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A new mononuclear Mn(III) derivative, [Mn(L)(H2O)2]ClO4 (1) was obtained by reacting manganese perchlorate with the tetradentate Schiff base precursor, H2L, [where H2L=C6H3(OMe)(OH)CH=N(CH2)3N=CH(OH)(OMe)C6H3] and characterized by various spectral techniques. Single crystal X-ray diffraction analysis revealed that in 1, the central Mn atom is hexa-coordinated via the NNOO donor sites of the Schiff base precursor and two water molecules, yielding a distorted octahedral geometry. Also, the EPR spectra of 1 were recorded at the solid state by varying the temperature (from 90 to 300 K) as well as in different organic solvents; DMSO, MeOH and a mixture CH2Cl2/toluene; the results obtained agree with the geometrical environment around the metal. The cytotoxic activity of the Mn(III) derivative was evaluated against normal and cancer cell lines. The derivative exhibited comparatively better cytotoxic activity against MCF-7 cells compared to SiHa and fibroblast cells.

Background Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of ‘tumor-associated antigens (TAAs) that elicit humoral response’ in early stage GBC patients. Methods Total protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins. Results Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p Conclusions The study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

Producing rice grain with superior quality along with higher productivity is very much needed to improve the food and nutrient security. Therefore, this experiment was designed to determine the effect of seaweed sap derived from the red seaweed Kappaphycus alvarezii (K–sap) on quality improvement of rice grown under rice–potato–greengram crop sequence. The experiment consisted of 12 treatments using K–sap and chemical fertilizer application in a randomized complete block design replicated thrice. The study was conducted at Uttar Chandamari village, India, during two consecutive years of 2013–2014 and 2014–2015. It was found that the maximum amounts of physical quality attributes, viz. hulling, milling, head rice recovery and biochemical quality attributes like amylose and carbohydrate contents of rice, were found with 7.5% K–sap + 100% RDF (recommended dose of fertilizer). This treatment also exhibited the highest system productivity. Concerning the efficiency of the system, it was documented that the maximum values of agronomic efficiency, physiological efficiency and recovery fraction of nutrient used were recorded in 7.5% K–sap + 50% RDF, 0.0% K–sap + 50% RDF and 7.5% K–sap + 100% RDF, respectively. It was also evaluated that the foliar spraying of K–sap at 2.5, 5 and 7.5% rate along with 100% RDF showed the positive nitrogen (N) balance of the system. From this study, it was observed that the foliar application of K–sap is able to improve the quality of rice besides improving yield and better system efficiency. Positive N balance was also accomplished through the application of K–sap in combination with RDF.

Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries. In March 2017, a group of experts from 10 Asian cholera-prone countries that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. This paper reports on the country situation, gaps identified in terms of cholera prevention and control and strategic interventions to bridge these gaps.

Leprosy, a progressive, mutilating and highly stigmatized disease caused by Mycobacterium leprae (ML), continues to prevail in the developing world. This is due to the absence of rapid, specific and sensitive diagnostic tools for its early detection since the disease gets notified only with the advent of physical scarring in patients. This study reports the development of a Loop-mediated isothermal amplification (LAMP) technique for fast, sensitive and specific amplification of 16S rRNA gene of ML DNA for early detection of leprosy in resource-limited areas. Various parameters were optimized to obtain robust and reliable amplification of ML DNA. Blind clinical validation studies were performed which showed that this technique had complete concurrence with conventional techniques. Total absence of amplification of negative control DNA confirmed the specificity of this test. Various visual detection methods viz. colorimetric, turbidity differentiation and bridge flocculation were standardized to establish easy-to-read and rapid diagnosis. This technique eliminates the lack of accuracy and sensitivity in skin smear tests in patients and the requirement for expensive lab equipments and trained technicians. The technique holds promise for further expansion and has the potential to cater to the unmet needs of society for a cheap, highly-sensitive and robust rapid diagnosis of ML.

