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6. Monitoring of Lactococcus Lactis Growth Based on Reduced-Graphene Oxide TFT for Dairy Industry Applications

Author

Franchin, L., Casalini, S., Cester, A., Paccagnella, A., and Bonaldo, S.

Abstract

Thin-film transistors (TFTs) are a cutting-edge technology for biosensing applications due to their fast response time, low signal-to-noise ratio, and straightforward miniaturization into electronic circuitry. Liquid-gated reduced graphene oxide TFTs (rGO-TFTs) are particularly promising as biosensors since they allow direct coupling between the active material and any (bio-) chemical species dissolved in aqueous solution. In this work, we explore the use of ambipolar rGO-TFTs as transducers for biosensing, focusing on the detection of bacteria proliferation in laboratory-made samples. We choose Lactococcus lactis (L. lactis) as a reference bacterial species due to the potential final applications for the dairy industry. We performed electrical characterization of two different rGO-TFTs based on Si substrate (Si-TFT) and PET substrate (PET-TFT), assessing the devices’ stability, and extrapolating the parameters through a suitable model. The characterization is carried out using M17 broth as the liquid gate. The L. lactis detection is based on the evident parametric shifts of threshold potential caused by the bacterial presence at the liquid gate. The experimental results are compared with optical absorbance measurements at 600 nm to validate the proposed method. Experimental tests with laboratory-made L. lactis samples confirm that PET-TFTs have a higher detection capability compared to Si-TFTs, being also suitable to monitor the bacteria proliferation during observation of 370 min. rGO-TFTs show evident shifts of threshold potential of more than −100 mV in L. lactis spiked M17 broth compared to the pristine one.

Published
2024
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7. Multiphysics Modeling of the Electrochemical Response of Screen-Printed Electrodes for Sensing Applications

Author

Bonaldo, Stefano, Franchin, Lara, Rosati, Giulio, Merkoci, Arben, and Paccagnella, Alessandro

Abstract

In this work, we present and validate a new 3-D COMSOL Multiphysics model capable of simulating the cyclic voltammetry (CV) and the electrochemical impedance spectroscopy (EIS) response of screen-printed devices. The proposed model considers the dominant electrical and electrochemical phenomena on the electrodes and in the electrolyte solution with redox reactions occurring at the metal/solution interface. The terminals of the simulated device are virtually connected to an equivalent circuit of a potentiostat in order to apply the potential and perform the CV readings with possibility to extend to other types of voltametric measurements. The model is calibrated on screen-printed devices through dedicated sets of experimental measurements that use CV and EIS with 10 mM [Fe(CN)6] $^{{3}-/{4}-}$ as redox mediator in phosphate-buffered saline (PBS) solution. The model parameters for each device are retrieved from the experimental measurements, e.g., double layer capacitance, red/ox diffusivity, electrolyte conductivity equilibrium, and so on. After the calibration, the model is capable of simulating CV responses using different scan rates and redox couple concentrations. The obtained simulated CV signals are significantly consistent with the experimental data, fitting well the experimental curves of both the devices. The simulated/experimental peaks differ less than 50 mV, while the anodic and cathodic current peaks vary only of few microamperes ( $\lt 11~\mu $ A), with values within the standard deviation of measurement experimental measurements. Finally, the proposed model will allow the simulation of more complex electrode morphologies and electrochemical conditions as well, as the model parameters are retrieved experimentally through specific measurements.

Published
2024
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22. Welding of 20 mm thick EH40 steel by means of a single-pass hybrid laser-arc welding technique

Author

Peli, Simone, Bonaldo, Federico, and Riva, Marco

Abstract

In the naval applications, as well as for infrastructure and construction sectors, welding of thick steel plates (>15 mm) has become of crucial importance. Nowadays, the common techniques involve several passes of traditional Gas Metal Arc Welding (GMAW) to fill a gap with a precise geometry. These techniques are, inevitably, time consuming due to the necessity of multiple passes, material consuming because of the volume of the gap which needs to be filled, and complicated due to the precise preparation of the joints. To overcome these drawbacks, we propose here a Hybrid Laser-Arc Welding (HLAW) technique in a configuration which allowed us to achieve a sound weld of two plates, 20 mm thick, of naval steel EH40 in a single pass. The goal has been obtained with a 15 kW fiber laser and a welding speed of 1500 mm/min. The most important result of this research is that the welds have been performed in a simple butt configuration, with straight edges of the plates and without any chamfer or additional preparation. Moreover, the length of the weld seam, 1 meter, guarantees the stability and the solidity of the process, its scalability over longer plates, and thus, an easy implementation on an industrial machine for massive production.

Published
2024
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23. Radiation-Induced Charge Trapping in Shallow Trench Isolations of FinFETs

Author

Bonaldo, Stefano, Wallace, Trace, Barnaby, Hugh, Borghello, Giulio, Termo, Gennaro, Faccio, Federico, Fleetwood, Daniel M., Mattiazzo, Serena, Bagatin, Marta, Paccagnella, Alessandro, and Gerardin, Simone

Abstract

We provide comprehensive experimental data and technology computer-aided design (TCAD) simulations to clarify total-ionizing-dose mechanisms in 16-nm Si FinFETs. In n-channel FinFETs irradiated to ultrahigh doses, the transconductance evolution rebounds (increase up to 3–10 Mrad followed by a decrease), while the drain-to-source leakage current steadily augments until reaching a plateau at very large doses. These effects result from positive charge trapping deep in the sidewalls of the shallow trench isolation (STI) and negative trapped charge accumulation localized in the upper STI corners. Larger sizes of inter-fin STI enhance the leakage current degradation of transistors with smaller numbers of fins. Hydrogen-induced border- and/or interface-trap generation at the Si/oxide interface at the STI corners leads to increased low-frequency noise (LFN) at doses $>{10}$ Mrad(SiO2). These results show that the quality of oxides and interfaces in the upper region of the STI adjacent to the device channel is crucial for the tolerance to ultrahigh radiation of modern FinFET technologies.

Published
2024
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24. Radiation-Induced Effects in SiC Vertical Power MOSFETs Irradiated at Ultrahigh Doses

Author

Bonaldo, S., Martinella, C., Race, S., Fur, N., Mattiazzo, S., Bagatin, M., Gerardin, S., Paccagnella, A., and Grossner, U.

Abstract

Total-ionizing dose (TID) and displacement damage (DD) are investigated in SiC power MOSFETs at ultrahigh doses with 10-keV X-ray and 3-MeV protons. Significant parametric shifts in the electrical responses of the devices are observed depending on the bias condition and on the fabrication technology. Worst TID degradation is measured when positive gate bias is applied during the irradiation, due to positive charge trapping in the gate oxide. Devices built in the latest generation SiC technology reveal a smaller subthreshold swing degradation, thanks to a better quality of the SiC/SiO2 interface. Devices exposed to 3-MeV protons exhibit a complex combination of TID and DD effects. The $I-V$ and capacitance–voltage ( $C-V$ ) measurements in SiC power MOSFETs identify two main degradation mechanisms: 1) TID-induced charge trapping in the gate oxide and SiC/SiO2 interface and 2) DD-induced lattice damage in the SiC drift region, which degrades the series resistance of the devices.

Published
2024
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25. Effects of Interface Traps and Hydrogen on the Low-Frequency Noise of Irradiated MOS Devices

Author

Fleetwood, Daniel M., Zhang, En Xia, Schrimpf, Ronald D., Pantelides, Sokrates T., and Bonaldo, Stefano

Abstract

A re-evaluation of experimental results within the context of first-principles calculations strongly suggests that interface traps can contribute significantly to low-frequency (1/ $f$ ) noise in irradiated MOS devices. Hydrogen-induced trap activation and passivation are likely origins of the observed fluctuations. Measured and calculated activation energies for hydrogen drift, diffusion, and dissociation are consistent with energetics of 1/ $f$ noise. The dominant noise source is determined by densities of relevant defect precursors, hydrogen concentrations, device processing, and history. When present, hydrogen-induced interface-trap activation and passivation adds to noise due to border traps. These results should help assess and assure the performance and reliability of analog integrated circuits in high radiation environments.

Published
2024
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26. Electrochemical Biosensor for the Monitoring of Phages of Lactococcus lactis in Milk-Based Samples

Author

Bonaldo, Stefano, Franchin, Lara, Cretaio, Erica, Pasqualotto, Elisabetta, Scaramuzza, Matteo, and Paccagnella, Alessandro

Abstract

Lactococcus lactis (LL) bacteriophage infections in milk prevent proper lactic fermentation, leading to the production of unsaleable low-quality products and great economic losses in the dairy industry. In this work, we present an innovative biosensing approach for the cost-effective detection of LL phages (PGs) in milk-based samples through electrochemical impedance spectroscopy (EIS). The detection is based on the evident parametric shifts in the charge transfer resistance and the impedance phase at 100 Hz caused by different bacteria proliferation due to PG activity. The EIS results are compared with optical absorbance measurements at 600 nm, in order to validate the proposed method. Preliminary experimental tests with filtered milk-based samples confirm the sensor capability to detect PGs at different concentrations in milk-based solutions in less than 4 h. In order to reach a higher sensitivity, we propose a new milk pretreatment adding calcium chloride (CaCl2) to the samples. The EIS results with CaCl2-treated milk evidence an enhanced PG activity, which leads to a much larger parametric shift. Lastly, the sensor is tested with CaCl2-treated milk-based samples at different PG concentrations, obtaining an enhanced performance reaching the limit of detection (LOD) of $10^{{3}}$ PFU/mL.

Published
2024
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27. Impedimetric Screen-Printed Immunosensor for the Rapid Detection of Chagas Disease

Author

Chain, Cecilia Y., Franchin, Lara, Cisneros, Jose S., Villagra, Andrea P. M., Labriola, Carlos A., Paccagnella, Alessandro, and Bonaldo, Stefano

Abstract

Chagas disease (CD) is an endemic parasitic condition affecting Latin America and recently Europe caused by the Trypanosoma cruzi (T. cruzi). This work proposes a new impedimetric immunosensor for the rapid, cost-effective, label-free, and low-volume detection of specific anti- T. cruzi antibodies, used as biomarkers of CD in human serum. The biosensor is based on gold screen-printed electrodes that are functionalized with isolated cruzipain (CrP) proteins by adsorption, following a highly reproducible 40 min chemical procedure. The biosensor is tested with clinical serum samples from patients with (positive) or without (negative) anti- T. cruzi antibodies as previously verified by ELISA testing. The detection is performed through electrochemical impedance spectroscopy (EIS), showing ~22% variation of the charge transfer resistance ( ${R}_{\text {ct}}$ ) for positive human serum due to the immunoreaction between the immobilized CrP and the specific antibodies contained in the samples. Based on the cutoff value of ${R}_{\text {ct}}$ ratios, the developed immunosensor is capable of successfully discriminating positive and negative human serum samples at a dilution factor of 1/6400 in phosphate-buffered saline (PBS) solution, showing an excellent agreement with the ELISA results.

