Issues

Summary: The alcohol flushing-associated ALDH2*2 variant is one of the most common genetic polymorphisms in humans. This variant exhibits complex pleiotropic effects associated with alcohol consumption and aldehyde toxicity, which diversely impact human health.

Summary: Variant effect predictors (VEPs) are algorithms that aim to predict the likelihood that a genetic or protein variant will be pathogenic. Herein, we review benchmarking procedures and deep mutational scanning as methods for validating VEPs.

Summary: The functionally replaced human genes in yeast generate humanized yeast, providing a simple growth-based readout for the functions of hundreds of critical human genes and allowing researchers to study them in a simplified organismal context.

Summary: This Review discusses challenges in neurodegenerative disease research and how deep phenotyping and genomics, alongside machine learning, can help the progress towards precision medicine.

Summary: This study shows, for the first time, a neuroprotective role of chaperone Hsp40 in suppressing circadian dysfunction associated with Huntington's disease in a Drosophila model.

Summary: We used a caspase-1 reporter mouse model to measure spatiotemporal dynamics of inflammation in obese mice, identifying tissue- and sex-specific caspase-1 activation patterns and inflammatory phenotypes, indicating mechanisms underlying the dynamics of inflammation.

Summary: We identified two types of cancer stem cell (CSC)-like populations in triple-negative breast cancer xenografts and patients. These CSC-like populations could potentially make tumors more drug resistant and thus more difficult to treat.

Summary: We report the first mouse model for cerebrocostomandibular syndrome, showing that mis-splicing of transcripts that regulate P53 activity and craniofacial-specific genes contributes to craniofacial malformations.

Summary: Transcriptome analysis of zebrafish slc39a14^−/− mutants demonstrates that loss of slc39a14 leads to concurrent manganese neurotoxicity and deficiency, both of which are associated with Ca²⁺ dyshomeostasis.

Summary: A series of physiological, histochemical and molecular analyses reveal that enriched environment decreases inflammation in adipose tissue and in hypothalamus, re-establishing glucose metabolism in metabolically compromised mice.

Summary: Conditional ablation of Lrp6 in dorsal neural folds causes spinal neural tube defects that can be rescued by genetic activation of β-catenin or maternal supplementation of Wnt signaling agonists.

Summary: Automated meiotic mapping, which allows rapid discovery of induced germline disease modifier mutations, reveals influential loci in mice with an autoimmune diabetes phenotype, identifying genes that may influence type 1 diabetes susceptibility in humans.

Summary: AMPK inhibition in conjunction with regular chemotherapy is likely to reduce the stem cell pool and improve chemosensitivity and therapeutic outcomes in breast cancers.

Summary: Phenotyping data for two novel mouse models combining glucocerebrosidase (GCase) deficiencies and alpha-synuclein pathology reveal the extent to which alpha-synuclein pathology is exacerbated by GCase deficiency.

Summary: Chronic unpredictable mild stress, a putative model of depression, reduced PPP4R3A expression in mice. PPP4R3A deficiency in mice leads to depression-like behaviors by inhibiting mTORC1-mediated synthesis of synaptic proteins.