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By leveraging diverse datasets from brain stimulation therapy for Tourette Syndrome and tic-inducing brain lesions, Baldermann et al. reveal a critical role of action-related functional networks in both the treatment and pathophysiology of tic disorders.

The climatic impact of ammonia emissions from Arctic seabird-colony guano is poorly understood. Here, using observations and a chemical transport model, Croftet al. illustrate that guano-associated particles promote cloud-droplet formation, resulting in a pan-Arctic cooling tendency of approximately −0.5 W m⁻².

In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.

Here the authors identify age-associated changes in the epithelial cell compartment of the thymus that form high-density nonproductive microenvironmental niches that contribute toward thymic involution and inhibit its repair following injury.

A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

The tumour microenvironment has not been fully characterised in high-grade serous ovarian cancers (HGSOC). Here, the authors use highly multiplexed imaging to analyse the HGSOC immune microenvironment at spatial and single-cell resolution, with clinically relevant findings for BRCA1/2-mutated tumours.

Cyclin B1 is a mitotic co-factor of CDK5.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

BRCA proteins have emerged as key stabilizing factors for the maintenance of replication forks following replication stress. Here the authors describe how reversed replication forks are degraded in the absence of BRCA2, and a MUS81 and POLD3-dependent mechanism of rescue following the withdrawal of genotoxic agent.

NocTE is a nonribosomal peptide synthetase thioesterase that completes the biosynthesis of pro-nocardicin G, the precursor for nocardicin β-lactam antibiotics. Here the authors provide mechanistic insights into NocTE by determining its crystal structures in the ligand-free form and covalently linked to a fluorophosphonate substrate mimic.

Cryo-EM, X-ray crystallography and crosslinking mass spectrometry are harnessed to solve the structure of the full-length Rho-GEF P-Rex1, uncovering a two-layered mechanism of autoinhibition released upon Gβγ and PI(3,4,5)P3 binding.

The anthraquinone and enediyne halves of the antitumor antibiotic dynemicin A were previously thought to be assembled by two separate polyketide synthases (PKS). Now, a single polyketide synthase has been proposed to be responsible for their production, and a working model for their biosynthesis from a common octaketide intermediate has been suggested.

Ecological models of species with diverse life history traits show that complementary combinations of life history strategy contribute, together with fitness and niche differences, to the maintenance of biodiversity.

PLX4032 is a selective inhibitor of the B-RAF protein that has shown promising results in an early clinical trial in melanoma patients with an activating mutation in B-RAF. Now the structure and function of this inhibitor are described. Translational data from a phase I trial show that clinical efficacy requires a substantial degree of inhibition of the ERK pathway downstream of B-RAF. The data also show that BRAF-mutant melanomas are highly dependent on B-RAF activity.

The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient.

The secondary bile acid 3β-hydroxy-deoxycholic (isodeoxycholic) acid, produced by gut bacteria, promotes the generation of colonic extrathymic regulatory T cells, whose immunosuppressive activities are known to be essential for intestinal health.

The study reveals the Acinetobacter baumannii T6SS Rhs effector, Tse15, uses its clade domain as an internal chaperone to facilitate toxin delivery and the Rhs cage is not secreted.

Most tumours associated with germline BRCA1/BRCA2 loss of function mutations respond to DNA damaging agents, however, some do not. Herein, the authors identify that a subset of breast/ovarian tumors retain a normal allele, which is associated with decreased overall survival after DNA damage-inducing platinum chemotherapy.

If neutrinos are their own antiparticles, neutrinoless double-β decay of ⁷⁶Ge should occur; a new lower-limit half-life of 5 × 10²⁵ years for this process has now been determined under background-free conditions.

This report identifies Cdk1's phosphorylation of BRCA1 as an important regulator of BRCA1's DNA repair function. Cdk1 inhibition renders cancer cells sensitive to PARP inhibition, and the combination treatment can inhibit tumor growth in vivo, expanding the potential application of PARP inhibitors beyond BRCA1-deficient tumors.

Hamish Scott and colleagues report that germline mutations in GATA2 segregate with myelodysplastic syndrome and acute myeloid leukemia in four pedigrees. The resulting alterations occur in a conserved zinc finger DNA-binding domain of GATA2.

Whole-exome sequencing of human brain metastases from lung adenocarcinoma uncovers new drivers by comparison of somatic alteration frequencies in brain metastasis cases to those in primary lung adenocarcinomas.

There have been objections to onshore wind turbines for aesthetic reasons, although a quantitative methodology to provide some assessment of the risk of such public objections has been missing. McKenna et al. develop a method to use geotagged photographs of landscapes to assess potential future public acceptance of projects.

Paz Polak, Jaegil Kim, Lior Z. Braunstein and colleagues have identified patterns of genome-wide mutation in certain breast cancers that can be used to identify those with DNA-repair deficiencies that make the tumor more likely to respond to therapies based on PARP inhibitors or platinum. In contrast, oncogenic mutations in several other DNA-repair genes do not generate these patterns.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements.

Here, the authors use ultrafast transient absorption spectroscopy with a broadband white-light probe to simultaneously resolve interlayer charge transfer and interlayer exciton formation dynamics in a MoSe₂/WSe₂ heterostructure.