the detritus by cleaning the bottom of the lake. The results evoke that raising awareness among farmers may be a plausible factor for the mitigation of algal bloom in the lake. Numerical simulations identify the most critical parameters that influence the blooms and provide indications to possibly mitigate it.

The impact of awareness campaigns and behavioral responses on epidemic outbreaks has been reported at times. However, to what extent does the provision of awareness and behavioral changes affect the epidemic trajectory is unknown, but important from the public health standpoint. To address this question, we formulate a mathematical model to study the effect of awareness campaigns by media on the outbreak of an epidemic. The awareness campaigns are treated as an intervention for the emergent disease. These awareness campaigns divide the whole populations into two subpopulation; aware and unaware, by inducing behavioral changes amongst them. The awareness campaigns are included explicitly as a separate dynamic variable in the modeling process. The model is analyzed qualitatively using stability theory of differential equations. We have also identified an optimal implementation rate of awareness campaigns so that disease can be controlled with minimal possible expenditure on awareness campaigns, using optimal control theory. The control setting is investigated analytically using optimal control theory, and the numerical solutions illustrating the optimal regimens under various assumptions are also shown., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A multispectral instrument based on Raman, laser-induced fluorescence (LIF), laser-induced breakdown spectroscopy (LIBS), and a lidar system provides high-fidelity scientific investigations, scientific input, and science operation constraints in the context of planetary field campaigns with the Jupiter Europa Robotic Lander and Mars Sample Return mission opportunities. This instrument conducts scientific investigations analogous to investigations anticipated for missions to Mars and Jupiter's icy moons. This combined multispectral instrument is capable of performing Raman and fluorescence spectroscopy out to a >100  m target distance from the rover system and provides single-wavelength atmospheric profiling over long ranges (>20  km). In this article, we will reveal integrated remote Raman, LIF, and lidar technologies for use in robotic and lander-based planetary remote sensing applications. Discussions are focused on recently developed Raman, LIF, and lidar systems in addition to emphasizing surface water ice, surface and subsurface minerals, organics, biogenic, biomarker identification, atmospheric aerosols and clouds distributions, i.e., near-field atmospheric thin layers detection for next robotic-lander based instruments to measure all the above-mentioned parameters.

Enterotoxigenic Escherichia coli (ETEC) like the O139 strain are mostly responsible for traveler's diarrhea and causes diseases in pigs, cattle, and poultry. A convenient synthetic strategy was developed for the synthesis of the heptasaccharide repeating unit of the cell wall lipopolysaccharide of the E. coli O139 strain. The p-methoxybenzyl (PMB) group was used as a temporary protecting group which was removed in situ under the glycosylation conditions by changing the reaction temperature during the synthesis of the target compound. All glycosylation steps gave high yields with good stereoselectivity. A (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)-mediated selective oxidation of the primary hydroxyl group was carried out using a biphasic reaction condition at the late stage of the synthesis. Such synthetic oligosaccharides could later be effectively conjugated with proteins to prepare glycoconjugate derivatives as vaccine candidates.

A convergent [3+2] block synthetic strategy was developed for the synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O11 strain in excellent yield in a minimum number of steps. Several suitably functionalized thioglycoside derivatives were used as glycosyl donors during the synthesis of the target compound. A thioglycoside was the glycosyl donor used to couple with another thioglycoside derivative in a highly stereoselective manner exploiting the difference of their reactivity profile. A combination of Niodosuccinimide (NIS) and perchloric acid supported over silica gel (HClO4-SiO2) was used as a thiophilic glycosylation activator system in all stereoselective glycosylation reactions. HClO4-SiO2 acted as a user-friendly solid acid catalyst. Yields were very good in all glycosylation steps with a high stereoselective outcome. The synthetic pentasaccharide could be coupled to an appropriate protein to furnish a glycoconjugate derivative for its use in immunochemical studies.

