Biology subjects

Zaman, M. H.

Publications and source records attributed to Zaman, M. H..

13 recordsLinked to original sources

bioRxiv2025

High-Density Multi-Distance fNIRS Enhances Detection of Brain Activity during a Word-Color Stroop Task

STRUCTURED ABSTRACTO_ST_ABSSignificanceC_ST_ABSFunctional Near-Infrared Spectroscopy (fNIRS) enables neuroimaging in scenarios where other modalities are less suitable, such as during motion tasks or in low-resource environments. Sparse fNIRS arrays with 30mm channel spacing are widely used but have limited spatial resolution. High-density (HD) arrays with overlapping, multi-distance channels improve sensitivity and localization but increase costs and setup times. A statistical comparison of HD and sparse arrays is needed for evaluating the benefits and trade-offs of HD arrays. AimThis study provides a statistical comparison of HD and sparse fNIRS performance to inform array selection in future research. ApproachWe measured prefrontal cortex (PFC) activation during congruent and incongruent Word-Color Stroop (WCS) tasks using both Sparse and HD arrays for 17 healthy adult participants, comparing dorsolateral PFC channel and image results at the group level. ResultsWhile both arrays detected activation in channel space during incongruent WCS, channel and image space results demonstrated superior localization and sensitivity with the HD array for all WCS. ConclusionsSparse channel data may suitably detect activation from cognitively demanding tasks, like incongruent WCS. However, the HD array outperformed Sparse in detecting and localizing brain activity in image space, particularly during lower cognitive load tasks, making them more suitable for neuroimaging applications.

bioengineering↗

bioRxiv2024

Characterization of antibiotic resistance development of E. coli in synthetic and real wastewater

Antimicrobial resistance (AMR) is a major threat to global health and resistant bacterial populations have been observed to develop and spread in and around wastewater. However, in vitro studies on AMR development are typically conducted in ideal media conditions which can differ in composition and nutrient density from wastewater. In this study, we compare the growth and AMR development of E. coli in standard LB broth to a synthetic wastewater recipe and autoclaved wastewater samples from the Massachusetts Water Resources Authority (MWRA). We found that synthetic wastewater and real wastewater samples both supported less bacterial growth compared to LB. Additionally, bacteria grown in synthetic wastewater and real wastewater samples had differing susceptibility to antibiotic pressure from Doxycycline, Ciprofloxacin, and Streptomycin. However, AMR development over time during continuous passaging under subinhibitory antibiotic pressure was similar in fold change across all media types. Thus, we find that while LB can act as a proxy for wastewater for AMR studies in E. coli, synthetic wastewater is a more accurate predictor of both E.coli growth and antibiotic resistance development. Moreover, we also show that antibiotic resistance can develop in real wastewater samples and components within wastewater likely have synergistic and antagonistic interactions with antibiotics. ImportanceAntimicrobial resistance (AMR) ranks among the leading global threats to public health and development. In 2019, bacterial AMR was estimated to have directly caused 1.27 million deaths worldwide and contributed to 4.95 million deaths overall (Murray, C. J., et al., (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet, 399(10325), 629-655.). With estimations of AMR only getting worse, it is imperative that we understand the complex dimensionalities that drive the genesis of antimicrobial resistance to where it begins-the environment. The paper investigates bacterial growth and AMR in real wastewater samples and highlights the importance of using a media that closely mimics real wastewater in AMR studies, compared to standard lab media like LB broth. This is crucial for understanding how E. coli and other bacteria develop AMR in environments similar to actual wastewater, which can inform more effective strategies to combat AMR in natural and engineered settings.

microbiology↗

bioRxiv2024

Microplastics as a novel substrate for antimicrobial resistance: Effects of concentration, composition, and size on E. coli multidrug resistance

