Compound heterozygous mutations in VPS41 were identified in patients with a neurodegenerative phenotype with dystonia and cerebellar atrophy. VPS41 variants obstruct the HOPS complex, leading to decreased endocytic and autophagy cargo transfer to lysosomes and inhibition of mTORC1 signaling.

T cells play a critical role in immune response. This study identifies a novel B7 family‐related T cell inhibitory molecule TAPBPL. Targeting the TAPBPL pathway may represent a new strategy to modulate T cell‐mediated immunity to treat autoimmune disease and cancer.

Quantitative immunohistochemistry (qIHC) reveals that high expression of the DNA repair protein RAD51 in epithelial ovarian cancer (EOC) is associated with early relapse after platinum chemotherapy, and also with decreased cytotoxic T‐cell infiltration into tumors.

This study describes a vanadium pentoxide (V₂O₅)‐based nanozyme that bolsters the anti‐HIV potential of immune cells and suppresses viral rebound in latently infected CD4⁺ T cells derived from HIV subjects.

We show that upon fat ingestion, Protein Kinase D2 stimulates chylomicron‐mediated triglyceride absorption in the intestine. Targeting PKD2, genetically or with small molecule inhibitors, reduces triglycerides absorption and prevents the development of obesity in mice and presumably in humans.

This preclinical study demonstrates the potential of radiotherapy to sensitize breast cancer brain metastasis to checkpoint inhibition. Myeloid cells contribute to immune suppression affecting long‐term survival and therefore represent a target for improved radio‐immunotherapy.

This study reveals a critical role of the positive feedback loop between mTORC1 signaling and cathelicidin in the pathogenesis of rosacea. Targeting mTORC1 may be a novel potential therapeutic strategy for rosacea treatment.

This study describes two cases of developmental regression with features resembling mucopolysaccharidosis‐like disease, caused by a recessive intronic variant in the HOPS/CORVET subunit VPS16. The cellular consequences of the mutation are characterized in patient‐derived cells and a zebrafish model.

Currently, no curative therapies exist for disorders caused by tandem duplication mutations. To address this critical need, CRISPR/Cas9‐mediated removal of a duplication mutation was demonstrated in‐vivo, leading to substantial improvement in disease phenotype in a tandem duplication DMD mouse model.

Prostate cancer becomes resistant to treatments targeting oncogenic androgen receptor (AR) via coordinated activity of multiple adaptive responses. This study defines metabolic reprogramming in response to AR pathway inhibition (ARPI) that supports AR reactivation.

Using a CRISPR activation screening, we identified genes involved in BRAF inhibitor (BRAFi) resistance in cutaneous melanoma. Their upregulation promoted tumour growth of therapy‐naïve melanoma cells and BRAFi‐resistance. Inhibition of these genes (not mutated) may be useful for therapy.

Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. Understanding the mechanism and regulation of compensatory beta cell proliferation may allow for improved treatment options for diabetes. Herein we elucidated that the menin/JunD/Pbk axis is important in compensatory beta‐cell proliferation.

NMR studies define how the P182L mutation alters intramolecular interactions to increase HSP27 accessibility for numerous binding proteins, compromising its chaperone function in patient cell‐derived motor neurons.

Mitochondrial dysfunction leads to decreased HIF1α‐Nmnat3‐dependent NAD⁺ production, inhibiting localized ATP production at the lysosomal membranes and vATPase function in mouse heart.

Refinement of dynactin cryo‐EM structures offers insights into dynactin subunit organization in the shoulder region and adaptor binding to its pointed end.

A new proteomic approach allows comprehensive characterisation of exosome heterogeneity in human T cells.

BIR‐mediated homologous recombination allows mammalian cells to cope with replication stress and is differently controlled at fork‐breakage‐induced vs endonucleases‐generated DSBs.

Based on genetically engineered mouse models (GEMMs) and human psoriasis biopsies, this study suggests that c‐Jun in Dendritic Cells (DC) contributes to psoriasis by controlling CCL2 and IL‐23 production, and further identifies the JNK/c‐Jun axis as a druggable target.