Conventional glycoconjugate vaccines are prepared with polysaccharides isolated from bacterial fermentation, an approach with some significant drawbacks such as handling of live bacterial strains, the presence of biological impurities, and inter-batch variations in oligosaccharide epitope structure. However, it has been shown in many cases that a synthetic fragment of appropriate structure conjugated to a protein can be an effective vaccine that circumvents the shortcomings of using full-length oligosaccharides. The development of synthetic strategies to prepare glycoconjugate derivatives against pathogenic bacterial strains is therefore of great interest. Oligosaccharide fragments corresponding to the repeat unit of the cell wall O-antigen of Salmonella enterica strain O53 were synthesized in good yield. Sequential and block glycosylation strategies were used for the synthesis of the target compounds. A number of recently developed reaction conditions were used in the synthetic strategy. A one-pot reaction scheme was also developed for the multiple glycosylation steps. The stereoselective outcomes of all glycosylation reactions were very good.

Background: Substance misuse is an increasing problem in urban and rural India. The utility of community-based interventions and preventive strategies are increasingly emphasized in this context. The drug de-addiction and treatment center, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, has been running a drug de-addiction and treatment clinic at Kharar Civil Hospital, Kharar, District Mohali, Punjab, since 1998. As part of an effort to enhance this community outreach program, community-based drug awareness and treatment camps have been organized since March 2004 in villages in and around Tehsil Kharar of Mohali., Aim: To study the impact of the drug awareness and treatment camps on the attendance of patients at the community outreach drug de-addiction and treatment clinic at Kharar Civil Hospital., Methods: Sociodemographic and clinical variables, including treatment outcome-related variables, of patients attending the clinic at Kharar Civil Hospital, before and after the camps were compared., Discussion and Conclusion: The study showed a positive impact on drug awareness and treatment camps held in the community on outpatient attendance at a community outreach clinic, with attendance increasing more than 1.8 times.

A 28-year-old male presented with fever with right-sided chest pain for 2 weeks. Clinicoradiological picture was suggestive of right-sided pleural effusion. He had history of polytrauma following a road traffic accident and had to undergo emergency laparotomy a month ago. Microscopic and culture examination of the pleural fluid showed neutrophilia, high bilirubin content and presence of gram-negative bacilli. Ultrasound of the abdomen showed the presence of biloma in the liver and right subdiaphragmatic space with fistulous communication into the right thoracic cavity. The patient was managed successfully with complete recovery.

The North-eastern (NE) India, comprising of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim and Tripura, possess diverse array of locally adapted non-Basmati aromatic germplasm. The germplasm collections from this region could serve as valuable resources in breeding for abiotic stress tolerance, grain yield and cooking/eating quality. To utilize such collections, however, breeders need information about the extent and distribution of genetic diversity present within collections. In this study, we report the result of population genetic analysis of 107 aromatic and quality rice accessions collected from different parts of NE India, as well as classified these accessions in the context of a set of structured global rice cultivars. A total of 322 alleles were amplified by 40 simple sequence repeat (SSR) markers with an average of 8.03 alleles per locus. Average gene diversity was 0.67. Population structure analysis revealed that NE Indian aromatic rice can be subdivided into three genetically distinct population clusters: P1, joha rice accessions from Assam, tai rices from Mizoram and those from Sikkim; P2, aromatic rice accessions from Nagaland; and P3, chakhao rice germplasm from Manipur [corrected]. Pair-wise FST between three groups varied from 0.223 (P1 vs P2) to 0.453 (P2 vs P3). With reference to the global classification of rice cultivars, two major groups (Indica and Japonica) were identified in NE Indian germplasm. The aromatic accessions from Assam, Manipur and Sikkim were assigned to the Indica group, while the accessions from Nagaland exhibited close association with Japonica. The tai accessions of Mizoram along with few chakhao accessions collected from the hill districts of Manipur were identified as admixed. The results highlight the importance of regional genetic studies for understanding diversification of aromatic rice in India. The data also suggest that there is scope for exploiting the genetic diversity of aromatic and quality rice germplasm of NE India for rice improvement.

