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Truong et al. developed a cell-based reporter system, EXSISERS, that enables non-invasive quantification of the protein expression levels of exon-specific isoforms via intein-mediated protein splicing.

PIEZO1 signalling mediates activation of a proinflammatory response to cyclical pressure fluctuations in immune cells.

Mouse models of severe congenital neutropenia using patient-derived mutations in the GFI1 locus are used to determine the mechanisms by which the disease progresses.

Motile ciliopathies are rare genetic diseases that result in defective beating of motile cilia on epithelial cells. The pathogenetic mechanisms and clinical manifestations depend on the specific mutated gene and the affected tissues. When mucociliary clearance in respiratory epithelia is impaired, the disease is called primary ciliary dyskinesia.

Several lines of evidence suggest the hippocampus plays a key role in navigation. Here, the authors show that during navigation hippocampal patterns represent context-specific, goal-oriented information.

Episomal DNA silencing by Smc5/6 is a three-step process, with the first step involving Smc5/6 binding to and entrapment of the DNA, followed by recruitment of Smc5/6 to promyelocytic leukemia nuclear bodies by SLF2. The third step requires Nse2 but not its SUMO ligase activity.

Hot and altered portions of steep volcanic edifices may collapse and remobilize large amounts of deposits, constituting precursors of highly mobile granular flows in basaltic volcanoes, as shown by the multidisciplinary analysis of the pyroclastic density current produced on Mt. Etna on February 10, 2022.

An unbiased functional gene knockout screen to identify genes implicated in Hedgehog signalling in primary cilia detected most components of the ciliary machinery and ciliopathy-associated genes, but no kidney-related ciliopathy genes. The 472 hits are a tremendous resource for identifying potential ciliopathy genes and for analysing ciliary function and signalling pathways.

The theme of tensions in cosmology has become increasingly important in the cosmological community, proving capable of attracting new generations of scientists who want to be there and contribute to the next paradigm shift.

Mitophagy is crucial for mitochondrial quality control and maintenance of cellular homeostasis. Here the authors identify an E3 ubiquitin ligase, HUWE1, that collaborates with LC3-interacting protein AMBRA1 to induce mitochondrial clearance.

Using JWST, the molecules seen in planetary atmospheres can be traced back to their cold origins in ices formed in dense interstellar clouds, before the onset of star formation, revealing that chemical diversity and complexity is achieved early.

Clinical oncology is rapidly adopting next-generation sequencing technology for nucleotide variant and indel detection. Here the authors present a three-platform approach (whole-genome, whole-exome, and whole-transcriptome) in pediatric patients for the detection of diverse types of germline and somatic variants.

Nicholas Katsanis and colleagues report that a common allele of RPGRIP1L is associated with photoreceptor loss in ciliopathies. An A229T variant in RPGRIP1L compromises binding to RPGR and modifies the retinal degeneration phenotype in ciliopathies caused by mutations in other genes.

Cancer-associated fibroblasts are transcriptionally rewired by signals from the cancer cells, resulting in heterogeneous populations. Here the authors show that loss of BRCA function in pancreatic cancer cells leads to HSF1–dependent accumulation of immune-regulatory clusterin-positive cancer associated fibroblasts.

It remains unclear whether surface water partial pressure of CO₂ (pCO₂) in continental shelves tracks with increasing atmospheric pCO₂. Here, the authors show that pCO₂ in shelf waters lags behind rising atmospheric CO₂ in a number of shelf regions, suggesting shelf uptake of atmospheric CO₂.

Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.

Ciliopathies are caused by alterations in the development and function of cilia. Now Jeffrey Martens and his colleagues demonstrate anatomic and functional rescue of cilia development in mature, differentiated neurons by adenovirus-mediated restoration of expression of the wild-type protein intraflagellar transport protein 88 (Ift88) and show restoration of olfactory function in a mouse model of ciliopathy. A loss-of-function mutation in IFT88 is also identified in individuals with ciliopathies.

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.

Agenesis of the corpus callosum (AgCC) shares anatomical and behavioural features with certain neurodevelopmental and psychiatric disorders. Providing insight into the developmental and molecular basis of AgCC, Lynn Paul and colleagues explain why AgCC may be a good model for other brain disorders.

In the past decade, rodent models have proven critical to study the molecular basis and natural history of polycystic kidney disease. Here, the authors provide an update on the models used to investigate the molecular pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and test potential therapies. They also highlight progress that has been made in understanding the pathophysiology of ADPKD in humans.