Expression and function of netrin‐3 have so far never been investigated in human cancers. Based on cohort analyses, this study shows that netrin‐3 is a putative therapeutic target in both small cell lung cancer (SCLC) and neuroblastoma (NB).

This study identifies that Wnt/β‐catenin signaling regulates homologous recombination and Fanconi anaemia DNA repair pathways in Wnt‐high cancers and intestinal stem cells. Wnt signaling inhibition induces a BRCA‐like state; and Wnt and PARP inhibitors synergize to inhibit Wnt‐addicted cancers.

Neuronal activity drives transcriptional and morphological changes that ensure maturation. Such mechanism is affected by Mecp2 absence. We show the rescue effects produced by enhancing Mecp2 null neurons activity and propose new therapeutic time windows for the treatment of Rett syndrome.

Ocular gene therapy aims to improve or preserve vision in patients with inherited blinding disorders. The current technology still relies on subretinal administration of therapeutic vectors, which harbours risks of collateral damage and only treats a small portion of the affected retina. This study presents two novel engineered viral vectors capable of widespread targeting of retinal cells through a less invasive delivery route.

Simulation in patient‐derived xenografts of the situation of patients with lung cancer, who receive first‐line EGFR kinase inhibitors, revealed that monoclonal antibodies can prevent emergence of resistance to the currently approved inhibitors.

The LDB2 gene is mapped at the breakpoint of a balanced chromosomal translocation seen in a patient with schizophrenia. This study investigates the role of LDB2 and transcriptional regulation exerted by the “LDB2‐EGR axis” in the pathogenesis of mental disorders.

This study explored the potential of RNA‐sequencing of peripheral blood to track non‐invasively disease progression and response to treatment in dystrophic mice and in patients affected by Duchenne Muscular Dystrophy (DMD).

Multi‐modal integration of single‐cell RNA‐seq data from lung tissue and proteomic data from body fluids across independent lung fibrosis patient cohorts revealed biomarker signatures that correspond with cell state changes during disease progression.

Transcriptional factor nuclear factor IB (NFIB) is sufficient to enhance lung metastatic colonization via enhanced angiogenesis, thus revealing a targetable network that promotes breast cancer colonization.

This study identifies novel combinatorial drug treatments to induce death of different tumor cells, and defines the mechanisms of synergism between a mitochondrial uncoupler and antidepressants or dopamine receptor antagonists.

We show that human and rodent malaria sporozoites move and enter blood vessels with similar efficiency in mouse skin. Our data demonstrate that intravital imaging of P. falciparum sporozoites at the dermal inoculation site can be used to assess the impact of antibody on sporozoite migration.

Key benchmarks for malaria vaccine design were investigated. Antigen immunogenicity and accessibility were studied with results indicating the proof‐of‐concept that a poorly immunogenic exo‐erythrocytic form (EEF) antigen is comparably vulnerable as a strongly immunogenic sporozoite antigen to targeting by vaccine‐induced effector CD8⁺ T cells.

Pathogenic involvement of SGK1 has been implicated in various neurodegenerative disorders. In this study, we show that inhibition of SGK1 in glia treats Parkinson disease (PD) via suppressing glial inflammation and potentiating glial neurotrophic functions.

This study presents a scalable, sensitive and reproducible mass spectrometry‐based proteomics workflow for urinary proteome profiling, and demonstrates it as a promising strategy for urine biomarker discovery for Parkinson’s disease (PD).

Patients suffering from heart failure have an increased risk to develop age‐associated dementia. This study elucidates the underlying mechanisms and provides evidence that heart‐failure induced cognitive decline is linked to epigenetic changes that affect neuronal gene expression.

A three‐step mechanism of CheY binding to the E. coli flagellar motor switches bacterial swimming behavior from swimming to tumbling to enable chemotaxis.

This study reveals the significant anti‐angiogenic properties of COCO/Dand5 in models of retinal and choroidal neovascularisation. Exogenous COCO inhibited endothelial cell proliferation and migration, limited TGFβ and BMP pathways and altered energy metabolism and cellular redox balance.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder of aging characterized by enlarged cerebral ventricles, gait and balance difficulty, incontinence and cognitive impairment. The cause of iNPH is not known.