Published
2024
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30. Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice

Author

Gambarotto, Lisa, Metti, Samuele, Corpetti, Matteo, Baraldo, Martina, Sabatelli, Patrizia, Castagnaro, Silvia, Cescon, Matilde, Blaauw, Bert, and Bonaldo, Paolo

Abstract

ABSTRACTCOL6 (collagen type VI)-related myopathies (COL6-RM) are a distinct group of inherited muscle disorders caused by mutations of COL6genes and characterized by early-onset muscle weakness, for which no cure is available yet. Key pathophysiological features of COL6-deficient muscles involve impaired macroautophagy/autophagy, mitochondrial dysfunction, neuromuscular junction fragmentation and myofiber apoptosis. Targeting autophagy by dietary means elicited beneficial effects in both col6a1null (col6a1–/–) mice and COL6-RM patients. We previously demonstrated that one-month per osadministration of the nutraceutical spermidine reactivates autophagy and ameliorates myofiber defects in col6a1–/–mice but does not elicit functional improvement. Here we show that a 100-day-long spermidine regimen is able to rescue muscle strength in col6a1–/–mice, with also a beneficial impact on mitochondria and neuromuscular junction integrity, without any noticeable side effects. Altogether, these data provide a rationale for the application of spermidine in prospective clinical trials for COL6-RM.Abbreviations:AChR: acetylcholine receptor; BTX: bungarotoxin; CNF: centrally nucleated fibers; Colch: colchicine; COL6: collagen type VI; COL6-RM: COL6-related myopathies; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NMJ: neuromuscular junction; Spd: spermidine; SQSTM1/p62: sequestosome 1; TA: tibialis anterior; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling.

Published
2023
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31. All-dielectric metaoptics for the compact generation of double-ring perfect vector beams

Author

Vogliardi, Andrea, Ruffato, Gianluca, Bonaldo, Daniele, Dal Zilio, Simone, and Romanato, Filippo

Abstract

Perfect vortices, whose ring profile is independent of the topological charge, play a key role in telecommunications and particle micro-manipulation. In this work, we report the compact generation of a new kind of double-ring perfect vortices, called double-ring perfect vector beams, by exploiting dual-functional silicon metaoptics. In particular, we develop and test a new paradigm to generate those beams with the possibility of selecting different topological charges between the two rings. The generated beams are characterized through a filtering method, proving that the two rings have a vectorial nature with the same magnitude and either the same or different topological charges. Their unique properties suggest promising applications for optical tweezing and manipulation of low refractive-index particles, trapping of cold atoms, and high-capacity communications.

Published
2023
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32. Total-Ionizing-Dose Effects at Ultrahigh Doses in AlGaN/GaN HEMTs

Author

Bonaldo, Stefano, Zhang, En Xia, Mattiazzo, Serena, Paccagnella, Alessandro, Gerardin, Simone, Schrimpf, Ronald D., and Fleetwood, Daniel M.

Abstract

Total-ionizing-dose (TID) effects in AlGaN/GaN high-electron-mobility transistors (HEMTs) are evaluated by dc and low-frequency noise measurements. Devices with and without passivation layers are irradiated with 10-keV X-rays up to 100 Mrad(SiO2) under different bias conditions. Irradiated devices show significant electrical shifts in threshold voltage and transconductance. At doses < 10 Mrad(SiO2), the TID-induced effects are related to the passivation of preexisting acceptor-like defects via hole capture, which induces negative threshold voltage shifts and improvement of transconductance. At doses $>$ 10 Mrad(SiO2), dehydrogenation of defects and impurity complexes leads to the creation of acceptor-like defects, which degrade the transconductance, shift positively the threshold voltage, and increase the low-frequency noise. Effects are enhanced in unpassivated devices and when the gate is biased at high voltage.

Published
2023
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33. Lack of COL6/collagen VI causes megakaryocyte dysfunction by impairing autophagy and inducing apoptosis

Author

Abbonante, Vittorio, Malara, Alessandro, Chrisam, Martina, Metti, Samuele, Soprano, Paolo, Semplicini, Claudio, Bello, Luca, Bozzi, Valeria, Battiston, Monica, Pecci, Alessandro, Pegoraro, Elena, De Marco, Luigi, Braghetta, Paola, Bonaldo, Paolo, and Balduini, Alessandra

Abstract

ABSTRACTEndoplasmic reticulum stress is an emerging significant player in the molecular pathology of connective tissue disorders. In response to endoplasmic reticulum stress, cells can upregulate macroautophagy/autophagy, a fundamental cellular homeostatic process used by cells to degrade and recycle proteins or remove damaged organelles. In these scenarios, autophagy activation can support cell survival. Here we demonstrated by in vitroand in vivoapproaches that megakaryocytes derived from col6a1−⁄−(collagen, type VI, alpha 1) null mice display increased intracellular retention of COL6 polypeptides, endoplasmic reticulum stress and apoptosis. The unfolded protein response is activated in col6a1−⁄−megakaryocytes, as evidenced by the upregulation of molecular chaperones, by the increased splicing of Xbp1mRNA and by the higher level of the pro-apoptotic regulator DDIT3/CHOP. Despite the endoplasmic reticulum stress, basal autophagy is impaired in col6a1−⁄−megakaryocytes, which show lower BECN1 levels and reduced autophagosome maturation. Starvation and rapamycin treatment rescue the autophagic flux in col6a1−⁄−megakaryocytes, leading to a decrease in intracellular COL6 polypeptide retention, endoplasmic reticulum stress and apoptosis. Furthermore, megakaryocytes cultured from peripheral blood hematopoietic progenitors of patients affected by Bethlem myopathy and Ullrich congenital muscular dystrophy, two COL6-related disorders, displayed increased apoptosis, endoplasmic reticulum stress and impaired autophagy. These data demonstrate that genetic disorders of collagens, endoplasmic reticulum stress and autophagy regulation in megakaryocytes may be interrelated.Abbreviations:7-AAD: 7-amino-actinomycin D; ATF: activating transcriptional factor; BAX: BCL2 associated X protein; BCL2: B cell leukemia/lymphoma 2; BCL2L1/Bcl-xL: BCL2-like 1; BM: bone marrow; COL6: collagen, type VI; col6a1−⁄−: mice that are null for Col6a1; DDIT3/CHOP/GADD153: DNA-damage inducible transcript 3; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; reticulophagy: endoplasmic reticulum-selective autophagy; HSPA5/Bip: heat shock protein 5; HSP90B1/GRP94: heat shock protein 90, beta (Grp94), member 1; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; Mk: megakaryocytes; MTOR: mechanistic target of rapamycin kinase; NIMV: noninvasive mechanical ventilation; PI3K: phosphoinositide 3-kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; RT-qPCR: reverse transcription-quantitative real-time PCR; ROS: reactive oxygen species; SERPINH1/HSP47: serine (or cysteine) peptidase inhibitor, clade H, member 1; sh-RNA: short hairpin RNA; SOCE: store operated calcium entry; UCMD: Ullrich congenital muscular dystrophy; UPR: unfolded protein response; WIPI2: WD repeat domain, phosphoinositide-interacting 2; WT: wild type; XBP1: X-box binding protein 1.

Published
2023
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34. A Graphical Method to Assess the Technical Feasibility of Intentional Islanding of Distributed Synchronous Generators

Author

Lima, Rogerio L., Bonaldo, Jakson P., Vieira, Jose C. M., and Monaro, Renato M.

Abstract

This article proposes a graphical method to evaluate the feasibility of intentional islanding of distributed synchronous generators. The approach is based on the combination of the performance and restriction curves. These curves are based on the islanding detection capability of the frequency-based protection at the point of common coupling and on the generator protection at its terminals. When relating the islanding detection time, the restriction time and the active power imbalance, the intersection of such curves defines two operating zones: i) the favorable island formation zone, in which the operation of the energized island is stable, and ii) the non-favorable island formation zone, in which the islanding is infeasible. The results showed that the proposed method is a useful tool to adjust and assess frequency-based protection so that an unscheduled islanding event can result in a stable island. In addition, the validation of the results confirmed the coherency of the graphical method.

Published
2023
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35. Amperometric Measurements by a Novel Aerosol Jet Printed Flexible Sensor for Wearable Applications

Author

Tonello, Sarah, Fapanni, Tiziano, Bonaldo, Stefano, Giorgi, Giada, Narduzzi, Claudio, Paccagnella, Alessandro, Serpelloni, Mauro, Sardini, Emilio, and Carrara, Sandro

Abstract

In the last years, increasing interest has been addressed on wearable devices for the continuous monitoring of biochemical profiles of patients and athletes. Among various markers, lactate represents one of the most interesting to deepen the knowledge on fatigue processes, in combination with traditional electromyographic features. In this work, we propose a new, low-cost, rapid, and flexible electrochemical amperometric lactate carbon biosensor fabricated by the novel technique of aerosol jet printing (AJP). The developed biosensors were combined with a paper-based microfluidic system and a chitosan-based stable functionalization to allow a long-term continuous monitoring of human daily activities. The sensor performances were evaluated by static and dynamic electrochemical tests in buffered media. The limit of detection is 11 ± 2 mM for the static setup and of 15 ± 6 mM for the dynamic setup, while sensitivity is 0.02 and 0.04 $\mu \text{A}$ /mM, respectively, with single sigma standard deviation lower than 8%. Increasing and decreasing concentration steps of lactate induces comparable response times below 30 s. These results obtained in vitro under controlled laboratory conditions represent a promising starting point to pursue with ex-vivo and in vivo validation for the future development of stand-alone wearable patches for noninvasive lactate measurements.

Published
2023
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36. Screen-Printed Electrochemical Biosensor for the Detection of Bacteriophage of Lactococcus Lactis for Dairy Production

Author

Bonaldo, Stefano, Cretaio, Erica, Pasqualotto, Elisabetta, Scaramuzza, Matteo, Franchin, Lara, Poggi, Sara, and Paccagnella, Alessandro

Abstract

In the dairy industry, the spreading of phages of Lactococcus lactis (LL) prevents the proper lactic fermentation, causing waste of contaminated products and economic losses. This work presents a cheap biosensing method for rapidly detecting the LL phages. The detection is based on live LL bacteria covering the sensor electrodes, whose electrical response is measured by electrochemical impedance spectroscopy (EIS). Solutions contaminated by phages induce bacteria lysis, clearly reducing the bacteria coverage over the electrodes and leading to evident parametrical shifts in the charge transfer resistance and in the impedance phase at 400 Hz. Experimental tests with laboratory contaminated samples confirm the better detection capability of screen-printed gold sensors compared to the interdigitated gold electrodes. Two measurement protocols, called spill-out and drop-in methods, are evaluated to optimize the sensor detection capability and time. The EIS results are compared with optical absorbance measurements at 600 nm, in order to validate the proposed detection method with $10^{{7}}$ -PFU/mL phages and with a detection time of about 5 h. Finally, the proposed method is tested successfully with milk-based solutions. Evident shifts between phage-contaminated and non-contaminated sensors are measured in the charge transfer resistance of more than one order of magnitude with impedance phase differences of 43°.

