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The WC1 cell surface family of molecules function as hybrid gamma delta (γδ) TCR co-receptors, augmenting cellular responses when cross-linked with the TCR, and as pattern recognition receptors, binding pathogens. It is known that following activation, key tyrosines are phosphorylated in the intracytoplasmic domains of WC1 molecules and that the cells fail to respond when WC1 is knocked down or, as shown here, when physically separated from the TCR. Based on these results we hypothesized that the colocalization of WC1 and TCR will occur following cellular activation thereby allowing signaling to ensue. We evaluated the spatio-temporal dynamics of their interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent γδ T cells both WC1 and TCR existed in separate and spatially stable protein domains (protein islands) but after activation using Leptospira, our model system, that they concatenated. The association between WC1 and TCR was close enough for fluorescence resonance energy transfer. Prior to concatenating with the WC1 co-receptor, γδ T cells had clustering of TCR-CD3 complexes and exclusion of CD45. γδ T cells may individually express more than one variant of the WC1 family of molecules and we found that individual WC1 variants are clustered in separate protein islands in quiescent cells. However, the islands containing different variants merged following cell activation and before merging with the TCR islands. While WC1 was previously shown to bind Leptospira in solution, here we showed that Leptospira bound WC1 proteins on the surface of γδ T cells and that this could be blocked by anti-WC1 antibodies. In conclusion, γδ TCR, WC1 and Leptospira interact directly on the γδ T cell surface, further supporting the role of WC1 in γδ T cell pathogen recognition and cellular activation.

Sergio Coda,1,2 Andrew V Thillainayagam1,2 1Section of Gastroenterology and Hepatology, Department of Medicine and Photonics Group, Department of Physics, Imperial College London, London, UK; 2Endoscopy Unit, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK Abstract: Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited. Keywords: image-enhanced endoscopy, narrowband imaging, autofluorescence imaging, confocal laser endomicroscopy, fluorescence lifetime imaging

Detection, characterization, and staging constitute the fundamental elements in the endoscopic diagnosis of gastrointestinal diseases, but histology still remains the diagnostic gold standard. New developments in endoscopic techniques may challenge histopathology in the near future. An ideal endoscopic technique should combine a wide-field, “red flag” screening technique with an optical contrast or microscopy method for characterization and staging, all simultaneously available during the procedure. In theory, biophotonic advances have the potential to unite these elements to allow in vivo “optical biopsy.” These techniques may ultimately offer the potential to increase the rates of detection of high risk lesions and the ability to target biopsies and resections, and so reduce the need for biopsy, costs, and uncertainty for patients. However, their utility and sensitivity in clinical practice must be evaluated against those of conventional histopathology. This review describes some of the most recent applications of biophotonics in endoscopic optical imaging and metrology, along with their fundamental principles and the clinical experience that has been acquired in their deployment as tools for the endoscopist. Particular emphasis has been placed on translational label-free optical techniques, such as fluorescence spectroscopy, fluorescence lifetime imaging microscopy (FLIM), two-photon and multi-photon microscopy, second harmonic generation (SHG) and third harmonic generation (THG) imaging, optical coherence tomography (OCT), diffuse reflectance, Raman spectroscopy, and molecular imaging.

An artificial diet and a rearing procedure for the polyphagous pest, Spodoptera frugiperda , were developed to facilitate its culturing under laboratory conditions [27 ± 1°C, 65 ± 5% relative humidity and a photoperiod of 14:10 (L:D) h] throughout the year. The efficiency of the diet was assessed through a comparative study with the natural host of the pest, maize. The biological, reproductive and population parameters of the pest on artificial diet were superior, especially the enhanced mean fecundity of 1796 per female which was more than that of the insect reared on its natural host. The meridic diet gave a higher mean pupal weight (0.217 g/pupa) than the natural diet (0.188 g/pupa). About 81.8% of neonates completed their developmental cycle on artificial diet and emerged as healthy adults, compared to only 57.5% normal adult emergence on the natural diet. On observation, there were 3678 and 3551 eupyrene sperm bundles in the adults emerged from larvae reared on artificial diet and natural diet, respectively. The net reproductive rate ( R 0 ) for adults reared on artificial diet was 945.26, it being 703.7 for adults reared on a natural diet. With a sex ratio of 0.55, the biotic potential of S. frugiperda reared on artificial diet was 5.104 × 1028, which is more than that of natural diet (5.740 × 1026). The fertility life table constructed in the present study can play a significant role in predicting population dynamics, which will further help in developing an effective integrated pest management and the developed meridic diet with rearing procedure will be helpful in insecticide resistance monitoring programmes for this folivorous pest. [ABSTRACT FROM AUTHOR]

1.0 GUIDELINES 1.1 Development of guidelines There is currently no clear national consensus for the optimal diagnosis and treatment of cholangiocarcinoma. The need for these guidelines was highlighted following the [...]