Microplastics (MPs) have emerged as a significant environmental pollutant with profound implications for public health, particularly as substrates to facilitate bacterial antimicrobial resistance (AMR). Recently, studies have shown that MPs may accommodate microbial communities, chemical contaminants and genetic material containing AMR genes. This study investigated the effects of MP concentration, composition, and size on the development of multidrug resistance in Escherichia coli. Specifically, we exposed E. coli to varying concentrations of different MP types, including polyethylene (PE), polystyrene (PS), and polypropylene (PP), across a range of sizes (3-10 {micro}m, 10-50 {micro}m, and 500 {micro}m). Results indicated a direct correlation between MP presence and elevated multidrug-resistant (MDR) in E. coli. Notably, MPs exhibited a higher propensity for facilitating resistance than control substrates such as glass, likely due to their hydrophobicity, greater adsorption capacities, and surface chemistries. Furthermore, we observed that co-culture with MPs resulted in biofilm formation. Notably, we found that the bacteria from passaged MPs formed stronger biofilms once the MPs were removed, associated with changes in motility. Thus, we find that MPs also select for cells that are better at forming biofilms, which can lead to recalcitrant infections in the environment and healthcare setting. Our study highlights the immediate need for comprehensive environmental management strategies to mitigate the risk posed by MPs. ImportanceAntimicrobial resistance is one of the worlds most pressing global health crises, with an estimated 10 million deaths per year forecasted by 2050. With the pipeline of antibiotics running dry, it is imperative that mitigation strategies understand the mechanisms that drive the genesis of antimicrobial resistance. One emerging dimension of antimicrobial resistance is the environment. This study highlights the relationship between a widespread environmental pollutant, (MPs), and the rise of drug-resistant bacteria. While it is known that MPs facilitate resistance through several modes (biofilm formation, plastic adsorption rates, etc.), this study fills the knowledge gap on how different types of MPs are contributing to antimicrobial resistance.

microbiology↗

bioRxiv2023

Metal Ions and their Effects on Antimicrobial Resistance Development in Wastewater

Antimicrobial resistance (AMR) is a global health challenge and there is increasing recognition of the role of the environment, particularly wastewater, in the development and spread of AMR. Although trace metals are common contaminants in wastewater, the quantitative effects of trace metals on AMR in wastewater settings remain understudied. We experimentally determined the interactions between common antibiotic residues and metal ions found in wastewater and investigated their effects on the development of antibiotic resistance in Escherichia coli over time. These data were then used to expand on a previously developed computational model of antibiotic resistance development in continuous flow settings to incorporate the effects of trace metals acting in combination with multiple antibiotic residues. We found that the common metal ions, copper and iron, interact with both ciprofloxacin and doxycycline at wastewater relevant concentrations. This can significantly affect resistance development due to antibiotic chelation of the metal ions causing a reduction in the antibiotics bioactivity. Furthermore, modeling the effect of these interactions in wastewater systems showed the potential for metal ions in wastewater to significantly increase the development of antibiotic resistant E. coli populations. These results demonstrate the need to quantitatively understand the effects of trace metal-antibiotic interactions on AMR development in wastewater.

bioengineering↗

bioRxiv2023

Impact of Zinc Pre-exposure on de novo Antibiotic Resistance Development

Antimicrobial resistance (AMR) is a global health crisis that is currently predicted to worsen. While the impact of improper antibiotics is an established driver, much less is known on the impacts of metal supplements. Here, we specifically probe the impact of zinc (Zn) on AMR. In conflict settings where diarrhea disease cases are high, Zn is both given as a supplement for treatment of these diseases prior to use of antibiotics such as ciprofloxacin and is associated with weapons of war. In this study, we find that the order with which E. coli is exposed to zinc impacts resistance development, with increasing pre-exposure time leading to accelerated ciprofloxacin resistance, while combined exposure of zinc with ciprofloxacin delays ciprofloxacin resistance. We did not find evidence that zinc pre-exposure leads to genetic changes or change in antibiotic tolerance, though it does increase both the lag phase and doubling time of E. coli, suggesting the mechanism may be due to changes in gene expression. While the zinc phenotype behavior is not permeant and would no longer be observed if ciprofloxacin exposure did not occur right after zinc pre-exposure, the elevated MIC phenotype resulting from the zinc pre-exposure was more stable than the zinc phenotype. These results are important as they highlight the need to reexamine the clinical role of zinc in treating diarrheal diseases and assess if changes in resistance development observed in vitro are also observed in vivo. ImportanceAntimicrobial resistance (AMR) is a global problem. According to a 2014 Review on Antimicrobial Resistance, it is projected to result in several million deaths by 2050 (Review on Antimicrobial Resistance, Tackling a Crisis for the Health and Wealth of Nations, 2014). While the improper usage of antibiotic treatments is an accepted driver of AMR, little work has focused on how non-antibiotic medication, such as supplements, might impact this when combined with antibiotics. One supplement of interest is the heavy metal zinc which is used in conjunction with ciprofloxacin to treat diarrheal diseases in children. We find that the order and duration of zinc exposure has significant impact on resistance development. More specifically, although the combined presence of zinc and ciprofloxacin delays the onset of resistance, when used successively as they often are in practice, zinc pre-exposure followed by ciprofloxacin exposure results in faster resistance development.