Published
2023
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37. Ambra1 deficiency impairs mitophagy in skeletal muscle

Author

Gambarotto, Lisa, Metti, Samuele, Chrisam, Martina, Cerqua, Cristina, Sabatelli, Patrizia, Armani, Andrea, Zanon, Carlo, Spizzotin, Marianna, Castagnaro, Silvia, Strappazzon, Flavie, Grumati, Paolo, Cescon, Matilde, Braghetta, Paola, Trevisson, Eva, Cecconi, Francesco, and Bonaldo, Paolo

Abstract

Maintaining healthy mitochondria is mandatory for muscle viability and function. An essential surveillance mechanism targeting defective and harmful mitochondria to degradation is the selective form of autophagy called mitophagy. Ambra1 is a multifaceted protein with well‐known autophagic and mitophagic functions. However, the study of its role in adult tissues has been extremely limited due to the embryonic lethality caused by full‐body Ambra1 deficiency. To establish the role of Ambra1 as a positive regulator of mitophagy, we exploited in vivooverexpression of a mitochondria‐targeted form of Ambra1 in skeletal muscle. To dissect the consequence of Ambra1 inactivation in skeletal muscle, we generated muscle‐specific Ambra1knockout (Ambra1fl/fl:Mlc1f‐Cre) mice. Mitochondria‐enriched fractions were obtained from muscles of fed and starved animals to investigate the dynamics of the mitophagic flux. Our data show that Ambra1 has a critical role in the mitophagic flux of adult murine skeletal muscle and that its genetic inactivation leads to mitochondria alterations and myofibre remodelling. Ambra1 overexpression in wild‐type muscles is sufficient to enhance mitochondria clearance through the autophagy‐lysosome system. Consistently with this, Ambra1‐deficient muscles display an abnormal accumulation of the mitochondrial marker TOMM20 by +76% (n= 6–7; P< 0.05), a higher presence of myofibres with swollen mitochondria by +173% (n= 4; P< 0.05), and an alteration in the maintenance of the mitochondrial membrane potential and a 34% reduction in the mitochondrial respiratory complex I activity (n= 4; P< 0.05). Lack of Ambra1 in skeletal muscle leads to impaired mitophagic flux, without affecting the bulk autophagic process. This is due to a significantly decreased recruitment of DRP1 (n= 6–7 mice; P< 0.01) and Parkin (n= 6–7 mice; P< 0.05) to the mitochondrial compartment, when compared with controls. Ambra1‐deficient muscles also show a marked dysregulation of the endolysosome compartment, as the incidence of myofibres with lysosomal accumulation is 20 times higher than wild‐type muscles (n= 4; P< 0.05). Histologically, Ambra1‐deficient muscles of both 3‐ and 6‐month‐old animals display a significant decrease of myofibre cross‐sectional area and a 52% reduction in oxidative fibres (n= 6–7; P< 0.05), thus highlighting a role for Ambra1 in the proper structure and activity of skeletal muscle. Our study indicates that Ambra1 is critical for skeletal muscle mitophagy and for the proper maintenance of functional mitochondria.

Published
2022
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39. Ablation of collagen VI leads to the release of platelets with altered function

Author

Abbonante, Vittorio, Gruppi, Cristian, Battiston, Monica, Zulian, Alessandra, Di Buduo, Christian Andrea, Chrisam, Martina, Sereni, Lucia, Laurent, Pierre-Alexandre, Semplicini, Claudio, Lombardi, Elisabetta, Mazzucato, Mario, Moccia, Francesco, Petronilli, Valeria, Villa, Anna, Bello, Luca, Pegoraro, Elena, Bernardi, Paolo, Braghetta, Paola, De Marco, Luigi, Bonaldo, Paolo, and Balduini, Alessandra

Abstract

Hemostatic abnormalities and impaired platelet function have been described in patients affected by connective tissue disorders. We observed a moderate bleeding tendency in patients affected by collagen VI–related disorders and investigated the defects in platelet functionality, whose mechanisms are unknown. We demonstrated that megakaryocytes express collagen VI that is involved in the regulation of functional platelet production. By exploiting a collagen VI–null mouse model (Col6a1−/−), we found that collagen VI–null platelets display significantly increased susceptibility to activation and intracellular calcium signaling. Col6a1−/−megakaryocytes and platelets showed increased expression of stromal interaction molecule 1 (STIM1) and ORAI1, the components of store-operated calcium entry (SOCE), and activation of the mammalian target of rapamycin (mTOR) signaling pathway. In vivo mTOR inhibition by rapamycin reduced STIM1 and ORAI1 expression and calcium flows, resulting in a normalization of platelet susceptibility to activation. These defects were cell autonomous, because transplantation of lineage-negative bone marrow cells from Col6a1−/−mice into lethally irradiated wild-type animals showed the same alteration in SOCE and platelet activation seen in Col6a1−/−mice. Peripheral blood platelets of patients affected by collagen VI–related diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy, displayed increased expression of STIM1 and ORAI1 and were more prone to activation. Altogether, these data demonstrate the importance of collagen VI in the production of functional platelets by megakaryocytes in mouse models and in collagen VI–related diseases.

Published
2021
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41. A blend of microalgae and cyanobacteria produced from industrial waste outputs for the enrichments of Artemia salina: Effects on growth performance, antioxidant status and anomalies rate of European seabass (Dicentrarchus labrax) larvae

Author

Bertini, Andrea, Marchi, Arianna, Benini, Elisa, Navarro-Guillén, Carmen, González, María J., Medina, Isabel, Yúfera, Manuel, Pousis, Chrysovalentinos, Ventriglia, Gianluca, Nys, Christel, Gatta, Pier Paolo, Bonaldo, Alessio, and Parma, Luca

Abstract

The recent fast development of the microalgae-related biotechnologies has enabled the availability of sustainable and nutrients-rich raw materials to be used as substitution of conventional sources in aquafeed formulation. However the cost of energy of the photobioreactors used to produce these microorganisms still constrained their wider inclusion into aquafeed compounds. By exploiting industrial waste outputs, Nannochloropsis sp.and Spirulina sp.were produced and utilised to formulate two experimental enrichments (LM1 and LM2). During a 60 days trial, their efficacy have been tested as Artemiametanauplii enrichments in the diet of European seabass (Dicentrarchus labrax) larvae, in comparison to a commercial control. Larvae were fed with isonitrogenous and isolipidic dietary treatments. Each dietary treatment presented a specific profile for the long chain polyunsaturated fatty acids ARA, DHA and EPA. Ratio of DHA/EPA in enriched Artemiaof 4:1 as in the case of LM1 and LM2 in the presence of 1.4% of ARA (as a % on total fatty acid) guaranteed equal results to the control which displayed a ratio of DHA/EPA of 2:1 with 2.2% of ARA. No significant effects of the dietary treatments were detected in final survival, growth performance and incidence of skeletal anomalies. Regarding oxidative status, larvae fed with LM2 enrichment presented lower catalase activity than control larvae with no signs of oxidative damage, suggesting a potential antioxidant effect of LM2. The present study contributes to expanding the existing literature on successful utilisation of microalgae and cyanobacteria, used to produce valuable nutrients, in a perspective of circular nutrients economy.

Published
2024
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42. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Author

