Biomarkers and OLGIM Stage for Prospective Preneoplastic Risk Stratification

serum pepsinogen (PG) tests correlate with the occurrence of gastric atrophy and intestinal metaplasia. However, because of its low sensitivity, Huang et al report that in North America, where Helicobacter pylori prevalence is low (8%) and the use of proton pump inhibitors is frequent, the discrimination value for gastric preneoplastic lesions, atrophic gastritis, and intestinal metaplasia of gastropanel biomarkers is too low to obtain good results

Zebrafish mutants and TEAD reporters reveal essential functions for Yap and Taz in posterior cardinal vein development

As effectors of the Hippo signaling cascade, YAP1 and TAZ are transcriptional regulators playing important roles in development, tissue homeostasis and cancer. A number of different cues, including mechanotransduction of extracellular stimuli, adhesion molecules, oncogenic signaling and metabolism modulate YAP1/TAZ nucleo-cytoplasmic shuttling. In the nucleus, YAP1/TAZ tether with the DNA binding proteins TEADs, to activate the expression of target genes that regulate proliferation, migration, cell plasticity, and cell fate. Based on responsive elements present in the human and zebrafish promoters of the YAP1/TAZ target gene CTGF, we established zebrafish fluorescent transgenic reporter lines of Yap1/Taz activity. These reporter lines provide an in vivo view of Yap1/Taz activity during development and adulthood at the whole organism level. Transgene expression was detected in many larval tissues including the otic vesicles, heart, pharyngeal arches, muscles and brain and is prominent in endothelial cells. Analysis of vascular development in yap1/taz zebrafish mutants revealed specific defects in posterior cardinal vein (PCV) formation, with altered expression of arterial/venous markers. The overactivation of Yap1/Taz in endothelial cells was sufficient to promote an aberrant vessel sprouting phenotype. Our findings confirm and extend the emerging role of Yap1/Taz in vascular development including angiogenesis

Feedback control of spin systems

The feedback stabilization problem for ensembles of coupled spin 1/2 systems is discussed from a control theoretic perspective. The noninvasive nature of the bulk measurement allows for a fully unitary and deterministic closed loop. The Lyapunov-based feedback design presented does not require spins that are selectively addressable. With this method, it is possible to obtain control inputs also for difficult tasks, like suppressing undesired couplings in identical spin systems.Comment: 16 pages, 15 figure

Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex

Summary: Cullin-RING ligases (CRLs) control key cellular processes by promoting ubiquitylation of a multitude of soluble cytosolic and nuclear proteins. Subsets of CRL complexes are recruited and activated locally at cellular membranes; however, few CRL functions and substrates at these distinct cellular compartments are known. Here, we use a proteomic screen to identify proteins that are ubiquitylated at cellular membranes and found that Lunapark, an endoplasmic reticulum (ER)-shaping protein localized to ER three-way junctions, is ubiquitylated by the CRL3KLHL12 ubiquitin ligase. We demonstrate that Lunapark interacts with mechanistic target of rapamycin complex-1 (mTORC1), a central cellular regulator that coordinates growth and metabolism with environmental conditions. We show that mTORC1 binds Lunapark specifically at three-way junctions, and lysosomes, where mTORC1 is activated, make contact with three-way junctions where Lunapark resides. Inhibition of Lunapark ubiquitylation results in neurodevelopmental defects indicating that KLHL12-dependent ubiquitylation of Lunapark is required for normal growth and development

A novel DSP zebrafish model reveals training- and drug-induced modulation of arrhythmogenic cardiomyopathy phenotypes

Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed “pale”, disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/β-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-β pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/β-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/β-catenin signalling cascade

Innovative approaches for measuring organism stress and behavioural integrity in flume facilities: Deliverable D8-IV

HYDRALAB+ aims to improve the usefulness and value of hydraulic laboratory facilities and is developing experimental guidelines that will allow researchers to successfully investigate complex scenarios representative of natural environments in a context of climate change. Within this framework it is often important to incorporate relevant biological elements in physical experiments, including the use of live vegetation. Notwithstanding efforts to maintain their health by careful husbandry, plants typically degenerate when introduced to flume settings. Physiological responses to degenerating health can affect their interactions with the flow so that experimental conditions are not representative of healthy specimens in situ. There is therefore a need to measure and evaluate the health of plants being used in hydraulic facilities, especially since behavioural integrity might be reduced before there are obvious signs of degeneration. Such measurements are not routinely made so there is a need to identify measurement techniques and methodological protocols for assessing vegetation health status in hydraulic laboratories. This deliverable identifies a technique established in plant physiology and horticulture for monitoring vegetation health status and shows how it can be applied in hydraulic laboratories with minimal impact on organisms. A simple and suitable test among those established in the relevant literature is validated by conducting experiments on freshwater macrophytes. From the relevant literature and the results of experiments reported herein, this deliverable provides an overview of the technique identified and establishes practical guidance on how to properly apply it in hydraulic experiments. The methodological protocol developed can potentially be integrated into established protocols used in ecohydraulics studies as a simple proxy of vegetation health status

3D printed masks for powders and viruses safety protection using food grade polymers: Empirical tests

The production of 3D printed safety protection devices (SPD) requires particular attention to the material selection and to the evaluation of mechanical resistance, biological safety and surface roughness related to the accumulation of bacteria and viruses. We explored the possibility to adopt additive manufacturing technologies for the production of respirator masks, responding to the sudden demand of SPDs caused by the emergency scenario of the pandemic spread of SARS‐COV‐ 2. In this study, we developed different prototypes of masks, exclusively applying basic additive manufacturing technologies like fused deposition modeling (FDM) and droplet‐based precision extrusion deposition (db‐PED) to common food packaging materials. We analyzed the resulting mechanical characteristics, biological safety (cell adhesion and viability), surface roughness and resistance to dissolution, before and after the cleaning and disinfection phases. We showed that masks 3D printed with home‐grade printing equipment have similar performances compared to the industrial‐grade ones, and furthermore we obtained a perfect face fit by customizing their shape. Finally, we developed novel approaches to the additive manufacturing post‐processing phases essential to assure human safety in the production of 3D printed custom medical devices