Enhancer, transcriptional, and cell fate plasticity precedes intestinal determination during endoderm development

After acquiring competence for selected cell fates, embryonic primordia may remain plastic for variable periods before tissue identity is irrevocably determined (commitment). We investigated the chromatin basis for these developmental milestones in mouse endoderm, a tissue with recognizable rostro-caudal patterning and transcription factor (TF)-dependent interim plasticity. Foregut-specific enhancers are as accessible and active in early midgut as in foregut endoderm, and intestinal enhancers and identity are established only after ectopic cis-regulatory elements are decommissioned. Depletion of the intestinal TF CDX2 before this cis element transition stabilizes foregut enhancers, reinforces ectopic transcriptional programs, and hence imposes foregut identities on the midgut. Later in development, as the window of chromatin plasticity elapses, CDX2 depletion weakens intestinal, without strengthening foregut, enhancers. Thus, midgut endoderm is primed for heterologous cell fates, and TFs act on a background of shifting chromatin access to determine intestinal at the expense of foregut identity. Similar principles likely govern other fate commitments

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Leprosy affects skin and peripheral nerves. Although we have antibiotics to treat the mycobacterial infection, the accompanying inflammation is a major part of the disease process. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called reactions. These are associated with worsening of nerve damage. However, diagnosing these reactions is not straightforward. They can be diagnosed clinically by examination or by microscopic examination of the skin biopsies. We studied a cohort of 303 newly diagnosed leprosy patients in India and compared the diagnosis rates by clinical examination and microscopy and found that the microscopic diagnosis has higher rates of diagnosis for both types of reaction. This suggests that clinicians and pathologists have different thresholds for diagnosing reactions. More work is needed to optimise both clinical and pathological diagnosis. In this cohort 43% of patients had Borderline Tuberculoid leprosy, an immunologically active type, and 20% of the biopsies showed only minimal inflammation, perhaps these patients had very early disease or self-healing. The public health implication of this work is that leprosy centres need to be supported by pathologists to help with the clinical management of difficult cases

High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing >160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