Klionsky, Daniel J., Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie H., Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis E., Adeli, Khosrow, Adolph, Timon E., Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat B., Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed N., Agrotis, Alexander, Aguilar, Patricia V., Ahmad, S. Tariq, Ahmed, Zubair M., Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed M., Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay A., Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M. Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo D., Altan-Bonnet, Nihal, Altieri, Dario C., Álvarez, Élida M. C., Alves, Sara, Alves da Costa, Cristine, Alzaharna, Mazen M., Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal O., Ammanathan, Veena, An, Zhenyi, Andersen, Stig U., Andrabi, Shaida A., Andrade-Silva, Magaiver, Andres, Allen M., Angelini, Sabrina, Ann, David, Anozie, Uche C., Ansari, Mohammad Y., Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner L., Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen R., Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela S., Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas G., Au, Alicia K., Auberger, Patrick, Auner, Holger W., Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan M., Backues, Steven K., Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H., Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima T., Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio S., Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter G., Barmada, Sami J., Barreiro, Esther, Barreto, George E., Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav R., Basagoudanavar, Suresh H., Bassham, Diane C., Bast, Robert C., Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne E., Baumgarner, Bradley L., Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz R.G., Beck, George R., Beers, Michael F., Begun, Jakob, Behrends, Christian, Behrens, Georg M.N., Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno A., Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin W., Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri G., Besteiro, Sebastien, Betin, Virginie M., Beyaert, Rudi, Bezbradica, Jelena S., Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md. Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor J., Bijian, Krikor, Billes, Viktor A., Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa B., Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice S., Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan S., Boone, Brian A., Bootman, Martin D., Bordi, Matteo, Borner, Christoph, Bornhauser, Beat C., Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, Botana, Luis M., Botas, Juan, Boulanger, Chantal M., Boulton, Michael E., Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig M., Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter V., Bozi, Luiz H. M., Bozkurt, Tolga O., Brackney, Doug E., Brandts, Christian H., Braun, Ralf J., Braus, Gerhard H., Bravo-Sagua, Roberto, Bravo-San Pedro, José M., Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V. Courtney, Brodersen, Peter, Brodsky, Jeffrey L., Brody, Steven L., Bronson, Paola G., Bronstein, Jeff M., Brown, Carolyn N., Brown, Rhoderick E., Brum, Patricia C., Brumell, John H., Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert J., Bucci, Cecilia, Buchrieser, Carmen, Bueno, Marta, Buitrago-Molina, Laura Elisa, Buraschi, Simone, Buch, Shilpa, Buchan, J. Ross, Buckingham, Erin M., Budak, Hikmet, Budini, Mauricio, Bultynck, Geert, Burada, Florin, Burgoyne, Joseph R., Burón, M. Isabel, Bustos, Victor, Büttner, Sabrina, Butturini, Elena, Byrd, Aaron, Cabas, Isabel, Cabrera-Benitez, Sandra, Cadwell, Ken, Cai, Jingjing, Cai, Lu, Cai, Qian, Cairó, Montserrat, Calbet, Jose A., Caldwell, Guy A., Caldwell, Kim A., Call, Jarrod A., Calvani, Riccardo, Calvo, Ana C., Calvo-Rubio Barrera, Miguel, Camara, Niels OS, Camonis, Jacques H., Camougrand, Nadine, Campanella, Michelangelo, Campbell, Edward M., Campbell-Valois, François-Xavier, Campello, Silvia, Campesi, Ilaria, Campos, Juliane C., Camuzard, Olivier, Cancino, Jorge, Candido de Almeida, Danilo, Canesi, Laura, Caniggia, Isabella, Canonico, Barbara, Cantí, Carles, Cao, Bin, Caraglia, Michele, Caramés, Beatriz, Carchman, Evie H., Cardenal-Muñoz, Elena, Cardenas, Cesar, Cardenas, Luis, Cardoso, Sandra M., Carew, Jennifer S., Carle, Georges F., Carleton, Gillian, Carloni, Silvia, Carmona-Gutierrez, Didac, Carneiro, Leticia A., Carnevali, Oliana, Carosi, Julian M., Carra, Serena, Carrier, Alice, Carrier, Lucie, Carroll, Bernadette, Carter, A. Brent, Carvalho, Andreia Neves, Casanova, Magali, Casas, Caty, Casas, Josefina, Cassioli, Chiara, Castillo, Eliseo F., Castillo, Karen, Castillo-Lluva, Sonia, Castoldi, Francesca, Castori, Marco, Castro, Ariel F., Castro-Caldas, Margarida, Castro-Hernandez, Javier, Castro-Obregon, Susana, Catz, Sergio D., Cavadas, Claudia, Cavaliere, Federica, Cavallini, Gabriella, Cavinato, Maria, Cayuela, Maria L., Cebollada Rica, Paula, Cecarini, Valentina, Cecconi, Francesco, Cechowska-Pasko, Marzanna, Cenci, Simone, Ceperuelo-Mallafré, Victòria, Cerqueira, João J., Cerutti, Janete M., Cervia, Davide, Cetintas, Vildan Bozok, Cetrullo, Silvia, Chae, Han-Jung, Chagin, Andrei S., Chai, Chee-Yin, Chakrabarti, Gopal, Chakrabarti, Oishee, Chakraborty, Tapas, Chakraborty, Trinad, Chami, Mounia, Chamilos, Georgios, Chan, David W., Chan, Edmond Y. W., Chan, Edward D., Chan, H.Y. Edwin, Chan, Helen H., Chan, Hung, Chan, Matthew T.V., Chan, Yau Sang, Chandra, Partha K., Chang, Chih-Peng, Chang, Chunmei, Chang, Hao-Chun, Chang, Kai, Chao, Jie, Chapman, Tracey, Charlet-Berguerand, Nicolas, Chatterjee, Samrat, Chaube, Shail K., Chaudhary, Anu, Chauhan, Santosh, Chaum, Edward, Checler, Frédéric, Cheetham, Michael E., Chen, Chang-Shi, Chen, Guang-Chao, Chen, Jian-Fu, Chen, Liam L., Chen, Leilei, Chen, Lin, Chen, Mingliang, Chen, Mu-Kuan, Chen, Ning, Chen, Quan, Chen, Ruey-Hwa, Chen, Shi, Chen, Wei, Chen, Weiqiang, Chen, Xin-Ming, Chen, Xiong-Wen, Chen, Xu, Chen, Yan, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Zhefan Stephen, Chen, Zhi, Chen, Zhi-Hua, Chen, Zhijian J., Chen, Zhixiang, Cheng, Hanhua, Cheng, Jun, Cheng, Shi-Yuan, Cheng, Wei, Cheng, Xiaodong, Cheng, Xiu-Tang, Cheng, Yiyun, Cheng, Zhiyong, Chen, Zhong, Cheong, Heesun, Cheong, Jit Kong, Chernyak, Boris V., Cherry, Sara, Cheung, Chi Fai Randy, Cheung, Chun Hei Antonio, Cheung, King-Ho, Chevet, Eric, Chi, Richard J., Chiang, Alan Kwok Shing, Chiaradonna, Ferdinando, Chiarelli, Roberto, Chiariello, Mario, Chica, Nathalia, Chiocca, Susanna, Chiong, Mario, Chiou, Shih-Hwa, Chiramel, Abhilash I., Chiurchiù, Valerio, Cho, Dong-Hyung, Choe, Seong-Kyu, Choi, Augustine M.K., Choi, Mary E., Choudhury, Kamalika Roy, Chow, Norman S., Chu, Charleen T., Chua, Jason P., Chua, John Jia En, Chung, Hyewon, Chung, Kin Pan, Chung, Seockhoon, Chung, So-Hyang, Chung, Yuen-Li, Cianfanelli, Valentina, Ciechomska, Iwona A., Cifuentes, Mariana, Cinque, Laura, Cirak, Sebahattin, Cirone, Mara, Clague, Michael J., Clarke, Robert, Clementi, Emilio, Coccia, Eliana M., Codogno, Patrice, Cohen, Ehud, Cohen, Mickael M., Colasanti, Tania, Colasuonno, Fiorella, Colbert, Robert A., Colell, Anna, Čolić, Miodrag, Coll, Nuria S., Collins, Mark O., Colombo, María I., Colón-Ramos, Daniel A., Combaret, Lydie, Comincini, Sergio, Cominetti, Márcia R., Consiglio, Antonella, Conte, Andrea, Conti, Fabrizio, Contu, Viorica Raluca, Cookson, Mark R., Coombs, Kevin M., Coppens, Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale P., Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter J., Crespo, Jose L., Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea C., Cybulsky, Andrey V., Czaja, Mark J., Czuczwar, Stanislaw J., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew C., D’Orazi, Gabriella, da Silva, James A., Dafsari, Hormos Salimi, Dagda, Ruben K., Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico P., Darling, April L., Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh K., Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian N., Davies, Jeffrey S., Dávila, Valeria A., Davis, Roger J., Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara G., De Meyer, Guido R.Y., De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian J., Decuypere, Jean-Paul, Deehan, Mark A., Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe R., Delbridge, Lea M. D., Delorme-Axford, Elizabeth, Delpino, M. Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas D., Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin L., Der, Channing J., Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni M., Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, Federica, Diallinas, George, Diao, Jiajie, Diaz-Araya, Guillermo, Díaz-Laviada, Inés, Dickinson, Jared M., Diederich, Marc, Dieudé, Mélanie, Dikic, Ivan, Ding, Shiping, Ding, Wen-Xing, Dini, Luciana, Dinić, Jelena, Dinic, Miroslav, Dinkova-Kostova, Albena T., Dionne, Marc S., Distler, Jörg H.W., Diwan, Abhinav, Dixon, Ian M.C., Djavaheri-Mergny, Mojgan, Dobrinski, Ina, Dobrovinskaya, Oxana, Dobrowolski, Radek, Dobson, Renwick C.J., Đokić, Jelena, Dokmeci Emre, Serap, Donadelli, Massimo, Dong, Bo, Dong, Xiaonan, Dong, Zhiwu, 2nd Dorn, Gerald W., Dotsch, Volker, Dou, Huan, Dou, Juan, Dowaidar, Moataz, Dridi, Sami, Drucker, Liat, Du, Ailian, Du, Caigan, Du, Guangwei, Du, Hai-Ning, Du, Li-Lin, du Toit, André, Duan, Shao-Bin, Duan, Xiaoqiong, Duarte, Sónia P., Dubrovska, Anna, Dunlop, Elaine A., Dupont, Nicolas, Durán, Raúl V., Dwarakanath, Bilikere S., Dyshlovoy, Sergey A., Ebrahimi-Fakhari, Darius, Eckhart, Leopold, Edelstein, Charles L., Efferth, Thomas, Eftekharpour, Eftekhar, Eichinger, Ludwig, Eid, Nabil, Eisenberg, Tobias, Eissa, N. Tony, Eissa, Sanaa, Ejarque, Miriam, El Andaloussi, Abdeljabar, El-Hage, Nazira, El-Naggar, Shahenda, Eleuteri, Anna Maria, El-Shafey, Eman S., Elgendy, Mohamed, Eliopoulos, Aristides G., Elizalde, María M., Elks, Philip M., Elsasser, Hans-Peter, Elsherbiny, Eslam S., Emerling, Brooke M., Emre, N. C. Tolga, Eng, Christina H., Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelsen, Agnete S.T., Enserink, Jorrit M., Escalante, Ricardo, Esclatine, Audrey, Escobar-Henriques, Mafalda, Eskelinen, Eeva-Liisa, Espert, Lucile, Eusebio, Makandjou-Ola, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Facchiano, Francesco, Fadeel, Bengt, Fader, Claudio, Faesen, Alex C., Fairlie, W. Douglas, Falcó, Alberto, Falkenburger, Bjorn H., Fan, Daping, Fan, Jie, Fan, Yanbo, Fang, Evandro F., Fang, Yanshan, Fang, Yognqi, Fanto, Manolis, Farfel-Becker, Tamar, Faure, Mathias, Fazeli, Gholamreza, Fedele, Anthony O., Feldman, Arthur M., Feng, Du, Feng, Jiachun, Feng, Lifeng, Feng, Yibin, Feng, Yuchen, Feng, Wei, Fenz Araujo, Thais, Ferguson, Thomas A., Fernández, Álvaro F., Fernandez-Checa, Jose C., Fernández-Veledo, Sonia, Fernie, Alisdair R., Ferrante, Anthony W., Ferraresi, Alessandra, Ferrari, Merari F., Ferreira, Julio C.B., Ferro-Novick, Susan, Figueras, Antonio, Filadi, Riccardo, Filigheddu, Nicoletta, Filippi-Chiela, Eduardo, Filomeni, Giuseppe, Fimia, Gian Maria, Fineschi, Vittorio, Finetti, Francesca, Finkbeiner, Steven, Fisher, Edward A., Fisher, Paul B., Flamigni, Flavio, Fliesler, Steven J., Flo, Trude H., Florance, Ida, Florey, Oliver, Florio, Tullio, Fodor, Erika, Follo, Carlo, Fon, Edward A., Forlino, Antonella, Fornai, Francesco, Fortini, Paola, Fracassi, Anna, Fraldi, Alessandro, Franco, Brunella, Franco, Rodrigo, Franconi, Flavia, Frankel, Lisa B., Friedman, Scott L., Fröhlich, Leopold F., Frühbeck, Gema, Fuentes, Jose M., Fujiki, Yukio, Fujita, Naonobu, Fujiwara, Yuuki, Fukuda, Mitsunori, Fulda, Simone, Furic, Luc, Furuya, Norihiko, Fusco, Carmela, Gack, Michaela