The WC1 cell surface family of molecules function as hybrid gamma delta (γδ) TCR co-receptors, augmenting cellular responses when cross-linked with the TCR, and as pattern recognition receptors, binding pathogens. It is known that following activation, key tyrosines are phosphorylated in the intracytoplasmic domains of WC1 molecules and that the cells fail to respond when WC1 is knocked down or, as shown here, when physically separated from the TCR. Based on these results we hypothesized that the colocalization of WC1 and TCR will occur following cellular activation thereby allowing signaling to ensue. We evaluated the spatio-temporal dynamics of their interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent γδ T cells both WC1 and TCR existed in separate and spatially stable protein domains (protein islands) but after activation using Leptospira , our model system, that they concatenated. The association between WC1 and TCR was close enough for fluorescence resonance energy transfer. Prior to concatenating with the WC1 co-receptor, γδ T cells had clustering of TCR-CD3 complexes and exclusion of CD45. γδ T cells may individually express more than one variant of the WC1 family of molecules and we found that individual WC1 variants are clustered in separate protein islands in quiescent cells. However, the islands containing different variants merged following cell activation and before merging with the TCR islands. While WC1 was previously shown to bind Leptospira in solution, here we showed that Leptospira bound WC1 proteins on the surface of γδ T cells and that this could be blocked by anti-WC1 antibodies. In conclusion, γδ TCR, WC1 and Leptospira interact directly on the γδ T cell surface, further supporting the role of WC1 in γδ T cell pathogen recognition and cellular activation. [ABSTRACT FROM AUTHOR]

The current study evaluates the adsorption capacity of Cocos Nucifera (Coconut) shell derived biochar for the basic dyes Basic Blue 41 (BB41) & Basic Red 09 (BR09) from aqueous solution. The adsorption experiments proved that 80% of dye removal was attained in the optimal operating conditions (adsorbent dosage of 4 g/L, pH of 8, temperature of 35°C, 50 mg/L of initial dye concentration). Four different isotherm models were used to derive the best fit isotherm model, based on the values of correlation coefficient and % of error BB41 sorption revealed that Toth model (R2 of 0.991 and % error of 0.010) has better fit, whereas the Sips model (R2 of 0.993 and % error of 0.529) was obtained as best fit for BR09 sorption when compared to other models. The regeneration studies were carried out with different elutants and the application of 0.1 M HCl as the elutant enables effective desorption of sorbent. [ABSTRACT FROM AUTHOR]

A series of eleven ethoxysubstituted chalcones (E1‐E11) were synthesized and investigated for their inhibitory potential towards human recombinant monoamine oxidase A and B (hMAO−A and hMAO−B, respectively) and acetylcholinesterase (AChE). IC50 values of 4.63 ± 0.15 and 0.053 ± 0.003 μM were obtained for MAO−A and MAO−B, respectively, by the most interesting compound (2E)‐1‐(4‐ethoxyphenyl)‐3‐(4‐fluorophenyl)prop‐2‐en‐1‐one (E7), and it was characterized by a high selectivity index (SI=87.4) for MAO−B. Inhibitions by E7 against MAO−A and MAO−B were recovered (75.9 and 74.5%, respectively) to near the levels of reversible references (77.1 and 77.4%, respectively). The inhibition modes of E7 for MAO−A and MAO−B were competitive with Ki values of 2.65 ± 0.064 and 0.011 ± 0.0011 μM, respectively. Compounds (2E)‐1‐(4‐ethoxyphenyl)‐3‐(4‐ethylphenyl) prop‐2‐en‐1‐one (E10) and (2E)‐1‐(4‐ethoxyphenyl)‐3‐[4‐(trifluoromethyl)phenyl]prop‐2‐en‐1‐one (E11) showed good inhibitions against AChE with IC50 values of 2.86 ± 0.041 and 3.23 ± 0.0073 μM, respectively. A combined molecular docking/MM‐GBSA approach was used that employed quantum mechanics (QM) partial charges; this technique revealed the molecular rationale behind the observed MAO−B selectivity for this molecular series. Taken together, these results indicate that E7 is a potent, selective and reversible competitive inhibitor of MAO−B with moderately potent AChE inhibitory activity that has potential as a multi‐targeting drug [ABSTRACT FROM AUTHOR]