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Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

A multi-modal analysis of pre-metastatic liver biopsies from patients with localized pancreatic cancer with a minimum of 3 years of follow-up shows that immunological, proliferative and metabolomic features distinguish patients who develop metastases from disease-free survivors and can be used to predict outcomes.

Human pluripotent stem cells were used to develop dorsal and ventral forebrain 3D spheroids, which can be assembled to study interneuron migration and to derive a functionally integrated forebrain system with cortical interneurons and glutamatergic neurons.

Non-proteinogenic (np) amino acids in the food chain present challenges for the human translation machinery. Here the authors show that, while AlaRS and ProRS activate toxic np azetidine-2-carboxylic acid (Aze) present in sugar beets and lilies, only the AlaRS editing system rejects Aze.

In mouse models of pancreatic cancer, a cooperative interaction between tissue damage and Kras gene mutation rapidly induces cancer-associated chromatin states in pre-malignant tissue, leading to gene dysregulation and neoplastic transformation.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

Emerging evidence suggests that there is an inverse comorbidity relationship between certain neurological disorders and certain cancers. In this Opinion article, Tabarés-Seisdedos and Rubenstein discuss the evidence for this intriguing association and possible underlying mechanisms.

GABAergic cortical interneurons have important roles in the computations of neural circuits, but their developmental origin in primates is controversial. Here the authors characterize neural stem cell and progenitor cell organization in the developing human ganglionic eminences and reveal that, just as in rodents, they give rise to a majority of cortical GABAergic neurons.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

IL-33 induces tertiary lymphoid structures.

An in vivo base editing approach targeting the PRNP gene led to a 52% increase in the lifespan of mouse models inoculated with the most common sporadic and genetic types of human pathogenic prion isolate.

Although cortical GABAergic interneuron (CIN) dysfunction is implicated in several neuropsychiatric disorders, we still know very little about how they attain their unique properties or how their dysfunction impacts neuropsychiatric disorders. In this study, authors show that conditional loss of Tsc1, causes SST+ CINs, which are distinct from PV+ CINs, to express PV and adopt fast-spiking properties, via MTOR activity

Immature excitatory neurons in the human amygdala persist throughout life and could be a substrate for plasticity. Here the authors find evidence that the maturation of these cells may be accelerated during puberty.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Mutagenesis of 23 ultraconserved enhancers and examination of their activities in transgenic mouse reporter assays show that overall their regulatory properties are robust to mutation. Manipulation of endogenous loci in mice corroborates reporter assay data.

Mutations in the methyl-CpG-binding protein 2 (MeCP2) gene cause Rett syndrome, a neurodevelopmental disorder with features of autism. Multiple mouse models of MeCP2 have been generated, but show only a subset of the symptoms of Rett syndrome. These authors find that mice with selective deletion of MeCP2 in GABA-mediated neurons show not only impaired GABA-mediated function, but capitulate multiple key features of Rett, further suggesting a role of inhibitory function in neuropsychiatric disease.

Specific retinal connectivity depends on laminar restriction of neuronal processes. The authors show that a single transcription factor specifies a common laminar identity in dendrites of four retinal cell types, albeit via cell-type-specific means.

In this study, the authors show that MGE-derived interneuron progenitors, when engrafted into the adult hippocampus, can migrate long distances and functionally integrate into the host tissue. In addition, if these cells are engrafted into the brain after the initiation of epilepsy, seizure frequency and behavioral deficits are reduced.

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Transient transcription factor expression rapidly induces a homogenous population of mature GABAergic neurons from human pluripotent stem cells, aiding the study of inhibitory neuron function and disease.

Haploinsufficiency of the gene SCN1A (SCN1A^+/−) causes Dravet’s syndrome in humans, a form of epilepsy with autistic features; this paper shows that Scn1a^+/− mice have the same symptoms, and that social behaviours can be improved by pharmacological treatment with clonazepam.

Garry Cutting and colleagues report a genome-wide association and linkage study for loci that affect lung disease severity in cystic fibrosis. They identify two loci that influence lung function in individuals with cystic fibrosis.

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.

In pancreatic cancer the Kras and Trp53 transgene driven KPC mouse model is used to experimentally study disease processes. Here, the authors analyse tumour evolution within the KPC model, finding both linear and branched evolution and highlighting the utility of this model in mechanistic research of tumour evolution.

In primates, the developmental origin of neocortical interneurons is controversial. Here the authors map out expression patterns of key transcription factors in the developing human and monkey brain and reveal that, just as in rodents, the majority of cortical GABAergic neurons originate from the ganglionic eminences.

In mouse, an axonal connectivity map showing the wiring patterns across the entire brain has been created using an EGFP-expressing adeno-associated virus tracing technique, providing the first such whole-brain map for a vertebrate species.

Using metabarcoding, we found that seasonal dietary shifts were associated with slower breeding and acacia are fallback foods for black rhino. Grass was the highest value food for Grevy’s zebra. Seasonal diet shifts did not drive microbiome shifts.

Tumour-infiltrating group 2 innate lymphoid cells prime CD8⁺ T cells and amplify the anti-tumour effects of PD-1 blockade in pancreatic ductal adenocarcinoma.