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Focused Electron Beam Induced Deposition is a consolidated technique for the growth of three-dimensional (3D) nanostructures. However, this single-step nanofabrication method requires further efforts to optimize simultaneously dimensional and compositional properties, in particular for deposits with a high aspect ratio. More specifically, ferromagnetic 3D nanowires (NWs) with diameters in the sub-50 nm regime and high metallic contents up to 95 at. % attract great interest to improve the final performance of magnetic nanodevices such as magnetic tips for scanning probe microscopy. In this work, we report on real-time monitoring during chemical purification and structural crystallization processes of ultra-narrow 3D Fe NWs (<50 nm in diameter achieved) by post-growth in situ annealing in a transmission electron microscope. NW heating up to 700 °C in very high vacuum reveals the local increase of the metallic content along the entire NW length concomitant with the growth of large Fe single crystals from initially amorphous compounds. A metallic purity of 95 at. % is observed in several regions, dramatically boosting the initial Fe content of 40 at. %. The real-time in situ tracking of 3D nanostructures during thermal annealing is a key element to design and optimize novel purification processes for the fabrication of customized components to be integrated in spintronic, logic and sensing devices. Image 1 [ABSTRACT FROM AUTHOR]

The ATP-dependent chromatin remodeling factor CHD1 is essential for the assembly of variant histone H3.3 into paternal chromatin during sperm chromatin remodeling in fertilized eggs. It remains unclear, however, if CHD1 has a similar role in normal diploid cells. Using a specifically tailored quantitative mass spectrometry approach, we show that Chd1 disruption results in reduced H3.3 levels in heads of Chd1 mutant flies. Chd1 deletion perturbs brain chromatin structure in a similar way as H3.3 deletion and leads to global de-repression of transcription. The physiological consequences are reduced food intake, metabolic alterations, and shortened lifespan. Notably, brain-specific CHD1 expression rescues these phenotypes. We further demonstrate a strong genetic interaction between Chd1 and H3.3 chaperone Hira. Thus, our findings establish CHD1 as a factor required for the assembly of H3.3-containing chromatin in adult cells and suggest a crucial role for CHD1 in the brain as a regulator of organismal health and longevity. [Display omitted] • Loss of chromatin assembly factor CHD1 reduces H3.3 levels in brain chromatin • Chd1 deletion perturbs global chromatin organization similar to H3.3 deletion • Chd1 deletion causes global upregulation of transcription in fly heads • Brain-specific roles of CHD1 are required for metabolic control and healthy lifespan In postmitotic brain cells, histones lost during transcription must be replenished by replication-independent mechanisms. Schoberleitner et al. show that the chromatin remodeling factor CHD1 is involved in this process. CHD1 loss results in reduced histone H3.3 levels, global chromatin perturbation, transcriptional dysregulation, and defects in feeding behavior, metabolism, and lifespan. [ABSTRACT FROM AUTHOR]

Hybrid maize (Zea mays L.) is one of the major grains used as food for humans and animals. Besides carbohydrates and amino acids, maize contains micronutrients such as vitamins and phytochemicals with health-promoting effects. In a current maize breeding program, the phytochemical profiles of 35 maize hybrids grown in three significant agroecologies of Mexico - highlands, subtropics and tropics - were evaluated. For the different locations, phytochemical traits, which are relevant for nutraceutical effects, and the antioxidative capacity, were determined. Statistical analyses indicate the importance of the pedigree/agroecology on the phytochemical profiles. Mass fingerprinting in combination with the Random Forest Tree algorithm allowed the building of models that predicted the antioxidative capacity of the maize hybrids. The methods are, therefore, suitable for the efficient selection of maize hybrids with improved nutraceutical value. • Thirty-five CIMMYT elite maize hybrids grown in highlands, subtropics and tropics. • Evaluation of phytochemicals, antioxidative capacity and Pearson correlations. • MANOVA suggested the importance of the environment for the nutraceutical content. • High-throughput chemical phenotyping of maize using mass fingerprinting (MSF). • Prediction of nutraceutical potential with MSF data, using data mining models. [ABSTRACT FROM AUTHOR]

• [Cu(C 18 tren)]Br is found a promising catalyst for the click-synthesis of organosilanes. • Reactions show high yields that are superior to more classic approaches. • Facile work-up thanks to precipitation of the catalyst in ethanol. The synthesis of organotriethoxysilanes by click chemistry was studied using the recyclable, multidentate catalyst [Cu(C 18 tren)]Br. For the evaluation, alkyne precursors containing some of the more common organic functions were reacted with a triethoxy silyl group containing azide. The procedure allowed the isolation of the desired products in high yields and high purity. Especially remarkable is the facility of the catalyst removal by simple filtration and evaporation. The catalyst is concluded to be ideal for the synthesis of moisture sensitive organotriethoxysilanes. [ABSTRACT FROM AUTHOR]

Hepatocarcinoma is one of the main causes of cancer-related deaths worldwide. Maize peptides have emerged a novel group of anticancer peptides to investigate. In this study, we evaluated the cytotoxic activity of α-zein hydrolysates obtained by three enzymatic treatments on HepG2 cells (T: trypsin, C: chymotrypsin, and TC: both enzymes). Their cytotoxic activity on HepG2 cells, showed an ICso of 542.09 ng/mL, 384.83 ng/mL, and 395.34 ng/mL for T, C, and TC, respectively. The latter group were further fractionated by ion-exchange chromatography and screened in terms of their cytotoxic activity resulting in two fractions responsible for most of the bioactivity observed. Twelve possible peptide sequences with potential cell regulatory activities were predicted considering the ct-zein sequences used. This study highlights the importance of food-derived peptides in the future development of anticancer pharmaceuticals. [ABSTRACT FROM AUTHOR]