The production of toxins by some species of phytoplankton is known to have several economic, ecological, and human health impacts. However, the role of toxins on the spatial distribution of phytoplankton is not well understood. In the present study, the spatial dynamics of a nutrient-phytoplankton system with toxic effect on phytoplankton is investigated. We analyze the linear stability of the system and obtain the condition for Turing instability. In the presence of toxic effect, we find that the distribution of nutrient and phytoplankton becomes inhomogeneous in space and results in different patterns, like stripes, spots, and the mixture of them depending on the toxicity level. We also observe that the distribution of nutrient and phytoplankton shows spatiotemporal oscillation for certain toxicity level., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the recent Mars 2020 Rover Science Definition Team Report, the National Aeronautics and Space Administration (NASA) has sought the capability to detect and identify elements, minerals, and most importantly, biosignatures, at fine scales for the preparation of a retrievable cache of samples. The current Mars rover, the Mars Science Laboratory Curiosity, has a remote laser-induced breakdown spectroscopy (LIBS) instrument, a type of quantitative elemental analysis, called the Chemistry Camera (ChemCam) that has shown that laser-induced spectroscopy instruments are not only feasible for space exploration, but are reliable and complementary to traditional elemental analysis instruments such as the Alpha Particle X-Ray Spectrometer. The superb track record of ChemCam has paved the way for other laser-induced spectroscopy instruments, such as Raman and fluorescence spectroscopy. We have developed a prototype remote LIBS-Raman-fluorescence instrument, Q-switched laser-induced time-resolved spectroscopy (QuaLITy), which is approximately 70 000 times more efficient at recording signals than a commercially available LIBS instrument. The increase in detection limits and sensitivity is due to our development of a directly coupled system, the use of an intensified charge-coupled device image detector, and a pulsed laser that allows for time-resolved measurements. We compare the LIBS capabilities of our system with an Ocean Optics spectrometer instrument at 7 m and 5 m distance. An increase in signal-to-noise ratio of at least an order of magnitude allows for greater quantitative analysis of the elements in a LIBS spectrum with 200-300 μm spatial resolution at 7 m, a Raman instrument capable of 1 mm spatial resolution at 3 m, and bioorganic fluorescence detection at longer distances. Thus, the new QuaLITy instrument fulfills all of the NASA expectations for proposed instruments.

Background: Interleukin 6 mediates graft-versus-host disease (GVHD) in experimental allogeneic stem-cell transplantation (allogeneic SCT) and represents an attractive therapeutic target. We aimed to assess whether the humanised anti-interleukin-6 receptor monoclonal antibody, tocilizumab, could attenuate the incidence of acute GVHD., Methods: We undertook a single-group, single-institution phase 1/2 study at the Royal Brisbane and Women's Hospital Bone Marrow Transplantation unit, QLD, Australia. Eligible patients were 18-65 years old and underwent T-replete HLA-matched allogeneic SCT with either total body irradiation-based myeloablative or reduced-intensity conditioning from unrelated or sibling donors. One intravenous dose of tocilizumab (8 mg/kg, capped at 800 mg, over 60 mins' infusion) was given the day before allogeneic SCT along with standard GVHD prophylaxis (cyclosporin [5 mg/kg per day on days -1 to +1, then 3 mg/kg per day to maintain therapeutic levels (trough levels of 140-300 ng/mL) for 100 days plus methotrexate [15 mg/m(2) on day 1, then 10 mg/m(2) on days 3, 6, and 11]). The primary endpoint was incidence of grade 2-4 acute GVHD at day 100, assessed and graded as per the Seattle criteria. Immunological profiles were compared with a non-randomised group of patients receiving allogeneic SCT, but not treated with tocilizumab. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12612000726853., Findings: Between Jan 19, 2012, and Aug 27, 2013, 48 eligible patients receiving cyclosporin and methotrexate as GVHD prophylaxis were enrolled into the study. The incidence of grade 2-4 acute GVHD in patients treated with tocilizumab at day 100 was 12% (95% CI 5-24), and the incidence of grade 3-4 acute GVHD was 4% (1-13). Grade 2-4 acute GVHD involving the skin developed in five (10%) patients of 48 treated with tocilizumab, involving the gastrointestinal tract in four (8%) patients; there were no reported cases involving the liver. Low incidences of grade 2-4 acute GVHD were noted in patients receiving both myeloablative total body irradiation-based conditioning (12% [95% CI 2-34) and fludarabine and melphalan reduced-intensity conditioning (12% [4-27]). Immune reconstitution was preserved in recipients of interleukin-6 receptor inhibition, but qualitatively modified with suppression of known pathogenic STAT3-dependent pathways., Interpretation: Interleukin 6 is the main detectable and dysregulated cytokine secreted after allogeneic SCT and its inhibition is a potential new and simple strategy to protect from acute GVHD despite robust immune reconstitution; a randomised, controlled trial assessing tocilizumab in addition to standard GVHD prophylaxis in these patients is warranted., Funding: National Health and Medical Research Council and Queensland Health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The tetrasaccharide repeating unit of the O-antigen of Escherichia coli O174 strain was synthesized applying sequential glycosylations of suitably functionalized monosaccharide intermediates. Activation of glycosyl trichloroacetimidate derivatives using nitrosyl tetrafluoroborate (NOBF4) has been used during the synthesis. The glycosylation steps were high yielding with satisfactory stereo outcome.

