Biology subjects

Muhammad, S. A.

Publications and source records attributed to Muhammad, S. A..

3 recordsLinked to original sources

bioRxiv2024

Freeze-dried porous collagen scaffolds for the repair of volumetric muscle loss injuries

Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a 3D aligned collagen-glycosaminoglycan (CG) scaffold platform that supported in vitro myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either non-conductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks post-injury by in vivo electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than non-treated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that was not observed in non-repaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in non-treated tissues. Finally, only tissues treated with non-conductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.

bioengineering↗

bioRxiv2020

Human immune system variation during one year

The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation. HIGHLIGHTSLongitudinal variation in immune cell composition during one year Inter-individual variation can be described along a principal curve Immune cell and protein relationships are inferred Variability over time is an individual feature correlating with markers of poor metabolic health

immunology↗

bioRxiv2018

Species tree-aware simultaneous reconstruction of gene and domain evolution

Most genes are composed of multiple domains, with a common evolutionary history, that typically perform a specific function in the resulting protein. As witnessed by many studies of key gene families, it is important to understand how domains have been duplicated, lost, transferred between genes, and rearranged. Analogously to the case of evolutionary events affecting entire genes, these domain events have large consequences for phylogenetic reconstruction and, in addition, they create considerable obstacles for gene sequence alignment algorithms, a prerequisite for phylogenetic reconstruction.\n\nWe introduce the DomainDLRS model, a hierarchical, generative probabilistic model containing three levels corresponding to species, genes, and domains, respectively. From a dated species tree, a gene tree is generated according to the DL model, which is a birth-death model generalized to occur in a dated tree. Then, from the dated gene tree, a pre-specified number of dated domain trees are generated using the DL model and the molecular clock is relaxed, effectively converting edge times to edge lengths. Finally, for each domain tree and its lengths, domain sequences are generated for the leaves based on a selected model of sequence evolution.\n\nFor this model, we present a MCMC-based inference framework called DomainDLRS that takes a dated species tree together with a multiple sequence alignment for each domain family as input and outputs an estimated posterior distribution over reconciled gene and domain trees. By requiring aligned domains rather than genes, our framework evades the problem of aligning full-length genes that have been exposed to domain duplications, in particular non-tandem domain duplications. We show that DomainDLRS performs better than MrBayes on synthetic data and that it outperforms MrBayes on biological data. We analyse several zincfinger genes and show that most domain duplications have been tandem duplications, some involving two or more domains, but non-tandem duplications have also been common.

bioinformatics↗