Background: The ideal adjuvant treatment of triple negative EBC remains to be defined. CIBOMA/2004-01_GEICAM/2003-11 is a multinational randomized phase III trial exploring adjuvant Cap after the conclusion of conventional chemotherapy in triple-negative EBC patients. Materials and Methods: Patients with operable, node-positive (or node-negative with tumour diameter ≥1 cm), hormone receptor-negative, HER2-negative EBC that have received 6–8 cycles of standard anthracycline and/or taxane-containing chemotherapy in the (neo)adjuvant setting (doxorubicin–cyclophosphamide x 4 allowed for node-negative disease), followed by radiotherapy (if indicated) are eligible. After central confirmation of triple negativity by immunohistochemistry, patients were randomised to either 8 cycles of Cap (1,000 mg/m2 bid, d1–14 q21d) or observation. Stratification factors: centre, prior taxane (yes vs. no), involved nodes (0 vs. 1–3 vs. ≥4) and phenotype (basal vs. non-basal). The primary endpoint is disease-free survival (DFS). Secondary endpoints include 5-year DFS, overall survival and safety. An optional pharmacogenetic sub-study will explore polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase in relation to efficacy and tolerability of Cap. Present Status: Recruitment of 876 randomized patients was completed in September 2011. Statistical assumptions: expected 30% reduction in the risk of recurrence at 5 years (64.7% to 73.7%, HR 0.701), power of 80% and 0.05 two-sided significance level. Final efficacy analysis will be triggered by 255 events. Baseline characteristics are well balanced and shown in the table below. 75.0% of the patients completed the 8 cycles of adjuvant Cap. Conclusions: This randomized phase III adjuvant trial in triple negative EBC patients has completed accrual and event follow up is ongoing. The trial is sponsored by CIBOMA/GEICAM. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-06.

Conventional agricultural production systems, coupled with lower productivity of the crops, need to be improved to accomplish sustainable production. It has been realized that any advance in an agricultural system resulting in higher crop production should reduce environmental impacts and enhance the sustainability of the system as a whole. In this context, the use of bio-stimulants in improving the effectiveness of conventional mineral fertilizers may be a good choice. Among many viable options, the use of seaweed extracts containing almost all major and minor plant nutrients, amino acids, vitamins and growth-promoting substances like cytokinins and auxins may be a possible option. Considering these, the present experiment was conducted to find out the impact of Kappaphycus seaweed sap (K-sap) on growth, yield and quality of potato. Different concentrations of Kappaphycus sap (0, 2.5, 5 and 7.5%) were sprayed on the foliage of the crop along with a varied dose of fertilizers [50, 75 and100% of the recommended dose of fertilizers (RDF)]. It was observed that the seaweed sap has a significant impact on the growth, yield and quality improvement of the crop. Results suggested that K-sap with the concentration of 7.5% along with 100% of the RDF is the best to improve growth, yield and quality of potato, and this treatment was followed by 5% K-sap + 100% RDF. It was also exhibited that 7.5% K-sap has the potentiality to substitute 25% of the RDF.

Objective Growing evidences suggest systemic pathogen-induced neuroimmune interaction is a major risk factor for several neurological disorders. Our goal was to investigate whether asymptomatic peripheral carriage of Staphylococcus aureus, a widespread opportunistic pathogen, could modulate selective molecular features in brain tissues. Methods To address this, a peripheral infection model was developed by challenging Wistar rats repeatedly with a clinical strain of S. aureus. Animals infected with S. aureus (10 CFU for three times in 10 days) showed significant changes in acetylation profile of selective lysine (K) residues K9 (H3K9), K14 (H3K14) and K27 (H3K27) of histone H3 in the hippocampus and prefrontal cortex (PFC). Results Although S. aureus was restricted peripherally, the infection induced hypoacetylation of H3K9, H3K14 and H3K27 in the hippocampus and H3K27 in the PFC. Histone H3 hypoacetylation in the hippocampus and PFC was also detected when rats were challenged with an engineered invasive strain of E. coli K12, SK3842. This confirmed that modulation of epigenetic landscape in distal brain tissues may not be specific to S. aureus. Moreover, the tyrosine hydroxylase protein, the rate limiting enzyme in dopamine synthesis pathway whose gene-expression is regulated by H3 acetylation at the promoter, was remarkably reduced in the brain tissues of the infected hosts. Conclusion The results indicate that commensals like S. aureus, in spite of being largely restricted to the peripheral tissues, could modulate the homeostasis of molecular features in brain tissues whose maintenance is critical for preserving normal neurological functions.