Ion-solid interactions are governed by a range of complex processes the direct experimental observation of which pose their own set of challenges. Here, the authors present a joint experimental and first-principles approach to study and describe the underlying mechanism of electron capture for an ion travelling through layers of graphene with monolayer precision.

Chemical approaches, such as those that leverage induced proximity, targeted degradation, synthetic gene regulators or protein design offer opportunities to therapeutically target cellular processes that have long been thought of as undruggable. We report on the progress and the potential for transformative collaborations between fields discussed at the 2023 Bringing Chemistry to Medicine symposium at St. Jude Children’s Research Hospital.

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote T_FH cell differentiation and vaccine responses through the induction of a specific cytokine profile.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

In acute leukemia with KMT2A rearrangements (KMT2A-R), activating signaling mutations are common. Here, the authors use a retroviral acute myeloid mouse leukemia model to show that subclonal de novo activating mutations drive clonal evolution in acute leukemia with KMT2A-R and enhance clonal fitness.

ABCC4 is a chemotherapeutic drug exporter highly expressed in acute myeloid leukemia. Here, the authors demonstrate that MPP1 anchors ABCC4 to the outer cell membrane mediating drug resistance in leukemic cells and identify antimycin A as a chemical probe that disrupts such interaction and restores sensitivity.

Elliot Stieglitz, Mignon Loh and colleagues report the whole-exome sequencing of diagnostic and relapsed samples from patients with juvenile myelomonocytic leukemia. They identify new recurrent mutations for this disease and find that the number of somatic alterations present at diagnosis may be predictive of clinical outcome.

A study reporting optical and near-infrared observations of quasars at redshifts 5.8–6.6 shows that about half have strong winds, up to 17% the speed of light, suppressing black-hole growth.

Unexpected omission of aversive outcome is encoded as reward via activation of reward-encoding dopaminergic neurons in animals. The authors identify the Drosophila neural circuit through which reward-encoding dopaminergic neurons are activated when an olfactory cue is no longer paired with punishment.

The presence and activity of sulfide-oxidizing denitrifying bacteria in sulfide-poor offshore oxygen minimum zone waters remains unclear. Here, the authors combine oceanography, molecular, biogeochemical and single-cell techniques to examine their distribution, metabolic capacity, and origins.

After outlining the rationale for injecting viable cells into the degenerating intervertebral disc (IVD), Sakai and Andersson provide an overview of basic and preclinical studies as well as ongoing clinical trials of cell therapies for IVD degeneration. Consideration is also given to various barriers to the development of these therapies and possible solutions to overcome such obstacles.

Joseph Gleeson and colleagues identify CEP41 mutations as a cause of Joubert syndrome. Their functional studies suggest that CEP41 regulates ciliary entry of TTLL6, an enzyme required for tubulin glutamylation at the cilium.

The planar cell polarity (PCP) effector Fuz had not been studied in mice. Due to disrupted ciliogenesis, Fuz mutant mice show neural tube and skeletal defects. Fuz regulates trafficking of membrane cargoes to cilia through its interaction with a GTPase of the Rab family.

Content-aware image restoration (CARE) uses deep learning to improve microscopy images. CARE bypasses the trade-offs between imaging speed, resolution, and maximal light exposure that limit fluorescence imaging to enable discovery.

Tania Attié-Bitach and colleagues report that biallelic mutations in KIF7, a component of the Hedgehog signaling pathway, cause hydrolethalus and acrocallosal syndromes. They also present evidence that heterozygous KIF7 mutations contribute to the allelic load and phenotypic spectrum of other cilia disorders.

L-form cells can derive from various bacterial species and do not possess a cell wall. It is shown that Bacillus subtilis can convert into L-form through a single point mutation, and that B. subtilus L-form cells are able to propagate independent of FtsZ, an essential component of the bacterial cell division machinery.

The S-layer is a proteinaceous envelope often found in bacterial and archaeal cells. Here, the authors use CRISPR-based technology to silence slaB, encoding the S-layer membrane anchor, to show that an intact S-layer is important for cell division and virus susceptibility in the archaeon Sulfolobus solfataricus.

A library of transgenic flies expressing RNAi in a conditional manner, for virtually every gene in the Drosophila melanogaster genome, has been generated. This resource will allow the community to test the function of every gene, in any cell type, at any development stage, or in response to various types of experimental stimulations.

The assembly of the genome of the koala provides insights into its adaptive biology and identifies gene expansions that contribute to its ability to detoxify eucalyptus-derived compounds and perceive plant secondary metabolites.