physiological relevance
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2022 ◽  
Vol 23 (2) ◽  
pp. 690
Author(s):  
Roberta Zerlotin ◽  
Angela Oranger ◽  
Patrizia Pignataro ◽  
Manuela Dicarlo ◽  
Filippo Maselli ◽  
...  

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.


Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 51
Author(s):  
Bernd Coester ◽  
Thomas A. Lutz ◽  
Christelle Le Foll

Amylin and leptin synergistically interact in the arcuate nucleus of the hypothalamus (ARC) to control energy homeostasis. Our previous rodent studies suggested that amylin-induced interleukin-6 release from hypothalamic microglia may modulate leptin signaling in agouti-related peptide expressing neurons. To confirm the physiological relevance of this finding, the calcitonin receptor (CTR) subunit of the amylin receptor was selectively depleted in microglia by crossing tamoxifen (Tx) inducible Cx3cr1-CreERT2 mice with CTR-floxed mice. Unexpectedly, male mice with CTR-depleted microglia (KO) gained the least amount of weight of all groups regardless of diet. However, after correcting for the tamoxifen effect, there was no significant difference for body weight, fat mass or lean mass between genotypes. No alteration in glucose tolerance or insulin release was detected. However, male KO mice had a reduced respiratory quotient suggesting a preference for fat as a fuel when fed a high fat diet. Importantly, amylin-induced pSTAT3 was decreased in the ARC of KO mice but this was not reflected in a reduced anorectic response. On the other hand, KO mice seemed to be less responsive to leptin’s anorectic effect while displaying similar ARC pSTAT3 as Tx-control mice. Together, these data suggest that microglial amylin signaling is not a major player in the control of energy homeostasis in mice.


2022 ◽  
Vol 8 ◽  
Author(s):  
Sucharita Dey ◽  
Jaime Prilusky ◽  
Emmanuel D. Levy

The identification of physiologically relevant quaternary structures (QSs) in crystal lattices is challenging. To predict the physiological relevance of a particular QS, QSalign searches for homologous structures in which subunits interact in the same geometry. This approach proved accurate but was limited to structures already present in the Protein Data Bank (PDB). Here, we introduce a webserver (www.QSalign.org) allowing users to submit homo-oligomeric structures of their choice to the QSalign pipeline. Given a user-uploaded structure, the sequence is extracted and used to search homologs based on sequence similarity and PFAM domain architecture. If structural conservation is detected between a homolog and the user-uploaded QS, physiological relevance is inferred. The web server also generates alternative QSs with PISA and processes them the same way as the query submitted to widen the predictions. The result page also shows representative QSs in the protein family of the query, which is informative if no QS conservation was detected or if the protein appears monomeric. These representative QSs can also serve as a starting point for homology modeling.


Author(s):  
Barbara Schreier ◽  
Virginie Dubourg ◽  
Stefanie Hübschmann ◽  
Sindy Rabe ◽  
Sigrid Mildenberger ◽  
...  

AbstractThe tyrosine kinase receptor EGFR and the G-protein-coupled receptor AT1R induce essential cellular responses, in part via receptor crosstalk with an unknown role in nuclear information transfer and transcription regulation. We investigated whether this crosstalk results in linear, EGFR-mediated nuclear signalling or in parallel, synergistic information transfer leading to qualitative and temporal variations, relevant for gene expression and environment interaction. AT1R and EGFR synergistically activate SRF via the ERK1/2-TCF and actin-MRTF pathways. Synergism, comprised of switch-like and graded single cell response, converges on the transcription factors AP1 and EGR, resulting in synergistic transcriptome alterations, in qualitative (over-additive number of genes), quantitative (over-additive expression changes of individual genes) and temporal (more late onset and prolonged expressed genes) terms. Gene ontology and IPA® pathway analysis indicate prolonged cell stress (e.g. hypoxia-like) and dysregulated vascular biology. Synergism occurs during separate but simultaneous activation of both receptors and during AT1R-induced EGFR transactivation. EGFR and AT1R synergistically regulate gene expression in qualitative, quantitative and temporal terms with (patho)physiological relevance, extending the importance of EGFR-AT1R crosstalk beyond cytoplasmic signalling.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3562
Author(s):  
Serena Mucciolo ◽  
Andrea Desiderato ◽  
Marika Salonna ◽  
Tomasz Mamos ◽  
Viviane Prodocimo ◽  
...  

Aquaporins (AQPs) are a family of membrane channels facilitating diffusion of water and small solutes into and out of cells. Despite their biological relevance in osmoregulation and ubiquitous distribution throughout metazoans, the presence of AQPs in annelids has been poorly investigated. Here, we searched and annotated Aqp sequences in public genomes and transcriptomes of annelids, inferred their evolutionary relationships through phylogenetic analyses and discussed their putative physiological relevance. We identified a total of 401 Aqp sequences in 27 annelid species, including 367 sequences previously unrecognized as Aqps. Similar to vertebrates, phylogenetic tree reconstructions clustered these annelid Aqps in four clades: AQP1-like, AQP3-like, AQP8-like and AQP11-like. We found no clear indication of the existence of paralogs exclusive to annelids; however, several gene duplications seem to have occurred in the ancestors of some Sedentaria annelid families, mainly in the AQP1-like clade. Three of the six Aqps annotated in Alitta succinea, an estuarine annelid showing high salinity tolerance, were validated by RT-PCR sequencing, and their similarity to human AQPs was investigated at the level of “key” conserved residues and predicted three-dimensional structure. Our results suggest a diversification of the structures and functions of AQPs in Annelida comparable to that observed in other taxa.


2021 ◽  
Author(s):  
Anita Santana Sanchez ◽  
Lauri Nikkanen ◽  
Gabor Toth ◽  
Maria Ermakova ◽  
Sergey Kosourov ◽  
...  

The model heterocyst-forming filamentous cyanobacterium, Anabaena sp. PCC 7120 (Anabaena) represents multicellular organisms capable of simultaneously performing oxygenic photosynthesis in vegetative cells and the O2-sensitive N2-fixation inside the heterocysts. The flavodiiron proteins (FDPs) have been shown to participate in photoprotection of photosynthesis by driving excess electrons to O2 (Mehler-like reaction). Here, we addressed the physiological relevance of the vegetative cell-specific Flv1A and Flv3A on the bioenergetic processes occurring in the diazotrophic Anabaena under variable CO2. We demonstrate that both Flv1A and Flv3A are required for proper induction of the Mehler-like reaction upon a sudden change in light intensity, which is likely important for the activation of carbon-concentrating mechanisms (CCM) and CO2 fixation. Nevertheless, Flv3A showed a more important role in photoprotection than Flv1A. Under low CO2 diazotrophic conditions, Flv3A is capable of mediating moderate O2 photoreduction, independently of Flv1A, but in coordination with Flv2 and Flv4. Strikingly, the lack of Flv3A resulted in strong downregulation of the heterocyst-specific uptake hydrogenase, which led to enhanced H2 photoproduction under both oxic and micro-oxic conditions. These results reveal a novel regulatory network between the Mehler-like reaction and the H2 metabolism, which is of great interest for future photobiological production of H2 in Anabaena.


2021 ◽  
Vol 10 (24) ◽  
pp. 5855
Author(s):  
Athanasios I. Lourbopoulos ◽  
Iordanis S. Mourouzis ◽  
Athanasios G. Trikas ◽  
Ioulia K. Tseti ◽  
Constantinos I. Pantos

Tissue hypoxia occurs in various conditions such as myocardial or brain ischemia and infarction, sepsis, and trauma, and induces cellular damage and tissue remodeling with recapitulation of fetal-like reprogramming, which eventually results in organ failure. Analogies seem to exist between the damaged hypoxic and developing organs, indicating that a regulatory network which drives embryonic organ development may control aspects of heart (or tissue) repair. In this context, thyroid hormone (TH), which is a critical regulator of organ maturation, physiologic angiogenesis, and mitochondrial biogenesis during fetal development, may be of important physiological relevance upon stress (hypoxia)-induced fetal reprogramming. TH signaling has been implicated in hypoxic tissue remodeling after myocardial infarction and T3 prevents remodeling of the postinfarcted heart. Similarly, preliminary experimental evidence suggests that T3 can prevent early tissue hypoxia during sepsis with important physiological consequences. Thus, based on common pathways between different paradigms, we propose a possible role of TH in tissue hypoxia after sepsis with the potential to reduce secondary organ failure.


2021 ◽  
Vol 22 (24) ◽  
pp. 13392
Author(s):  
Camila Campos-Escamilla ◽  
Dritan Siliqi ◽  
Luis A. Gonzalez-Ramirez ◽  
Carmen Lopez-Sanchez ◽  
Jose Antonio Gavira ◽  
...  

Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.


Author(s):  
Bharat Kwatra ◽  
Anusha Chaudhary ◽  
Lubdha Patil ◽  
Priti Yadav ◽  
Rituparna Saha

This meta-review is an examination of the therapeutic properties of colostrum. The scientific development and subsequent implementation of new therapeutics continues to influence researchers all over the globe today. Therefore, this review examines previously published research on colostrum and its effects on physiological functioning to determine its role as a potential therapeutic. Additionally, this review explores options for the potential therapeutic use of colostrum in immunology, IBS, diabetes and thyroid. There is abundant research supporting the immunomodulatory properties of colostrum, while also implicating its roles in alleviating IBS which is presented in this review. There is also evidence for the presence of IGF-1, T4, T3 and iodine in colostrum. Therefore, this review will also examine the current research examining the detection and respective physiological relevance for diabetes and thyroid functioning.


Author(s):  
Aleix Bayona-Feliu ◽  
Andrés Aguilera

DNA replication ensures the correct copying of the genome and the faithful transfer of the genetic information to the offspring. However, obstacles to replication fork (RF) progression cause RF stalling and compromise efficient genome duplication. Since replication uses the same DNA template as transcription, both transcription and replication must be coordinated to prevent Transcription-Replication Conflicts (TRCs) that could stall RF progression. Several factors contribute to limit the occurrence of such conflicts and their harmful impact on genome integrity. Increasing evidence indicates that chromatin homeostasis plays a key role in the cellular response to TRCs as well as in the preservation of genome integrity. Indeed, chromatin regulating enzymes are frequently mutated in cancer cells, a common characteristic of which is genome instability. Therefore, understanding the role of chromatin in TRC occurrence and resolution may help identify the molecular mechanism by which chromatin protects genome integrity, and the causes and physiological relevance of the high mutation rates of chromatin regulating factors in cancer. Here we review the current knowledge in the field, as well as the perspectives and future applications.


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