Averting wildlife-borne infectious disease epidemics requires a focus on socio-ecological drivers and a redesign of the global food system.

A debate has emerged over the potential socio-ecological drivers of wildlife-origin zoonotic disease outbreaks and emerging infectious disease (EID) events. This Review explores the extent to which the incidence of wildlife-origin infectious disease outbreaks, which are likely to include devastating pandemics like HIV/AIDS and COVID-19, may be linked to excessive and increasing rates of tropical deforestation for agricultural food production and wild meat hunting and trade, which are further related to contemporary ecological crises such as global warming and mass species extinction. Here we explore a set of precautionary responses to wildlife-origin zoonosis threat, including: (a) limiting human encroachment into tropical wildlands by promoting a global transition to diets low in livestock source foods; (b) containing tropical wild meat hunting and trade by curbing urban wild meat demand, while securing access for indigenous people and local communities in remote subsistence areas; and (c) improving biosecurity and other strategies to break zoonosis transmission pathways at the wildlife-human interface and along animal source food supply chains

Preventing Left Ventricular Hypertrophy by ACE Inhibition in Hypertensive Patients With Type 2 Diabetes: A prespecified analysis of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT)

OBJECTIVE—In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH)

Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state

cber eine neue Ctenodrilusart und ihre Vermehrung

Volume: 97Start Page: 546End Page: 60