microbiology↗

bioRxiv2023

Effects of Antibiotic Interaction on Antimicrobial Resistance Development in Wastewater

While wastewater is understood to be a critically important reservoir of antimicrobial resistance due to the presence of multiple antibiotic residues from industrial and agricultural runoff, there is little known about the effects of antibiotic interactions in the wastewater on the development of resistance. We worked to fill this gap in quantitative understanding of antibiotic interaction in constant flow environments by experimentally monitoring E. coli populations under subinhibitory concentrations of combinations of antibiotics with synergistic, antagonistic, and additive interactions. We then used these results to expand our previously developed computational model to account for the complex effects of antibiotic interaction. We found that while E. coli populations grown in additively interacting antibiotic combinations grew predictably according to the previously developed model, those populations grown under synergistic and antagonistic antibiotic conditions exhibited significant differences from predicted behavior. E. coli populations grown in the condition with synergistically interacting antibiotics developed less resistance than predicted, indicating that synergistic antibiotics may have a suppressive effect on antimicrobial resistance development. Furthermore E. coli populations grown in the condition with antagonistically interacting antibiotics showed an antibiotic ratio-dependent development of resistance, suggesting that not only antibiotic interaction, but relative concentration is important in predicting resistance development. These results provide critical insight for quantitatively understanding the effects of antibiotic interactions in wastewater and provide a basis for future studies in modelling resistance in these environments. ImportanceAntimicrobial resistance (AMR) is a growing global threat to public health expected to impact 10 million people by 2050, driving mortality rates globally and with a disproportionate effect on low- and middle-income countries. Communities in proximity to wastewater settings and environmentally contaminated surroundings are at particular risk due to resistance stemming from antibiotic residues from industrial and agricultural runoff. Currently, there is a limited quantitative and mechanistic understanding of the evolution of AMR in response to multiple interacting antibiotic residues in constant flow environments. Using an integrated computational and experimental methods, we find that interactions between antibiotic residues significantly affect the development of resistant bacterial populations.

bioengineering↗

bioRxiv2022

Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma of South African origin in 2D and 3D environments

During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia and pancreatic and prostate cancer. Such cellular changes may act as physical biomarkers for chemoresistance and cancer recurrence. This study aimed to determine how exposure to paclitaxel affects the intracellular stiffness of human oesophageal cancer of South African origin in vitro. A human oesophageal squamous cell carcinoma cell line WHCO1 was cultured on glass substrates (2D) and in collagen gels (3D) and exposed to paclitaxel for up to 48 hours. Cellular morphology and stiffness were assessed with confocal microscopy, visually aided morpho-phenotyping image recognition, and mitochondrial particle tracking microrheology at 24 and 48 hours. In the 2D environment, the intracellular stiffness was higher for the paclitaxel-treated than for untreated cells at 24 and 48 hours. In the 3D environment, the paclitaxel-treated cells were stiffer than the untreated cells at 24 hours, but no statistically significant differences in stiffness were observed at 48 hours. In 2D, paclitaxel-treated cells were significantly larger at 24 and 48 hours and more circular at 24 but not at 48 hours than the untreated controls. In 3D, there were no significant morphological differences between treated and untreated cells. The distribution of cell shapes was not statistically significant different across the different treatment conditions in 2D and 3D environments. Future studies with patient-derived primary cancer cells and prolonged drug exposure will help identify physical cellular biomarkers to detect chemoresistance onset and assess therapy effectiveness in oesophageal cancer patients. InsightMechanical changes in cancer cells by chemotherapeutic drugs exposure offer possible physical biomarkers for chemoresistance and cancer recurrence. This study on human oesophageal squamous cell carcinoma indicated that in vitro paclitaxel treatment induced stiffening and enlarging of malignant cells in two-dimensional environments at 24 and 48 hours. In physiologically more relevant three-dimensional collagen matrices the paclitaxel treatment led to cellular stiffening at 24 hours but softening thereafter, without significant changes in cellular size at any time. The outcomes need to be confirmed in future studies with prolonged drug exposure and patient-derived primary cancer cells.