This study shows the development of a new method for the classification of human blood donors according to the presence of anti‐Spike (S) antibodies of SARS‐CoV‐2 that bind to the native S protein expressed on the surface of the human Jurkat human T cell line.

DR5 agonists moved to clinical trials after successfully controlling tumors in immunodeficient xenograft models. By stabling introducing human DR5 extracellular domain into murine tumor cells, this study identifies PD‐L1 pathway as a contributing factor for potential immune evasion in solid tumors.

Intraductal xenografts of invasive lobular carcinoma (ILC) cells faithfully model this breast cancer subtype, and reveal tumor cell intrinsic ECM remodeling as a critical feature of disease progression that can be exploited therapeutically by targeting LOXL1.

Here we report a comprehensive set of preclinical studies, performed both in vitro on X‐linked hyper‐IgM syndrome (HIGM1) patient‐derived cells and in vivo in HIGM1 mice, which uncovers crucial guiding principles towards clinical translation of CD40LG targeted gene correction in T cells or hematopoietic stem cells (HSC) for the treatment of HIGM1.

A chemistry campaign has developed a small molecule that stabilises the severe Z deficiency mutant of α1‐antitrypsin. The lead compound binds to a cryptic pocket and blocks the conformational change and pathological polymerisation that underlie α1‐antitrypsin deficiency.

This study reveals the plasticity of LKB1‐deficient tumors, and identifies the Nanog‐Notch axis in regulating gastric differentiation. Combinational treatment of γ‐secretase inhibitor LY‐411575 and phenformin effectively blocked invasive mucinous adenocarcinoma IMA formation.

This study reveals NFAT‐NF45/NF90‐mediated rDNA transcription as a key regulating axis in modulating T cell activation. Targeting ribosome biogenesis could be a novel immunosuppressive therapy for organ transplantation.

The regenerative capability of skeletal muscle tissue is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. By exploiting the potentials of our biofabrication approach, one can manufacture advanced cell‐laden myo‐substitutes that ultimately may restore the functionalities of severely damaged skeletal muscles in vivo.

Group B Streptococci (GBS) exploit specific host factors S1P2, EGFR and CysLT1 to penetrate the blood‐brain barrier, which is the essential step in the development of GBS meningitis. These host factors function as a distinct network, with S1P2 and CysLT1 acting as upstream and downstream molecules of EGFR.

Analysis of individual synapses reveal that the ability of auditory inner hair cells to translate a wide range of sound intensities is linked to presynaptic heterogeneity in Ca²⁺ channel‐mediated glutamate release.

piRNA biogenesis requires RBP‐9 mediated transcriptional termination at complex piRNA genes.

Cytosolic antibody receptor and ubiquitin ligase TRIM21 promotes antigen presentation and T cell activation by targeting immune complexes for efficient proteasomal degradation.

Transcription termination and release of short capped piRNA precursors extends the small RNA biogenesis roles of the Integrator complex beyond snRNA.

Loss of the autism spectrum disorders linked gene Shank2 in mice leads to loss of social bonding due to functional changes in the social attachment circuit including the MPOA.

The common oxidative DNA base lesion thymine glycol can surprisingly be bypassed by reconstituted yeast replisomes in the absence of dedicated translesion synthesis polymerases.

Macropinosome‐dependent delivery of the phospholipid PI(3,4)P2 to the trailing edge of the cell establishes its polarized distribution required for correct migratory behavior.

Structure‐function analyses of the full‐length Yersinia pseudotuberculosis toxin CNFY offer insights into individual domain contributions to stepwise receptor binding, endocytosis, and translocation into the host cell cytosol.

The vertebrate transcription factor PLZF/ZBTB16 emerges as potential key mediator of limb defects caused by CRBN ubiquitin ligase modulators, providing insight into the teratogenic contributions of thalidomide metabolites.

Post‐translational processing of the transcription factor Shavenbaby defines its dichotomous function in fly midgut homeostasis.

ANKRD26‐dependent PIDD1 recruitment is involved in p53 activation both upon genotoxic stress and in the presence of supernumerary centrosomes.