A 52-year-old female was diagnosed with rheumatoid arthritis and was on methotrexate and prednisolone. She developed fever, cough, hemoptysis, and cavitary lesion on chest skiagram. She was put on antitubercular therapy without any improvement, meanwhile she developed painful right foot drop. Clinicoradiology and C-ANCA study confirmed the diagnosis of granulomatosis with polyangitis (GPA). She was started on cyclophosphamide, corticosteroid, and co-trimoxazole. While her treatment was being continued she showed significant improvement of pulmonary manifestations. About 1 year later, there was reappearance of fever, cough, and radiological opacity with oropharyngeal candidiasis. She became very ill with disseminated intravascular coagulation (DIC)-like features. Immunological markers were negative but bronchoalveolar lavage fluid study showed growth of Aspergillus spp. The patient was promptly put on intravenous voriconazole but unfortunately she succumbed to her illness.

A series of glycosyl triazol linked 18β-glycyrrhetinic acid (GA) derivatives have been synthesized using 1,3-dipolar cycloaddition reaction of per-O-acetylated glycosyl azide derivatives (4a-h) with propargyl ester of 18β-glycyrrhetinic acid (GA) (2 and 3) following the concept of 'Click chemistry'. The synthesized triazole derivatives were de-O-acetylated to furnish compounds (7a-h and 8a-c) with free hydroxyl groups in the carbohydrate moieties, which were evaluated for their anticancer potential against human cervical cancer cells (HeLa) and normal kidney epithelial (NKE) cells. GA (1), compound 7d, compound 7g and compound 8c showed promising anticancer activities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Synthesis of the pentasaccharide repeating unit of the O-antigen of Escherichia coli O13 strain has been achieved using a straightforward linear synthetic strategy. Similar reaction conditions have been used for all glycosylations as well as protective group manipulations. All intermediate steps are high yielding and the glycosylation steps are stereoselective. The synthesized pentasaccharide was subjected to conformational analysis using 2D ROESY NMR spectral analysis and molecular dynamics (MD) simulation to get detailed information on conformation of the molecule in aqueous solution., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A straightforward convergent synthesis has been carried out for the tetrasaccharide repeating unit of the O-specific cell wall lipopolysaccharide of the strain Sp7 of Azospirillum brasilense. The target tetrasaccharide has been synthesized from suitably protected monosaccharide intermediates in 42% overall yield in seven steps by using a [2 + 2] block glycosylation approach.

An integrated Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) instrument is a valuable geoanalytical tool for future planetary missions to Mars, Venus, and elsewhere. The ChemCam instrument operating on the Mars Curiosity rover includes a remote LIBS instrument. An integrated Raman-LIBS spectrometer (RLS) based on the ChemCam architecture could be used as a reconnaissance tool for other contact instruments as well as a primary science instrument capable of quantitative mineralogical and geochemical analyses. Replacing one of the ChemCam spectrometers with a miniature transmission spectrometer enables a Raman spectroscopy mineralogical analysis to be performed, complementing the LIBS chemical analysis while retaining an overall architecture resembling ChemCam. A prototype transmission spectrometer was used to record Raman spectra under both Martian and Venus conditions. Two different high-pressure and high-temperature cells were used to collect the Raman and LIBS spectra to simulate surface conditions on Venus. The resulting LIBS spectra were used to generate a limited partial least squares Venus calibration model for the major elements. These experiments demonstrate the utility and feasibility of a combined RLS instrument.