cancer biology↗

bioRxiv2021

Decreased cell stiffness facilitates cell detachment and cell migration from breast cancer spheroids in 3D collagen matrices of different rigidity

BackgroundTumour-cell detachment is a critical early event in the metastatic cascade. However, the role of the cells mechanical properties in detachment and migration is not well understood. This exploratory study aimed to assess how intracellular stiffness changes these processes. MethodsMDA-MB-231 cells were embedded as 10,000-cell spheroids in 2 and 4 mg/ml collagen matrices. Intracellular stiffness was assessed with mitochondria tracking microrheology of cells that migrated distances equivalent to four and six times the cell diameter (dC) from the spheroid and compared to cells at the spheroid surface (0dC), representing medium, high and no migration, respectively. Results and discussionThe mitochondrial mean square displacement and intracellular stiffness decreased during detachment and migration for both collagen concentrations (i.e. rigidities). The mean square displacement of 4dC and 6dC cells was similar, whereas cell stiffness was lower for 4dC than for 6dC cells. With increasing matrix rigidity, the intracellular stiffness decreased for 0dC cells and did not change for 4dC and 6dC cells. It is proposed that decreased cell stiffness drives detachment and migration and increased matrix rigidity physically hinders migration, and cells need to become softer or remodel the environment to migrate. The independence of the stiffness of migrated cells from matrix rigidity suggests that cells remodel their environment through matrix proteins cleavage to migrate. ConclusionsThe study revealed the collective effects of enhanced migratory conditions and increased matrix rigidity on the mechanical properties of the cells. The expression of matrix metalloproteinases and transforming growth factor {beta} and the role of cell volume on detachment and migration in matrices with varying pore sizes are proposed targets for further studies on metastatic cancer cells.

cancer biology↗

bioRxiv2020

Computational Model to Quantify the Growth of Antibiotic Resistant Bacteria in Wastewater

Although wastewater and sewage systems are known to be significant reservoirs of antibiotic resistant bacterial populations and periodic outbreaks of drug resistant infection, there is little quantitative understanding of the drivers behind resistant population growth in these settings. In order to fill this gap in quantitative understanding of the development of antibiotic resistant infections in wastewater, we have developed a mathematical model synthesizing many known drivers of antibiotic resistance in these settings to help predict the growth of resistant populations in different environmental scenarios. A number of these drivers of drug resistant infection outbreak including antibiotic residue concentration, antibiotic interaction, chromosomal mutation and horizontal gene transfer, have not previously been integrated into a single computational model. We validated the outputs of the model with quantitative studies conducted on the eVOLVER continuous culture platform. Our integrated model shows that low levels of antibiotic residues present in wastewater can lead to increased development of resistant populations, and the dominant mechanism of resistance acquisition in these populations is horizontal gene transfer rather than acquisition of chromosomal mutations. Additionally, we found that synergistic antibiotic interactions lead to increased resistant population growth. These findings, consistent with recent experimental and field studies, provide new quantitative knowledge on the evolution of antibiotic resistant bacterial reservoirs, and the model developed herein can be adapted for use as a prediction tool in public health policy making, particularly in low income settings where water sanitation issues remain widespread and disease outbreaks continue to undermine public health efforts. ImportanceThe rate at which antimicrobial resistance (AMR) has developed and spread throughout the world has increased in recent years, and according to the Review on Antimicrobial Resistance in 2014 it is suggested that the current rate will lead several million people AMR-related deaths by 205025. One major reservoir of resistant bacterial populations that has been linked to outbreaks of drug resistant bacterial infections, but is not well understood, is in wastewater settings, where antibiotic pollution is often present. Using ordinary differential equations incorporating several known drivers of resistance in wastewater, we find that interactions between antibiotic residues and horizontal gene transfer significantly affect the growth of resistant bacterial reservoirs.