Continuous rice–wheat cropping system with intensive conventional tillage operations have been showing natural resource degradation. Hence, the sustainability of this major cropping system in eastern India is under a threat. Adoption of resource conservation such as conservation tillage practice with residue retention on the soil and diversification of the rice–wheat cropping system with the inclusion of pulses, oilseeds may lead towards achieving overall sustainability of the system. Attempts were made to evaluate the different tillage practices viz. zero tillage (ZT), reduced tillage (RT) and conventional tillage (CT) under rice based various cropping systems viz. rice–wheat–greengram, rice–Lathyrus–greengram, rice–lentil–greengram and rice–rapeseed–greengram in terms of system productivity, nutrient uptake by the system, recovery efficiency (RE) of added nutrients, soil microbial population and nitrous oxide (N2O) emission in alluvial soil of eastern India. Results revealed significant increase in system productivity, nutrient uptake and RE of N, P and K in RT. The maximum microbial population was found in ZT. Cereal dominated cropping system (rice–wheat–greengram) showed higher productivity and nutrient uptake, however, the recovery efficiency of nutrient and microbial population was recorded higher in legume dominated cropping systems (rice–lentil–greengram or rice–Lathyrus–greengram). The maximum N2O emission was recorded in ZT, which was almost 3–6% higher than that of RT and CT, respectively. Overall, reduced tillage was found to be the most suitable tillage option under rice based diversified cropping systems.

In this study, we report the simple fabrication of an active substrate assisted by gold nanostructures (AuNS) for application in surface-enhanced Raman scattering (SERS) using copier paper, which is a biodegradable and cost-effective material. As cellulose is the main component of paper, it can behave as a reducing agent and as a capping molecule for the synthesis of AuNS on the paper substrate. AuNS can be directly generated on the surface of the copier paper by addition of halides. The AuNS thus synthesized were characterized by ultraviolet–visible spectroscopy, SEM, XRD, and XPS. In addition, the SERS effect of the AuNS–paper substrates synthesized by using various halides was investigated by using rhodamine 6G and melamine as probe molecules.

Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage. Therefore, the purpose of this study was to determine whether one such agent, melatonin (Mel), could confer protection against Oxa-induced neurotoxicity in SH-SY5Y cells. Results from the present study found Oxa to significantly reduce SH-SY5Y cell viability in a dose-dependent manner. Alternatively, we found Mel pre-treatment to SH-SY5Y cells to attenuate Oxa-induced toxicity, resulting in a markedly increased cell viability. Mel exerted its protective effects by regulating reactive oxygen species (ROS) production and reducing superoxide radicals inside Oxa-exposed. In addition, we observed pre-treatment with Mel to rescue Oxa-treated cells by protecting mitochondria. As Oxa-treatment alone decreases mitochondrial membrane potential (Δψm), resulting in an altered Bcl-2/Bax ratio and release of sequestered cytochrome c, so Mel was shown to inhibit these pathways. Mel was also found to inhibit proteolytic activation of caspase 3, inactivation of Poly (ADP Ribose) polymerase, and DNA damage, thereby allowing SH-SY5Y cells to resist apoptotic cell death. Collectively, our results suggest a role for melatonin in reducing Oxa induced neurotoxicity. Further studies exploring melatonin's protective effects may prove successful in eliciting pathways to further alter the neurotoxic pathways of platinum compounds in cancer treatment.

