Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.

Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1.

Investing in entropy: the strategy of cucurbit[]urils to accelerate the intramolecular Diels-Alder cycloaddition reaction of tertiary furfuryl amines.

Cucurbit[]urils, renowned for their host-guest chemistry, are becoming versatile biomimetic receptors. Herein, we report that cucurbit[7]uril (CB[7]) accelerates the intramolecular Diels-Alder (IMDA) reaction for previously elusive and unreactive tertiary -methyl--(homo)allyl-2-furfurylamines by up to 4 orders of magnitude under mild conditions. Using H NMR titrations and ITC experiments, we characterize the dissimilar thermodynamic and kinetic properties of the complexes.

Shaping human brain development and vulnerability through alternative splicing.

Alternative splicing contributes to shaping lineage-specific gene expression and phenotypes. In this issue of Cell Genomics, Recinos, Bao, Wang, et al. report that the balance between splicing isoforms of the microtubule-associated protein Tau in the brain is differentially regulated among primates by the RNA-binding protein MBNL2, with consequences for protein aggregation and neurodegeneration in humans.

and mutations in a patient with a neurodevelopmental disorder and immunodeficiency.

The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) 'Intellectual Disability, Autosomal Dominant 57' (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown.

Strand-resolved mutagenicity of DNA damage and repair.

DNA base damage is a major source of oncogenic mutations. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair.

Profiling Bacteria in the Lungs of Patients with Severe Influenza Versus COVID-19 with or without Aspergillosis.

The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) has yet to be explored. To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission.

Detection of capillary abnormalities in early diabetic retinopathy using scanning laser ophthalmoscopy and optical coherence tomography combined with adaptive optics.

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy.

A TdT-driven amplification loop increases CRISPR-Cas12a DNA detection levels.

Recent findings on CRISPR-Cas enzymes with collateral DNAse/RNAse activity have led to new and innovative methods for pathogen detection. However, many CRISPR-Cas assays necessitate DNA pre-amplification to boost sensitivity, restricting their utility for point-of-care applications. Achieving higher sensitivity without DNA pre-amplification presents a significant challenge.

Erratum: Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies: erratum.

[This corrects the article on p. 5994 in vol. 14, PMID: 38021143.

Dynamic Light Scattering in Biomedical Applications: feature issue introduction.

The feature Issue on "Dynamic Light Scattering in Biomedical Applications" presents a compilation of research breakthroughs and technological advancements that have shaped the field of biophotonics, particularly in the non-invasive exploration of biological tissues. Highlighting the significance of dynamic light scattering (DLS) alongside techniques like laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), and laser speckle contrast imaging (LSCI), this issue underscores the versatile applications of these methods in capturing the intricate dynamics of microcirculatory blood flow across various tissues. Contributions explore developments in fluorescence tomography, the integration of machine learning for data processing, enhancements in microscopy for cancer detection, and novel approaches in optical biophysics, among others.

Emergence of activation or repression in transcriptional control under a fixed molecular context.

For decades, studies have noted that transcription factors (TFs) can behave as either activators or repressors of different target genes. More recently, evidence suggests TFs can act on transcription simultaneously in positive and negative ways. Here we use biophysical models of gene regulation to define, conceptualize and explore these two aspects of TF action: "duality", where TFs can be overall both activators and repressors at the level of the transcriptional response, and "coherent and incoherent" modes of regulation, where TFs act mechanistically on a given target gene either as an activator or a repressor (coherent) or as both (incoherent).

The relationship between nanoscale genome organization and gene expression in mouse embryonic stem cells during pluripotency transition.

During early development, gene expression is tightly regulated. However, how genome organization controls gene expression during the transition from naïve embryonic stem cells to epiblast stem cells is still poorly understood. Using single-molecule microscopy approaches to reach nanoscale resolution, we show that genome remodeling affects gene transcription during pluripotency transition.

Several secondary metabolite gene clusters in the genomes of ten Penicillium spp. raise the risk of multiple mycotoxin occurrence in chestnuts.

Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for Penicillium spp.

Partitioning to ordered membrane domains regulates the kinetics of secretory traffic.

The organelles of eukaryotic cells maintain distinct protein and lipid compositions required for their specific functions. The mechanisms by which many of these components are sorted to their specific locations remain unknown. While some motifs mediating subcellular protein localization have been identified, many membrane proteins and most membrane lipids lack known sorting determinants.

Fisher information for smart sampling in time-domain spectroscopy.

Time-domain spectroscopy encompasses a wide range of techniques, such as Fourier-transform infrared, pump-probe, Fourier-transform Raman, and two-dimensional electronic spectroscopies. These methods enable various applications, such as molecule characterization, excited state dynamics studies, or spectral classification. Typically, these techniques rarely use sampling schemes that exploit the prior knowledge scientists typically have before the actual experiment.

Predictive Biophysical Neural Network Modeling of a Compendium of Transcription Factor DNA Binding Profiles for .

The DNA binding of most Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of DNA binding for 139 TFs using ChIP-Seq. We used these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence.

Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models.

Impairment of autophagy leads to an accumulation of misfolded proteins and damaged organelles and has been implicated in plethora of human diseases. Loss of autophagy in actively respiring cells has also been shown to trigger metabolic collapse mediated by the depletion of nicotinamide adenine dinucleotide (NAD) pools, resulting in cell death. Here we found that the deficit in the autophagy-NAD axis underpins the loss of viability in cell models of a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease.

Boosting the Efficiency of Photoactive Rod-Shaped Nanomotors via Magnetic Field-Induced Charge Separation.

Photocatalytic nanomotors have attracted a lot of attention because of their unique capacity to simultaneously convert light and chemical energy into mechanical motion with a fast photoresponse. Recent discoveries demonstrate that the integration of optical and magnetic components within a single nanomotor platform offers novel advantages for precise motion control and enhanced photocatalytic performance. Despite these advancements, the impact of magnetic fields on energy transfer dynamics in photocatalytic nanomotors remains unexplored.

Giant oligomeric porous cage-based molecules.

Most reported porous materials are either extended networks or monomeric discrete cavities; indeed, porous structures of intermediate size have scarcely been explored. Herein, we present the stepwise linkage of discrete porous metal-organic cages or polyhedra (MOPs) into oligomeric structures with a finite number of MOP units. The synthesis of these new oligomeric porous molecules entails the preparation of 1-connected (1-c) MOPs with only one available azide reactive site on their surface.