U., Gaffke, Lidia, Galadari, Sehamuddin, Galasso, Alessia, Galindo, Maria F., Gallolu Kankanamalage, Sachith, Galluzzi, Lorenzo, Galy, Vincent, Gammoh, Noor, Gan, Boyi, Ganley, Ian G., Gao, Feng, Gao, Hui, Gao, Minghui, Gao, Ping, Gao, Shou-Jiang, Gao, Wentao, Gao, Xiaobo, Garcera, Ana, Garcia, Maria Noé, Garcia, Verónica E., García-Del Portillo, Francisco, Garcia-Escudero, Vega, Garcia-Garcia, Aracely, Garcia-Macia, Marina, García-Moreno, Diana, Garcia-Ruiz, Carmen, García-Sanz, Patricia, Garg, Abhishek D., Gargini, Ricardo, Garofalo, Tina, Garry, Robert F., Gassen, Nils C., Gatica, Damian, Ge, Liang, Ge, Wanzhong, Geiss-Friedlander, Ruth, Gelfi, Cecilia, Genschik, Pascal, Gentle, Ian E., Gerbino, Valeria, Gerhardt, Christoph, Germain, Kyla, Germain, Marc, Gewirtz, David A., Ghasemipour Afshar, Elham, Ghavami, Saeid, Ghigo, Alessandra, Ghosh, Manosij, Giamas, Georgios, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibson, Gary E., Gibson, Spencer B., Ginet, Vanessa, Giniger, Edward, Giorgi, Carlotta, Girao, Henrique, Girardin, Stephen E., Giridharan, Mridhula, Giuliano, Sandy, Giulivi, Cecilia, Giuriato, Sylvie, Giustiniani, Julien, Gluschko, Alexander, Goder, Veit, Goginashvili, Alexander, Golab, Jakub, Goldstone, David C., Golebiewska, Anna, Gomes, Luciana R., Gomez, Rodrigo, Gómez-Sánchez, Rubén, Gomez-Puerto, Maria Catalina, Gomez-Sintes, Raquel, Gong, Qingqiu, Goni, Felix M., González-Gallego, Javier, Gonzalez-Hernandez, Tomas, Gonzalez-Polo, Rosa A., Gonzalez-Reyes, Jose A., González-Rodríguez, Patricia, Goping, Ing Swie, Gorbatyuk, Marina S., Gorbunov, Nikolai V., Görgülü, Kıvanç, Gorojod, Roxana M., Gorski, Sharon M., Goruppi, Sandro, Gotor, Cecilia, Gottlieb, Roberta A., Gozes, Illana, Gozuacik, Devrim, Graef, Martin, Gräler, Markus H., Granatiero, Veronica, Grasso, Daniel, Gray, Joshua P., Green, Douglas R., Greenhough, Alexander, Gregory, Stephen L., Griffin, Edward F., Grinstaff, Mark W., Gros, Frederic, Grose, Charles, Gross, Angelina S., Gruber, Florian, Grumati, Paolo, Grune, Tilman, Gu, Xueyan, Guan, Jun-Lin, Guardia, Carlos M., Guda, Kishore, Guerra, Flora, Guerri, Consuelo, Guha, Prasun, Guillén, Carlos, Gujar, Shashi, Gukovskaya, Anna, Gukovsky, Ilya, Gunst, Jan, Günther, Andreas, Guntur, Anyonya R., Guo, Chuanyong, Guo, Chun, Guo, Hongqing, Guo, Lian-Wang, Guo, Ming, Gupta, Pawan, Gupta, Shashi Kumar, Gupta, Swapnil, Gupta, Veer Bala, Gupta, Vivek, Gustafsson, Asa B., Gutterman, David D., H.B., Ranjitha, Haapasalo, Annakaisa, Haber, James E., Hać, Aleksandra, Hadano, Shinji, Hafrén, Anders J., Haidar, Mansour, Hall, Belinda S., Halldén, Gunnel, Hamacher-Brady, Anne, Hamann, Andrea, Hamasaki, Maho, Han, Weidong, Hansen, Malene, Hanson, Phyllis I., Hao, Zijian, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Hariharan, Nirmala, Haroon, Nigil, Harris, James, Hasegawa, Takafumi, Hasima Nagoor, Noor, Haspel, Jeffrey A., Haucke, Volker, Hawkins, Wayne D., Hay, Bruce A., Haynes, Cole M., Hayrabedyan, Soren B., Hays, Thomas S., He, Congcong, He, Qin, He, Rong-Rong, He, You-Wen, He, Yu-Ying, Heakal, Yasser, Heberle, Alexander M., Hejtmancik, J. Fielding, Helgason, Gudmundur Vignir, Henkel, Vanessa, Herb, Marc, Hergovich, Alexander, Herman-Antosiewicz, Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier H., Hesselson, Daniel, Hetz, Claudio, Heussler, Volker T., Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph A., Hlavacek, William S., Ho, Emmanuel A., Ho, Idy H.T., Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G. 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Razaul, Karmakar, Parimal, Katare, Rajesh G., Kato, Masaru, Kaufmann, Stefan H.E., Kauppinen, Anu, Kaushal, Gur P., Kaushik, Susmita, Kawasaki, Kiyoshi, Kazan, Kemal, Ke, Po-Yuan, Keating, Damien J., Keber, Ursula, Kehrl, John H., Keller, Kate E., Keller, Christian W., Kemper, Jongsook Kim, Kenific, Candia M., Kepp, Oliver, Kermorgant, Stephanie, Kern, Andreas, Ketteler, Robin, Keulers, Tom G., Khalfin, Boris, Khalil, Hany, Khambu, Bilon, Khan, Shahid Y., Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha, Kho, Widuri, Khobrekar, Noopur V., Khuansuwan, Sataree, Khundadze, Mukhran, Killackey, Samuel A., Kim, Dasol, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Eun, Kim, Eun Young, Kim, Eun-Kyoung, Kim, Hak-Rim, Kim, Hee-Sik, Kim, Hyung-Ryong, Kim, Jeong Hun, Kim, Jin Kyung, Kim, Jin-Hoi, Kim, Joungmok, Kim, Ju Hwan, Kim, Keun Il, Kim, Peter K., Kim, Seong-Jun, Kimball, Scot R., Kimchi, Adi, Kimmelman, Alec C., Kimura, Tomonori, King, Matthew A., Kinghorn, Kerri J., Kinsey, Conan G., Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kiselev, Sergey L., Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard N., Kittler, Josef T., Kjaerulff, Ole, Klein, Peter S., Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland L., Ko, Ben C.B., Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan C., Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp D., Kocaturk, Nur M., Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin T., Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor I., Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica L., Kou, Yanjun, Koukourakis, Michael I., Koustas, Evangelos, Kovacs, Attila L., Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna D., Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas T., Kuchitsu, Kazuyuki, Kuenen, Sabine, Kuerschner, Lars, Kukar, Thomas, Kumar, Ajay, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad, Kume, Shinji, Kumsta, Caroline, Kundu, Chanakya N., Kundu, Mondira, Kunnumakkara, Ajaikumar B., Kurgan, Lukasz, Kutateladze, Tatiana G., Kutlu, Ozlem, Kwak, SeongAe, Kwon, Ho Jeong, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert, Labonté, Patrick, Ladoire, Sylvain, Laface, Ilaria, Lafont, Frank, Lagace, Diane C., Lahiri, Vikramjit, Lai, Zhibing, Laird, Angela S., Lakkaraju, Aparna, Lamark, Trond, Lan, Sheng-Hui, Landajuela, Ane, Lane, Darius J. R., Lane, Jon D., Lang, Charles H., Lange, Carsten, Langel, Ülo, Langer, Rupert, Lapaquette, Pierre, Laporte, Jocelyn, LaRusso, Nicholas F., Lastres-Becker, Isabel, Lau, Wilson Chun Yu, Laurie, Gordon W., Lavandero, Sergio, Law, Betty Yuen Kwan, Law, Helen Ka-wai, Layfield, Rob, Le, Weidong, Le Stunff, Herve, Leary, Alexandre Y., Lebrun, Jean-Jacques, Leck, Lionel Y.W., Leduc-Gaudet, Jean-Philippe, Lee, Changwook, Lee, Chung-Pei, Lee, Da-Hye, Lee, Edward B., Lee, Erinna F., Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason S., Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella Y., Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu L., Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia M., Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy S., Levine, Beth, Lewis, Patrick A., Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P. Y., Lilly, Mary A., Lim, Hyunjung J., Lima, Thania R.R., Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie D., Lin, Kurt M., Lin, Kwang-Huei, Lin, Liang-Tzung, Lin, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia K., Liou, Yih-Cherng, Lipinski, Marta M., Lipovšek, Saška, Lira, Vitor A., Lisiak, Natalia, Liton, Paloma B., Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yang, Liu, Yueyang, Liu, Yule, Livingston, J. Andrew, Lizard, Gerard, Lizcano, Jose M., Ljubojevic-Holzer, Senka, LLeonart, Matilde E., Llobet-Navàs, David, Llorente, Alicia, Lo, Chih Hung, Lobato-Márquez, Damián, Long, Qi, Long, Yun Chau, Loos, Ben, Loos, Julia A., López, Manuela G., López-Doménech, Guillermo, López-Guerrero, José Antonio, López-Jiménez, Ana T., López-Pérez, Óscar, López-Valero, Israel, Lorenowicz, Magdalena J., Lorente, Mar, Lorincz, Peter, Lossi, Laura, Lotersztajn, Sophie, Lovat, Penny E., Lovell, Jonathan F., Lovy, Alenka, Lőw, Péter, Lu, Guang, Lu, Haocheng, Lu, Jia-Hong, Lu, Jin-Jian, Lu, Mengji, Lu, Shuyan, Luciani, Alessandro, Lucocq, John M., Ludovico, Paula, Luftig, Micah A., Luhr, Morten, Luis-Ravelo, Diego, Lum, Julian J., Luna-Dulcey, Liany, Lund, Anders H., Lund, Viktor K., Lünemann, Jan D., Lüningschrör, Patrick, Luo, Honglin, Luo, Rongcan, Luo, Shouqing, Luo, Zhi, Luparello, Claudio, Lüscher, Bernhard, Luu, Luan, Lyakhovich, Alex, Lyamzaev, Konstantin G., Lystad, Alf Håkon, Lytvynchuk, Lyubomyr, Ma, Alvin C., Ma, Changle, Ma, Mengxiao, Ma, Ning-Fang, Ma, Quan-Hong, Ma, Xinliang, Ma, Yueyun, Ma, Zhenyi, MacDougald, Ormond A., Macian, Fernando, MacIntosh, Gustavo C., MacKeigan, Jeffrey P., Macleod, Kay F., Maday, Sandra, Madeo, Frank, Madesh, Muniswamy, Madl, Tobias, Madrigal-Matute, Julio, Maeda, Akiko, Maejima, Yasuhiro, Magarinos, Marta, Mahavadi, Poornima, Maiani, Emiliano, Maiese, Kenneth, Maiti, Panchanan, Maiuri, Maria Chiara, Majello, Barbara, Major, Michael B., Makareeva, Elena, Malik, Fayaz, Mallilankaraman, Karthik, Malorni, Walter, Maloyan, Alina, Mammadova, Najiba, Man, Gene Chi Wai, Manai, Federico, Mancias, Joseph D., Mandelkow, Eva-Maria, Mandell, Michael A., Manfredi, Angelo A., Manjili, Masoud H., Manjithaya, Ravi, Manque, Patricio, Manshian, Bella B., Manzano, Raquel, Manzoni, Claudia, Mao, Kai, Marchese, Cinzia, Marchetti, Sandrine, Marconi, Anna Maria, Marcucci, Fabrizio, Mardente, Stefania, Mareninova, Olga A., Margeta, Marta, Mari, Muriel, Marinelli, Sara, Marinelli, Oliviero, Mariño, Guillermo, Mariotto, Sofia, Marshall, Richard S., Marten, Mark R., Martens, Sascha, Martin, Alexandre P.J., Martin, Katie R., Martin, Sara, Martin, Shaun, Martín-Segura, Adrián, Martín-Acebes, Miguel A., Martin-Burriel, Inmaculada, Martin-Rincon, Marcos, Martin-Sanz, Paloma, Martina, José A., Martinet, Wim, Martinez, Aitor, Martinez, Ana, Martinez, Jennifer, Martinez Velazquez, Moises, Martinez-Lopez, Nuria, Martinez-Vicente, Marta, Martins, Daniel O., Martins, Joilson O., Martins, Waleska K., Martins-Marques, Tania, Marzetti, Emanuele, Masaldan, Shashank, Masclaux-Daubresse, Celine, Mashek, Douglas G., Massa, Valentina, Massieu, Lourdes, Masson, Glenn R., Masuelli, Laura, Masyuk, Anatoliy I., Masyuk, Tetyana V., Matarrese, Paola, Matheu, Ander, Matoba, Satoaki, Matsuzaki, Sachiko, Mattar, Pamela, Matte, Alessandro, Mattoscio, Domenico, Mauriz, José L., Mauthe, Mario, Mauvezin, Caroline, Maverakis, Emanual, Maycotte, Paola, Mayer, Johanna, Mazzoccoli, Gianluigi, Mazzoni, Cristina, Mazzulli, Joseph R., McCarty, Nami, McDonald, Christine, McGill, Mitchell R., McKenna, Sharon L., McLaughlin, BethAnn, McLoughlin, Fionn, McNiven, Mark A., McWilliams, Thomas G., Mechta-Grigoriou, Fatima, Medeiros, Tania Catarina, Medina, Diego L., Megeney, Lynn A., Megyeri, Klara, Mehrpour, Maryam, Mehta, Jawahar L., Meijer, Alfred J., Meijer, Annemarie H., Mejlvang, Jakob, Meléndez, Alicia, Melk, Annette, Memisoglu, Gonen, Mendes, Alexandrina F., Meng, Delong, Meng, Fei, Meng, Tian, Menna-Barreto, Rubem, Menon, Manoj B., Mercer, Carol, Mercier, Anne E., Mergny, Jean-Louis, Merighi, Adalberto, Merkley, Seth D., Merla, Giuseppe, Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, Christian, Meyer, Hemmo, Mi, Wenyi, Mialet-Perez, Jeanne, Miao, Junying, Micale, Lucia, Miki, Yasuo, Milan, Enrico, Milczarek, Małgorzata, Miller, Dana L., Miller, Samuel I., Miller, Silke, Millward, Steven W., Milosevic, Ira, Minina, Elena A., Mirzaei, Hamed, Mirzaei, Hamid Reza, Mirzaei, Mehdi, Mishra, Amit, Mishra, Nandita, Mishra, Paras Kumar, Misirkic Marjanovic, Maja, Misasi, Roberta, Misra, Amit, Misso, Gabriella, Mitchell, Claire, Mitou, Geraldine, Miura, Tetsuji, Miyamoto, Shigeki, Miyazaki, Makoto, Miyazaki, Mitsunori, Miyazaki, Taiga, Miyazawa, Keisuke, Mizushima, Noboru, Mogensen, Trine H., Mograbi, Baharia, Mohammadinejad, Reza, Mohamud, Yasir, Mohanty, Abhishek, Mohapatra, Sipra, Möhlmann, Torsten, Mohmmed, Asif, Moles, Anna, Moley, Kelle H., Molinari, Maurizio, Mollace, Vincenzo, Møller, Andreas Buch, Mollereau, Bertrand, Mollinedo, Faustino, Montagna, Costanza, Monteiro, Mervyn J., Montella, Andrea, Montes, L. 