Commensal Escherichia coli has been identified as a major protagonist of microbe-induced colorectal oncogenesis. Its tumour-promoting attribute is linked to the expression of DNA-damaging genotoxins. Using a constitutively invasive variant of non-pathogenic E. coli, we demonstrate that chronic presence of internalized E. coli leads to enhanced oncogenicity in colon cancer cells. Instead of genomic damage, the tumorigenic effect is mediated through an expansion of the cancer stem cell (CSC) population, likely through dedifferentiation of lineage-committed intestinal epithelial cells. Stemness-linked intestinal tumorigenicity is directly correlated to absence of microbial virulence factor expression and is specific for intestinal cells. The enriched CSC fraction remains stable in the absence of the instigating bacteria and can foster stemness traits in unexposed cells through secreted factors. Mechanistically, aberrant host invasion leads to realignment of multiple host signal transduction cascades, notably mutually re-enforcing NF-κB and β-catenin activation, through reciprocal modulation of microbe sensing pathways Nod1/Rip2 and TLR/MyD88. The expanded tumorigenic CSC population is marked by enhanced malignancy traits, long-term self-renewal capacity and robust tumorigenic ability, both in vitro and in vivo. Our study shows that microbe-induced oncogenicity is not a strict correlate of commensal virulence and can be invoked by even non-pathogenic E. coli by engendering tumorigenic stemness in host cells.

A small organic molecule of 2,3-bis(5-bromothiophene-2-yl)acrylonitrile (DTDBAL) was synthesized for the first time and introduced into an active layer consisting of poly-3-hexylthiophene (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), in order to improve the performance of an inverted bulk heterojunction organic photovoltaic. The short-circuit current of the device was improved owing to the formation of a cascade band alignment of P3HT/DTDBAL/PCBM which enhanced the exciton dissociation and charge transport. Meanwhile, the open-circuit voltage and fill factor were simultaneously improved due to the optimization of the active layer morphology. The best power conversion efficiency achieved was 3.45% under simulated AM 1.5G illumination of 100 mW/cm 2 , which is an increase of 36% compared to a solar cell without the additive and featuring only P3HT/PCBM as the active layer.

Phytanic acid, a saturated branched chain fatty acid and a major constituent of human diet, is predominantly found in dairy products, meat, and fish. It is a degradation product from the phytol side chain of chlorophyll. Degradation of PA is known to occur mainly in peroxisomes via α-oxidation and in mitochondria via β-oxidation. Due to its β-methyl group present at the 3-position of the carbon atoms, PA cannot be β-oxidized. Although alteration in the metabolism of PA may play an important role in neurodegeneration, the exact mechanism behind it remains to be evaluated. In this study, we have described the potential of PA to induce neurotoxicity as an in vitro model (neuronal cell line, SH-SY5Y cells). Cells were pretreated with melatonin (10 μM) for 1 h followed by with and without PA (100 μM) for 24 h. In the present study, our data has confirmed that PA markedly increased both intracellular reactive oxygen species and reactive nitrogen species levels. Our results have shown that PA treatment did not induce cell death by cleavage of caspase-3/PARP-1 mediated by mitochondria through intrinsic pathways; however, PA induced nitric oxide-dependent apoptosis in SH-SY5Y cells. Additionally, melatonin pretreatment reduced the cell death in SH-SY5Y cells. Melatonin also effectively exerted an antiapoptotic and anti-inflammatory action by regulating Bax, Bcl-2, p-NFκB, and iNOS expressions in SH-SY5Y cells. These results suggested that melatonin acted as an antioxidative and antiapoptotic agent by modulating ROS, apoptotic proteins, and inflammatory responses under BCFA-induced neurotoxic conditions. The protective effects of melatonin depend on direct scavenging activity of free radicals and indirect antioxidant effects. Further deciphering of the cellular and molecular mechanism associated with neuroprotection by melatonin is warranted in BCFA-induced neurotoxicity.

The development of novel molecules for the creation of nanometer structures with specific properties has been the current interest of this research. We have developed a set of molecules from hydrophobic ω- and α-amino acids by protecting the –NH2 with Boc (t-butyloxycarbonyl) group and –CO2H with para-nitroanilide such as BocHN–Xx–CONH–(p–NO2)·C6H4, where Xx is γ-aminobutyric acid (γ-Abu), (l)-isoleucine, α-aminoisobutyric acid, proline, etc. These molecules generate various nanometer structures, such as nanofibrils, nanotubes and nanovesicles, in methanol/water through the self-assembly of bilayers in which the nitro benzene moieties are stacked in the middle and the Boc-protected amino acids parts are packed in the outer surface. The bilayers can be further stacked one over the other through hydrophobic interactions to form multilayer structure, which helps to generate different kinds of nanoscopic structures. The formation of the nanostructures has been facilitated through the participation of various noncovalent interactions, such as hydrophobic interactions, hydrogen bonding and aromatic π-stacking interactions. Fluorescence microscopy and UV studies reveal that the nanovesicles generated from pro-based molecule can encapsulate dye molecules which can be released by addition of acid (at pH 2). These single amino acid based molecules are both easy to synthesize and cost-effective and therefore offer novel scaffolds for the future design of nanoscale structures.

