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Biology subjects

Ahmed, S. T.

Publications and source records attributed to Ahmed, S. T..

6 recordsLinked to original sources

Functional Differentiation of Type II and Type I Collagen Articular Models in Synovial Fluid Film Formation and Recombinant Lubricin Retention

Collagen type II (Col-II) and collagen type I (Col-I) are major components of articular cartilage present at different ratios at its surface. Understanding how each of these components mediates the assembly of molecular films derived from synovial fluid (SF), the native lubricant of synovial joints, is critical to explain the loss of mechanical performance in pathological conditions, guide the design of biomaterial implants meant to be in contact with SF, and develop molecular therapies to restore SF properties. This work demonstrates that Col-II articular surface model assists in scaffolding of full SF-derived films, while Col-I model lacks SF film scaffolding capabilities. However, when Col-II and Col-I are exposed to recombinant lubricin (rLub) alone, the major boundary lubricant in SF, both adsorbed and retained similar amounts. These insights, deduced from quartz crystal microbalance with dissipation, diffuse reflectance circular dichroism, and atomic force microscopy, reveal possible mechanisms underlying the loss of mechanical performance of synovial joints in pathology, where Col-I becomes the major collagenous component of the articular cartilage surface, as well as considerations for designing functional biomaterial implants. Furthermore, this work reinforces the idea of rLub as an intra-articular osteoarthritis therapy with the ability to bind to Col-II and Col-I, irrespectively. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/726594v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@138a77borg.highwire.dtl.DTLVardef@7b8512org.highwire.dtl.DTLVardef@15d7060org.highwire.dtl.DTLVardef@17ccf20_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Vibrio cholerae adhesin-derived peptide mediates strong pull-off forces in aqueous high ionic strength environments

In this letter, the pull-off forces of adsorbed films of four Bap1-inspired peptides in various solvents were investigated on negatively charged mica substrates using the surface forces apparatus (SFA), complemented with dynamic light scattering (DLS) for characterizing the aggregation behavior of peptides in solution. Bap1-inspired peptides consisted of the 57 amino acid wild-type sequence (WT); a scrambled version of the WT used to investigate the impact of the primary amino acid sequence in pull-off forces (Scr); a ten amino acid sequence rich in hydrophobic content (CP) of the WT sequence, and an eight amino acid sequence (Sh1) that corresponds to the pseudo-repeating sequence in the 57 AA. SFA results showed remarkable pull-off forces for CP, particularly in the presence of salts: measured pull-off forces were 26.0 {+/-} 7.0 mN/m for no dwell-time and up to 42.0 {+/-} 8.8 mN/m when surfaces were left in contact for 30 minutes. DLS observations indicate that salts favor large peptide aggregation for all constructs (Hz > 1 {micro}m), as compared to milliQ (Hz {approx} 100-500 nm) water and DMSO (Hz {approx} 100 nm), resulting in heterogeneous peptide film thicknesses. This letter concludes with a comparison to the pull-off forces of mussel foot protein-inspired peptides reported in the literature.

biophysics↗

Surface-immobilized fibronectin conformation drives synovial fluid adsorption and film formation