bioengineering↗

bioRxiv2020

Epithelial layer unjamming shifts energy metabolism toward glycolysis

In development of an embryo, healing of a wound, or progression of a carcinoma, a requisite event is collective epithelial cellular migration. For example, cells at the advancing front of a wound edge tend to migrate collectively, elongate substantially, and exert tractions more forcefully compared with cells many ranks behind. With regards to energy metabolism, striking spatial gradients have recently been reported in the wounded epithelium, as well as in the tumor, but within the wounded cell layer little is known about the link between mechanical events and underlying energy metabolism. Using the advancing confluent monolayer of MDCKII cells as a model system, here we report at single cell resolution the evolving spatiotemporal fields of cell migration speeds, cell shapes, and traction forces measured simultaneously with fields of multiple indices of cellular energy metabolism. Compared with the epithelial layer that is unwounded, which is non-migratory, solid-like and jammed, the leading edge of the advancing cell layer is shown to become progressively more migratory, fluid-like, and unjammed. In doing so the cytoplasmic redox ratio becomes progressively smaller, the NADH lifetime becomes progressively shorter, and the mitochondrial membrane potential and glucose uptake become progressively larger. These observations indicate that a metabolic shift toward glycolysis accompanies collective cellular migration but show, further, that this shift occurs throughout the cell layer, even in regions where associated changes in cell shapes, traction forces, and migration velocities have yet to penetrate. In characterizing the wound healing process these morphological, mechanical, and metabolic observations, taken on a cell-by-cell basis, comprise the most comprehensive set of biophysical data yet reported. Together, these data suggest the novel hypothesis that the unjammed phase evolved to accommodate fluid-like migratory dynamics during episodes of tissue wound healing, development, and plasticity, but is more energetically expensive compared with the jammed phase, which evolved to maintain a solid-like non-migratory state that is more energetically economical. Two sentence summaryAt the leading front of an advancing confluent epithelial layer, each cell tends to migrate, elongate, and pull on its substrate far more than do cells many ranks behind, but little is known about underlying metabolic events. Using the advancing monolayer of MDCKII cells as a model of wound healing, here we show at single cell resolution that physical changes associated with epithelial layer unjamming are accompanied by an overall shift toward glycolytic metabolism.

biophysics↗

bioRxiv2020

Tumor invasion as non-equilibrium phase separation

Tumor invasion depends upon properties of both cells and of the extracellular matrix (ECM). Despite ample evidence that cancer cells can modulate their material state during invasion, underlying biophysical mechanisms remain unclear. Here, we show the potential for coexistence of - and transition between - solid-like, fluid-like, and gas-like phases in invading breast cancer spheroids. Epithelial spheroids are nearly jammed and solid-like in the core but unjam at the periphery to invade as a fluid-like collective. Conversely, post-metastatic spheroids are unjammed and fluid-like in the core and - depending on ECM density - can further unjam and invade as gas-like single cells, or re-jam to invade as a fluid-like collective. A novel jamming phase diagram predicts material phases that are superficially similar to inanimate systems at thermodynamic equilibrium, but here arising in living systems, which exist far from equilibrium. We suggest that non-equilibrium phase separation may provide a unifying physical picture of tumor invasion. TWO-SENTENCE SUMMARYUsing tumor spheroids invading into an engineered three-dimensional matrix, we show here that the cellular collective exhibits coexistent solid-like, fluid-like, and gas-like phases. The spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front, as captured by a jamming phase diagram.

biophysics↗

bioRxiv2020

Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment

Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions, however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present an in silico model that couples chemokine-mediated signaling with mechanosensing networks to explain our in vitro observations. The model proposes IL-8, CCL2 and {beta}-integrin as key pathways that commonly regulate various Rho GTPases. In agreement, in vitro macrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2, or to the co-addition of a sub-optimal concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integrated in silico and 3D in vitro approach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies.

systems biology↗

bioRxiv2020

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

The formation of membrane protrusions during migration is reliant upon the cells cytoskeletal structure and stiffness. It has been reported that actin disruption blocks protrusions and decreases cell stiffness whereas microtubule disruption blocks protrusion but increases stiffness in several cell types. In melanoma, cell migration is of concern as this cancer spreads unusually rapidly during early tumour development. The aim of this study was to characterise motility, structural properties and stiffness of human melanoma cells at radial growth phase (RGP), vertical growth phase (VGP), and metastatic stage (MET) in two-dimensional in vitro environments. Wound assays, western blotting and mitochondrial particle tracking were used to assess cell migration, cytoskeletal content and intracellular fluidity. Our results indicate that cell motility increase with increasing disease stage. Despite their different motility, RGP and VGP cells exhibit similar fluidity, actin and tubulin levels. MET cells, however, display increased fluidity which was associated with increased actin and tubulin content. Our findings demonstrate an interplay between actin and microtubule activity and their role in increasing motility of cells while minimizing cell stiffness at advanced disease stage. In earlier disease stages, cell stiffness may however not serve as an indicator of migratory capabilities.

cancer biology↗