The dynamic genetic determinants of increased transcriptional divergence in spermatids.

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic differentiation at single-cell resolution in an F1 hybrid mouse system, allowing for the comprehensive characterisation of cis- and trans-genetic effects, including their dynamics across cellular differentiation.

Exceptionally Stable And Super-Efficient Electrocatalysts Derived From Semiconducting Metal Phosphonate Frameworks.

Two new isostructural semiconducting metal-phosphonate frameworks are reported. Co [1,4-NDPA] and Zn [1,4-NDPA] (1,4-NDPA is 1,4-naphthalenediphosphonate) have optical bandgaps of 1.7 eV and 2.

Halogen Bonding in Sulphonamide Co-Crystals: X···π Preferred over X···O/N?

Sulphonamides have been one of the major pharmaceutical compound classes since their introduction in the 1930s. Co-crystallisation of sulphonamides with halogen bonding (XB) might lead to a new class of pharmaceutical-relevant co-crystals. We present the synthesis and structural analysis of seven new co-crystals of simple sulphonamides N-methylbenzenesulphonamide (NMBSA), N-phenylmethanesulphonamide (NPMSA), and N-phenylbenzenesulphonamide (BSA), as well as of an anti-diabetic agent Chlorpropamide (CPA), with the model XB-donors 1,4-diiodotetrafluorobenzene (14DITFB), 1,4-dibromotetrafluorobenzene (14DBTFB), and 1,2-diiodotetrafluorobenzene (12DITFB).

CellRegMap: a statistical framework for mapping context-specific regulatory variants using scRNA-seq.

Single-cell RNA sequencing (scRNA-seq) enables characterizing the cellular heterogeneity in human tissues. Recent technological advances have enabled the first population-scale scRNA-seq studies in hundreds of individuals, allowing to assay genetic effects with single-cell resolution. However, existing strategies to analyze these data remain based on principles established for the genetic analysis of bulk RNA-seq.

Microwave-assisted synthesis of iridium oxide and palladium nanoparticles supported on a nitrogen-rich covalent triazine framework as superior electrocatalysts for the hydrogen evolution and oxygen reduction reaction.

Iridium oxide (IrO-NP) and palladium nanoparticles (Pd-NP) were supported on a 2,6-dicyanopyridine-based covalent-triazine framework (DCP-CTF) by energy-saving and sustainable microwave-assisted thermal decomposition reactions in propylene carbonate and in the ionic liquid [BMIm][NTf]. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) confirm well-distributed NPs with sizes from 2 to 13 nm stabilized on the CTF particles. Metal contents between 10 and 41 wt% were determined by flame atomic absorption spectroscopy (AAS).

Simultaneous cellular and molecular phenotyping of embryonic mutants using single-cell regulatory trajectories.

Developmental progression and cellular diversity are largely driven by transcription factors (TFs); yet, characterizing their loss-of-function phenotypes remains challenging and often disconnected from their underlying molecular mechanisms. Here, we combine single-cell regulatory genomics with loss-of-function mutants to jointly assess both cellular and molecular phenotypes. Performing sci-ATAC-seq at eight overlapping time points during Drosophila mesoderm development could reconstruct the developmental trajectories of all major muscle types and reveal the TFs and enhancers involved.

Evolution of a New Testis-Specific Functional Promoter Within the Highly Conserved Gene of the Mouse.

(synonym ) is a conserved regulatory kinase gene and a central component of the JNK signaling cascade with key functions during cellular differentiation. It shows complex transcription patterns, and different transcript isoforms are known in the mouse (). We have previously identified a newly evolved testis-specific transcript for the gene in the subspecies .

scDALI: modeling allelic heterogeneity in single cells reveals context-specific genetic regulation.

While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore this heterogeneity or use sorted cell populations, reducing discovery and explanatory power. Here, we develop scDALI, a versatile computational framework that integrates information on cellular states with allelic quantifications of single-cell sequencing data to characterize cell-state-specific genetic effects.

Capture and Separation of SO Traces in Metal-Organic Frameworks via Pre-Synthetic Pore Environment Tailoring by Methyl Groups.

Herein, we report a pre-synthetic pore environment design strategy to achieve stable methyl-functionalized metal-organic frameworks (MOFs) for preferential SO binding and thus enhanced low (partial) pressure SO adsorption and SO /CO separation. The enhanced sorption performance is for the first time attributed to an optimal pore size by increasing methyl group densities at the benzenedicarboxylate linker in [Ni (BDC-X) DABCO] (BDC-X=mono-, di-, and tetramethyl-1,4-benzenedicarboxylate/terephthalate; DABCO=1,4-diazabicyclo[2,2,2]octane). Monte Carlo simulations and first-principles density functional theory (DFT) calculations demonstrate the key role of methyl groups within the pore surface on the preferential SO affinity over the parent MOF.

Prediction of single-cell gene expression for transcription factor analysis.

Background: Single-cell RNA sequencing is a powerful technology to discover new cell types and study biological processes in complex biological samples. A current challenge is to predict transcription factor (TF) regulation from single-cell RNA data.

Results: Here, we propose a novel approach for predicting gene expression at the single-cell level using cis-regulatory motifs, as well as epigenetic features.

Emergence of a new gene from an intergenic region.

It is generally assumed that new genes would arise by gene duplication mechanisms, because the signals for regulation and transcript processing would be unlikely to evolve in parallel with a new gene function. We have identified here a transcript in the house mouse (Mus musculus) that has arisen within the past 2.5-3.

Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion.

B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5.

A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.

A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT.