89 research outputs found
Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years
Objective The incidence of colorectal cancer (CRC)
declines among subjects aged 50 years and above. An
opposite trend appears among younger adults. In Europe,
data on CRC incidence among younger adults are
lacking. We therefore aimed to analyse European trends
in CRC incidence and mortality in subjects younger than
50 years.
Design Data on age-related CRC incidence and
mortality between 1990 and 2016 were retrieved from
national and regional cancer registries. Trends were
analysed by Joinpoint regression and expressed as
annual percent change.
Results We retrieved data on 143.7million people
aged 20–49 years from 20 European countries. Of
them, 187 918 (0.13%) were diagnosed with CRC. On
average, CRC incidence increased with 7.9% per year
among subjects aged 20–29 years from 2004 to 2016.
The increase in the age group of 30–39 years was 4.9%
per year from 2005 to 2016, the increase in the age
group of 40–49 years was 1.6% per year from 2004
to 2016. This increase started earliest in subjects aged
20–29 years, and 10–20 years later in those aged 30–39
and 40–49 years. This is consistent with an age-cohort
phenomenon. Although in most European countries the
CRC incidence had risen, some heterogeneity was found
between countries. CRC mortality did not significantly
change among the youngest adults, but decreased with
1.1%per year between 1990 and 2016 and 2.4% per
year between 1990 and 2009 among those aged 30–39
years and 40–49 years, respectively.
Conclusion CRC incidence rises among young
adults in Europe. The cause for this trend needs to be
elucidated. Clinicians should be aware of this trend. If
the trend continues, screening guidelines may need to be
reconsidered
Rh-POP Pincer Xantphos Complexes for C-S and C-H Activation. Implications for Carbothiolation Catalysis
The neutral Rh(I)–Xantphos
complex [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)Cl]<sub><i>n</i></sub>, <b>4</b>, and cationic Rh(III) [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(H)<sub>2</sub>][BAr<sup>F</sup><sub>4</sub>], <b>2a</b>, and [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos-3,5-C<sub>6</sub>H<sub>3</sub>(CF<sub>3</sub>)<sub>2</sub>)(H)<sub>2</sub>][BAr<sup>F</sup><sub>4</sub>], <b>2b</b>, are described [Ar<sup>F</sup> = 3,5-(CF<sub>3</sub>)<sub>2</sub>C<sub>6</sub>H<sub>3</sub>; Xantphos
= 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; Xantphos-3,5-C<sub>6</sub>H<sub>3</sub>(CF<sub>3</sub>)<sub>2</sub> = 9,9-dimethylxanthene-4,5-bis(bis(3,5-bis(trifluoromethyl)phenyl)phosphine].
A solid-state structure of <b>2b</b> isolated from C<sub>6</sub>H<sub>5</sub>Cl solution shows a κ<sup>1</sup>-chlorobenzene
adduct, [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos-3,5-C<sub>6</sub>H<sub>3</sub>(CF<sub>3</sub>)<sub>2</sub>)(H)<sub>2</sub>(κ<sup>1</sup>-ClC<sub>6</sub>H<sub>5</sub>)][BAr<sup>F</sup><sub>4</sub>], <b>3</b>. Addition of H<sub>2</sub> to <b>4</b> affords,
crystallographically characterized, [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(H)<sub>2</sub>Cl], <b>5</b>. Addition of diphenyl
acetylene to <b>2a</b> results in the formation of the C–H
activated metallacyclopentadiene [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(ClCH<sub>2</sub>Cl)(σ,σ-(C<sub>6</sub>H<sub>4</sub>)C(H)CPh)][BAr<sup>F</sup><sub>4</sub>], <b>7</b>, a rare example of a crystallographically characterized Rh–dichloromethane
complex, alongside the Rh(I) complex <i>mer</i>-[Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(η<sup>2</sup>-PhCCPh)][BAr<sup>F</sup><sub>4</sub>], <b>6</b>. Halide abstraction from [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)Cl]<sub><i>n</i></sub> in the presence of diphenylacetylene affords <b>6</b> as the
only product, which in the solid state shows that the alkyne binds
perpendicular to the κ<sup>3</sup>-POP Xantphos ligand plane.
This complex acts as a latent source of the [Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)]<sup>+</sup> fragment and facilitates
<i>ortho</i>-directed C–S activation in a number
of 2-arylsulfides to give <i>mer</i>-[Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(σ,κ<sup>1</sup>-Ar)(SMe)][BAr<sup>F</sup><sub>4</sub>] (Ar = C<sub>6</sub>H<sub>4</sub>COMe, <b>8</b>; C<sub>6</sub>H<sub>4</sub>(CO)OMe, <b>9</b>; C<sub>6</sub>H<sub>4</sub>NO<sub>2</sub>, <b>10</b>; C<sub>6</sub>H<sub>4</sub>CNCH<sub>2</sub>CH<sub>2</sub>O, <b>11</b>; C<sub>6</sub>H<sub>4</sub>C<sub>5</sub>H<sub>4</sub>N, <b>12</b>).
