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Article ; Online: Muscle stiffness indicating mission crew health in space.

Schoenrock, Britt / Muckelt, Paul E / Hastermann, Maria / Albracht, Kirsten / MacGregor, Robert / Martin, David / Gunga, Hans-Christian / Salanova, Michele / Stokes, Maria J / Warner, Martin B / Blottner, Dieter

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4196

Abstract: Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate ...

Abstract	Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate inflight assessment to inform exercise programmes is critical due to lack of technologies suitable for spaceflight. Changes in mechanical properties indicate muscle health status and can be measured rapidly and non-invasively using novel technology. A hand-held MyotonPRO device enabled monitoring of muscle health for the first time in spaceflight (> 180 days). Greater/maintained stiffness indicated countermeasures were effective. Tissue stiffness was preserved in the majority of muscles (neck, shoulder, back, thigh) but Tibialis Anterior (foot lever muscle) stiffness decreased inflight vs. preflight (p < 0.0001; mean difference 149 N/m) in all 12 crewmembers. The calf muscles showed opposing effects, Gastrocnemius increasing in stiffness Soleus decreasing. Selective stiffness decrements indicate lack of preservation despite daily inflight countermeasures. This calls for more targeted exercises for lower leg muscles with vital roles as ankle joint stabilizers and in gait. Muscle stiffness is a digital biomarker for risk monitoring during future planetary explorations (Moon, Mars), for healthcare management in challenging environments or clinical disorders in people on Earth, to enable effective tailored exercise programmes.
MeSH term(s)	Humans ; Space Flight ; Astronauts ; Muscle, Skeletal/physiology ; Exercise/physiology ; Gait
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54759-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nitrosative Stress in Astronaut Skeletal Muscle in Spaceflight.

Blottner, Dieter / Moriggi, Manuela / Trautmann, Gabor / Furlan, Sandra / Block, Katharina / Gutsmann, Martina / Torretta, Enrica / Barbacini, Pietro / Capitanio, Daniele / Rittweger, Joern / Limper, Ulrich / Volpe, Pompeo / Gelfi, Cecilia / Salanova, Michele

Antioxidants (Basel, Switzerland)

2024 Volume 13, Issue 4

Abstract: Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR ... ...

Abstract	Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR changes in deep calf soleus muscle. Nitro-DIGE analyses identified functional proteins (structural, metabolic, mitochondrial) that were over-nitrosylated post- vs. preflight. In a short-duration mission (SDM) astronaut (9 ISS days), s-nitrosylation of a nodal protein of the glycolytic flux, specific proteins in tricarboxylic acid (TCA) cycle, respiratory chain, and over-nitrosylation of creatine kinase M-types as signs of impaired ATP production and muscle contraction proteins were seen. S-nitrosylation of serotransferrin (TF) or carbonic anhydrase 3 (CA3b and 3c) represented signs of acute response microgravity muscle maladaptation. LDM nitrosoprofiles reflected recovery of mitochondrial activity, contraction proteins, and iron transporter TF as signs of muscle adaptation to microgravity. Nitrosated antioxidant proteins, alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR), and selenoprotein thioredoxin reductase 1 (TXNRD1) levels indicated signs of altered redox homeostasis and reduced protection from nitrosative stress in spaceflight. This work presents a novel spaceflight-generated dataset on s-nitrosylated muscle protein signatures from astronauts that helps both to better understand the structural and molecular networks associated to muscular nitrosative stress and to design countermeasures to dysfunction and impaired performance control in human spaceflight missions.
Language	English
Publishing date	2024-04-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox13040432
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effects of Omega-3 and Antioxidant Cocktail Supplement on Prolonged Bed Rest: Results from Serum Proteome and Sphingolipids Analysis.

Barbacini, Pietro / Blottner, Dieter / Capitanio, Daniele / Trautmann, Gabor / Block, Katharina / Torretta, Enrica / Moriggi, Manuela / Salanova, Michele / Gelfi, Cecilia

Cells

2022 Volume 11, Issue 13

Abstract: Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such ... ...