Proper neuromuscular junction formation in flies depends on a key mRNA modification guiding translational repression by the Fragile X mental retardation (FMRP) RNA‐binding protein.

Syne4 deficiency leads to hearing loss in humans. In this work, auditory function was rescued in Syne4 knockout mice by a synthetic AAV that enables safe and efficient transduction of hair cells in the cochlea.

Insufficient penetration of immune cells and therapeutic antibodies into the tumor core is a major limitation in the immunotherapy field. This study reports the development of a novel bispecific antibody, named CC‐1, for improved dual targeting of tumor‐ and vascular cells in PSMA positive tumors.

Histone posttranslational modifications play a major role in the regulation of α‐synuclein expression in Parkinson’s disease (PD). Locus‐specific editing of H3K4me3 at the SNCA promoter reverts the deregulated expression of α‐synuclein in neurons in the context of PD.

This study reveals that SLC6A20A, an amino acid transporter previously known to transport proline, also transports glycine, a co‐agonist of NMDA receptors. SLC6A20A inhibition holds therapeutic potential for brain disorders with suppressed NMDAR function such as schizophrenia.

Tumor suppressor TP53 is mutated in a large fraction of tumors. APR‐246/Eprenetapopt is the most clinically advanced mutant p53‐targeting drug candidate (Phase III). Besides restoring wild type p53 activity, the active product MQ also disrupts the redox balance, resulting in cancer cell death.

Nutritional and metabolic effects of strict vegan diets in young children are poorly understood. This first cross‐sectional study of preschool children reports that vegan diet remodels metabolome and lipidome and raises concern of their vitamin A and D statuses and essential amino acids.

Two familial cohorts of ALSP, with novel pathological CSF1R variants were examined and an associating cerebrovascular amyloid‐β pathology identified. Deficits in peripheral macrophage function and blood‐brain barrier maintenance identified and suggested to contribute to ALSP.

Using mice with constitutive activation of autophagy and treating mice deficient for ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL) with the autophagy inducing Tat‐Beclin‐1 (TB‐1), this study shows that Beclin‐1‐dependent activation of autophagy improves the phenotypes of proximal and distal defects of the urea cycle.

EC8042 is identified as an inhibitor of oncogenic SWI/SNF and a promising therapeutic candidate for rhabdoid tumor. The mechanism of target inhibition is elucidated and used to optimize compound administration, characterize an associated biomarker, and cure mice bearing rhabdoid tumor xenografts.

This study demonstrates the use of MOTS‐c peptide to promote oligonucleotides uptake in muscle cells by augmenting glycolytic flux and energy production. This approach may be used to improve the success of DMD exon‐skipping therapy and potentially be used for other diseases with hallmarks of energy deficiency.

A human airway in vitro culture permissive to COVID‐19 demonstrates a drug‐sensitive IFN response.

The findings identify that miR‐574 fine‐tunes FAM210A expression and modulates mitochondrial encoded protein expression, thereby maintaining normal mitochondrial function and protecting the heart from cardiac stress induced pathological remodeling.

The study shows that increased lamin B1 levels contribute to altered nuclear function of specific neurons in Huntington's disease (HD) brain. Results highlight this alteration as a new pathogenic mechanism for HD and provide a novel target for HD intervention.

Arabidopsis roots adjust their growth to the type of nitrogen source via phosphorylation of auxin carrier PIN2 and adjustment of auxin distribution between neighboring tissues.

A member of the pseudo response regulator (PRR) family in rice is induced upon salt stress to decrease expression of a sodium transporter via chromatin modifications.

The short linear motif NLxxxl present in several yeast cyclin‐dependent kinase substrates like Far1 and Slx4 targets them specifically to Clb5‐Cdk1 complexes active in S‐phase.

In vivo silencing reveals a pro‐survival role for the developmental axon guidance cue netrin‐1 in the adult mouse substantia nigra, which may be lost in Parkinson's patients and thus offering potential therapeutic options.

ALKAL2 misregulation facilitates ALK receptor tyrosine kinase signaling and drives ALK‐dependent cancer irrespective of oncogenic mutations.