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Patrick, Murthy, Aditya, Myöhänen, Timo T., Mysorekar, Indira U., Mytych, Jennifer, Nabavi, Seyed Mohammad, Nabissi, Massimo, Nagy, Péter, Nah, Jihoon, Nahimana, Aimable, Nakagawa, Ichiro, Nakamura, Ken, Nakatogawa, Hitoshi, Nandi, Shyam S., Nanjundan, Meera, Nanni, Monica, Napolitano, Gennaro, Nardacci, Roberta, Narita, Masashi, Nassif, Melissa, Nathan, Ilana, Natsumeda, Manabu, Naude, Ryno J., Naumann, Christin, Naveiras, Olaia, Navid, Fatemeh, Nawrocki, Steffan T., Nazarko, Taras Y., Nazio, Francesca, Negoita, Florentina, Neill, Thomas, Neisch, Amanda L., Neri, Luca M., Netea, Mihai G., Neubert, Patrick, Neufeld, Thomas P., Neumann, Dietbert, Neutzner, Albert, Newton, Phillip T., Ney, Paul A., Nezis, Ioannis P., Ng, Charlene C.W., Ng, Tzi Bun, Nguyen, Hang T. T., Nguyen, Long T., Ni, Hong-Min, Ní Cheallaigh, Clíona, Ni, Zhenhong, Nicolao, M. Celeste, Nicoli, Francesco, Nieto-Diaz, Manuel, Nilsson, Per, Ning, Shunbin, Niranjan, Rituraj, Nishimune, Hiroshi, Niso-Santano, Mireia, Nixon, Ralph A., Nobili, Annalisa, Nobrega, Clevio, Noda, Takeshi, Nogueira-Recalde, Uxía, Nolan, Trevor M., Nombela, Ivan, Novak, Ivana, Novoa, Beatriz, Nozawa, Takashi, Nukina, Nobuyuki, Nussbaum-Krammer, Carmen, Nylandsted, Jesper, O’Donovan, Tracey R., O’Leary, Seónadh M., O’Rourke, Eyleen J., O’Sullivan, Mary P., O’Sullivan, Timothy E., Oddo, Salvatore, Oehme, Ina, Ogawa, Michinaga, Ogier-Denis, Eric, Ogmundsdottir, Margret H., Ogretmen, Besim, Oh, Goo Taeg, Oh, Seon-Hee, Oh, Young J., Ohama, Takashi, Ohashi, Yohei, Ohmuraya, Masaki, Oikonomou, Vasileios, Ojha, Rani, Okamoto, Koji, Okazawa, Hitoshi, Oku, Masahide, Oliván, Sara, Oliveira, Jorge M. A., Ollmann, Michael, Olzmann, James A., Omari, Shakib, Omary, M. Bishr, Önal, Gizem, Ondrej, Martin, Ong, Sang-Bing, Ong, Sang-Ging, Onnis, Anna, Orellana, Juan A., Orellana-Muñoz, Sara, Ortega-Villaizan, Maria Del Mar, Ortiz-Gonzalez, Xilma R., Ortona, Elena, Osiewacz, Heinz D., Osman, Abdel-Hamid K., Osta, Rosario, Otegui, Marisa S., Otsu, Kinya, Ott, Christiane, Ottobrini, Luisa, Ou, Jing-hsiung James, Outeiro, Tiago F., Oynebraten, Inger, Ozturk, Melek, Pagès, Gilles, Pahari, Susanta, Pajares, Marta, Pajvani, Utpal B., Pal, Rituraj, Paladino, Simona, Pallet, Nicolas, Palmieri, Michela, Palmisano, Giuseppe, Palumbo, Camilla, Pampaloni, Francesco, Pan, Lifeng, Pan, Qingjun, Pan, Wenliang, Pan, Xin, Panasyuk, Ganna, Pandey, Rahul, Pandey, Udai B., Pandya, Vrajesh, Paneni, Francesco, Pang, Shirley Y., Panzarini, Elisa, Papademetrio, Daniela L., Papaleo, Elena, Papinski, Daniel, Papp, Diana, Park, Eun Chan, Park, Hwan Tae, Park, Ji-Man, Park, Jong-In, Park, Joon Tae, Park, Junsoo, Park, Sang Chul, Park, Sang-Youel, Parola, Abraham H., Parys, Jan B., Pasquier, Adrien, Pasquier, Benoit, Passos, João F., Pastore, Nunzia, Patel, Hemal H., Patschan, Daniel, Pattingre, Sophie, Pedraza-Alva, Gustavo, Pedraza-Chaverri, Jose, Pedrozo, Zully, Pei, Gang, Pei, Jianming, Peled-Zehavi, Hadas, Pellegrini, Joaquín M., Pelletier, Joffrey, Peñalva, Miguel A., Peng, Di, Peng, Ying, Penna, Fabio, Pennuto, Maria, Pentimalli, Francesca, Pereira, Cláudia MF, Pereira, Gustavo J.S., Pereira, Lilian C., Pereira de Almeida, Luis, Perera, Nirma D., Pérez-Lara, Ángel, Perez-Oliva, Ana B., Pérez-Pérez, María Esther, Periyasamy, Palsamy, Perl, Andras, Perrotta, Cristiana, Perrotta, Ida, Pestell, Richard G., Petersen, Morten, Petrache, Irina, Petrovski, Goran, Pfirrmann, Thorsten, Pfister, Astrid S., Philips, Jennifer A., Pi, Huifeng, Picca, Anna, Pickrell, Alicia M., Picot, Sandy, Pierantoni, Giovanna M., Pierdominici, Marina, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierzynowska, Karolina, Pietrocola, Federico, Pietruczuk, Miroslawa, Pignata, Claudio, Pimentel-Muiños, Felipe X., Pinar, Mario, Pinheiro, Roberta O., Pinkas-Kramarski, Ronit, Pinton, Paolo, Pircs, Karolina, Piya, Sujan, Pizzo, Paola, Plantinga, Theo S., Platta, Harald W., Plaza-Zabala, Ainhoa, Plomann, Markus, Plotnikov, Egor Y., Plun-Favreau, Helene, Pluta, Ryszard, Pocock, Roger, Pöggeler, Stefanie, Pohl, Christian, Poirot, Marc, Poletti, Angelo, Ponpuak, Marisa, Popelka, Hana, Popova, Blagovesta, Porta, Helena, Porte Alcon, Soledad, Portilla-Fernandez, Eliana, Post, Martin, Potts, Malia B., Poulton, Joanna, Powers, Ted, Prahlad, Veena, Prajsnar, Tomasz K., Praticò, Domenico, Prencipe, Rosaria, Priault, Muriel, Proikas-Cezanne, Tassula, Promponas, Vasilis J., Proud, Christopher G., Puertollano, Rosa, Puglielli, Luigi, Pulinilkunnil, Thomas, Puri, Deepika, Puri, Rajat, Puyal, Julien, Qi, Xiaopeng, Qi, Yongmei, Qian, Wenbin, Qiang, Lei, Qiu, Yu, Quadrilatero, Joe, Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Ragusa, Michael J., Rahimi, Nader, Rahmati, Marveh, Raia, Valeria, Raimundo, Nuno, Rajasekaran, Namakkal-Soorappan, Ramachandra Rao, Sriganesh, Rami, Abdelhaq, Ramírez-Pardo, Ignacio, Ramsden, David B., Randow, Felix, Rangarajan, Pundi N., Ranieri, Danilo, Rao, Hai, Rao, Lang, Rao, Rekha, Rathore, Sumit, Ratnayaka, J. Arjuna, Ratovitski, Edward A., Ravanan, Palaniyandi, Ravegnini, Gloria, Ray, Swapan K., Razani, Babak, Rebecca, Vito, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S., Reigada, David, Reiling, Jan H., Rein, Theo, Reipert, Siegfried, Rekha, Rokeya Sultana, Ren, Hongmei, Ren, Jun, Ren, Weichao, Renault, Tristan, Renga, Giorgia, Reue, Karen, Rewitz, Kim, Ribeiro de Andrade Ramos, Bruna, Riazuddin, S. Amer, Ribeiro-Rodrigues, Teresa M., Ricci, Jean-Ehrland, Ricci, Romeo, Riccio, Victoria, Richardson, Des R., Rikihisa, Yasuko, Risbud, Makarand V., Risueño, Ruth M., Ritis, Konstantinos, Rizza, Salvatore, Rizzuto, Rosario, Roberts, Helen C., Roberts, Luke D., Robinson, Katherine J., Roccheri, Maria Carmela, Rocchi, Stephane, Rodney, George G., Rodrigues, Tiago, Rodrigues Silva, Vagner Ramon, Rodriguez, Amaia, Rodriguez-Barrueco, Ruth, Rodriguez-Henche, Nieves, Rodriguez-Rocha, Humberto, Roelofs, Jeroen, Rogers, Robert S., Rogov, Vladimir V., Rojo, Ana I., Rolka, Krzysztof, Romanello, Vanina, Romani, Luigina, Romano, Alessandra, Romano, Patricia S., Romeo-Guitart, David, Romero, Luis C., Romero, Montserrat, Roney, Joseph C., Rongo, Christopher, Roperto, Sante, Rosenfeldt, Mathias T., Rosenstiel, Philip, Rosenwald, Anne G., Roth, Kevin A., Roth, Lynn, Roth, Steven, Rouschop, Kasper M.A., Roussel, Benoit D., Roux, Sophie, Rovere-Querini, Patrizia, Roy, Ajit, Rozieres, Aurore, Ruano, Diego, Rubinsztein, David C., Rubtsova, Maria P., Ruckdeschel, Klaus, Ruckenstuhl, Christoph, Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra, Ruparelia, Avnika Ashok, Rusmini, Paola, Russell, Ryan R., Russo, Gian Luigi, Russo, Maria, Russo, Rossella, Ryabaya, Oxana O., Ryan, Kevin M., Ryu, Kwon-Yul, Sabater-Arcis, Maria, Sachdev, Ulka, Sacher, Michael, Sachse, Carsten, Sadhu, Abhishek, Sadoshima, Junichi, Safren, Nathaniel, Saftig, Paul, Sagona, Antonia P., Sahay, Gaurav, Sahebkar, Amirhossein, Sahin, Mustafa, Sahin, Ozgur, Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem H., Saluja, Ashok K., Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose A., Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J. Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda M., Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy J., Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K. Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary T., Schaible, Ulrich E., Schapira, Anthony H.V., Scharl, Michael, Schatzl, Hermann M., Schein, Catherine H., Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen D., Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca E., Schober, Romana, Schoijet, Alejandra C., Schott, Micah B., Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan J., Schürmanns, Lea, Schwamborn, Jens C., Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie J., Scotto, Kathleen W., Scovassi, A. Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per O., Seiliez, Iban, Seki, Ekihiro, Selleck, Scott B., Sellke, Frank W., Selsby, Joshua T., Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John J., Shah, Javeed A., Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa M., Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher J., Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra V., Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind K., Shutt, Timothy E., Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno J. de Andrade, Silva, Johnatas D., Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel E., Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit P., Singh, Rajat, Singh, Shivendra V., Singh, Shrawan K., Singh, Sudha B., Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios L., Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya S., Smertenko, Andrei, Smith, Matthew D., Soenen, Stefaan J., Sohn, Eun Jung, Sok, Sophia P. M., Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott A., Soler, Rosa M., Solovchenko, Alexei, Somarelli, Jason A., Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro R., Sorice, Maurizio, Soukas, Alexander A., Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul A., Spector, Stephen A., Srinivas Bharath, M. M., St. Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint A., Stankov, Metodi V., Stathopulos, Peter B., Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan S., Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne G., Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana M., Subauste, Carlos S., Subbian, Selvakumar, Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M., Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, Sun, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen K.S., Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J. David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel J., Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen W. G., Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory A., Taylor, Joan M., Tchetina, Elena, Tee, Andrew R., Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal A., Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei V., Testillano, Pilar S., Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind A., Thellung, Stefano, Thinwa, Josephine W., Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul G., Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir I., Todi, Sokol V., Todorova, Krassimira, Toivonen, Janne M., Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon A., Torgersen, Maria L., Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina G., Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo H., Trelford, Charles B., Tremel, Shirley, Trougakos, Ioannis P., Tsao, Betty P., Tschan, Mario P., Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey S., Tumbarello, David A., Tumtas, Yasin, Tuñón, María J., Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley J., Tuxworth, Richard I., Tyler, Jessica K., Tyutereva, Elena V., Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm H., Ułamek-Kozioł, Marzena, Ulasov, Ilya V., Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir N, Vaccari, Thomas, Vaccaro, Maria I., Vahsen, Björn F., Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria J., Valko, Ayelén, Vallee, Richard B., Valverde, Angela M., Van den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd J.L., Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos A., Vannini, Nicola, Vanrell, M. 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Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith C., Stallings, Christina L., and Tong, Chun-Kit