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe (I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: α-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while β-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated β-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

The tripeptides Boc-Gly-Aib- m -ABA-OMe ( I ), Boc-βAla-Aib- m -ABA-OMe ( II ) and Boc-γAbu-Aib- m -ABA-OMe ( III ) (Aib: α-aminoisobutyric acid, βAla: β-alanine, γAbu: γ-aminobutyric acid, m -ABA: meta -aminobenzoic acid) with homologated amino acids at the N-terminus, the rigid γ-amino acid m -ABA at the C-terminus and the helicogenic Aib at the central position have been chosen to create unusual turns. Single crystal X-ray diffraction studies, solvent dependent NMR titrations and 2D NMR analysis reveal that peptides II and III adopt unusual turns of 11- and 12-membered rings stabilized by modified 4 → 1 type intramolecular hydrogen bonds. Solution phase studies indicate that peptide I exists in the β-turn conformation stabilized by 10-membered intramolecular hydrogen bonding.

Single crystal X-ray diffraction studies show that the three designed tripeptides Boc-Leu-Aib-m-NA-NO2 (I), Boc-Phe-Aib-m-NA-NO2 (II) and Boc-Pro-Aib-m-ABA-OMe (III) (Aib, α-aminoisobutyric acid; m-NA, m-nitroaniline; m-ABA, m-aminobenzoic acid; Boc, t-butyloxycarbonyl) containing aromatic rings in the backbones adopt β-turn structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of β-sheets. Solvent-dependent NMR titration and CD studies show that the β-turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic and transmission electron microscopic images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through β-sheet mediated self-assembly of the preorganised β-turn building blocks.

Three tripeptides Boc-Phe-Aib-Val-OMe (1), Boc-Leu-Aib-p-NA-NO2 (2) and Boc-Pro-Aib-m-NA-NO2 (3) (Aib: alpha-aminoisobutyric acid; p- and m-NA: para- and meta-nitroaniline) have been designed by incorporating aromatic rings to study the self-assembly and fibril formation. Single crystal X-ray diffraction studies show that all the peptides adopt turn-like structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of beta-sheets. Solvent dependent NMR titration and CD studies show that the turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic (FE-SEM) images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through beta-sheet mediated self-assembly of the preorganized turn building blocks.

Single crystal X-ray diffraction studies and solvent dependent (1)H NMR titrations reveal that a set of four tetrapeptides with general formula Boc-Xx(1)-Aib(2)-Yy(3)-Zz(4)-OMe, where Xx, Yy and Zz are coded L-amino acids, adopt equivalent conformations that can be described as overlapping double turn conformations stabilized by two 4-->1 intramolecular hydrogen bonds between Yy(3)-NH and Boc C=O and Zz(4)-NH and Xx(1)C=O. In the crystalline state, the double turn structures are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. Field emission scanning electron microscopic (FE-SEM) images of the tetrapeptides in the solid state reveal that they can form flat tape-like structures. The results establish that synthetic Aib containing supramolecular helices can form highly ordered self-aggregated amyloid plaque like human amylin.

Single crystal X-ray diffraction study reveals that the water soluble tetrapeptide H 2 N–Ile–Aib–Leu– m -ABA–CO 2 H, containing non-coded Aib (α-amino isobutyric acid) and m -ABA ( meta -amino benzoic acid), crystallizes with two smallest possible diastereomeric β-hairpin molecules in the asymmetric unit. Although in both of the molecules the chiralities at Ile(1) and Leu(3) are S, a conformational reversal in the back bone chain is observed to produce the β-hairpins with β-turn conformations of type II and II′. Interestingly Aib which is known to adopt helical conformation, adopts unusual semi-extended conformation with ϕ : −49.5(5)°, ψ : 135.2(5)° in type II and ϕ : 50.6(6)°, ψ : −137.0(4)° in type II′ for occupying the i + 1 position of the β-turns. The two hairpin molecules are further interlocked through intermolecular hydrogen bonds and electrostatic interactions between – CO 2 - and − + NH 3 groups to form dimeric supramolecular β-hairpin aggregate in the crystal state. The CD measurement and 2D NMR study of the peptide in aqueous medium support the existence of β-hairpin structure in water.