Arsenic is hazardous and causes several ill effects on human beings. Phytoremediation is the use of aquatic plants for the removal of toxic pollutants from external media. In the present research work, the removal efficiency as well as the arsenic uptake capacity of duckweed Lemna minor has been studied. Arsenic concentration in water samples and plant biomass were determined by AAS. The relative growth factor of Lemna minor was determined. The duckweed had potential to remove as well as uptake arsenic from the aqueous medium. Maximum removal of more than 70% arsenic was achieved atinitial concentration of 0.5 mg/1 arsenic on 15th day of experimental period of 22 days. Removal percentage was found to decrease with the increase in initial concentration. From BCF value, Lemna minor was found to be a hyperaccumulator of arsenic at initial concentration of 0.5 mg/L, such that accumulation decreased with increase in initial arsenic concentration.

The present study investigates the ability of two genus of duckweed (Lemna minor and Spirodela polyrhiza) to phytoremediate cadmium from aqueous solution. Duckweed was exposed to six different cadmium concentrations, such as, 0.5,1.0,1.5, 2.0, 2.5, and 3.0 mg/L and the experiment was continued for 22 days. Water samples were collected periodically for estimation of residual cadmium content in aqueous solution. At the end of treatment period plant samples were collected and accumulated cadmium content was measured. Cadmium toxicity was observed through relative growth factor and changes in chlorophyll content Experimental results showed that Lemna minor and Spirodela polyrhiza were capable of removing 42-78% and 52-75% cadmium from media depending upon initial cadmium concentrations. Cadmium was removed following pseudo second order kinetic model Maximum cadmium accumulation in Lemna minor was 4734.56 mg/kg at 2 mg/L initial cadmium concentration and 7711.00 mg/kg in Spirodela polyrhiza at 3 mg/L initial cadmium concentration at the end of treatment period. Conversely in both cases maximum bioconcentration factor obtained at lowest initial cadmium concentrations, i.e., 0.5 mg/L, were 3295.61 and 4752.00 for Lemna minor and Spirodela polyrhiza respectively. The present study revealed that both Lemna minor and Spirodela polyrhiza was potential cadmium accumulator.

Trees of Myrica sp. grow abundantly in the forests of Meghalaya, India. These trees are actinorhizal and harbour nitrogen-fixing Frankia in their root nodules and contribute positively towards the enhancement of nitrogen status of forest areas. They can be used in rejuvenation of mine spoils and nitrogen-depleted fallow lands generated due to slash and burn agriculture practiced in the area. We have studied the association of amplicon restriction patterns (ARPs) of Myrica ribosomal RNA gene and internal transcribed spacer (ITS) region and nitrogenase activity of its root nodules. We found that ARPs thus obtained could be used as markers for early screening of seedlings that could support strains of Frankia that fix atmospheric nitrogen more efficiently.

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a severe cutaneous drug reaction with a high mortality. Immune response is the possible cause in its pathogenesis. Levofloxacin is one of the most commonly used quinolones and has been reported to cause of TEN. On the other hand, furazolidone was proposed to augment the action of immediate hypersensitivity of levofloxacin by its cytotoxic effect and by the generation of free radicals. Here, we present a case of TEN where, levofloxacin and furazolidone were the probable cause of these adverse drug reactions.

The reconstitution of anti-viral cellular immunity following hematopoietic stem cell transplantation (HSCT) is crucial in preventing cytomegalovirus (CMV)-associated complications. Thus immunological monitoring has emerged as an important tool to better target pre-emptive anti-viral therapies. However, traditional laboratory-based assays are too cumbersome and complicated to implement in a clinical setting. Here we conducted a prospective study of a new whole blood assay (referred to as QuantiFERON-CMV®) to determine the clinical utility of measuring CMV-specific CD8+ T-cell responses as a prognostic tool. Forty-one evaluable allogeneic HSCT recipients underwent weekly immunological monitoring from day 21 post-transplant and of these 21 (51.2%) showed CMV reactivation and 29 (70.7%) developed acute graft-versus-host disease (GvHD). Patients with acute GvHD (grade ≥ 2) within 6 weeks of transplant showed delayed reconstitution of CMV-specific T-cell immunity (p = 0.013) and a higher risk of CMV viremia (p = 0.026). The median time to stable CMV-specific immune reconstitution was 59 days and the incidence of CMV reactivation was lower in patients who developed this than those who did not (27% versus 65%; p = 0.031). Furthermore, a failure to reconstitute CMV-specific immunity soon after the onset of CMV viraemia was associated with higher peak viral loads (5685 copies/ml versus 875 copies/ml; p = 0.002). Hence, QuantiFERON-CMV® testing in the week following CMV viremia can be useful in identifying HSCT recipients at risk of complicated reactivation.