Combination of NMR, in vitro and in vivo assays reveal that phosphorylation of the RNA binding protein hnRNPA2, linked to protein aggregation diseases and a component of transport granules, reduces liquid‐liquid phase separation and protein aggregation pointing to new strategies for the treatment of neurodegenerative diseases.

In cortical neurons, a chromosomal scaffold protein and an inner nuclear membrane protein orchestrate activity‐dependent nuclear shape changes and transcription of genes associated with cognitive function.

PID‐2 and its newly‐identified interactors PID‐4 and PID‐5 modulate size and appearance of Z granules to establish and maintain stable heritable silencing (RNAe) by maternal piRNAs.

Ablation of the nuclear envelope protein lamin B1 in neural stem/progenitor cells disrupts neurogenesis and causes aging‐associated behavioral changes in mice.

Real lncRNAs are bound, but not degraded by miRNA‐loaded RNA‐induced silencing complexes, establishing different susceptibilities of coding and non‐coding RNA to miRNA‐dependent repression.

The neural tube‐closure regulator LUZP1 drives apical constriction of epithelial cells by inhibiting myosin phosphatase activity in a microtubule‐dependent manner

Intrinsic mechanical properties and BCL9L expression in tumor cells determine their stemness and are linked to cancer progression.

Deficiency of the X‐linked MECP2 gene profoundly impairs neurodevelopment. Clinically, mutations in MECP2 most commonly present as the severe and untreatable disease Rett syndrome. Innovative human pluripotent stem cell (PSC) technology enables the investigation of therapeutic candidates.

The functional redundancy of two terminal oxidases in mycobacteria limits the efficacy of phase 2 clinical candidate Telacebec (Q203). In this study we identified a cytochrome bd oxidase inhibitor ND‐011992 that together with Q203 forms a bactericidal drug combination against Mycobacterium tuberculosis.

This study presents a novel treatment strategy for the severe epileptic encephalopathies associated with Munc18‐1 mutations. Using an in silico screen followed by validations in mouse neurons and C. elegans models, three compounds that target Munc18‐1 and reverse neuronal dysfunction are identified.

Immunosuppressive myeloid cells (IMCs) are a prominent driver of immunotherapy resistance in colorectal cancer. This study identifies EP4 as a master regulator of IMCs and highlights blockade of EP4 as a novel therapeutic strategy for enhancing immunotherapy in colorectal cancer.

Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.

Enteric gliosis was shown to be part of an intestinal immune response upon abdominal surgery. ATP activates enteric glial cells via selective purinergic receptor signalling in mice and humans. Inhibition of this pathogenic pathway by the newly identified P2X2 antagonist ambroxol blocks ATP‐induced enteric gliosis and protects against postoperative ileus.

Single nucleotide polymorphisms (SNPs) previously identified through genome‐wide association studies as risk factors for amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) further associate in a polygenic manner with risk for cognitive dysfunction in ALS and related disorders.

This study introduces a novel strategy to accelerate the revascularization of transplanted islets by the fusion of microvascular fragments (MVF) with pancreatic islet cells. These prevascularized islet organoids may be used to improve the success rate of clinical islet transplantation.

Structures of ISC th4 transposase/DNA complexes at different stages of the transposition pathway provide first insight into transpososome architecture and reaction mechanism of this major bacterial DNA mobility pathway.

Imaging of the early viral replication cycle reveals that conversion of incoming viral DNA into DNA can occur inside target cell nuclei, challenging the prevalent notion that HIV‐1 genome reverse transcription and host chromosomal integration are spatiotemporally separate.

Kinetic and mutational studies show that reaching the inward‐facing configuration is rate‐limiting during the archaeal aspartic acid transport cycle.

Preventing knotting and interlinking of juxtaposed DNA segments requires yeast condensin but not cohesin or Smc5/6 complexes, suggesting an in vivo role for the DNA loop‐extrusion activity of this particular SMC protein complex.

Identification of native PIN‐FORMED (PIN) auxin transporter complexes in Arabidopsis thaliana shows formation of dimers that are stabilized by the auxin transport inhibitor NPA and natural flavonols.