The articular cartilage extracellular matrix (ECM) is a complex network of biomolecules that includes fibronectin (FN). FN acts as an extracellular glue, controlling the assembly of other macromolecular constituents to the ECM. However, how FN participates in the binding and retention of synovial fluid components, the natural lubricant of articulated joints, to form a wear-protecting and lubricating film has not been established. This study reports on the role of FN and its molecular conformation in mediating macromolecular assembly of synovial fluid ad-layers. FN films as precursor films on functionalized surfaces, a model of FNs articular cartilage surface, adsorbed and retained different amounts of synovial fluid (SF) depending on FN conformation. FN conformational changes were induced by depositing FN from bulk solution at pH 7 (extended state) or at pH 4 (unfolded state) on self-assembled monolayers on gold-coated quartz crystals, followed by adsorption of diluted SF (25%) onto FN precursor films. Mass density, thin film compliance, surface morphologies, and the secondary and tertiary structures of adsorbed FN films reveal pH-induced differences. FN films deposited at pH 4 were thicker, more rigid, showed a more homogeneous morphology, and had altered -helix and {beta}-sheet content, compared to FN films deposited at pH 7. FN precursor films deposited at pH 7 adsorbed and retained more synovial fluid than those at pH 4, revealing the importance of FN conformation at the articular cartilage surface to bind and maintain a thin layer of synovial fluid constituents. This knowledge will enable a better understanding of the molecular interactions and synergies between the articular cartilage ECM components and SF. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/650860v2_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@871413org.highwire.dtl.DTLVardef@3712a5org.highwire.dtl.DTLVardef@1a92b78org.highwire.dtl.DTLVardef@164e79f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

pyQCM-BraTaDio: A tool for visualization, data mining, and modeling of Quartz crystal microbalance with dissipation data

Here, we present a Python based software that allows for the rapid visualization, data mining, and basic model applications of quartz crystal microbalance with dissipation data. Our implementation begins with a Tkinter GUI to prompt the user for all required information, such as file name/location, selection of baseline time, and overtones for visualization (with customization capabilities). These inputs are then fed to a workflow that will use the baseline time to scrub and temporally shift data using the Pandas and Numpy libraries and carry out the plot options for visualization. The last stage consists of an interactive plot, that presents the data and allows the user to select ranges in MatPlotLib-generated panels, followed by application of data models, including Sauerbrey, thin films in liquid, among others, that are carried out with NumPy and SciPy. The implementation of this software allows for simple and expedited data analysis, in lieu of time consuming and labor-intensive spreadsheet analysis. Metadata O_TBL View this table: org.highwire.dtl.DTLVardef@1da584dorg.highwire.dtl.DTLVardef@1db3baborg.highwire.dtl.DTLVardef@2a90ecorg.highwire.dtl.DTLVardef@90877aorg.highwire.dtl.DTLVardef@ae672f_HPS_FORMAT_FIGEXP M_TBL C_TBL

bioengineering↗

Genomic and phenotypic evolution of Escherichia coli in a novel citrate-only resource environment

Evolutionary innovations allow populations to colonize new, previously inaccessible ecological niches. We previously reported that aerobic growth on citrate (Cit+) evolved in a population of Escherichia coli during adaptation to a minimal glucose medium containing citrate (DM25). Cit+ can grow in citrate-only medium (DM0), which is a novel environment for E. coli. To study adaptation to this new niche, we evolved one set of Cit+ populations for 2,500 generations in DM0 and a control set in DM25. We identified numerous parallel mutations, many mediated by transposable elements. Several lineages evolved multi-copy amplifications containing the maeA gene, constituting up to [~]15% of the genome. We also found substantial cell death in ancestral and evolved clones. Our results demonstrate the importance of copy-number variation and transposable elements in the refinement of the Cit+ trait. However, the observed mortality suggests a persistent evolutionary mismatch between E. coli physiology and a citrate-only environment.

evolutionary biology↗

Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe the first highly-penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)--which these fish also develop. Zebrafish pre-B ALL shares in vivo features and expression profiles with human pre-B ALL, and these profiles differ from zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant lymphocyte development. As the only robust zebrafish pre-B ALL model and only example where T-ALL also develops, this model can reveal differences between MYC-driven pre-B vs. T-ALL and be exploited to discover novel pre-B ALL therapies.\n\nStatement of significanceWe describe the first robust zebrafish pre-B ALL model in MYC-transgenic animals known to develop T-ALL, revealing the only animal model with both human ALL types. We also describe aberrant multi-lineage lymphopoiesis. This powerful system can be used to study MYC-driven leukemogenesis and discover new pre-B ALL targeted therapies.

cancer biology↗