Ultrasound-assisted extraction of natural products

Ultrasound-assisted extraction (USAE) is an interesting process to obtain high valuable compounds and could contribute to the increase in the value of some food by-products when used as sources of natural compounds. The main benefits will be a more effective extraction, thus saving energy, and also the use of moderate temperatures, which is beneficial for heat-sensitive compounds. For a successful application of the USAE, it is necessary to consider the influence of several process variables, the main ones being the applied ultrasonic power, the frequency, the extraction temperature, the reactor characteristics, and the solvent-sample interaction. The highest extraction rate is usually achieved in the first few minutes, which is the most profitable period. To optimize the process, rate equations and unambiguous process characterization are needed, aspects that have often been lacking. © 2011 Springer Science+Business Media, LLC.The authors thank the Generalitat Valenciana for their financial support in project PROMETEO/2010/062 and the Caja de Ahorros del Mediterraneo for M.D. Esclapez's pre-doctoral grant.Esclapez Vicente, MD.; García Pérez, JV.; Mulet Pons, A.; Cárcel Carrión, JA.; Esclapez, MD. (2011). Ultrasound-assisted extraction of natural products. Food Engineering Reviews. 3(2):108-120. https://doi.org/10.1007/s12393-011-9036-6S10812032Abad Romero B, Bou-Maroun E, Reparet JM, Blanquet J, Cayot N (2010) Impact of lipid extraction on the dearomatisation of an Eisenia foetida protein powder. Food Chem 119:459–466Adewuyi YG (2001) Sonochemistry: environmental science and engineering applications. Ind Eng Chem Res 40:4681–4715Atchley AA, Crum LA (1988) Acoustic cavitation and bubble dynamics. 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Ultrason Sonochem 15:1075–1079Cárcel JA, Benedito J, Bon J, Mulet A (2007) High intensity ultrasound effects on meat brining. Meat Sci 76:611–619Cárcel JA, Benedito J, Rosselló C, Mulet A (2007) Influence of ultrasound intensity on mass transfer in apple immersed in a sucrose solution. J Food Eng 78:472–479Cavitus (2009) Grape colour and flavour extraction (Pat. Pend.) for red must extraction http://www.cavitus.com . Crafers. Accessed 10 Jan 2011Chea Chua S, Ping Tan C, Mirhosseini H, Ming Lai O, Long K, Sham Baharin B (2009) Optimization of ultrasound extraction condition of phospholipids from palm-pressed fiber. J Food Eng 92:403–409Chena R, Menga F, Zhang S, Liu Z (2009) Effects of ultrahigh pressure extraction conditions on yields and antioxidant activity of ginsenoside from ginseng. Sep Purif Technol 66:340–346Chivate MM, Pandit AB (1995) Quantification of cavitation intensity in fluid bulk. Ultrason Sonochem 2:19–25Da Porto C, Decorti D (2009) Ultrasound-assisted extraction coupled with under vacuum distillation of flavour compounds from spearmint (carvone-rich) plants: comparison with conventional hydrodistillation. Ultrason Sonochem 16:795–799Da Porto C, Decorti D, Kikic I (2009) Flavour compounds of Lavandula angustifolia L. to use in food manufacturing: Comparison of three different extraction methods. Food Chem 112:1072–1078Domínguez H, Núñez MJ, Lema JM (1994) Enzymatic pretreatment to enhance oil extraction from fruits and oilseeds: a review. Food Chem 49:271–286Dong J, Liu Y, Liang Z, Wanga W (2010) Investigation on ultrasound-assisted extraction of salvianolic acid B from Salvia miltiorrhiza root. Ultrason Sonochem 17:61–65Entezari MH, Kruus P (1994) Effect of frequency on sonochemical reactions. I: oxidation of iodide. Ultrason Sonochem 1:75–79Esclapez MD, Sáez V, Milán-Yáñez D, Tudela I, Louisnard O, González-García J (2010) Sonoelectrochemical treatment of water polluted with trichloroacetic acid: from sonovoltammetry to pre-pilot plant scale. Ultrason Sonochem 17:1010–1020Ferraro V, Cruz IB, Ferreira R, Malcata JFX, Pintado ME, Castro PML (2010) Valorisation of natural extracts from marine source focused on marine by-products: review. Food Res Int 43:2221–2233Fischer CH, Hart EJ, Henglein AJ (1986) Hydrogen/deuterium isotope exchange in the hydrogen deuteride-water system under the influence of ultrasound. Phys Chem 90:3059–3060Garcia-Noguera J, Weller CL, Oliveira FIP, Rodrigues S, Fernandes FAN (2010) Dual-stage sugar substitution in strawberries with a Stevia-based sweetener. Innovative Food Sci Emerg Technol 11:225–230García-Pérez JV, Cárcel JA, de la Fuente-Blanco S, Riera-Franco de Sarabia E (2006) Ultrasonic drying of foodstuff in a fluidized bed: parametric study. Ultrasonics 44:539–543García-Pérez JV, García-Alvarado MA, Carcel JA, Mulet A (2010) Extraction kinetics modeling of antioxidants from grape stalk (Vitis vinifera var. Bobal): Influence of drying conditions. J Food Eng 101:49–58González-García J, Sáez V, Tudela I, Díez-Garcia MI, Esclapez MD, Louisnard O (2010) Sonochemical treatment of water polluted by chlorinated organocompounds. A review. Water 2:28–74Handa SS, Preet S, Khanuja S, Longo G, Rakesh DD (2008) Extraction Technologies for Medicinal and Aromatic Plants. United Nations Industrial Development Organization and the International Centre for Science and High Technology, TriesteHemwimol S, Pavasant P, Shotipruk A (2006) Ultrasound-assisted extraction of anthraquinones from roots of Morinda citrifolia. Ultrason Sonochem 13:543–548Hielscher (2011) Teltow http:// www.hielscher.com . 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Ultrason Sonochem 10:331–335Karki B, Lamsal BP, Jung S, van Leeuwen JH, Pometto AL III, Grewell D, Khanal SK (2010) Enhancing protein and sugar release from defatted soy flakes using ultrasound technology. J Food Eng 96:270–278Kardos N, Luche J-L (2001) Sonochemistry of carbohydrate compounds. Carbohydr Res 332:115–131Kotronarou A, Mills G, Hoffmann MR (1991) Ultrasonic Irradiation of para-Nitrophenol in Aqueous Solution. J Phys Chem 95:3630–3638Kuijpers MWA, Kemmere MF, Keurentjes JTF (2002) Calorimetric study of the energy efficiency for ultrasound-induced radical formation. Ultrasonics 40:675–678Leighton TG (2007) What is ultrasound? Prog Biophys Mol Biol 93:3–83Leonelli C, Mason TJ (2010) Microwave and ultrasonic processing: now a realistic option for industry. Chem Eng Process 49:885–900Li H, Pordesimo L, Weiss J (2004) High intensity ultrasound-assisted extraction of oil from soybeans. Food Res Int 37:731–738Liu J, Li J-W, Tang J (2010) Ultrasonically assisted extraction of total carbohydrates from Stevia rebaudiana Bertoni and identification of extracts. Food Bioprod Process 88:215–221Lianfu Z, Zelong L (2008) Optimization and comparison of ultrasound/microwave assisted extraction (UMAE) and ultrasonic assisted extraction (UAE) of lycopene from tomatoes. Ultrason Sonochem 15:731–737Liazid A, Schwarz M, Varela RM, Palma M, Guillén DA, Brigui J, Macías FA, Barroso CG (2010) Evaluation of various extraction techniques for obtaining bioactive extracts from pine seeds. Food Bioprod Process 88:247–252Londoño-Londoño J, Rodrigues de Lima V, Lara O, Gil A, Crecsynski Pasa TB, Arango GJ, Ramirez Pineda JR (2010) Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method. Food Chem 119:81–87Lou Z, Wang H, Zhang M, Wang Z (2010) Improved extraction of oil from chickpea under ultrasound in a dynamic system. J Food Eng 98:13–18Louisnard O, González-García J, Tudela I, Klima J, Sáez V, Vargas-Hernández Y (2009) FEM simulation of a sono-reactor accounting for vibrations of the boundaries. Ultrason Sonochem 16:250–259Luque de Castro MD, Priego-Capote F (2007) Analytical Applications of Ultrasound, Vol. 26, Techniques and Instrumentation in Analytical Chemistry. Elsevier Science, AmsterdamMa Y, Ye X, Hao Y, Xu G, Xu G, Liu D (2008) Ultrasound-assisted extraction of hesperidin from Penggan (Citrus reticulata) peel. Ultrason Sonochem 15:227–232Ma Y, Chen J-C, Liu Dong-Hong, Ye X-Q (2009) Simultaneous extraction of phenolic compounds of citrus peel extracts: effect of ultrasound. Ultrason Sonochem 16:57–62Makino K, Mossoba MM, Riesz P (1982) Chemical effects of ultrasound on aqueous solutions. Evidence for hydroxyl and hydrogen free radicals (.cntdot. OH and. cntdot. H) by spin trapping. J Chem Soc 104:3537–3539Margulis MA, Margulis IM (2003) Calorimetric method for measurement of acoustic power absorbed in a volume of liquid. Ultrason Sonochem 10:343–345Martin CJ, Law ANR (1983) Design of thermistor probes for measurement of ultrasound intensity distributions. Ultrasonics 21:85–90Mason TJ, Lorimer JP, Bates DM, Zhao Y (1994) Dosimetry in sonochemistry: the use of aqueous terephthalate ion as a fluorescence monitor. Ultrason Sonochem 1:91–95Meinhardt (2011) Leipzig. http://www.meinhardt-ultraschall.de . Accessed 10 Jan 2011Montalbo-Lomboy M, Khanal SK, van Leeuwen JH, Raman DR, Dunn L Jr, Grewell D Jr (2010) Ultrasonic pretreatment of corn slurry for saccharification: a comparison of batch and continuous Systems. Ultrason Sonochem 17:939–946Mulet A, Cárcel JA, Sanjuán N, Bon J (2003) New food drying technologies. Use of ultrasound. Food Sci Technol Int 9:215–221Naguleswaran S, Vasanthan T (2010) Dry milling of field pea (Pisum sativum L.) groats prior to wet fractionation influences the starch yield and purity. Food Chem 118:627–633Orozco-Solano M, Ruiz-Jiménez J, Luque de Castro MD (2010) Ultrasound-assisted extraction and derivatization of sterols and fatty alcohols from olive leaves and drupes prior to determination by gas chromatography–tandem mass spectrometry. J Chromatogr A 1217:1227–1235Patist A, Bates D (2008) Ultrasonic innovations in the food industry: from the laboratory to commercial production. Innovative Food Sci Emerg Technol 9:147–154Price GJ (1990) The use of ultrasound for the controlled degradation of polymer solutions. In: Mason TJ (ed) Advances in sonochemistry, vol 1. Jai Press, Cambridge, pp 231–287Riener J, Noci G, Cronin DA, Morgan DJ, Lyng JG (2010) A comparison of selected quality characteristics of yoghurts prepared from thermosonicated and conventionally heated milks. 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Spectroscopic methods for the identification of sesquiterpene lactones

The most widely used spectroscopic methods for the identification ofsesquiterpene lactones are discussed. The most distinctive and characteristic signals in the UV, IR, MS, 1H-MNR and 13C-NMR spectra are discussed. In addition, some examples of the application of these techniques for the structure elucidation of some representative sesquiterpene lactones with different skeletal types are presented.Fil: Sülsen, Valeria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Donadel, Osvaldo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Catalan, Cesar Atilio Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentin