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Jafari, A.

Publications and source records attributed to Jafari, A..

4 recordsLinked to original sources

Legumain is a paracrine regulator of osteoblast differentiation and mediates the inhibitory effect of TGF-β1 on osteoblast maturation

1.Transforming growth factor-beta 1 (TGF-{beta}1) is a critical regulator of skeletal homeostasis and has diverse promoting effects on osteoblastogenesis. However, the mechanisms behind the intriguing inhibitory effect of TGF-{beta}1 on osteoblast maturation are not fully understood. Here, we demonstrate a novel mechanism by which TGF-{beta}1 modulates osteoblast maturation through lysosomal protease legumain. We observed that presence of TGF-{beta}1 in osteogenic cultures of human bone marrow derived mesenchymal stromal (stem) cells enhanced legumain activity and secretion, in-spite of decreased legumain mRNA expression, suggesting post-transcriptional regulation. We further showed that osteogenic cells internalize and activate prolegumain, associated with inhibited osteoblast maturation, revealing legumain as a paracrine regulator of osteoblast maturation. Interestingly, TGF-{beta}1 treatment exacerbated legumain internalization and activity, and showed an additive effect on legumain-induced inhibition of osteoblast maturation. Importantly, legumain inhibition abolished the inhibitory effect of TGF-{beta}1 on osteoblast maturation. Our findings reveal that TGF-{beta}1 inhibits osteoblast maturation through stimulating secretion and activity of endogenous legumain, as well as increasing the internalization and activation of extracellular legumain. Therefore, our study provides a deeper understanding of the complex regulation of osteoblastogenesis and unveils a novel TGF-{beta}1-legumain axis in regulation of osteoblast maturation and offer novel insights for possible therapeutic interventions related to bone diseases associated with aberrant TGF-{beta}1 signaling.

cell biology↗

Unique cortical and subcortical activation patterns for different conspecific calls in marmosets

The common marmoset (Callithrix jacchus) is known for its highly vocal nature, displaying a diverse range of different calls. Functional imaging in marmosets has shown that the processing of conspecific calls activates a brain network that includes fronto-temporal cortical and subcortical areas. It is currently unknown whether different call types activate the same or different networks. Here we show unique activation patterns for different calls. Nine adult marmosets were exposed to four common vocalizations (phee, chatter, trill, and twitter), and their brain responses were recorded using event-related fMRI at 9.4T. We found robust activations in the auditory cortices, encompassing core, belt, and parabelt regions, and in subcortical areas like the inferior colliculus, medial geniculate nucleus, and amygdala in response to these conspecific calls. Different neural activation patterns were observed among the vocalizations, suggesting vocalization-specific neural processing. Phee and twitter calls, often used over long distances, activated similar neural circuits, whereas trill and chatter, associated with closer social interactions, demonstrated a closer resemblance in their activation patterns. Our findings also indicate the involvement of the cerebellum and medial prefrontal cortex (mPFC) in distinguishing particular vocalizations from others. Significance StatementThis study investigates the neural processing of vocal communications in the common marmoset (Callithrix jacchus), a species with a diverse vocal repertoire. Utilizing event-related fMRI at 9.4T, we demonstrate that different marmoset calls (phee, chatter, trill, and twitter) elicit distinct activation patterns in the brain, challenging the notion of a uniform neural network for all vocalizations. Each call type distinctly engages various regions within the auditory cortices and subcortical areas, reflecting the complexity and context-specific nature of primate communication. These findings offer insights into the evolutionary mechanisms of primate vocal perception and provide a foundation for understanding the origins of human speech and language processing.

neuroscience↗

A vocalization-processing network in marmosets

Vocalizations play an important role in the daily life of primates and likely form the basis of human language. Functional imaging studies have demonstrated that listening to language or reading activates a left-lateralized fronto-temporal language network in human participants. Here we acquired whole-brain ultrahigh field (9.4 Tesla) fMRI in awake marmosets (Callithrix jacchus) and demonstrate that these highly vocal small New World primates possess a similar fronto-temporal network, including subcortical regions, that is activated by the presentation of conspecific vocalizations. The findings suggest that the human language network has evolved from an ancestral vocalization network that predates the separation of New and Old World primates.

neuroscience↗

Assessing the Involvement of Platelet Degranulation in the Therapeutic Properties of Exosome Derived from Amniotic Epithelial Cells through Enrichment and Interaction Network Analysis

Platelet degranulation allows the release of large secretable pools of biologically active proteins which are critical in wound healing initiation and angiogenesis. Exosomes, which can transport a diverse suite of macromolecules, derived from amniotic epithelial cells (AEC-Exo) improve wound healing and angiogenesis. However, the underlying mechanisms are still unclear. In this investigation, we performed a user-friendly bioinformatics analysis system to identify association among the angiogenic and wound healing effects of AEC-Exo treatments. To this end, FunRich software was used, and linked to the Universal Protein Resource (UniProt) as a background database. Several enrichment analyses, including biological process, cellular component, molecular function, and protein domains were conducted on AEC-Exo proteome. Furthermore, to identify the proteins involved in platelet degranulation and evaluate protein-protein association information, comparative analyses and interaction network analyses were illustrated using the NCBI BioSystems, ExoCarta, and STRING databases. Our results indicated the statistically significant association between the proteome in AEC-Exo, platelet degranulation, and their corresponding processes. Therefore, the involvement of platelet degranulation in AEC-Exo proteins may elucidate the angiogenic and wound-healing effects of AEC-Exo treatments.

cell biology↗