Stirring of N-(2-carboxybenzoyl) anthranilic acid with anilines and amines such as p-toluidine, benzylamine, methyl esters of Leu, Phe, Ile and Val in presence of DCC produces N- 2 substituted 3-phenyliminoisoindolinones in very good yields. Single crystal X-ray diffraction studies and solution phase NMR and CD studies reveal that the 3-phenyliminoisoindolinone moiety is a turn-inducing scaffold which should be useful for reverse-turn mimetics.

The pseudopeptide Gly-m-ABA (m-ABA = m-amino benzoic acid) has been chosen to study the formation of supramolecular structures through self-assembly. Single crystal X-ray diffraction studies reveal that the pseudopeptide Boc-Gly-m-ABA-OMe (1), where both N- and C-terminus are protected, self-assembles to a supramolecular helical structure, whereas the pseudopeptide Boc-Gly-m-ABA-OH (2) with free –CO2H at the C-terminus produces molecular staircase through self-assembly. Again the terminally unprotected pseudopeptide + NH3-Gly-m-ABA-CO2 (3) aggregates to a water mediated supramolecular β-sheet structure stabilized by intermolecular hydrogen bonds and π-π interactions. The study reveals that the terminally modified Gly-m-ABA generates various kinds of self-assembling building blocks that can fabricate different types of supramolecular architectures such as helix, β-sheet and staircase.

Single crystal X-ray diffraction studies and solvent dependent NMR titration reveal that the designed peptides I and II, Boc-Xx(1)-Aib(2)-Yy(3)-NH(CH2)2NH-Yy(3)-Aib(2)-Xx(1)-Boc, where Xx and Yy are Ile and Leu in peptide I and Leu and Val in peptide II, respectively, fold into a turn-linker-turn (T-L-T) conformation both in the solid state and in solution. In the crystalline state the T-L-T foldamers of peptide I and II self-assemble to form a three-dimensional framework of channels. The insides of the channels are hydrophilic and found to contain solvent CHCl3 hydrogen bonded to exposed C O of Aib located at the turn regions.

In this study two positional isomeric dipeptides Boc–m-ABA–Aib–OMe (1) and Boc–Aib–m-ABA–OMe (2) synthesized by reversal of the positions of two rigid amino acids (m-ABA: m-aminobenzoic acid, Aib: α-aminoisobutyric acid) showed marked difference in morphology under the same environmental conditions. Investigation of single crystal structures reveals the difference in crystal packing and higher order self-assembly pattern for both the isomeric peptides, which might be the responsible factor for their different morphological patterns. Moreover, these isomeric dipeptides have produced different cellular viability effects towards normal bone cells. These two peptides would have utilities in the model study of isomeric peptides/proteins, where morphological difference under identical conditions brings changes in their individual bio-activities and where the reversal of sequence causes different cellular viability and generates health hazard.

In bacteria, the contribution of global nucleoid organization in determining cellular transcription programs is unclear. Using a mutant form of the most abundant nucleoid-associated protein HU, HUαE38K,V42L, we previously showed that nucleoid remodeling by the mutant protein re-organizes the global transcription pattern. Here, we demonstrate that, unlike the dimeric wild-type HU, HUαE38K,V42L is an octamer and wraps DNA around its surface. The formation of wrapped nucleoprotein complexes by HUαE38K,V42L leads to a high degree of DNA condensation. The DNA wrapping is right-handed, which restrains positive supercoils. In vivo, HUαE38K,V42L shows altered association and distribution patterns with the genetic loci whose transcription are differentially affected in the mutant strain.

