Autophagy is emerging as a key regulatory process during skeletal muscle development, regeneration and homeostasis, and deregulated autophagy has been implicated in muscular disorders and age-related ...muscle decline. We have monitored autophagy in muscles of mdx mice and human Duchenne muscular dystrophy (DMD) patients at different stages of disease. Our data show that autophagy is activated during the early, compensatory regenerative stages of DMD. A progressive reduction was observed during mdx disease progression, in coincidence with the functional exhaustion of satellite cell-mediated regeneration and accumulation of fibrosis. Moreover, pharmacological manipulation of autophagy can influence disease progression in mdx mice. Of note, studies performed in regenerating muscles of wild-type mice revealed an essential role of autophagy in the activation of satellite cells upon muscle injury. These results support the notion that regeneration-associated autophagy contributes to the early compensatory stage of DMD progression, and interventions that extend activation of autophagy might be beneficial in the treatment of DMD. Thus, autophagy could be a 'disease modifier' targeted by interventions aimed to promote regeneration and delay disease progression in DMD.
Plastic pollution in the environment has become a much-discussed issue worldwide. In recent decades, the contamination of all environments has become increasingly evident, in particular, that of ...water is highly concerning. Ingestion by different animal species under natural conditions has also been demonstrated. Among these is the Talitrid Amphipod Cryptorchestia garbinii, which lives on the banks of the internal waterways and lakes' shorelines. As detritivores species, it is very exposed to microplastics that can be ingested, probably mistaking them for food. Aiming to highlight the microplastic ingestion and the role of this species as an entry point for the food web, we analyzed 80 specimens from 4 sites along the shores of Garda Lake, one of the first lakes in Italy to be studied for this type of contamination. The microplastics ingested were observed and quantified through the Nile Red staining method. We were able to verify the presence of ingested microplastics in all the samples analyzed and, therefore, in the food web. This species could serve as valuable natural models of plastic exposure. Microplastic sentinel species can be used as a proxy for environmental exposure and ecosystem monitoring tools to quantify and assess the impacts of microplastic contamination.
Previous works have established a unique function of MyoD in the control of muscle gene expression during DNA damage response in myoblasts. Phosphorylation by DNA damage-activated ABL tyrosine kinase ...transiently inhibits MyoD-dependent activation of transcription in response to genotoxic stress. We show here that ABL-MyoD signaling is also an essential component of the DNA repair machinery in myoblasts exposed to genotoxic stress. DNA damage promoted the recruitment of MyoD to phosphorylated Nbs1 (pNbs1)-containing repair foci, and this effect was abrogated by either ABL knockdown or the ABL kinase inhibitor imatinib. Upon DNA damage, MyoD and pNbs1 were detected on the chromatin to MyoD target genes without activating transcription. DNA damage-mediated tyrosine phosphorylation was required for MyoD recruitment to target genes, as the ABL phosphorylation-resistant MyoD mutant (MyoD Y30F) failed to bind the chromatin following DNA damage, while retaining the ability to activate transcription in response to differentiation signals. Moreover, MyoD Y30F exhibited an impaired ability to promote repair in a heterologous system, as compared with MyoD wild type (WT). Consistently, MyoD-null satellite cells (SCs) displayed impaired DNA repair that was rescued by reintroduction of MyoD WT but not by MyoD Y30F. In addition, inhibition of ABL kinase prevented MyoD WT-mediated rescue of DNA repair in MyoD-null SCs. These results identify an unprecedented contribution of MyoD to DNA repair and suggest that ABL-MyoD signaling coordinates DNA repair and transcription in myoblasts.
A new species of Talitridae, Cryptorchestia garbinii , is here described and illustrated. It was collected in Lake Garda in 1895 and initially identified by Adriano Garbini, one of the first Italian ...hydrobiologists, as Orchestia littorea ; then as O. gammarellus in a second publication, and finally as O. bottae . In 1925, Spandl identified the specimens from Lake Garda and other localities in Europe, as O. cavimana while noticing some morphological differences with the specimens from Cyprus, the type locality of the species. These differences in taxonomic characters were disregarded or less considered by other authors over the years. Very recently, Lowry and Fanini included Orchestia cavimana in the new genus Cryptorchestia. In this paper, the populations from Lake Garda, Europe and the Balkan area are identified as a new species, named, in accordance with the new genus created by Lowry and Fanini, Cryptorchestia garbinii sp. nov. We ascribe to C. cavimana only the population from Cyprus.
The species commonly known as Orchestia cavimana belonging to the Talitridae family (Amphipoda) has been used as crustacean model species. Here, we point out that this talitrid amphipod species is ...related to species in the genus Orchestia but now falls under what is described as Cryptorchestia garbinii, which is a different species from the nominal species Cryptorchestia cavimana endemic to the Island of Cyprus. It is therefore important that future basic research and applied studies involving this model organism refer to it as C. garbinii. Its old assignment O. cavimana, or even C. cavimana, as still reported in the National Center for Biotechnology Information (NCBI) GenBank and in recent papers, may lead to confusion.
The response to high temperatures in adults of two cold stenothermal cave-dwelling leptodirins,
Neobathyscia mancinii and
Neobathyscia pasai (Coleoptera, Cholevidae) was evaluated by determinating ...levels of gene expression of two members of the family of heat shock proteins 70
kDa by qPCR. In both species,
hsc70 mRNA level was constant with increasing temperature, whereas a significant increase in the inducible member (
hsp70) mRNA was observed, higher in
N. pasai. This difference could be due to their in-cave distribution:
N. pasai colonizes the cave entrance where the temperature is more variable than the internal part where
N. mancinii is confined. These results demonstrated for the first time the occurrence of a heat shock response in troglobite insects and suggest the correlation between the intensity of this response and the adaptation to the cave environment.
During skeletal myogenesis, genomic reprogramming toward terminal differentiation is achieved by recruiting chromatin-modifying enzymes to muscle-specific loci. The relative contribution of ...extracellular signaling cascades in targeting these enzymes to individual genes is unknown. Here we show that the differentiation-activated p38 pathway targets the SWI-SNF chromatin-remodeling complex to myogenic loci. Upon differentiation, p38 kinases were recruited to the chromatin of muscle-regulatory elements. Blockade of p38α/β repressed the transcription of muscle genes by preventing recruitment of the SWI-SNF complex at these elements without affecting chromatin binding of muscle-regulatory factors and acetyltransferases. The SWI-SNF subunit BAF60 could be phosphorylated by p38α-β in vitro, and forced activation of p38α/β in myoblasts by expression of a constitutively active MKK6 (refs. 5,6,7) promoted unscheduled SWI-SNF recruitment to the myogenin promoter. Conversely, inactivation of SWI-SNF enzymatic subunits abrogated MKK6-dependent induction of muscle gene expression. These results identify an unexpected function of differentiation-activated p38 in converting external cues into chromatin modifications at discrete loci, by selectively targeting SWI-SNF to muscle-regulatory elements.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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