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Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme

Background Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, i ...

Frontiers Media Sa2024

Convalescent human plasma candidate reference materials protect against Crimean-Congo haemorrhagic fever virus (CCHFV) challenge in an A129 mouse model

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of ...

Elsevier2024

The role of LRRK2 in lung adenocarcinoma

Aspasia Gkasti

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models

Johan Auwerx, Xiaoxu Li, Alessia De Masi, Tanes Imamura de Lima, Keno Strotjohann

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progress ...

Wiley2024

Mechanism of KRAS-driven T cell infiltration in colorectal cancer

Amber Dawn Bowler

Colorectal cancer is the second-leading cause of cancer death worldwide. Early-stage disease can be detected with preventative medical screening and is treatable with surgical resection. Sixty-percent of patients, however, are diagnosed with advanced-stage ...

EPFL2023

Upregulation of the ERR γ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis

Johan Auwerx, Changmyung Oh, Jiale Wang

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported t ...

National Academy of Sciences2023

Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice

Maria del Carmen Sandi Perez

The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association bet ...

Nature Research2023

Enabling Stroke Theranostics with Hyperpolarized Magnetic Resonance

Thanh Phong Kevin Lê

The severe social and economic burden of stroke is a strong motivation for the exploration of innovative medical approaches. In this context, magnetic resonance (MR) of hyperpolarized (HP) molecular agents via dissolution dynamic nuclear polarization (dDNP ...

EPFL2023

Influence of DNP Polarizing Agents on Biochemical Processes: TEMPOL in Transient Ischemic Stroke

Mor-Miri Mishkovsky, Jean-Noël Hyacinthe, Mario Gaetano Lepore, Thanh Phong Kevin Lê, Lara Buscemi Estefanell

Hyperpolarization of 13C by dissolution dynamic nuclear polarization (dDNP) boosts the sensitivity of magnetic resonance spectroscopy (MRS), making possible the monitoring in vivo and in real time of the biochemical reactions of exogenously infused 13C-lab ...

2023

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn(2B/-) spinal muscular atrophy mice

Bernard Schneider

Structural, functional and molecular cardiac defects have been reported in spinal muscular atrophy (SMA) patients and mouse models. Previous quantitative proteomics analyses demonstrated widespread molecular defects in the severe Taiwanese SMA mouse model. ...

Oxford University Press2023

Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity

Simona Frateschi, Sévan Stroh

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating proteases in vitro, highly suggesting that they are required for proteolytic activation of ENaC in vivo. The present study tested whether CAP3/St14 is relevant for rena ...

MDPI2023

Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning

Friedhelm Christoph Hummel, Takuya Morishita, Pablo Maceira Elvira, Pierre Theopistos Vassiliadis, Elena Beanato, Fabienne Windel, Esra Neufeld, Maximilian Jonas Wessel, Chang-Hyun Park, Traian Popa, Pauline Menoud

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-co ...

Nature Portfolio2023

Digital reconstruction of the mammalian spinal cord: from anatomical reference volume to cell type atlas of the mouse spinal cord

Ihor Kuras

The spinal cord is an elongated nervous structure that together with the brain forms the central nervous system. It relays sensory and motor information between the brain and the body, thus controlling most somatic and autonomic body functions. In recent y ...

EPFL2023

Hyperthermic intrathoracic chemotherapy to control malignant pleural mesothelioma

Yameng Hao

OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare disease that has a poor response to conventional therapy. Hyperthermic intrathoracic chemotherapy (HITOC), a treatment combining fever-range hyperthermia with intrapleural cisplatin chemotherapy, ha ...

EPFL2023

Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range

Didier Trono, Henning Paul-Julius Stahlberg, Priscilla Turelli, Florence Pojer, Dongchun Ni, Sergey Nazarov, Kelvin Ka Ching Lau, Alexander Myasnikov, Emiko Uchikawa

nvestigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after req ...

2023

Sporadic type VI secretion in seventh pandemic Vibrio cholerae

Melanie Blokesch, Sandrine Stutzmann, Nicolas René Chiaruttini, Alexis Joseph Proutière, Loriane Bader, Lisa Christina Metzger, Natalia Carolina Drebes Dorr, Sandrine Natacha Isaac

Vibrio cholerae is a pathogen that causes disease in millions of people every year by colonizing the small intestine and then secreting the potent cholera toxin. How the pathogen overcomes the colonization barrier created by the host’s natural microbiota i ...

2023

Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions

Silvestro Micera, Maria Pasquini

Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly unde ...

SOC NEUROSCIENCE2023

Elucidating and modulating regulatory pathways so as to reprogram the immunosuppressive tumor microenvironment for therapeutic benefit

Agnieszka Alicja Chryplewicz

Glioblastoma (GBM) is the most frequent and highly malignant form of brain cancer. New therapeutic regimens are urgently needed as GBM patients present with a minimal response to currently-approved therapies. The goal of this project is to identify new the ...

EPFL2023

Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal

João Miguel das Neves Duarte, Adélaïde Alice Mohr

Diabetes impacts on brain metabolism, structure, and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. Howe ...

INT SOC AGING & DISEASE2022

Data-driven whole mouse brain modeling for multi-scale simulations

Dimitri Bruno Marie Rodarie

In this thesis, we present a data-driven iterative pipeline to generate, simulate and validate point-neuron models of the whole mouse brain. The ultimate goal is to replicate close loop experiments with a virtual body in a virtual world. This pipeline was ...

EPFL2022