Issues
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Cover image
Cover Image
Cover: Histological sections of the ovaries from a 4-month-old (upper left part) and 18-month-old (lower right part) female zebrafish, stained with haematoxylin and eosin. Ovaries in young zebrafish display a compact structure, characterised by the presence of follicles at different stages of maturation. In old zebrafish, ovaries experience spontaneous degeneration. Their structure is characterised by a much looser organisation and the presence of several atretic follicles. Ovarian senescence in zebrafish is spontaneous; this offers a very convenient experimental model to study the effects of reproductive stages on the onset and progression of several pathological conditions (such as experimental diet-induced NAFLD). See article by Turola et al. on page 1037.
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EDITORIAL
The case of philanthropy: bringing scientists and philanthropic donors together, for good
Summary: Philanthropists and scientists share many common interests, and yet they are not familiar with each other's ways of thinking. This Editorial highlights how to improve their mutual understanding to advance research and life sciences.
REVIEW
Ribosomopathies: how a common root can cause a tree of pathologies
Summary: This paper reviews recent data on Diamond Blackfan anemia and discusses them in connection with other ribosomopathies.
RESEARCH ARTICLES
Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome
Editor’s Choice: WHS is associated with sensorineural deafness. Here, the authors show that, although cochlear hair cells are specified normally in a WHS mouse model, they are disorganised and display sterocilia defects.
Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis
Summary: This study provides clinical and experimental evidence for the different roles played by excess calorie intake in the development of NAFLD and fibrosis; these diseases are dependent on age and reproductive status.
Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway
Summary: This research demonstrates that dysregulation of signaling pathways is a very early event in the pathogenesis of Huntington disease and that these pathways are already dysregulated in cells at the stage of pluripotency.
The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice
Summary: The activation of mTOR signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization.
Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition
Summary: We developed a model to study the dynamics of atherosclerotic plaque growth and stability following surgery, and show that IL-6 inhibition and statins beneficially affect plaque volume and complexity.
miR-146a targets Fos expression in human cardiac cells
Summary: These findings demonstrate that Fos is a direct target of miR-146a activity and that downregulation of the Fos–AP-1 pathway by miR-146a can inhibit MMP-9 activity.
HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer
Summary: HIF1α deficiency reduces inflammation in the mouse proximal colon but is associated with defective E-cadherin expression in colon epithelial cells when mice lacking intestinal epithelium expression of Hif1α are challenged with sulindac.
Suppression of β3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis
Summary: Targeting both β3-integrin and neuropilin-1 prevents anti-angiogenic treatment escape.
Scaffold attachment factor B2 (SAFB2)-null mice reveal non-redundant functions of SAFB2 compared with its paralog, SAFB1
Summary: Analysis of SAFB2−/− mice reveals lack of redundancy between the closely related paralogs SAFB1 and SAFB2, and a role for SAFB2 in the male reproductive system, specifically in Sertoli cells.
The anti-fibrotic effect of inhibition of TGFβ-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection
Summary: This article describes newly identified intricacies for the TGFβ-ALK5 signalling axis in experimental lung fibrosis and reports different outcomes in response to ALK5 inhibition depending on the presence of viral infection. These findings raise important considerations for the future targeting of TGFβ signalling responses in the context of pulmonary fibrosis.
Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice
Summary: Molecular biomarkers of tuberculosis are identified and used to classify disease status of Diversity Outbred mice that have been infected with Mycobacterium tuberculosis.
RESOURCE ARTICLE
The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis
Summary: We generated two mouse strains expressing Cre-ERT2 under Flp-FRT regulation. These tools enable sequential mutagenesis in the same or different cells to study development, tissue homeostasis and diseases such as cancer.
CORRECTIONS
Call for papers: Moving Heart Failure to Heart Success

Disease Models & Mechanisms is pleased to welcome submissions for consideration for an upcoming special issue, Moving Heart Failure to Heart Success: Mechanisms, Regeneration & Therapy. The deadline for submitting articles to the special issue has been extended to 1 August 2022.
Modelling interactions at the blood–brain barrier

In their Review, Yvonne Adams and Anja Ramstedt Jensen review the available in vitro models to investigate the impact of adhesion of Plasmodium falciparum-infected red blood cells on the blood–brain barrier, a process associated with cerebral malaria.
Call for new preLighters

preLights is the preprint highlighting community supported by The Company of Biologists. At the heart of preLights are our preLighters: early-career researchers who select and write about interesting new preprints for the research community. We are currently looking for new preLighters to join our team. Find out more and apply here.
Focus on Genetic Variance in Human Disease

New technologies, computational methods and model systems are revealing how human genetic variance contributes to disease mechanisms. DMM’s new Subject Focus highlights this evolving area of research.
Apply for a DMM Conference Travel Grant

Aimed at early-career researchers wanting to attend in-person and virtual meetings, the next application deadline for a DMM Conference Travel Grant is 1 September 2022. Find out more and hear from past recipients about their experience of the grant.