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Biomedical subjects

Arnab Majumdar

Publications and source records attributed to Arnab Majumdar.

14 recordsLinked to original sources

Soil erosion and landscape elevation as unnoticed determinants of environmental antibiotic resistance distribution.

Climate change is reshaping the global antibiotic resistance gene (ARG) landscape through geomorphological processes that remain largely overlooked in the One Health framework. This critical review synthesises evidence on how soil erosion and landscape elevation gradients redistribute, select for, and disseminate ARGs across terrestrial and aquatic ecosystems. Erosion physically removes and transports ARG-bearing microbes, depletes nutrients, and co-selects for resistance via heavy metal exposure and horizontal gene transfer, creating source-sink dynamics that connect eroding hillslopes to downstream water bodies and food systems. Elevation gradients impose abiotic stressors-declining temperature, elevated UV radiation, and shifting pH-that drive microbial community reassembly through environmental selection and dispersal limitation, with emerging evidence linking bacterial competition at high altitude to enhanced multidrug efflux and resistome complexity. The review identifies critical knowledge gaps, including unquantified ARG mass fluxes across erosion-deposition gradients, unresolved dispersal-versus-selection mechanisms along elevation transects, and the absence of integrated One Health surveillance linking environmental ARG reservoirs to clinical outcomes. A synthesis of global case studies illustrates how these processes converge across diverse landscapes. The review concludes with a mechanistic research agenda-including reciprocal transplant experiments, landscape connectivity modelling, and cross-sectoral surveillance-needed to translate these emerging drivers into actionable climate-AMR mitigation policy.

Drug Resistance, Microbial↗

Dynamics of prestressed semiflexible polymer chains as a model of cell rheology.

We report on a model of a prestressed nonlinear semiflexible polymer chain that links thermally driven dynamics to the creep behavior of living cells. Numerical simulations show that the chain's creep follows a power law with an exponent that decreases with increasing prestress. This is related to the propagation of free energy through the chain in response to stretching, where the propagation speed is regulated by the prestress via the chain's nonlinear elasticity. These results indicate that the main aspects of cell rheology are consistent with the dynamics of single polymer chains under tension.

Actins↗

Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces.

The nature of the development of emphysema in the tight skin (Tsk) and the pallid (Pa) mice are not well understood. We assessed the mechanical and nonlinear properties of the respiratory system, the alveolar structure, and the levels of microfibril-associated glycoproteins (MAGP) 1 and 2 in Tsk mice with developmental emphysema; in Pa mice, which are thought to develop adult onset emphysema; and their background, the C57BL/6 mice, at an age of 7 wk. Minor differences between collagen-related elastic properties of the lungs of the Pa and C57BL/6 mice were seen at this early age. The lungs of the Tsk mice were significantly softer yet more nonlinear than those of the Pa and C57BL/6 mice. The MAGP-1 levels were similar in all three groups. However, the level of MAGP-2, which is associated with both fibrillin-1 and collagen, was higher in the Tsk than in the Pa mice, which also had more MAGP-2 than the C57BL/6. Both the mean and the variance of alveolar diameters were larger in the Tsk than in the other two groups, while the variance in the Pa was larger than in the C57BL/6 mice, implying early development of heterogeneity. Using a network model of the parenchyma, we linked the pathophysiologic changes in the Tsk mice to mechanical forces and failure of the alveolar walls. Our findings suggest the possibility that MAGP-2-related abnormal collagen assembly, combined with mechanical forces, is involved in the progression of emphysema in the Tsk mice.

Animals↗

Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue: roles of mechanical force and the cytoskeleton.

The viscoelastic and dynamic nonlinear properties of guinea pig tracheal smooth muscle tissues were investigated by measuring the storage (G') and loss (G") moduli using pseudorandom small-amplitude length oscillations between 0.12 and 3.5 Hz superimposed on static strains of either 10 or 20% of initial length. The G" and G' spectra were interpreted using a linear viscoelastic model incorporating damping (G) and stiffness (H), respectively. Both G and H were elevated following an increase in strain from 10 to 20%. There was no change in harmonic distortion (K(d)), an index of dynamic nonlinearity, between 10 and 20% strains. Application of methacholine at 10% strain significantly increased G and H while it decreased K(d). Cytochalasin D, isoproterenol, and HA-1077, a Rho-kinase inhibitor, significantly decreased both G and H but increased K(d). Following cytochalasin D, G, H, and K(d) were all elevated when mean strain increased from 10 to 20%. There were no changes in hysteresivity, G/H, under any condition. We conclude that not all aspects of the viscoelastic properties of tracheal smooth muscle strips are similar to those previously observed in cultured cells. We attribute these differences to the contribution of the extracellular matrix. Additionally, using a network model, we show that the dynamic nonlinear behavior, which has not been observed in cell culture, is associated with the state of the contractile stress and may derive from active polymerization within the cytoskeleton.

