Table of Contents
Research Articles
The TUDOR domain of SMN is an H3K79me1 histone mark readerThe survival of motor neuron (SMN) protein is depleted in spinal muscular atrophy (SMA) pathology and herein defined as the first reader of histone H3 mono-methylated on lysine 79 through its central TUDOR domain.
The ERK activator, BCI, inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangementERK1/2 not only controls the cell cycle but also has new roles impacting various mechanisms affecting ciliogenesis. DUSP6 inhibition activates ERK to immediately inhibit ciliary assembly and upstream pathways.
Potency assessment of IFNγ-producing SARS-CoV-2-specific T cells from COVID-19 convalescent subjectsSARS-CoV-2-specific T-cells from convalescent donors present phenotypical and functional characteristics that make them a suitable candidate for a future development of an advanced cellular therapy.
MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer’s diseaseThis study demonstrated the translational potential of deregulated tear fluid miRNAs associated with amyloid beta production and proinflammation in a transgenic AD mouse model.
Mitochondrial dysfunction rapidly modulates the abundance and thermal stability of cellular proteinsThe combination of thermal proteome profiling and pulsed SILAC labelling shows that mitochondrial dysfunction imprints a characteristic pattern on the abundance and thermal stability of the proteome.
Structure-based design and characterization of Parkin-activating mutationsParkin, an E3 ubiquitin ligase involved in Parkinson’s disease, is inactive in the basal state and is activated by PINK1 to mediate mitophagy. Here, we characterized 31 mutations and discovered three that activate Parkin and rescue loss of PINK1 phosphorylation.
Cell death and barrier disruption by clinically used iodine concentrationsClinically used concentrations of povidone-iodine (PVP-I) are toxic to eukaryotic cells by attacking the lipid bilayer and tight junctions with fast kinetics and urge the reappraisal of PVP-I use.
Filopodia-like protrusions of adjacent somatic cells shape the developmental potential of oocytesFilopodia-like protrusions sent by the somatic cells to the oocyte play a role in the structural integrity of the germline–somatic complex, and regulate gene expression in the oocyte and thus its developmental potential and chances to produce a viable embryo.
Characterisation of the OTU domain deubiquitinase complement of Toxoplasma gondiiThe OTU deubiquitinase family is expanded in Toxoplasma parasites, and members show preferences for Lys6-, Lys11-, Lys48-, and Lys63-linked ubiquitin chains, and additional specificity for NEDD8. AlphaFold-guided structural analysis reveals cryptic ubiquitin-binding domains with functional importance.
Interaction hub critical for telomerase recruitment and primer-template handling for catalysisBy deleting, mutating, and adding back parts of the telomerase enzyme that extends chromosome ends, we uncover features important for its proper functioning in the cell.
Local tissue mechanics control cardiac pacemaker cell embryonic patterningMicroenvironmental patterning during sinoatrial node morphogenesis is critical for sustaining cardiac pacemaker cell function.
Crystal structures of dimeric and heptameric mtHsp60 reveal the mechanism of chaperonin inactivationThe crystal structure of the dimeric mtHsp60 from grouper fish has been determined, revealing a symmetrical subunit interaction with an exchanged α-helix connecting the two subunits. This structure provides new insights into the conformational changes of this important chaperonin
The association of lipid transfer protein VPS13A with endosomes is mediated by sorting nexin SNX5Binding of sorting nexin SNX5 to the VAB domain of VPS13A mediates its recruitment to membrane contact sites between SNX5-containing endosomal membranes, mitochondria, and ER.
Reduced replication but increased interferon resistance of SARS-CoV-2 Omicron BA.1The SARS-CoV-2 Omicron BA.1 variant of concern is highly resistant against exogenous interferons, suggesting that effective innate immune evasion contributed to its success.
FBXO11 governs macrophage cell death and inflammation in response to bacterial toxinsFBXO11 regulates the expression of the complement receptor C5aR1 and the inflammatory cytokine IL-1β, affecting how macrophages respond to Staphylococcus aureus pore–forming toxins.
The role of Limch1 alternative splicing in skeletal muscle functionThis works identifies a novel, alternatively spliced isoform of LIMCH1, that is, developmentally regulated and specific to skeletal muscle. Knocking out the six skeletal muscle–specific exons of LIMCH1 leads to impaired skeletal muscle function in vivo and ex vivo.