Abstract

ABSTRACTIn 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fideautophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Published
2021
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43. Zebrafish ambra1aand ambra1bSilencing Affect Heart Development

Author

Meneghetti, Giacomo, Skobo, Tatjana, Chrisam, Martina, Fontana, Camilla Maria, Facchinello, Nicola, Nazio, Francesca, Cecconi, Francesco, Bonaldo, Paolo, and Dalla Valle, Luisa

Abstract

In zebrafish, two paralogous genes, activating molecule in beclin-1 (BECN1)–regulated autophagy ambra1aand ambra1b, both required for the autophagic process and during development, encode the protein AMBRA1, a positive regulator of early steps of autophagosome formation. As transcripts for both genes are expressed during embryogenesis in the heart region, in this work, we investigated the effects of ambra1aand ambra1bknockdown on heart development by means of morpholino oligonucleotides (MOs). Silencing of the two proteins by MOs directed against the ATG translation initiation codon affects cardiac morphogenesis, resulting in a small, string-like heart with pericardial edema, whereas treatment with splice-blocking MOs does not lead to overt cardiac phenotypes, thus revealing the relevance of maternally supplied ambra1transcripts for heart development. Co-injection of both ATG-MOs determines a more severe cardiac phenotype, with prominent pericardial edema. Whole-mount in situhybridization (WMISH) for myosin light chain 7 (myl7), as well as ambra1ATG-MO microinjection in zebrafish transgenic line expressing green fluorescent protein in the heart, revealed defects with the heart jogging process followed by imperfect cardiac looping. Moreover, WMISH of homeodomain transcription factor 2 isoform c (pitx2c) transcripts showed both bilateral and reversed pitx2cexpression in morphants. The morphants' cardiac phenotypes were effectively rescued by co-injection of MOs with human AMBRA1(hAMBRA1) messenger RNA (mRNA), pointing at the conservation of Ambra1 functions during evolution. Co-injections of ambra1ATG-MOs with a hAMBRA1mRNA mutated in the protein phosphatase 2a (PP2A) binding sites (hAMBRA1PXP) were not able to rescue the cardiac phenotypes, at the difference from wild-type hAMBRA1mRNA, and treatment of zebrafish embryos with the specific PP2A inhibitor cantharidin resulted in similar developmental cardiac defects. These results suggest a critical role for AMBRA1 in vertebrate heart development, likely involving the binding site for the PP2A phosphatase.

Published
2020
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44. Collagen VI Deficiency Results in Structural Abnormalities in the Mouse Lung

Author

Mereness, Jared A., Bhattacharya, Soumyaroop, Ren, Yue, Wang, Qian, Anderson, Christopher S., Donlon, Kathy, Dylag, Andrew M., Haak, Jeannie, Angelin, Alessia, Bonaldo, Paolo, and Mariani, Thomas J.

Abstract

Collagen VI (COL6) is known for its role in a spectrum of congenital muscular dystrophies, which are often accompanied by respiratory dysfunction. However, little is known regarding the function of COL6 in the lung. We confirmed the presence of COL6 throughout the basement membrane region of mouse lung tissue. Lung structure and organization were studied in a previously described Col6a1−/−mouse, which does not produce detectable COL6 in the lung. The Col6a1−/−mouse displayed histopathologic alveolar and airway abnormalities. The airspaces of Col6a1−/−lungs appeared simplified, with larger (29%; P < 0.01) and fewer (31%; P < 0.001) alveoli. These airspace abnormalities included reduced isolectin B4+alveolar capillaries and surfactant protein C–positive alveolar epithelial type-II cells. Alterations in lung function consistent with these histopathologic changes were evident. Col6a1−/−mice also displayed multiple airway changes, including increased branching (59%; P < 0.001), increased mucosal thickness (34%; P < 0.001), and increased epithelial cell density (13%; P < 0.001). Comprehensive transcriptome analysis revealed that the loss of COL6 is associated with reductions in integrin-paxillin–phosphatidylinositol 3-kinase signaling in vivo. In vitro, COL6 promoted steady-state phosphorylated paxillin levels and reduced cell density (16% to 28%; P < 0.05) at confluence. Inhibition of phosphatidylinositol 3-kinase, or its downstream effectors, resulted in increased cell density to a level similar to that seen on matrices lacking COL6.