Bacterial nucleoid organization is believed to have minimal influence on the global transcription program. Using an altered bacterial histone-like protein, HUα, we show that reorganization of the nucleoid configuration can dynamically modulate the cellular transcription pattern. The mutant protein transformed the loosely packed nucleoid into a densely condensed structure. The nucleoid compaction, coupled with increased global DNA supercoiling, generated radical changes in the morphology, physiology, and metabolism of wild-type K-12 Escherichia coli . Many constitutive housekeeping genes involved in nutrient utilization were repressed, whereas many quiescent genes associated with virulence were activated in the mutant. We propose that, as in eukaryotes, the nucleoid architecture dictates the global transcription profile and, consequently, the behavior pattern in bacteria.

Most HIV transmission occurs on the mucosal surfaces of the gastrointestinal and cervicovaginal tracts, both of which are normally coated by a biofilm of nonpathogenic commensal bacteria. We propose to genetically engineer such naturally occurring bacteria to protect against HIV infection by secreting antiviral peptides. Here we describe the development and characterization of Nissle 1917, a highly colonizing probiotic strain of Escherichia coli , secreting HIV-gp41-hemolysin A hybrid peptides that block HIV fusion and entry into target cells. By using an appropriate combination of cis- and transacting secretory and regulatory signals, micromolar secretion levels of the anti-HIV peptides were achieved. The genetically engineered Nissle 1917 were capable of colonizing mice for periods of weeks to months, predominantly in the colon and cecum, with lower concentrations of bacteria present in the rectum, vagina, and small intestine. Histological and immunocytochemical examination of the colon revealed bacterial growth and peptide secretion throughout the luminal mucosa and in association with epithelial surfaces. The use of genetically engineered live microbes as anti-HIV microbicides has important potential advantages in economy, efficacy, and durability.

Molecular dynamics (MD) studies of helium and argon diffusion in all-silica analogues of ZSM-5, ZSM-11 and ferrierite are used to study diffusional anisotropy. All three zeolites have channels running parallel to only two of the three crystallographic axes. ZSM-5 and ZSM-11, however, allow for three-dimensional diffusional motion due to the presence of geometrical correlations. Motion in the correlated direction, which has no direct displacement channels, is distinctly subdiffusional on time scales of the order of 1 ns. The ballistic to diffusional crossover times are much greater for displacements in the direction showing correlated, as opposed to, direct displacements.

The meta-aminobenzoic acid-inserted peptide β-turns are found to generate well-structured vesicles from methanol/water solution through molecular self-assembly. Fluorescence microscopy and UV studi...

A single ω-amino acid based molecule “Boc-β-Ala–N,N′-dicyclohexylurea” can form diverse nanostructures such as nano-vesicles, nano-tubes, nano-rods and nano-fibrils by self-assembly, in response to various environmental conditions. Interestingly, the nano-vesicular structures generated from this molecule can encapsulate the highly potent anticancer drug methotrexate, which can be released by salt triggered disruption of these vesicles. This phenomenon indicates the probability of its use in targeted delivery of drugs or any bio-active molecule, utilizing this encapsulation efficiency. Moreover, a surface-induced morphological transformation of these nano-vesicles to nano-fibers can be realized while they interact with hydrocarbon-functionalized surfaces. This phenomenon indicates the probability of their utilization in model study of peptide interaction behavior at liquid–solid interfaces and can be used in advanced study of various biological phenomena and bio-technological applications.

A small peptide mimetic molecule can form diverse nanostructures such as nano-vesicles, nano-tubes and nano-ribbons/fibrils by self-assembly, in response to various physical and chemical stimulations.

Henry's constants and isosteric heats of sorption at infinite dilution are calculated for Lennard-Jones sorbates, including the rare gases Ar, Kr and Xe, in Na-Y zeolite. Isosteric heats of sorption are calculated as a function of sorbate size by molecular dynamics (MD) as well as from the temperature dependence of Henry's constants. The MD approach samples the low potential energy regions which form part of the dynamically connected pore space. In contrast, the Henry's constants are evaluated from the infinite dilution limit of the Widom particle insertion method and therefore can, in principle, sample all available, low potential energy pore regions regardless of dynamical connectivity. We show that the difference in the results obtained by the two approaches depends significantly on sorbate size. For a certain range in the sorbate size parameter, the extent of consistency between the two approaches will be sensitive to both temperature and the MD run lengths, providing an interesting illustration of th...

