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When applied to functional analysis results, structured visual inspection criteria have resulted in improvements in the levels of agreement between raters as well as earlier identification of the function of challenging behavior. However, multistep criteria can be difficult to apply in real time, which could be a barrier to widespread adoption in practice. This study evaluated a Microsoft‐Excel‐based functional analysis decision support system (FADSS), which could aid behavior analysts with interpreting functional analysis results. Final overall agreement between the FADSS and post hoc visual inspection was high at 95%. Final overall agreement between the post hoc results generated by FADSS and ongoing results generated by FADSS was acceptable at 81%, representing a 50% increase in efficiency. These results indicate that FADSS could aid behavior analysts when interpreting functional analysis results in real time.

Domino Knoevenagel-cyclization reactions of N-arylcinnamylamines were carried out with active methylene reagents, which took place with five competing cyclization mechanisms: intramolecular hetero Diels–Alder reaction, stepwise polar [2 + 2] cycloaddition, styryl or aza-Diels–Alder reactions followed by rearomatization, and [1,5]-hydride shift-6-endo cyclization. In the stepwise aza-Diels–Alder reaction, the N-vinylpyridinium moiety acted as an azadiene, producing a condensed heterocycle with tetrahydroquinolizinium and tetrahydroquiniline subunits. Antiproliferative activity with low micromolar IC50values was identified for some of the novel scaffolds.

Autophagy is a conserved, lysosome-dependent catabolic process of eukaryotic cells which is involved in cellular differentiation. Here, we studied its specific role in the differentiation of spermatogonial cells in the Drosophilatestis. In the apical part of the Drosophilatestis, there is a niche of germline stem cells (GSCs), which are connected to hub cells. Hub cells emit a ligand for bone morhphogenetic protein (BMP)-mediated signalling that represses Bam (bag of marbles) expression in GSCs to maintain them in an undifferentiated state. GSCs divide asymmetrically, and one of the daughter cells differentiates into a gonialblast, which eventually generates a cluster of spermatogonia (SG) by mitoses. Bam is active in SG, and defects in Bam function arrest these cells at mitosis. We show that BMP signalling represses autophagy in GSCs, but upregulates the process in SG. Inhibiting autophagy in SG results in an overproliferating phenotype similar to that caused by bam mutations. Furthermore, Bam deficiency leads to a failure in downstream mechanisms of the autophagic breakdown. These results suggest that the BMP-Bam signalling axis regulates developmental autophagy in the Drosophilatestis, and that acidic breakdown of cellular materials is required for spermatogonial differentiation.

Transgenic mice expressing green fluorescent protein (GFP) are useful in transplantation experiments. When we used ubiquitin‐GFP (UBC‐GFP) transgenic mice to study the availability of niches for transplanted hematopoietic stem and progenitor cells, the results were strikingly different from the corresponding experiments that used congenic mice polymorphic in the CD45 antigen. Analysis of these unexpected results revealed that the hematopoiesis of UBC‐GFP mice was outcompeted by the hematopoiesis of wild‐type (WT) mice. Importantly, UBC‐GFP mice engrafted the transplanted bone marrow of WT mice without conditioning. There was a significant bias toward lymphopoiesis in the WT branch of chimeric UBC‐GFP/WT hematopoiesis. A fraction of immature Sca‐1+cells in the spleen of UBC‐GFP mice expressed GFP at a very high level. The chimeric hematopoiesis was stable in the long term and also after transplantation to secondary recipient mice. The article thus identifies a specific defect in the hematopoiesis of UBC‐GFP transgenic mice that compromises the lymphoid‐primed hematopoietic stem cells in the bone marrow and spleen. StemCells2018;36:1237–1248 UBC‐GFP transgenic mice engraft, without conditioning, lymphoid‐primed hematopoietic stem cells (MPP4) transplanted from wild‐type mice. Engraftment is higher in the spleen as compared with the bone marrow.

AbstractConsider the Diophantine equation in unknown non-empty disjoint subsets of natural numbers I, Jand positive integer exponents αi, βi, where u= (un)∞n=0 is a Lucas sequence and A, Bare given integers. We derive effective upper bounds on max Iand max Jand present a method to effectively enumerate all solutions when uis given. As an application we solve a partial case of a problem of Kimberling on distinct products.

