Folding of a donor–acceptor polyrotaxane by using noncovalent bonding interactions

Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain π electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT4+), a π electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined “folded” secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT4+. This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures

Severe neonatal enterovirus infection in twins with different outcomes:A case report

Enteroviruses are among the most common causes of acute viral illness worldwide, and in neonates, the clinical course of these infections is heterogeneous. Severe complications, such as myocarditis, are associated with high mortality rates. In this case report, we present the clinical course of premature twins born at 35 weeks of gestational age, suffering from a severe neonatal enterovirus infection with cardiac involvement, which proved fatal in one of the twins. This course led to prompt identification in the other twin and facilitated timely transfer to a neonatal intensive care unit with neonatal hemodynamic expertise, and facilitated the timely transfer to a neonatal intensive care nit with hemodynamic expertise and immediate availability of AZCMO would it have been indicated. Early supportive therapy in the other twin contributed to a positive outcome. Therefore, we emphasize the importance of early recognition in averting adverse consequences. As a recommendation, we propose routine screening of enterovirus in viral panels for febrile newborns.</p

Large CO\u3csub\u3e2\u3c/sub\u3e and CH\u3csub\u3e4\u3c/sub\u3e emissions from polygonal tundra during spring thaw in northern Alaska

The few prethaw observations of tundra carbon fluxes suggest that there may be large spring releases, but little is known about the scale and underlying mechanisms of this phenomenon. To address these questions, we combined ecosystem eddy flux measurements from two towers near Barrow, Alaska, with mechanistic soil-core thawing experiment. During a 2 week period prior to snowmelt in 2014, large fluxes were measured, reducing net summer uptake of CO2 by 46% and adding 6% to cumulative CH4 emissions. Emission pulses were linked to unique rain-on-snow events enhancing soil cracking. Controlled laboratory experiment revealed that as surface ice thaws, an immediate, large pulse of trapped gases is emitted. These results suggest that the Arctic CO2 and CH4 spring pulse is a delayed release of biogenic gas production from the previous fall and that the pulse can be large enough to offset a significant fraction of the moderate Arctic tundra carbon sink

High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults: Results from the Nord-Trøndelag Health Study

Although autoimmune diabetes in adults is a common form of diabetes, knowledge on risk factors and long term consequences of the disease is limited. The aims of this thesis were to investigate the influence of socioeconomic factors (education and occupation), sleep disturbances and psychological well-being on the risk of developing autoimmune diabetes in adults, to investigate whether genetic variation in the melatonin receptor 1B (MTNR1B) contributes to the association between poor sleep and type 2 diabetes which has been previously suggested, and finally to investigate the risk of mortality from all causes, cardiovascular disease and ischemic heart disease in adult-onset autoimmune diabetes, with consideration of the possible influence of metabolic risk factors, glycaemic control, lifestyle factors and socioeconomic position. These studies are based on data from the Norwegian HUNT Study, to date the largest population-based study where incident cases of autoimmune diabetes in adults can be separated from cases of type 2 diabetes. The HUNT Study consists of three separate surveys performed on three occasions in 1984-2008 and contains information from questionnaires, clinical examinations and blood samples. Information on mortality was obtained by linkage to the national Cause of Death Registry. Individuals who were positive for antibodies against glutamic acid decarboxylase and with onset of diabetes at ≥35 years were classified as having autoimmune diabetes in adults. The main finding of Study I was that high educational levels (university versus primary school) were associated with an increased risk of autoimmune diabetes in adults (HR 1.98, 95% CI 1.21-3.26) after adjustment for BMI, physical activity, smoking, alcohol consumption, and family history of diabetes, whereas type 2 diabetes was more common in those with low education. An increased risk of autoimmune diabetes in adults was also seen in individuals who reported having sleep disturbances and low psychological well-being (HR 1.84, 95% CI 1.10-3.09), a risk similar to that seen in type 2 diabetes (HR 1.31, 95% CI 1.13-1.50) (Study II). The results from Study III indicated that there was no influence of the MTNR1B genetic variant on the association between poor sleep and type 2 diabetes. The association remained after adjustment for genotype and was seen in non-carriers as well as in carriers of the risk allele. Mortality from all causes (HR 1.55, 95% CI 1.25-1.92), cardiovascular disease (HR 1.87, 95% CI 1.40-2.48) and ischemic heart disease (HR 2.39, 95% CI 1.57-3.64) was increased in autoimmune diabetes in adults compared to individuals without diabetes. Importantly, mortality risk was as high as in type 2 diabetes, despite a more favourable metabolic risk profile in patients with autoimmune diabetes. In these patients, excess mortality appeared to be primarily associated with poor glycaemic control. These findings suggest, for the first time, that socioeconomic and psychosocial factors contribute to the development of autoimmune diabetes in adults. The results are in line with previous data indicating that the aetiology of autoimmune diabetes is partly similar to that of type 2 diabetes but suggest, also, that there are other, currently unidentified, environmental risk factors for autoimmune diabetes that remain to be explored. Finally, the results indicate that survival in individuals with autoimmune diabetes with adult onset would be improved by a more effective treatment

On the existence of the logarithmic surface layer in the inner-core of hurricanes

Q. J. R. Meteorol. Soc., 1394128

Severe neonatal enterovirus infection in twins with different outcomes: A case report

Enteroviruses are among the most common causes of acute viral illness worldwide, and in neonates, the clinical course of these infections is heterogeneous. Severe complications, such as myocarditis, are associated with high mortality rates. In this case report, we present the clinical course of premature twins born at 35 weeks of gestational age, suffering from a severe neonatal enterovirus infection with cardiac involvement, which proved fatal in one of the twins. This course led to prompt identification in the other twin and facilitated timely transfer to a neonatal intensive care unit with neonatal hemodynamic expertise, and facilitated the timely transfer to a neonatal intensive care nit with hemodynamic expertise and immediate availability of AZCMO would it have been indicated. Early supportive therapy in the other twin contributed to a positive outcome. Therefore, we emphasize the importance of early recognition in averting adverse consequences. As a recommendation, we propose routine screening of enterovirus in viral panels for febrile newborns

Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application

Background The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). Results The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection. Conclusions E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Expanding the chemical scope of RNA:methyltransferases to site-specific alkynylation of RNA for click labeling

This work identifies the combination of enzymatic transfer and click labeling as an efficient method for the site-specific tagging of RNA molecules for biophysical studies. A double-activated analog of the ubiquitous co-substrate S-adenosyl-l-methionine was employed to enzymatically transfer a five carbon chain containing a terminal alkynyl moiety onto RNA. The tRNA:methyltransferase Trm1 transferred the extended alkynyl moiety to its natural target, the N2 of guanosine 26 in tRNAPhe. LC/MS and LC/MS/MS techniques were used to detect and characterize the modified nucleoside as well as its cycloaddition product with a fluorescent azide. The latter resulted from a labeling reaction via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition click chemistry, producing site-specifically labeled RNA whose suitability for single molecule fluorescence experiments was verified in fluorescence correlation spectroscopy experiments

Pulse‐labeling studies of carbon cycling in Arctic tundra ecosystems: The contribution of photosynthates to methane emission

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94952/1/gbc790.pd