A straightforward synthesis of the tetrasaccharide repeating unit of the O-antigen of Escherichia coli O16 has been achieved following a sequential glycosylation strategy. A minimum number of steps was used for the synthesis of the target compound involving a one-pot glycosylation and a protecting group manipulation. All intermediate reactions afford their products in high yield, and the glycosylation steps are stereoselective.

In this paper, a non-linear mathematical model for removing an inorganic pollutant such as chromium from a water body using fungi is proposed and analyzed. It is assumed that the inorganic pollutant is discharged in a water body with a constant rate, which is depleted due to natural factors as well as by fungal absorption using dissolved oxygen in the process. The model is analyzed by using stability theory of differential equations and simulation. The analysis shows that the inorganic pollutant can be removed from the water body by fungal absorption, the rate of removal depends upon the concentration of inorganic pollutant, the density of fungal population and various interaction processes. The simulation analysis of the model confirms the analytical results. It is noted here this theoretical result is qualitatively in line with the experimental observations of one of the authors (Sanghi)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We discuss the novel design of a sensitive, normal-Raman spectrometer interfaced to an ultra-high vacuum chamber (5 × 10(-11) Torr) utilized to investigate the interaction of ionizing radiation with low temperature ices relevant to the solar system and interstellar medium. The design is based on a pulsed Nd:YAG laser which takes advantage of gating techniques to isolate the scattered Raman signal from the competing fluorescence signal. The setup incorporates innovations to achieve maximum sensitivity without detectable heating of the sample. Thin films of carbon dioxide (CO2) ices of 10 to 396 nm thickness were prepared and characterized using both Fourier transform infrared (FT-IR) spectroscopy and HeNe interference techniques. The ν+ and ν- Fermi resonance bands of CO2 ices were observed by Raman spectroscopy at 1385 and 1278 cm(-1), respectively, and the band areas showed a linear dependence on ice thickness. Preliminary irradiation experiments are conducted on a 450 nm thick sample of CO2 ice using energetic electrons. Both carbon monoxide (CO) and the infrared inactive molecular oxygen (O2) products are readily detected from their characteristic Raman bands at 2145 and 1545 cm(-1), respectively. Detection limits of 4 ± 3 and 6 ± 4 monolayers of CO and O2 were derived, demonstrating the unique power to detect newly formed molecules in irradiated ices in situ. The setup is universally applicable to the detection of low-abundance species, since no Raman signal enhancement is required, demonstrating Raman spectroscopy as a reliable alternative, or complement, to FT-IR spectroscopy in space science applications.

A series of glycosyl hemiacetal derivatives have been transformed into thioglycosides and glycosyl thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium carbonotrithioate. The reaction conditions are reasonably simple and yields were very good.

A short synthetic approach was developed for the synthesis of a common trisaccharide core found in kankanose, kankanoside F, H1, H2, and I isolated from the medicinally active plant Cistanche tubulosa. All glycosylations were carried out under nonmetallic reaction conditions. Yields were very good in all intermediate steps.

A significantly fast reaction condition for the exclusive preparation β-glycosyl thiol derivatives has been developed successfully. The reaction condition is one-step, fast, high yielding, highly stereoselective, and requires only benchtop chemicals. Further reaction of glycosyl thiol derivatives with Michael acceptors and alkylating agents furnished thioglycosides and (1,1)-thiolinked trehalose analogs.

Clean deprotection of carbohydrate derivatives containing benzylidene acetals and benzyl ethers was achieved under catalytic transfer hydrogenation conditions by using a combination of triethylsilane and 10% Pd/C in CH(3)OH at room temperature. A variety of carbohydrate diol derivatives were prepared from their benzylidene derivatives in excellent yield.