Abstract	Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study). The serum proteome, sphingolipidome and nitrosoproteome were analyzed adopting different mass spectrometry-based approaches. Results in placebo-treated BR subjects indicated a marked decrease of proteins associated with high-density lipoproteins (HDL) involved in lipemic homeostasis not found in the cocktail-treated BR group. Moreover, long-chain ceramides decreased while sphingomyelin increased in the BR cocktail-treated group. In placebo, the ratio of
MeSH term(s)	Antioxidants/pharmacology ; Bed Rest ; Dietary Supplements ; Fatty Acids, Omega-3/pharmacology ; Humans ; Male ; Proteome ; Sphingolipids
Chemical Substances	Antioxidants ; Fatty Acids, Omega-3 ; Proteome ; Sphingolipids
Language	English
Publishing date	2022-07-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11132120
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book: The neuromuscular system: from earth to space life science

Blottner, Dieter / Salanova, Michele

neuromuscular cell signalling in disuse and exercise

(SpringerBriefs in space life sciences,)

2015

Author's details	Dieter Blottner, Michele Salanova
Series title	SpringerBriefs in space life sciences,
MeSH term(s)	Neuromuscular Junction/cytology ; Space Flight ; Signal Transduction/physiology ; Cell Communication/physiology ; Extraterrestrial Environment
Language	English
Size	xiv, 92 pages :, illustrations (chiefly color) ;, 24 cm.
Document type	Book
ISBN	9783319122977 ; 3319122975 ; 9783319122984 ; 3319122983
Database	Catalogue of the US National Library of Medicine (NLM)

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Book ; Online: The NeuroMuscular System: From Earth to Space Life Science

Blottner, Dieter / Salanova, Michele

Neuromuscular Cell Signalling in Disuse and Exercise

(SpringerBriefs in Space Life Sciences)

2015

Abstract: The book provides fundamental new insights in the structure and function of the healthy NeuroMuscular system. Recent findings suggest that the musculoskeletal system that supports movement control on Earth is controlled by unique principles of ... ...

Author's details	by Dieter Blottner, Michele Salanova
Series title	SpringerBriefs in Space Life Sciences
Abstract	The book provides fundamental new insights in the structure and function of the healthy NeuroMuscular system. Recent findings suggest that the musculoskeletal system that supports movement control on Earth is controlled by unique principles of structural, biochemical and molecular characteristics. Mechanical loading by working against normal gravity helps to support principal structures in bone, muscle and associated subcellular scaffold components. Disuse or immobilization of the body in bed rest on Earth or in microgravity in Space result in considerable loss of bone, muscle and force with downregulation of neuromuscular activity resulting in impaired performance control. The goal is to develop exercise prescriptions to maintain postural control in normal life, aging and rehabilitation on Earth as well as for an adequate human performance management in Space.
Keywords	Astronautics ; Human anatomy ; Human physiology ; Medicine ; Neurosciences
Language	English
Size	Online-Ressource (XIV, 92 p. 34 illus., 30 illus. in color), online resource
Publisher	Springer International Publishing
Publishing place	Cham ;s.l
Document type	Book ; Online
ISBN	9783319122977 ; 9783319122984 ; 3319122975 ; 3319122983
DOI	10.1007/978-3-319-12298-4
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions.

Blottner, Dieter / Moriggi, Manuela / Trautmann, Gabor / Hastermann, Maria / Capitanio, Daniele / Torretta, Enrica / Block, Katharina / Rittweger, Joern / Limper, Ulrich / Gelfi, Cecilia / Salanova, Michele

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International ... ...

Abstract	The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration.
MeSH term(s)	Humans ; Male ; Astronauts ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Space Flight ; Time Factors ; Muscular Atrophy/etiology ; Muscular Atrophy/metabolism ; Muscular Atrophy/pathology ; Biopsy
Language	English
Publishing date	2023-02-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24044095
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Opposite Regulation of Homer Signal at the NMJ Postsynaptic Micro Domain between Slow- and Fast-Twitch Muscles in an Experimentally Induced Autoimmune Myasthenia Gravis (EAMG) Mouse Model.

Schubert, Martin / Pelz, Andreas / Trautmann, Gabor / Block, Katharina / Furlan, Sandra / Gutsmann, Martina / Kohler, Siegfried / Volpe, Pompeo / Blottner, Dieter / Meisel, Andreas / Salanova, Michele

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are ... ...

Abstract	Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity.
Language	English
Publishing date	2022-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232315052
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Reactive Jumps Preserve Skeletal Muscle Structure, Phenotype, and Myofiber Oxidative Capacity in Bed Rest.