Similar C–S bond cleavage is observed with allyl sulfide,
to give <i>fac</i>-[Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)(SPh)][BAr<sup>F</sup><sub>4</sub>], <b>13</b>. These products of C–S
activation have been crystallographically characterized. For <b>8</b> in situ monitoring of the reaction by NMR spectroscopy reveals
the initial formation of <i>fac</i>-κ<sup>3</sup>-<b>8</b>, which then proceeds to isomerize to the <i>mer</i>-isomer. With the <i>para</i>-ketone aryl sulfide, 4-SMeC <sub>6</sub>H<sub>4</sub>COMe, C–H activation <i>ortho</i> to the ketone occurs to give <i>mer</i>-[Rh(κ<sup>3</sup>-<sub>P,O,P</sub>-Xantphos)(σ,κ<sup>1</sup>-4-(COMe)C<sub>6</sub>H<sub>3</sub>SMe)(H)][BAr<sup>F</sup><sub>4</sub>], <b>14</b>. The temporal evolution of carbothiolation catalysis using <i>mer</i>-κ<sup>3</sup>-<b>8</b>, and phenyl acetylene
and 2-(methylthio)acetophenone substrates shows initial fast catalysis
and then a considerably slower evolution of the product. We suggest
that the initially formed <i>fac</i>-isomer of the C–S
activation product is considerably more active than the <i>mer</i>-isomer (i.e., <i>mer</i>-<b>8</b>), the latter of
which is formed rapidly by isomerization, and this accounts for the
observed difference in rates. A likely mechanism is proposed based
upon these data
Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme
Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change – protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA) by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases
Genera of phytopathogenic fungi : GOPHY 4
This paper is the fourth contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions
and information about the pathology, distribution, hosts and disease symptoms, as well as DNA barcodes for the taxa covered. Moreover, 12 whole-genome
sequences for the type or new species in the treated genera are provided. The fourth paper in the GOPHY series covers 19 genera of phytopathogenic fungi
and their relatives, including Ascochyta, Cadophora, Celoporthe, Cercospora, Coleophoma, Cytospora, Dendrostoma, Didymella, Endothia, Heterophaeomoniella, Leptosphaerulina, Melampsora, Nigrospora, Pezicula, Phaeomoniella, Pseudocercospora, Pteridopassalora, Zymoseptoria, and one genus of
oomycetes, Phytophthora. This study includes two new genera, 30 new species, five new combinations, and 43 typifications of older names.https://www.journals.elsevier.com/studies-in-mycologydm2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog
Multiscale Coarse-Graining of the Protein Energy Landscape
A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states
Enfermedad Mínima Residual (EMR) en Leucemia Linfoblástica Aguda pediátrica (LLA). Estudio multicéntrico
En las últimas 4 décadas se profundizó el conocimiento en la cinética de la respuesta temprana al tratamiento en pacientes con Leucemia Linfoblástica Aguda (LLA) para predecir riesgo de recaída1. Sin embargo, 20% de los pacientes que inicialmente responden al tratamiento y morfológicamente no presentan blastos en médula ósea, recidivan durante el tratamiento o luego de la finalizar el mismo.Fil: Soria, Rose Mari. Hospital de Niños Dr. Ricardo Gutiérrez; Argentina.Fil: Agriello, Evangelina. Laboratorio de Especialidades Bioquímicas; Argentina.Fil: Agriello, Evangelina. Hospital Interzonal General Dr. José Penna; Argentina.Fil: Agriello, Evangelina. Grupo Argentino de Tratamiento de la Leucemia Aguda; Argentina.Fil: Gutierrez, María. Hospital de Niños Dr. Ricardo Gutiérrez; Argentina.Fil: Gil, Gimena. Hospital de Niños Dr. Ricardo Gutiérrez; Argentina.Fil: Iommi, María Paula. Laboratorio de Especialidades Bioquímicas; Argentina.Fil: Torreguitart, Federico Andrés. Laboratorio de Especialidades Bioquímicas; Argentina.Fil: Caferri, Horacio. Hospital Interzonal General Dr. José Penna; Argentina.Fil: Cédola, Alejandra. Sanatorio San Lucas; Argentina.Fil: Majek, Elena. Hospital de Niños Dr. Héctor Quintana; Argentina.Fil: Hiramatsu, Elizabeth. Hospital Pediátrico del Niño Jesús; Argentina.Fil: Morell, Daniela. Hospital Pediátrico del Niño Jesús; Argentina.Fil: Rizzi, María Laura. Sanatorio Allende; Argentina.Fil: Rodríguez Cuimbra, Silvia. Hospital Pediátrico Juan Pablo II; Argentina.Fil: Gomel De Baraja, María E. Hospital Pediátrico Juan Pablo II; Argentina.Fil: Cabral Castella, Antonia C. Hospital Pediátrico Juan Pablo II; Argentina.Fil: Pistaccio, Luis. Hospital Interzonal de Agudos Especializado en Pediatría Sor María Ludovica; Argentina.Fil: Schuttemberg, Virginia. Hospital Interzonal de Agudos Especializado en Pediatría Sor María Ludovica; Argentina.Fil: Riccieri, Cecilia.Fil: Solari, Liliana. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Solari, Liliana. Grupo Argentino de Tratamiento de la Leucemia Aguda; Argentina.Fil: Riccieri, Cecilia. Hospital Nacional Profesor Alejandro Posadas; Argentina.Fil: Gaillard, María I. Hospital de Niños Dr. Ricardo Gutiérrez; Argentina.Fil: Gaillard, María I. Grupo Argentino de Tratamiento de la Leucemia Aguda; Argentina.Fil: Ferraro, C. Hospital de Niños Dr. Ricardo Gutiérrez; Argentina.Fil: Hernández, M. Clínica Dr. Matera; Argentina.Fil: Drosovsky, C. Sanatorio San Lucas; Argentina.Hematologí
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