Metallic/intermetallic materials with BCC structures hold an intrinsic instability due to phonon softening along [110] direction, causing BCC to lower-symmetry phases transformation when the BCC structures are thermally or mechanically stressed. Fe 50 Rh 50 binary system is one of the exceptional BCC structures (ordered-B2) that has not been yet showing such transformation upon application of thermal stress, although mechanical deformation results in B2 to disordered FCC (γ) and L1 0 phases transformation. Here, a comprehensive transmission electron microscopy (TEM) study is conducted on thermally-stressed samples of Fe 50 Rh 50 induced by quenching in water and liquid nitrogen from 1150 °C and 1250 °C. We demonstrated that samples quenched from 1150 °C into water and liquid nitrogen show the presence of 1/4{110} and 1/2{110} satellite reflections, the latter of which is expected from phonon dispersion curves obtained by density functional theory calculation. Therefore, it is proposed that Fe 50 Rh 50 maintains the B2 structure that is in premartensite state. Once Fe 50 Rh 50 is quenched from 1250 °C into liquid nitrogen, formation of two short-range ordered tetragonal phases with various c / a ratios (∼1.15 and 1.4) is observed in line with phases formed from mechanically deformed (30 %) sample. According to our observations, an accurate atomistic shear model ({110}〈 1 1 ¯ 0 〉) is presented that describes the martensitic transformation of B2 to these tetragonal phases. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population.Methods: TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries. Patients aged 18 years or older with histologically confirmed, non-resectable, metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) as defined by the American Joint Committee on Cancer staging classification (7th edition) who had received at least two previous chemotherapy regimens and had experienced radiological disease progression were eligible for inclusion. Patients were randomly assigned (2:1) via dynamic randomisation from a centralised interactive voice-response system to receive either oral trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 days) plus best supportive care or placebo plus best supportive care. Participants were allocated to groups by study-site personnel. Randomisation was stratified by region (Japan vs rest of world), ECOG performance status (0 vs 1), and previous treatment with ramucirumab (yes vs no). Both patients and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT02500043. The trial, including follow-up of all participants, has been completed.Findings: Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group. Median overall survival was 5·7 months (95% CI 4·8-6·2) in the trifluridine/tipiracil group and 3·6 months (3·1-4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56-0·85]; one-sided p=0·00029, two-sided p=0·00058). Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group and abdominal pain (n=15 [9%]) and general deterioration of physical health (n=15 [9%]) in the placebo group. Serious adverse events of any cause were reported in 143 (43%) patients in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group).Interpretation: Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need.Funding: Taiho Oncology and Taiho Pharmaceutical. [ABSTRACT FROM AUTHOR]

Background In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Methods Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue ( KRAS ) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Conclusions Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status. This trial is registered with ClinicalTrials.gov: NCT01607957 . [ABSTRACT FROM AUTHOR]

FMN hydrolases catalyze dephosphorylation of FMN to riboflavin. Although these enzymes have been described in many organisms, few had their corresponding genes cloned and their recombinant proteins biochemically characterized, and none had their physiological roles determined. We found previously that FMN hydrolase activity in pea chloroplasts is Mg2+-dependent, suggesting an enzyme of the haloacid dehalogenase (HAD) superfamily. In this study, a new FMN hydrolase was purified by multistep chromatography after ammonium sulfate precipitation. The molecular weight of the native protein was estimated at ~59,400, a dimer of about twice the predicted molecular weight of most HAD superfamily phosphatases. After SDS-PAGE of the partially purified material, two separate protein bands within 25-30 kDa were extracted from the gel and analyzed by nanoLC-MS/MS. Peptide sequence matching to the protein samples suggested the presence of three HAD-like hydrolases. cDNAs for sequence homologs from Arabidopsis thaliana of these proteins were expressed in Escherichia coli. Activity screening of the encoded proteins showed that the At1g79790 gene encodes an FMN hydrolase (AtcpFHy1). Plastid localization of AtcpFHy1 was confirmed using fluorescence microscopy of A. thaliana protoplasts transiently expressing the N-terminal fusion of AtcpFHy1 to enhanced green fluorescent protein. Phosphatase activity of AtcpFHy1 is FMN-specific, as assayed with 19 potential substrates. Kinetic parameters and pH and temperature optima for AtcpFHy1 were determined. A phylogenetic analysis of putative phosphatases of the HAD superfamily suggested distinct evolutionary origins for the plastid AtcpFHy1 and the cytosolic FMN hydrolase characterized previously. [ABSTRACT FROM AUTHOR]

Abstract: The polymer-salt rich environment of aqueous two-phase systems disturbs standard protein quantification methods, like UV measurement or Bradford assay. Therefore, we systematically investigated the influence of high polyethylene glycol and phosphate salt concentrations on the readings of three colorimetric protein assays: Bradford, DC (Bio-Rad) and ninhydrin assay. All three assays are troubled by the aqueous two-phase systems components, but disturbances can be significantly reduced by diluting the samples to 1% PEG and 10% salt. But additionally, the Bradford and the DC assay are strongly dependent on the protein composition, which lead to analytical protein recoveries from 0% to 181% in the current study. Especially for salt-rich fractions with low protein concentration and for measuring analytically problematic proteins like RNase A we therefore suggest a ninhydrin assay, which displays minimal protein-to-protein variation and high sensitivity. [ABSTRACT FROM AUTHOR]