Improving the laser-induced damage threshold of optical components is a basic endeavor in femtosecond technology. By testing more than 30 different femtosecond mirrors with 42 fs laser pulses at 1 kHz repetition rate, we found that a combination of high-bandgap dielectric materials and improved design and coating techniques enable femtosecond multilayer damage thresholds exceeding 2  J/cm^2 in some cases. A significant ×2.5 improvement in damage resistance can also be achieved for hybrid Ag–multilayer mirrors exhibiting more than 1  J/cm^2 threshold with a clear anticorrelation between damage resistance and peak field strength in the stack. Slight dependence on femtosecond pulse length and substantial decrease for high (megahertz) repetition rates are also observed.

Ion beam analysis (IBA) is an established method to determine the concentration and the distribution of elements in art and archaeological objects. However, especially for organic specimens, caution must be taken to avoid harmful effects. In this work, the possible modification of recent calf parchment samples by proton beam irradiation was investigated applying fluences (given as deposited charge per unit area) both within and beyond the usual analytical practice. Attenuated Total Reflection Fourier Transform Infra-red Spectroscopy (FTIR-ATR) and Optical Coherence Tomography (OCT) were employed to assess changes, inspected from the surface of the samples. Although both techniques are apt to detect alterations of parchment in general, in the case of particles, which deposit the majority of their energy below the surface these techniques could not detect changes at low fluences. However, a simple “bath test” (short immersion in liquid) proved that disintegration within the material had already happened. After the “bath test”, OCT and digital 3D microscopy were used to check the discontinuities in the material, especially for low fluences when the visual inspection might have missed them. Unfortunately, simply monitoring organic objects such as parchment during or after ion beam irradiation, non-destructively, is not sufficient to claim absolute harmlessness, as some studies in the past did. In line with our former findings using electron microscopy on cross sections, we found that 2.3 MeV protons with a deposited charge of 0.5 µC/cm2caused no changes affecting the integrity of parchment but 2 µC/cm2apparently did under the applied experimental conditions. To ensure the required analytical signal at a relatively low deposited charge, the detection system must be optimized for efficiency. Nevertheless, since the variability of the historic materials and the measurement set-ups are considerable, these values cannot be taken as absolutes, but only as guides, both for further IBA studies and for studies conducted in the past.

AbstractFor a sequence of arbitrary integers let GBdenote the smallest number such that for every k≥ GBone can find kconsecutive terms of Bwith the property that none of these terms is coprime to all the others. If GBexists we say that Bis a Pillai sequence. This paper links up with our recent works by giving a full characterization of this property for associated Lucas and Lehmer sequences. The more general T-Pillai property is also considered.

An HPLC monitoring protocol has been developed to follow the reaction of flavanone [(±)-1] with thallium(III) nitrate, lead tetracetate, phenyliodonium diacetate (PIDA) or [hydroxyl( tosyloxy)iodo]benzene in trimethyl orthoformate. Besides the major ring-contraction product, the 2,3-dihydrobenzo[b]furan derivative (±)-4a, minor components were also identified, and their structures including the relative stereochemistry and a plausible mechanism of formation are reported and compared with literature data. The oxidation reactions were monitored by HPLC at different conditions, and the structure and the ratio of the products were determined and compared. The preferred formation of flavone (5) from (±)-flavanone (1) by PIDA is explained by quantum-chemical calculations on the intermediate formed by the addition of this reagent to the enol ether derivative of (±)-1.

The microwave-assisted solvent-free synthesis of (E)-3-styrylchromones from 3-formylchromones and phenylmalonic acid on sodium acetate support has been developed; the method affords the styryl derivatives in moderate to good yields and with complete diastereoselectivity. Protocols for the highly regioselective epoxidation of (E)- and (Z)-3-styrylchromones have been elaborated. Treatment of the alkenes with dimethyldioxirane led to the exclusive formation of 3-(3-aryloxiran-2-yl)chromones with complete diastereoselectivity, whereas treatment with hydrogen peroxide under alkaline conditions afforded the corresponding 2,3-epoxy-3-styrylchromanones as the only products. Epoxidation performed in the presence of chiral, nonracemic cinchona-alkaloid-based quaternary ammonium salts allowed the synthesis of enantiomerically enriched 2,3-epoxy-3-styrylchromanones, but with only moderate ee values. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

131I whole-body scintigraphy is a highly sensitive method for the detection of differentiated thyroid tumours and metastases. However, a lack of anatomical landmarks and the physiological excretion of the tracer complicates the evaluation of the images. Therefore, we determined whether additional bone scintigraphy in combination with 131I scintigraphy, simultaneously acquired via planar and tomographic techniques, positively contributes to the treatment plan in patients with non-conclusive 131I images.