Blottner, Dieter / Hastermann, Maria / Weber, Robert / Lenz, Regina / Gambara, Guido / Limper, Ulrich / Rittweger, Jörn / Bosutti, Alessandra / Degens, Hans / Salanova, Michele

Frontiers in physiology

2020 Volume 10, Page(s) 1527

Abstract: Identification of countermeasures able to prevent disuse-induced muscle wasting is crucial to increase performance of crew members during space flight as well as ameliorate patient's clinical outcome after long immobilization periods. We report on the ... ...

Abstract	Identification of countermeasures able to prevent disuse-induced muscle wasting is crucial to increase performance of crew members during space flight as well as ameliorate patient's clinical outcome after long immobilization periods. We report on the outcome of short but high-impact reactive jumps (JUMP) as countermeasure during 60 days of 6° head-down tilt (HDT) bed rest on myofiber size, type composition, capillarization, and oxidative capacity in tissue biopsies (pre/post/recovery) from the knee extensor
Language	English
Publishing date	2020-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.01527
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Article: Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse.

Huang, Yunfei / Fan, Yubo / Salanova, Michele / Yang, Xiao / Sun, Lianwen / Blottner, Dieter

Frontiers in physiology

2018 Volume 9, Page(s) 616

Abstract: The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, ... ...

Abstract	The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups (
Language	English
Publishing date	2018-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2018.00616
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused Vastus lateralis Muscle in Long-Term Bedrest (Toulouse Cocktail Study)

Blottner, Dieter / Capitanio, Daniele / Trautmann, Gabor / Furlan, Sandra / Gambara, Guido / Moriggi, Manuela / Block, Katharina / Barbacini, Pietro / Torretta, Enrica / Py, Guillaume / Chopard, Angèle / Vida, Imre / Volpe, Pompeo / Gelfi, Cecilia / Salanova, Michele

Antioxidants. 2021 Mar. 03, v. 10, no. 3

2021

Abstract: Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the ... ...

Abstract	Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the Toulouse Cocktail bedrest (BR) study were used to assess efficacy of an antioxidant cocktail (polyphenols, omega-3, vitamin E, and selenium) to counteract the increased redox homeostasis and enhance the antioxidant defense response by using label-free LC–MS/MS and NITRO-DIGE (nitrosated proteins), qPCR, and laser confocal microscopy. Label-free LC–MS/MS indicated that treatment prevented the redox homeostasis dysregulation and promoted structural remodeling (TPM3, MYH7, MYBPC, MYH1, MYL1, HRC, and LUM), increment of RyR1, myogenesis (CSRP3), and skeletal muscle development (MUSTN1, LMNA, AHNAK). These changes were absent in the Placebo group. Glycolysis, tricarboxylic acid cycle (TCA), oxidative phosphorylation, fatty acid beta-oxidation, and mitochondrial transmembrane transport were normalized in treated subjects. Proteins involved in protein folding were also normalized, whereas protein entailed in ion homeostasis decreased. NITRO-DIGE analysis showed significant protein nitrosylation changes for CAT, CA3, SDHA, and VDAC2 in Treatment vs. Placebo. Similarly, the nuclear factor erythroid 2-related factor 2 (Nrf-2) antioxidant response element (Nrf-2 ARE) signaling pathway showed an enhanced response in the Treatment group. Increased nitrosative redox homeostasis and decreased antioxidant defense response were found in post-BR control (Placebo, n = 10) vs. the antioxidant cocktail treated group (Treatment, n = 10). Taken together, increased nitrosative redox homeostasis and muscle deterioration during BR-driven physical inactivity were prevented, whereas decreased antioxidant nitrosative stress defense response was attenuated by Treatment suggesting positive effects of the nutritional intervention protocol in bedrest.
Keywords	antioxidant activity ; beta oxidation ; confocal microscopy ; fatty acids ; glycolysis ; homeostasis ; males ; mitochondria ; muscle development ; muscles ; muscular atrophy ; nitrosylation ; nutritional intervention ; oxidative phosphorylation ; oxidative stress ; placebos ; polyphenols ; reactive nitrogen species ; reactive oxygen species ; selenium ; skeletal muscle ; tricarboxylic acid cycle ; vitamin E
Language	English
Dates of publication	2021-0303
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10030378
Database	NAL-Catalogue (AGRICOLA)

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