A straightforward synthesis of the pentasaccharide with all α-linked glycosyl linkages corresponding to the cell wall O-antigen of Escherichia coli 19ab has been achieved in excellent yield using sequential glycosylations of monosaccharide intermediates. The structure of the target compound and its synthetic intermediates were unambiguously characterized using their spectral analysis. A generalized glycosylation condition has been used in all glycosylations and minimum number of protecting group manipulations were involved during the synthesis of the target compound., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The aim of this study is to examine the role of GCH1 among Indians affected with dopa responsive dystonia (DRD) and early onset Parkinson's disease (EOPD). The patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were screened for variants in GCH1 by PCR amplification of exons, splice junctions and 1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants (p.Met1Val, p.Val204&#95;205del, IVS3+68A>G, and IVS5-6T>G) were identified in 10 patients but not in the controls. In addition to two nonsynonymous changes, identified in four DRD patients in heterozygous condition, one intronic variant (IVS5-6T>G) could be linked to pathogenesis of the disease since it has the potential of altering the splice site as assessed by in silico analysis. Patients carrying different nonsynonymous variants had remarkable variation in clinical phenotype. Consistent with earlier reports, severity of clinical phenotype and the age of onset varied among family members harboring the same mutation. No mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene have been found and are shown to be associated with variable clinical phenotypes mostly within the spectrum of DRD. The mutations identified represent 15.79% (3/19) of east Indian DRD patient cohort.

The capability to analyze and detect the composition of distant samples (minerals, organics, and chemicals) in real time is of interest for various fields including detecting explosives, geological surveying, and pollution mapping. For the past 10 years, the University of Hawaii has been developing standoff Raman systems suitable for measuring Raman spectra of various chemicals in daytime or nighttime. In this article we present standoff Raman spectra of various minerals and chemicals obtained from a distance of 120 m using single laser pulse excitation during daytime. The standoff Raman system utilizes an 8-inch Meade telescope as collection optics and a frequency-doubled 532 nm Nd : YAG laser with pulse energy of 100 mJ/pulse and pulse width of 10 ns. A gated intensified charge-coupled device (ICCD) detector is used to measure time-resolved Raman spectra in daytime with detection time of 100 ns. A gate delay of 800 ns (equivalent to target placed at 120 m distance) was used to minimize interference from the atmospheric gases along the laser beam path and near-field scattering. Reproducible, good quality single-shot Raman spectra of various inorganic and organic chemicals and minerals such as ammonium nitrate, potassium perchlorate, sulfur, gypsum, calcite, benzene, nitrobenzene, etc., were obtained through sealed glass vials during daytime. The data indicate that various chemicals could easily be identified from their Raman fingerprint spectra from a far standoff distance in real time using single-shot laser excitation.

Reaction of glycal derivatives with alcohols or glycosyl acceptors in the presence of N-bromosuccinimide (NBS) and diphenyldiselenide resulted in the formation of alkyl 2-deoxy-2-phenylselenyl glycosides or disaccharide derivatives in excellent yield. The reactions are reasonably fast and considerable stereo-selectivity was observed in the preparation of disaccharide derivatives., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Isoniazid and orlistat were reported to have inhibitory effect on mycobacterial ES-31 serine protease in vitro and bacterial cell growth in axenic culture., Aim: To study the cumulative effect and understand drug - drug interaction, if any, when isoniazid and orlistat used in combination., Material and Methods: Inhibition of mycobacterial ES-31 serine protease by different combinations of orlistat and isoniazid together and individually were studied using azocasein assay. Inhibition of secretion of excretory secretory ES-31 antigen in Sautan culture medium was studied under axenic condition and growth of M. tuberculosis H37Ra bacilli by CFU count on LJ-medium., Results: Orlistat and isoniazid both showed inhibitory activity of ES-31 serine protease in in vitro as well as in vivo. Individually, isoniazid showed 90% inhibition at 200 ng/ml while orlistat at 250 ng/ml showed 65% inhibition of mycobacterial ES-31 serine protease in vitro. A combination of orlistat (250 ng/ml) and isoniazid (200 ng/ml) showed 86% inhibition in vitro while 73% inhibition was observed by orlistat (25 ng/ml) and isoniazid (200 ng/ml) on bacterial growth in axenic culture., Conclusion: Significant inhibition by orlistat suggests that it could be tried in patients with intolerance to isoniazid or in those already developed isoniazid resistance. It may also be explored in the suspected TB patients as initial medication in place of antibiotics for clinical relief.