Published
2020
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45. Partial substitution of soybean meal with microalgae meal (Arthrospira spp.– Spirulina) in grower and finisher diets for broiler chickens: implications on performance parameters, footpad dermatitis occurrence, breast meat quality traits, amino acid digestibility and plasma metabolomics profile

Author

Zampiga, Marco, Laghi, Luca, Soglia, Francesca, Piscitelli, Raffaela, Dayan, Jonathan, Petracci, Massimiliano, Bonaldo, Alessio, and Sirri, Federico

Abstract

This trial was conducted to evaluate the effects of replacing soybean meal with microalgae meal (MM; Arthrospira spp.) during grower and finisher phases on productive performance, footpad dermatitis (FPD) occurrence, breast meat quality, amino acid digestibility and plasma metabolomics profile of broiler chickens. One thousand day-old Ross 308 male chicks were divided into 5 experimental groups (8 replicates, 25 birds/each): CON, fed a commercial soybean-based diet throughout the trial (0–41 d); F3and F6, fed the CON diet up to 28 d of age and then a finisher diet (29–41 d) with either 30 or 60 g MM/kg, respectively; and GF3and GF6, receiving CON diet until 14 d and then diets containing 30 or 60 g MM/kg from 15 to 41 d, respectively. All diets were iso-energetic and with a similar amino acid profile. Growth performances were recorded on a pen basis at the end of each feeding phase and apparent ileal amino acid digestibility was determined at 41 d. Footpad dermatitis occurrence was assessed on all processed birds, while breast and plasma samples were collected for meat quality and metabolomics analysis (proton nuclear magnetic resonance - 1H-NMR). At 41 d, CON group showed higher body weight than F6 and GF6 ones (2,541 vs. 2,412 vs. 2,384 g, respectively; P< 0.05). Overall, GF6 group exhibited the highest feed conversion ratio, while F3 did not present significant differences compared to CON (1.785 vs. 1.810 vs. 1.934 g feed/g gain, respectively for CON, F3 and GF6; P< 0.01). The occurrence and the risk of developing FPD were similar among groups. MM administration increased breast meat yellowness and reduced amino acid digestibility (P< 0.001). The 1H-NMR analysis revealed variations in the levels of some circulating metabolites, including histidine, arginine and creatine, which play important metabolic roles. Overall, these findings can contribute to expand the knowledge about the use of Arthrospira spp.as protein source in broiler diets.

Published
2024
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46. The epg5knockout zebrafish line: a model to study Vici syndrome

Author

Meneghetti, Giacomo, Skobo, Tatjana, Chrisam, Martina, Facchinello, Nicola, Fontana, Camilla Maria, Bellesso, Stefania, Sabatelli, Patrizia, Raggi, Flavia, Cecconi, Francesco, Bonaldo, Paolo, and Dalla Valle, Luisa

Abstract

ABSTRACTThe EPG5 protein is a RAB7A effector involved in fusion specificity between autophagosomes and late endosomes or lysosomes during macroautophagy/autophagy. Mutations in the human EPG5gene cause a rare and severe multisystem disorder called Vici syndrome. In this work, we show that zebrafish epg5-/-mutants from both heterozygous and incrossed homozygous matings are viable and can develop to the age of sexual maturity without conspicuous defects in external appearance. In agreement with the dysfunctional autophagy of Vici syndrome, western blot revealed higher levels of the Lc3-II autophagy marker in epg5-/-mutants with respect to wild type controls. Moreover, starvation elicited higher accumulation of Lc3-II in epg5-/-than in wild type larvae, together with a significant reduction of skeletal muscle birefringence. Accordingly, muscle ultrastructural analysis revealed accumulation of degradation-defective autolysosomes in starved epg5-/-mutants. By aging, epg5-/-mutants showed impaired motility and muscle thinning, together with accumulation of non-degradative autophagic vacuoles. Furthermore, epg5-/-adults displayed morphological alterations in gonads and heart. These findings point at the zebrafish epg5mutant as a valuable model for EPG5-related disorders, thus providing a new tool for dissecting the contribution of EPG5 on the onset and progression of Vici syndrome as well as for the screening of autophagy-stimulating drugs.AbbreviationsATG: autophagy related; cDNA: complementary DNA; DIG: digoxigenin; dpf: days post-fertilization; EGFP: enhanced green fluorescent protein; EPG: ectopic P granules; GFP: green fluorescent protein; hpf: hours post-fertilization; IL1B: interleukin 1 beta; Lc3-II: lipidated Lc3; mpf: months post-fertilization; mRNA: messenger RNA; NMD: nonsense-mediated mRNA decay; PCR: polymerase chain reaction; qPCR: real time-polymerase chain reaction; RAB7A/RAB7: RAB7a, member RAS oncogene family; RACE: rapid amplification of cDNA ends; RFP: red fluorescent protein; RT-PCR: reverse transcriptase-polymerase chain reaction; SEM: standard error of the mean; sgRNA: guide RNA; UTR: untranslated region; WMISH: whole mount in situ hybridization; WT: wild type.

Published
2019
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47. Loss of mitochondrial calcium uniporter rewires skeletal muscle metabolism and substrate preference

Author

Gherardi, Gaia, Nogara, Leonardo, Ciciliot, Stefano, Fadini, Gian Paolo, Blaauw, Bert, Braghetta, Paola, Bonaldo, Paolo, De Stefani, Diego, Rizzuto, Rosario, and Mammucari, Cristina

Abstract

Skeletal muscle mitochondria readily accumulate Ca2+in response to SR store-releasing stimuli thanks to the activity of the mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca2+uptake. MCU positively regulates myofiber size in physiological conditions and counteracts pathological loss of muscle mass. Here we show that skeletal muscle-specific MCU deletion inhibits myofiber mitochondrial Ca2+uptake, impairs muscle force and exercise performance, and determines a slow to fast switch in MHC expression. Mitochondrial Ca2+uptake is required for effective glucose oxidation, as demonstrated by the fact that in muscle-specific MCU−/−myofibers oxidative metabolism is impaired and glycolysis rate is increased. Although defective, mitochondrial activity is partially sustained by increased fatty acid (FA) oxidation. In MCU−/−myofibers, PDP2 overexpression drastically reduces FA dependency, demonstrating that decreased PDH activity is the main trigger of the metabolic rewiring of MCU−/−muscles. Accordingly, PDK4 overexpression in MCUfl/flmyofibers is sufficient to increase FA-dependent respiration. Finally, as a result of the muscle-specific MCU deletion, a systemic catabolic response impinging on both liver and adipose tissue metabolism occurs.

Published
2019
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48. Enrichment tools for undocked heavy pigs: effects on body and gastric lesions and carcase and meat quality parameters

Author

Vitali, Marika, Nannoni, Eleonora, Sardi, Luca, Bassi, Patrizia, Militerno, Gianfranco, Faucitano, Luigi, Bonaldo, Alessio, and Martelli, Giovanna

Abstract

AbstractTwo independent trials were carried out to assess the effect of two enrichment tools on the prevalence of skin and tail lesions recorded prior of slaughtering, lesions of the pars oesophagea(OGL) of the stomach, and on carcase and meat quality traits in Italian heavy pigs (body weight range: 25–160 kg). Eighty undocked barrows (Landrace × Large White) were used in two trials (20 pigs/experimental group, 5 pigs/pen). In Trial 1, the control group received a hanging metal chain (C1), while the other group received wood logs (WL) placed inside a metal rack. In Trial 2, the control group was provided with hanging chain (C2), while the pen of the other group was enriched with a vegetal edible block (EB) placed inside the metal rack. In both trials, no differences were observed in the prevalence and severity of skin, tail and gastric lesions (p > .05). In Trial 1, WL pigs presented lower backfat (p = .01), higher lean meat percentage (p = .03) and higher drip loss in the loin muscle (p = .02) than C1 pigs. Tail score and gastric lesions showed a moderate correlation (r = 0.42; p = .01) in Trial 1. Treatments had no effect on carcase or meat quality traits in Trial 2 (p > .05). In conclusion, the two enrichments provided did not affect body and gastric lesions, carcase and meat quality of Italian heavy pigs, if compared to the metal chains.

Published
2019
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49. Annotated expressed sequence tags and cDNA microarrays for studies of brain and behavior in the honey bee

Author

Whitfield, Charles W., Band, Mark R., Bonaldo, Maria F., Kumar, Charu G., Liu, Lei, Pardinas, Jose R., Robertson, Hugh M., Soares, M. Bento, and Robinson, Gene E.

Subjects
Astrogeology -- Research, Honeybee -- Genetic aspects, Honeybee -- Research, DNA microarrays -- Research, Genetic research, Health
Abstract

An analysis was conducted by creating expressed sequence tag (EST) and cDNA microarray resources for the bee brain, to find out the behavior in the honey bee. Through some molecular functions and biological processes, it was found that Apis cDNAs are greater than exogenous control cDNAs.

Published
2002

50. Zebrafish ambra1bknockout reveals a novel role for Ambra1 in primordial germ cells survival, sex differentiation and reproduction

Author

Fontana, Camilla Maria, Terrin, Francesca, Facchinello, Nicola, Meneghetti, Giacomo, Dinarello, Alberto, Gambarotto, Lisa, Zuccarotto, Annalisa, Caichiolo, Micol, Brocca, Ginevra, Verin, Ranieri, Nazio, Francesca, Carnevali, Oliana, Cecconi, Francesco, Bonaldo, Paolo, and Dalla Valle, Luisa

Abstract

Background: AMBRA1 is an intrinsically disordered protein, working as a scaffold molecule to coordinate, by protein-protein interaction, many cellular processes, including autophagy, mitophagy, apoptosis and cell cycle progression. The zebrafish genome contains two ambra1paralogous genes (aand b), both involved in development and expressed at high levels in the gonads. Characterization of the zebrafish paralogous genes mutant lines generated by CRISPR/Cas9 approach showed that ambra1bknockout leads to an all-male population. Results: We demonstrated that the silencing of the ambra1bgene determines a reduction of primordial germ cells (PGCs), a condition that, in the zebrafish, leads to the development of all-male progeny. PGC reduction was confirmed by knockdown experiments and rescued by injection of ambra1band human AMBRA1mRNAs, but not ambra1amRNA. Moreover, PGC loss was not rescued by injection with human AMBRA1mRNA mutated in the CUL4-DDB1 binding region, thus suggesting that interaction with this complex is involved in PGC protection from loss. Results from zebrafish embryos injected with murine Stat3mRNA and stat3morpholino suggest that Ambra1b could indirectly regulate this protein through CUL4-DDB1 interaction. According to this, Ambra1+/−mice showed a reduced Stat3expression in the ovary together with a low number of antral follicles and an increase of atretic follicles, indicating a function of Ambra1 in the ovary of mammals as well. Moreover, in agreement with the high expression of these genes in the testis and ovary, we found significant impairment of the reproductive process and pathological alterations, including tumors, mainly limited to the gonads. Conclusions: By exploiting ambra1aand ambra1bknockout zebrafish lines, we prove the sub-functionalization between the two paralogous zebrafish genes and uncover a novel function of Ambra1 in the protection from excessive PGC loss, which seems to require binding with the CUL4-DDB1 complex. Both genes seem to play a role in the regulation of reproductive physiology.

Published
2023
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