C(1)‐Ammonium enolates are powerful, catalytically generated synthetic intermediates applied in the enantioselective α‐functionalisation of carboxylic acid derivatives. This minireview describes the ...recent developments in the generation and application of C(1)‐ammonium enolates from various precursors (carboxylic acids, anhydrides, acyl imidazoles, aryl esters, α‐diazoketones, alkyl halides) using isothiourea Lewis base organocatalysts. Their synthetic utility in intra‐ and intermolecular enantioselective C−C and C−X bond forming processes on reaction with various electrophiles will be showcased utilising two distinct catalyst turnover approaches.
C(1)‐Ammonium enolates have found widespread application for the enantioselective α‐functionalisation of carboxylic acid derivatives. This minireview highlights the recent advances in the generation of C(1)‐ammonium enolate intermediates by using isothiourea Lewis base organocatalysts and various precursors. The synthetic utility is showcased in intra‐ and intermolecular enantioselective C−C and C−X bond forming processes on reaction with various electrophiles utilising two distinct catalyst turnover approaches.
Maternal smoking during pregnancy has been found to influence newborn DNA methylation in genes involved in fundamental developmental processes. It is pertinent to understand the degree to which the ...offspring methylome is sensitive to the intensity and duration of prenatal smoking. An investigation of the persistence of offspring methylation associated with maternal smoking and the relative roles of the intrauterine and postnatal environment is also warranted. In the Avon Longitudinal Study of Parents and Children, we investigated associations between prenatal exposure to maternal smoking and offspring DNA methylation at multiple time points in approximately 800 mother-offspring pairs. In cord blood, methylation at 15 CpG sites in seven gene regions (AHRR, MYO1G, GFI1, CYP1A1, CNTNAP2, KLF13 and ATP9A) was associated with maternal smoking, and a dose-dependent response was observed in relation to smoking duration and intensity. Longitudinal analysis of blood DNA methylation in serial samples at birth, age 7 and 17 years demonstrated that some CpG sites showed reversibility of methylation (GFI1, KLF13 and ATP9A), whereas others showed persistently perturbed patterns (AHRR, MYO1G, CYP1A1 and CNTNAP2). Of those showing persistence, we explored the effect of postnatal smoke exposure and found that the major contribution to altered methylation was attributed to a critical window of in utero exposure. A comparison of paternal and maternal smoking and offspring methylation showed consistently stronger maternal associations, providing further evidence for causal intrauterine mechanisms. These findings emphasize the sensitivity of the methylome to maternal smoking during early development and the long-term impact of such exposure.
The ribosome small subunit is expressed in all living cells. It performs numerous essential functions during translation, including formation of the initiation complex and proofreading of base-pairs ...between mRNA codons and tRNA anticodons. The core constituent of the small ribosomal subunit is a ~1.5 kb RNA strand in prokaryotes (16S rRNA) and a homologous ~1.8 kb RNA strand in eukaryotes (18S rRNA). Traditional sequencing-by-synthesis (SBS) of rRNA genes or rRNA cDNA copies has achieved wide use as a 'molecular chronometer' for phylogenetic studies, and as a tool for identifying infectious organisms in the clinic. However, epigenetic modifications on rRNA are erased by SBS methods. Here we describe direct MinION nanopore sequencing of individual, full-length 16S rRNA absent reverse transcription or amplification. As little as 5 picograms (~10 attomole) of purified E. coli 16S rRNA was detected in 4.5 micrograms of total human RNA. Nanopore ionic current traces that deviated from canonical patterns revealed conserved E. coli 16S rRNA 7-methylguanosine and pseudouridine modifications, and a 7-methylguanosine modification that confers aminoglycoside resistance to some pathological E. coli strains.
Whole-genome bisulfite sequencing currently provides the highest-precision view of the epigenome, with quantitative information about populations of cells down to single nucleotide resolution. ...Several studies have demonstrated the value of this precision: meaningful features that correlate strongly with biological functions can be found associated with only a few CpG sites. Understanding the role of DNA methylation, and more broadly the role of DNA accessibility, requires that methylation differences between populations of cells are identified with extreme precision and in complex experimental designs.
In this work we investigated the use of beta-binomial regression as a general approach for modeling whole-genome bisulfite data to identify differentially methylated sites and genomic intervals.
The regression-based analysis can handle medium- and large-scale experiments where it becomes critical to accurately model variation in methylation levels between replicates and account for influence of various experimental factors like cell types or batch effects.
Semiconductor nanocrystals are tiny light-emitting particles on the nanometer scale. Researchers have studied these particles intensely and have developed them for broad applications in solar energy ...conversion, optoelectronic devices, molecular and cellular imaging, and ultrasensitive detection. A major feature of semiconductor nanocrystals is the quantum confinement effect, which leads to spatial enclosure of the electronic charge carriers within the nanocrystal. Because of this effect, researchers can use the size and shape of these “artificial atoms” to widely and precisely tune the energy of discrete electronic energy states and optical transitions. As a result, researchers can tune the light emission from these particles throughout the ultraviolet, visible, near-infrared, and mid-infrared spectral ranges. These particles also span the transition between small molecules and bulk crystals, instilling novel optical properties such as carrier multiplication, single-particle blinking, and spectral diffusion. In addition, semiconductor nanocrystals provide a versatile building block for developing complex nanostructures such as superlattices and multimodal agents for molecular imaging and targeted therapy. In this Account, we discuss recent advances in the understanding of the atomic structure and optical properties of semiconductor nanocrystals. We also discuss new strategies for band gap and electronic wave function engineering to control the location of charge carriers. New methodologies such as alloying, doping, strain-tuning, and band-edge warping will likely play key roles in the further development of these particles for optoelectronic and biomedical applications.
Researchers worldwide are taking advantage of novel, commercially available, technologies, such as ion mobility mass spectrometry (IM‐MS), for metabolomics and lipidomics applications in a variety of ...fields including life, biomedical, and food sciences. IM‐MS provides three main technical advantages over traditional LC‐MS workflows. Firstly, in addition to mass, IM‐MS allows collision cross‐section values to be measured for metabolites and lipids, a physicochemical identifier related to the chemical shape of an analyte that increases the confidence of identification. Second, IM‐MS increases peak capacity and the signal‐to‐noise, improving fingerprinting as well as quantification, and better defining the spatial localization of metabolites and lipids in biological and food samples. Third, IM‐MS can be coupled with various fragmentation modes, adding new tools to improve structural characterization and molecular annotation. Here, we review the state‐of‐the‐art in IM‐MS technologies and approaches utilized to support metabolomics and lipidomics applications and we assess the challenges and opportunities in this growing field.
Methods for the catalytic hydrogenation of carboxamides were investigated. Advances in catalytic chemistry have been made that have resulted in the progress of catalytic amide hydrogenation.
Root systems of most land plants form arbuscular mycorrhizal (AM) symbioses in the field, and these contribute to nutrient uptake. AM roots have two pathways for nutrient absorption, directly through ...the root epidermis and root hairs and via AM fungal hyphae into root cortical cells, where arbuscules or hyphal coils provide symbiotic interfaces. New physiological and molecular evidence shows that for phosphorus the mycorrhizal pathway (MP) is operational regardless of plant growth responses (positive or negative). Amounts delivered cannot be determined from plant nutrient contents because when responses are negative the contribution of the direct pathway (DP) is reduced. Nitrogen (N) is also delivered to roots via an MP, but the contribution to total N requirement and the costs to the plant are not clear. The functional interplay between activities of the DP and MP has important implications for consideration of AM symbioses in ecological, agronomic, and evolutionary contexts.
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