Articles

The hexahydropyrrolo[2, 3-b]indole (HPI) framework is found in many natural products. Here, the authors discover a P450 enzyme and develop a whole-cell biocatalysis system that produces the HPI naseseazine C (NAS-C) and 30 NAS-C analogs, several of which show neuroprotective properties.

High-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and current evidences link E7 to HPV-associated carcinogenesis. Here the authors propose a model in which the infection of epithelial cells with high risk HPV results in a burst of reactive oxygen species, translocation of LDHA to the nucleus and activation of a gene profile that supports the growth of cervical cancer.

Humans compensate for sensory noise by biasing sensory estimates toward prior expectations, as predicted by models of Bayesian inference. Here, the authors show that humans perform ‘late inference’ downstream of sensory processing to mitigate the effects of noisy internal mental computations.

On-chip spectrometers typically have limited spectral channels and low signal to noise ratios. Here the authors introduce a digital architecture that uses switches to change the interferometer path lengths, enabling exponentially more spectral channels per circuit element and lower noise by leveraging a machine learning reconstruction algorithm.

It is known that full-term pregnancies can reduce a woman’s breast cancer risk. Here, the authors interrogate data from 2.3 million Danish women, showing that this protective effect arises at precisely the 34th week of the pregnancy, and replicated this finding in 1.6 million women from Norway.

Mutations in pantotenate kinase (PANK) cause neurodegneration. Here the authors carry out achemical screen and identify a PANK activator that is orally available, crosses the blood brain barrierand show that it effecttive in improving pathology and life span in a mouse model of the disease.

TDP-43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTD-TDP). Here, the authors identify the transcriptional elongation factor Ell as a strong modifier of TDP-43-mediated neurodegeneration through the Ell transcriptional elongation complexes LEC and SEC.

Understanding how one metal nanocluster transforms into another is of synthetic and fundamental importance. Here, the authors use mass spectrometry to reveal an acid-induced structural transformation between two Ag clusters that proceeds via a breakage-growth-reassembly mechanism.

RNA interactome capture allows the detailed investigation of RNA-bound proteomes. Here the authors describe enhanced RNA-interactome capture using LNA-modified probes for increased sensitivity and specificity.

Organic electrode materials could enable novelty chemistry required by the new generation of batteries. Here the authors show the synthesis and electrochemical performance of Mg(Li₂)-p-DHT as a lithiated cathode material that cycles at 3.4 V due to the presence of a spectator cation in the host structure.

Short-tandem repeats (STR), similar to single nucleotide polymorphisms (SNP), contribute to complex traits, but their ascertainment by next-generation sequencing is costly. Here, Saini et al. provide a SNP+STR haplotype reference panel that allows imputation of STRs from SNP array data.

Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps.

Small molecules and peptide inhibitors have their benefits and faults when it comes to inhibiting protein-protein interactions. Here, the authors designed a peptoid-peptide hybrid that inhibited β-catenin/TCF interactions, leading to inhibition of Wnt signalling in models of prostate cancer.

The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.

Transcription elongation (TE) is a key point of inducible gene expression regulation. Here, the authors report widespread TE defects (TE^deff) in a high proportion of cancers that correlate with poor immunotherapy response, highlighting TE defects as potential routes for immune resistance.

Peripheral nerves have a complex physiology and it is therefore difficult to measure axonal activity in vitro. Here the authors make a nerve-on-a-chip platform to align peripheral nerves and permit measurement of conduction amplitude and velocity along several axons in a single experiment.

“Diffusing diffusivity” concept has been recently put forward to account for rapid structural rearrangements in soft matter and biological systems. Here the authors propose a general mathematical framework to compute the distribution of first-passage times in a dynamically heterogeneous medium.

Though the Preisach model successfully describes hysteretic switching in ferroelectrics, the physical reality of the model remains elusive. Here, the authors explained the origin of the experimental Preisach distribution and its effect on switching kinetics and materials’ potential applications

Tobacco smoking and cold exposure are environmental modulators of human energy metabolism suppressing appetite and increasing energy expenditure, respectively. Here, the authors develop a novel pharmacological strategy in which they simultaneously mimic the metabolic benefits of both phenomena through small-molecule combination therapy, and show that this treatment improves metabolic health of obese mice.

Transformation of strong C-F bonds into C-Si bonds is an extremely useful strategy for further derivatization of organic molecules. Here, the authors report a nickel-catalyzed strategy to convert aryl fluorides into sylylated arenes while defluorosilylation of alkyl fluorides is achieved under metal-free conditions.