Seven new metabolites, 3-hydroxy-1-(2,6-dihydroxyphenyl)butan-1-one (1), 1-(2-hydroxy-6-methoxyphenyl)butan-1-one (3), 2,3-dihydro-5-methoxy-2-methylchromen-4-one (6), the dimeric naphthalenes nodulisporin A (9) and B (10), and the first naturally occurring dimeric indanone, nodulisporin C (12), as well as (4E,6E)-2,4,6-trimethylocta-4,6-dien-3-one (13) were isolated together with ten known compounds (2, 4, 5, 7, 8, 11, 14–17) from the culture extract of the endophytic fungus Nodulisporium sp. from Juniperus cedre from Gomera Island. The structure of dictafolin-A, previously erroneously assigned as structure 6, is not identical with 2,3-dihydro-5-methoxy-2-methylchromen-4-one, isolated in this investigation. The structures of new compounds were determined by spectroscopic methods (mainly extensive 1D and 2D NMR experiments and mass spectral measurements) and X-ray single crystal analysis. All but one of the thirteen tested compounds exhibit herbicidal, antifungal and/or antibacterial activities. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Summary. Enolacetates of benzocyclanones and chromanones were synthesized and treated with dimethyldioxirane and the asymmetric oxidizing system dimethyldioxirane/chiral, non-racemic Mn(III) salen complex/axial ligand. The latter reagent resulted in the corresponding enantiomerically enriched cyclic a-hydroxy ketones and their acetates in moderate-to-good yields and modest enantioselectivity under mild and neutral conditions from tetralone and chromanone. On the contrary, flavanone provided poor yields due to the competitive C–H insertion at position 2. The use of R, R-Mn(III)salen catalyst induced an S absolute configuration at the position a in the whole series.

Investigation of the methanol extract of the roots of Gnidia involucrata (Thymelaeaceae) led to the isolation and characterization of two new 3,8"-biflavonoid diastereoisomers, named GB-4 (6a) and GB-4a (6b). Their absolute configurations were determined in mixture by on-line LC/CD measurements, which also allowed the revision of absolute configurations of the biflavanoids GB-1 and GB-2, and the configurational assignment of GB-3.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with a high risk of transformation to acute myeloid leukemia (AML). One of the processes implicated in MDS pathogenesis is RNA splicing. Its alterations are caused by somatic mutations in splicing factor genes. Mutations in SF3B1(Splicing Factor 3b Subunit 1) gene are the most frequently found mutations in MDS. Circular RNAs (circRNAs) are covalently closed RNAs that are produced by back-splicing process. CircRNAs can regulate multiple biological processes through various molecular mechanisms, such as microRNA sponging. Their deregulation is frequently found in cancer. It is likely that they also contribute to the development of MDS, however, their role in MDS has not been researched yet. Therefore, our aim was to explore circRNA levels in MDS and analyze their association with patient prognosis. We further hypothesized that mutations in splicing factor genes can affect production of circRNAs and thus, we examined circRNA levels with respect to the mutational status. We explored transcriptome of 78 MDS patients, 7 AML patients, and 13 healthy donors using Illumina RNA-seq of total RNA isolated from CD34+ bone marrow cells. To associate circRNA levels with mutational status, Illumina TruSight Myeloid Sequencing Panel Kit examining 54 genes was applied. Of 8,620 circRNAs identified by RNA-seq, 204 circRNAs were deregulated in MDS (e.g., MENTRNL, EBF1, and PPM1L-derived circRNAs) and 246 circRNAs were altered between lower- and higher-risk patients (e.g., CHST15, TMTC2, and PDE3B-derived circRNAs). Most of the progression-related circRNAs (n = 234) showed elevated levels in higher-risk patients, suggesting that the back-splicing process might be stimulated during the disease progression. In MDS patients with SF3B1mutations, other 40 circRNAs were deregulated (e.g., ZNF91, ZEB1, and ZNF124-derived circRNAs). This circRNA profile was substantially different from the profiles associated with the rest of recurrently mutated splicing factor genes (SRSF2, U2AF1, and ZRSR2). To study alterations in forward- and back-splicing in SF3B1-mutated patients, we examined transcriptional differences on the levels of whole genes, transcript variants, and circRNAs and searched for specificities in transcription within individual gene loci. A set of circRNAs whose levels differed specifically without affecting expression of corresponding forward-spliced mRNAs included several oncology/hematopoiesis-relevant genes (e.g., ATM, CBL, ERCC5, ETV6, FLT3, and MAPK6). Gene loci with changed expression of both, alternative mRNA transcripts and circRNAs, but stable transcription on whole gene level included for example CDK14, KDM1A, and ZEB1. Because ZEB1(Zinc Finger E-Box Binding Homeobox 1) serves as an essential hematopoietic transcription factor, we focused on ZEB1-derived circRNAs (hsa_circ_0000228 and hsa_circ_0003793) in more detail. We demonstrated that upregulation of these circRNAs is SF3B1-specific and not related to any other clinical or molecular characteristics. Finally, using RNA-seq data from CRISPR/Cas9 edited K562 cells (Liberante FG, et al., Sci Rep. 2019; 9:2678), we confirmed that SF3B1K700E mutation leads to strong upregulation of ZEB1 circRNAs. To conclude, this is an early report showing for the first time that the levels of specific circRNAs are altered in MDS. We demonstrated that particular circRNAs may have potential to become markers that would contribute to more accurate prognosis of MDS patients. Further, we identified circRNAs with deregulated levels specifically in MDS patients with SF3B1mutation, suggesting that this mutation affects circRNA production.

No relevant conflicts of interest to declare.

A carboncarbon bond forming reaction has been developed by modifying the Nozaki–Hiyama reaction using a chromium(II)-aminopolycarboxylate complexes in a neutral aqueous medium at room temperature. Aldehydes and ketones can be coupled with aralkyl and aryl halides in good yields.

No relevant conflicts of interest to declare.

Background and Aims

Introduction: Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with a tendency to transform to acute myeloid leukemia. Several prognostic systems based almost entirely on clinicopathological characteristics have been developed. However, considering large heterogeneity of MDS, there is an ongoing substantial effort to identify new molecular markers, which would improve patient stratification.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Background and Aims

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders characterized by dysplastic and ineffective blood cell production and a tendency for transformation to acute myeloid leukemia (AML). Because of the heterogeneity of MDS, the development of additional molecular tools able to refine the Revised International Prognosis Scoring System (IPSS-R), predict outcome and monitor the response to treatment would be highly beneficial.

Myelodysplastic syndromes (MDS) represent a heterogeneous spectrum of hematopoietic stem cell disorders characterized by inefficient hematopoiesis, peripheral blood cytopenia, dysplasia in one or more myeloid cell lineages, and a tendency to evolve into acute myeloid leukemia (AML). Hypomethylating agent azacitidine (AZA) is a standard therapy for patients with higher-risk MDS and AML with myelodysplasia-related changes (AML-MRC).

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

The hematopoietic tissue is the most suitable tissue for studies into the biology of regeneration. We examined bone marrow regeneration starting from a very low number of repopulating cells.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

For Abstract see ChemInform Abstract in Full Text.

Effective enantiomeric separations of erythro- and threo-8.O.4′-neolignans with different aromatic substitution pattern (1a-i, 2a-i) are achieved on the commercially available chiral stationary phase cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD). It is shown that the chiral recognition of the stationary phase is significantly dependent on the substitution pattern of the racemic compounds. Online liquid chromatography (LC)-circular dichroism (CD) analysis allows for the establishment of a correlation between the absolute configuration of the separated erythro-8.O.4′-neolignans and their characteristic CD transitions, which could be used to determine or revise the configuration of previously isolated erythro-8.O.4′-neolignans. Although the absolute configurations of threo-isomers is not determined unambiguously from the LC-CD analysis, it is proven that both their elution order and chiroptical properties are significantly influenced by the substitution pattern of the aromatic rings.

For Abstract see ChemInform Abstract in Full Text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.