Shared midgut binding sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa proteins from Bacillus thuringiensis in two important corn pests, Ostrinia nubilalis and Spodoptera frugiperda

First generation of insect-protected transgenic corn (Bt-corn) was based on the expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination of two or more genes expressing proteins that bind to different targets. In addition to broadening the spectrum of action, this strategy helps to delay the evolution of resistance in exposed insect populations. One of such examples is the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C-terminal half of the protein from Cry1Ac, and domain III almost identical to Cry1Fa. The aim of the present study was to determine whether the chimeric Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles (BBMV) from last instar larval midguts were used in competition binding assays with 125I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete for the binding sites of Cry1 proteins. Therefore, according to our results, the development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins is possible in these two insect species if the alteration of shared binding sites occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is very unlikely in such case

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Effects of luteectomy in early pregnancy on the maintenance of gestation and plasma progesterone concentrations in the viviparous temperate lizard Barisia imbricata imbricata

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that the corpus luteum is the principal source of progesterone during the gravidity period in reptiles; however, its participation in the maintenance of gestation in the viviparous squamata is in dispute. The effects of ovariectomy or luteectomy vary according to the species and the time at which the procedure is performed. In this paper, we describe the effects of luteectomy during early pregnancy on the maintenance of gestation and progesterone concentrations in the temperate Mexican viviparous lizard <it>Barisia imbricata imbricata.</it></p> <p>Methods</p> <p>Twenty-four lizards were subjected to three different treatments: luteectomy, sham luteectomy or non-surgical treatment, and blood samples were obtained before and after surgical treatment at different stages of gestation to determine the effects of luteectomy on the maintenance of gestation and progesterone concentrations.</p> <p>Results</p> <p>Spontaneous abortion was not observed in any of the females. However, luteectomy provoked abnormal parturition and a significant reduction in the number of young born alive. Parturition was normal in untreated females as well as those submitted to sham luteectomy. The surgical treatment also caused a significant reduction in progesterone concentrations in luteectomised females during early and middle gestation. However, no significant differences in hormone concentrations were observed among the three groups during late gestation or immediately post-parturition.</p> <p>Conclusions</p> <p>Our observations indicate that the presence of the corpus luteum is not necesary for the maintenance of gestation, but that it does participate in parturition control. Moreover, the corpus luteum of the viviparous lizard <it>B. i. imbricata</it> produces progesterone, at least during the first half of pregnancy, and that an extra-ovarian source of progesterone must maintain gestation in the absence of luteal tissue.</p

Evaluation of IL-12 and CXCL-10 in patients with hepatitis C, non-alcoholic fatty liver disease and liver damage for alcohol consumption

Introduction and Objectives: To Compare serum levels of IL-12 and CXCL-10 in different etiologies of liver disease. Materials and methods: A cross-sectional and multicenter study was carried out, including subjects with alcoholism according to criteria WHO, without (OH) and with liver injury (cirrhosis, CiOH) and (Alcoholic Hepatitis, HA); non-alcoholic fatty liver (NAFLD) and chronic Hepatitis C (CHC), diagnosed by clinical, biochemical data. They were compared with subjects control (CT). For determination of IL-12 and CXCL-10 with Multiplex®-MERCK©. Statistical analysis by SPSS V.22 using U de Mann Whitney, p<0.05; values expressed as mean ± standard error. Results: Included 20 subjects with NAFLD, 78 CHC, 14 HA, 20 CiOH, 15 OH y 60 CT. IL-12 was found elevated in OH, HA, CHC vs. CT in OH vs. HCc y HGNA (p≤0.05). CXCL-10 was found elevated in CiOH, HA and CHC vs. CT(p≤0.050). Discussion: The IL-12 showed elevated levels in subjects with alcohol consumption and CHC vs. CT that activates other cell types involved in inflammation. CXCL-10 is induced by IFN-γ, was found elevated in CiOH, HA and CHC, exerting their biological effects through CXCR3, including activation of peripheral immune cells and apoptosis. The ratio of IL-12/CXCL-10 in OH increased 4.6 times, ratifying the participation in chronic and continual inflammatory response by alcohol consumption. Conclusions: IL-12 and CXCL-10 have an important role in alcohol-induced liver disease, confirming their contribution to inflammation, being evident CXCL-10 in advanced stages of the disease, by stimulating and favoring the migration of immune cells to the damage sites. Funding: This work was partially financed by CONACyT SALUD-2016-272579 and PAPIIT- UNAM TA200515. Declaration of interest: The authors declare no potential conflicts of interest

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Epidermolysis bullosa (EB): Pathogenesis, clinical, diagnostic and genetic aspects, molecular basis, epidemiological aspects, management of patients with EB and translational implications of mutation analysis

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCUnder the term "Epidermolysis Bullosa" (EB), there is a heterogeneous group of vesicular disorders that are generally congenital and of genetic origin, and affect skin and often mucosas. It is remarkable the extreme fragility of these epithelia; the vesicles arise spontaneously as well as induced by even slight trauma or the influence of high temperatures. Their content is sero-hemorrhagic and in the scarring can be very difficult. As a consecuence of the scarring processes, joint contractures and fusion of digits (pseudo-syndactyly) can occur. Pathogenetically, EB is caused by abnormal blistering at the basement membrane zone in the dermal-epidermal attachment zone and its surroundings. This is due to alterations in the attachment complexes, and some mutations have been identified in a total of 10 genes expressed in such level. Four main types of EB can be distinguished (simple, junctional, dystrophic and hemidesmosomal), depending on the level at which the cleavage that forms the bulla takes place, although about 30 subtypes have been described. The clinical characteristics or optic microscopy are not adequate for diagnosis, and it is mandatory to perform electron microscopy, immunofluorescent and immunohistochemical studies, as well as mutation analysis if available. Regarding the epidemiological aspects, in the Spanish Collaborative Study of Congenital Malformations (ECEMC), since 1976 up to December 2004, a total of 2,204,264 liveborn infants were controlled and, among them 27 cases have been identified, for a minimum frequency of 0.12 per 10,000 (95% confidence interval:0.08-0.18). It seems generally accepted that the determination of the frequency of EB is subject to multiple biases and registration of cases is always incomplete. We have also reviewed the issues related to management of EB patients by clinicians.N

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. METHODS: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. RESULTS: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). CONCLUSIONS: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased

Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

[EN] In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.The authors acknowledge the Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46641-R and to the Generalitat Valenciana for Programme PROMETEO 2016/007. 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