Microcanonical ensemble molecular dynamics simulations are used to study anisotropy in diffusional and related dynamical properties for five spherical sorbates of varying size and polarizability in silicalite. Silicalite has straight and zigzag channels, parallel to the y and x-axes of the unit cell, respectively, which are interconnected in such a way that diffusion along the z direction is possible only by alternation of the sorbate between straight and zigzag channel segments. Helium, the smallest and most weakly bound sorbate, is found to comply most closely with the behavior expected on the basis of the simple random walk model developed to understand the geometrical correlation between the principal elements of the diffusional tensor in silicalite (J. Karger, J. Phys. Chem. 1991, 95, 5558). The larger and more strongly bound sorbates, Ne, Ar, CH4, and Xe, show significant deviations from this model. The diffusion of these particles along the z direction is distinctly subdiffusional with the mean squ...

An instantaneous normal mode (INM) analysis of the levitation effect in zeolites is presented in this paper. Lennard-Jones sorbates of variable size and polarizability diffusing in Na−Y zeolite are studied using microcanonical molecular dynamics (MD) simulations. A comparison of the dynamical information from the MD simulations with predictions based on INM analysis shows that the INM spectrum carries several striking signatures of the levitation effect. The fraction of imaginary modes mirrors the trend in the diffusion coefficient as a function of sorbate size and shows an anomalous levitation peak. The Einstein frequency, as a function of sorbate size, shows a minimum at the position of the anomalous peak. The qualitative shape of the INM spectrum changes in the anomalous regime, reflecting the availability of 12-ring window sites for adsorption, in addition to the α-cage sites. The velocity autocorrelation functions of the sorbate are well-reproduced from INM data for short time scales of one picosecon...

A temperate bacteriophage isolated from Vibrio cholerae O139, the new epidemic strain of cholera, was found to have a polyhedral head 65 nm in diameter and a rigid contractile tail 120 nm in length. The phage chromosome was a double-stranded DNA of 35 kb, with unique cohesive ends and had a G + C content of 58.8%. A restriction map of the phage DNA was constructed using the restriction endonucleases AvaI and BstEII. The phage, whose presence could be detected in nine out of 13 V. cholerae O139 isolates tested, was found to have identical chromosomal integration sites in all the strains. The phage attachment site (attP) was found to be located very close to one end of the genome.

Four outbreak strains of Vibrio cholerae O139 from endemic areas of India and Bangladesh were found to carry lysogenic phage(s). All of these phage(s) produced turbid plaques characteristic of lysogeny on V. cholerae MAK 757 (El Tor, Ogawa) cells as well as on their VcA-1 lysogens but were unable to infect V. cholerae 154 (classical) cells, the universal host for all classical phages. Colonies in the turbid plaques were O139 lysogens and these developed an auxotrophic requirement, mainly for purines suggesting the integration of the prophage into the host chromosome. The immunity profile of the O139 phage(s) was similar to that of phage alpha but differed in the sensitivity of the phage lysogen of V. cholerae MAK 757 to subsequent infection by phage beta.

Summary. Four lines of evidence suggest that the recent outbreak strains of Vibrio cholerae 0139 could have emerged from serogroup 01 strains typified by isolates MOl and M0477 described in this paper, which are neither truly classical nor truly El Tor in their biotype attributes. Firstly, like all 0139 isolates, these 01 strains, isolated in Madras during and before the 0139 outbreak, were resistant not only to polymyxin B but also to all biotypespecific choleraphages, i.e. classical phage (Dl49 and El Tor phages e4 and e5. Secondly, the restriction fragment pattern (RFP) polymorphism displayed by these strains for the cholera toxin (ctx) gene, were identical with those produced by 0139 isolates but were different from those of 01 type strains, namely V. cholerae 569B (classical) and V. cholerae MAK757 (El Tor). Thirdly, all the 0139 isolates and the two 01 isolates carried an identical large number of copies of cholera toxin gene in their chromosomes. Finally, the outer-membrane protein profiles of strains MO 1 and M0477 were identical to those of 0 139 isolates but were different from those displayed by strains 569B and MAK757.