The role of the mitochondrial outer membrane protein SLC25A46 in mitochondrial fission and fusionThe mitochondrial outer membrane protein SLC25A46 localizes to mitochondrial fusion and fission sites, and loss of function alters mitochondrial morphology and oligomerization states of MFN2 and OPA1.
UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cellsWe generated a new Upf3a-inducible knockout mouse model and showed that UPF3A does not repress expressions of NMD target genes in embryonic stem cells, somatic fibroblasts, and multiple tissues from adult mice.
Bats experience age-related hearing loss (presbycusis)Bats exhibited age-related hearing loss. Bats are exposed to immense conspecific noise, but the frequency-dependent hearing loss was not correlated to the noise.
RopB represses the transcription of speB in the absence of SIP in group A StreptococcusSIP-free RopB, in contrast to SpeB-inducing peptide (SIP)-bound RopB, is a transcriptional repressor of speB and mediates speB repression in the covS mutant.
arfA antisense RNA regulates MscL excretory activityBacteria coordinate how they respond to translation and osmotic stress by using antisense RNA crosstalk between the genes involved in the respective stress response pathways.
Dynamic changes of enhancer and super enhancer landscape in degenerated nucleus pulposus cellsSuper-enhancers mediate inflammatory cascade and extracellular matrix remodeling in degenerated nucleus pulposus cells.
The ubiquitin-like modifier FAT10 is degraded by the 20S proteasome in vitro but not in celluloThe ubiquitin-like modifier FAT10 is degraded by the 20S proteasome in vitro, whereas FAT10 degradation depends on the 26S proteasome in cellulo, shown by impairing 26S function via Rpt2 knockdown.
Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosisUssing chamber studies of intestinal organoid monolayers compare favorably to established preclinical tools to assess individual responses to CFTR modulator drugs in people with cystic fibrosis.
Multidimensional conservation analysis decodes the expression of conserved long noncoding RNAsThe authors demonstrate the transcriptional codes that govern the expression of conserved long noncoding RNAs through multi-dimensional conservation analysis.
Retinitis pigmentosa–associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule cellsThis study shows that Prpf8 mutations associated with human retinal degeneration in mice alter circRNA expression in cerebellar granule cells and induce their apoptosis.
An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicityThis work describes how a mutation affecting mitochondrial metabolism in a sarcoma model induces protective immunity against the tumor and how this result might be relevant for sarcoma patients.
Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencingDicer-dependent small non-coding vault RNA1-2 employs nascent RNA silencing to modulate the expression of a group of genes associated with membrane function.
Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in gliomaGlioma patients often relapse because of resistance to radiation therapy. The transfer of the metabolic enzyme NAMPT via microvesicles and the accompanying elevated levels of NAD are found to be a mechanism by which glioma cells become resistant to radiation.
EZH2 controls epicardial cell migration during heart developmentEZH2 influences epicardial cell migration into the myocardium via TIMP3-dependent fine tuning of basement membrane degradation, which leads to cardiac malformations and embryonic lethality.
New botulinum neurotoxin constructs for treatment of chronic painA new technique to make therapeutic botulinum neurotoxins via isopeptide bonding is described. The novel elongated botulinum neurotoxin can treat nerve injury pain without causing muscle paralysis.
Sleep–wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in miceThis study found that age-associated sleep changes are ameliorated by DR in the presence of Prdm13 signaling in the DMH, suggesting Prdm13+ DMH neurons will be of great interest to explore a potential intervention on age-associated sleep changes.
Cognitive decline in diabetic mice predisposed to Alzheimer’s disease is greater than in wild typeThis work proposes that T2DM is particularly harmful to brain function in individuals with a genetic predisposition to neurodegenerative pathology via, among others, γ-secretase inhibition.
Yolk-deprived Caenorhabditis elegans secure brood size at the expense of competitive fitnessMany egg-laying species lower fecundity when yolk is in short supply, but not C. elegans. They still produce abundant offspring, yet of decreased quality.
Methods
Rapid and precise genotyping of transgene zygosity in mice using an allele-specific methodA novel, precise, rapid, and generalizable method to determine transgene zygosity in mice by allele-specific restriction enzyme digestion of PCR products from transgenes or homologous endogenous genes.