Animals↗

Risk of severe asthma episodes predicted from fluctuation analysis of airway function.

Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

Adult↗

Relating airway diameter distributions to regular branching asymmetry in the lung.

We study the distribution Pi(n)(D) of airway diameters D as a function of generation N in asymmetric airway trees of mammalian lungs. We find that the airway bifurcations are self-similar in four species studied. Specifically, the ratios of diameters of the major and minor daughters to their parent are constants independent of N until a cutoff diameter is reached. We derive closed form expressions for Pi(N)(D) and examine the flow resistance of the tree based on an asymmetric flow division model. Our findings suggest that the observed diameter heterogeneity is consistent with an underlying regular branching asymmetry.

Animals↗

Quantitative characterization of airspace enlargement in emphysema.

The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities.

Algorithms↗

Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue.

Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers. We measured the quasi-static, uniaxial stress-strain curves of lung tissue sheets in hypotonic, normal, and hypertonic solutions. We found that the stress-strain curve was sensitive to osmolarity, but this sensitivity decreased after proteoglycan digestion. Images of immunofluorescently labeled collagen networks showed that the fibers follow the alveolar walls that form a hexagonal-like structure. Despite the large heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased linearly with osmolarity. We developed a two-dimensional hexagonal network model of the alveolar structure incorporating the mechanical properties of the collagen-elastin fibers and their interaction with proteoglycans. The model accounted for the stress-strain curves observed under all experimental conditions. The model also predicted how aspect ratio changed with osmolarity and strain, which allowed us to estimate the Young's modulus of a single alveolar wall and a collagen fiber. We therefore identify a novel and important role for the proteoglycans: they stabilize the collagen-elastin network of connective tissues and contribute to lung elasticity and alveolar stability at low to medium lung volumes.

Animals↗

A spatial and temporal analysis of safety-belt usage and safety-belt laws.

Safety-belt usage has increased significantly in the US since the introduction of mandatory safety-belt usage laws in the 1980s. This paper analyzes the impact of these laws on increasing safety-belt usage while controlling for other state-specific variables. A fixed effects cross-sectional time-series analyses shows the relative significance of various state-level attributes in explaining safety-belt usage, including whether or not primary or secondary safety-belt laws have been passed. To further explore these relationships we employ spatial analyses techniques and find spatial autocorrelation in the data. Spatial correlation also exhibits a clear east-west direction. When the analyses is further corrected for temporal autocorrelation we find that the spatial autocorrelation is greatly diminished and that many variables lose their statistical significance, though safety-belt laws are still statistically significant. Results suggest that for this data, it is critical to control for temporal autocorrelation while spatial autocorrelation is less important. We also find that our spatial analyses does provide interesting information on similarities between various regions on the effectiveness of safety-belt laws.

Adolescent↗

Perimeter growth of a branched structure: application to crackle sounds in the lung.

We study an invasion percolation process on Cayley trees and find that the dynamics of perimeter growth is strongly dependent on the nature of the invasion process, as well as on the underlying tree structure. We apply this process to model the inflation of the lung in the airway tree, where crackling sounds are generated when airways open. We define the perimeter as the interface between the closed and opened regions of the lung. In this context we find that the distribution of time intervals between consecutive openings is a power law with an exponent beta approximately 2. We generalize the binary structure of the lung to a Cayley tree with a coordination number Z between 2 and 4. For Z=4, beta remains close to 2, while for a chain, Z=2 and beta=1, exactly. We also find a mean field solution of the model.

Airway Resistance↗

Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment.

We investigated the relationship between the microscopic elastic and hysteretic behavior of the alveolar walls and the macroscopic mechanical properties of the whole lung in an in vivo elastase-treated rat model of emphysema. We measured the input impedance of isolated lungs at three levels of transpulmonary pressure (Ptp) and used a linear model to estimate the dynamic elastance and hysteresivity of the lungs. The elastance of the normal lungs increased steeply with Ptp, whereas this dependence diminished in the treated lungs. Hysteresivity decreased significantly with Ptp in the normal lungs, but this dependence disappeared in the treated lungs. To investigate the microscopic origins of these changes, the alveolar walls were immunofluorescently labeled in small tissue strips. By using a fluorescent microscope, the lengths and angular orientations of individual alveolar walls were followed during cyclic uniaxial stretching of the tissue strips. The microstrains (relative change in segment length) and changes in angle of the alveolar walls showed considerable heterogeneity, which was interpreted in terms of a network model. In the normal strips, the alveolar walls showed larger angular changes compared with the treated tissue, whereas the alveolar walls of the treated tissue tended to be more extensible. Hysteresis in the average angle change was also larger in the treated tissue than in the normal tissue. We conclude that the decreased Ptp dependence of elastance and the constant hysteresivity in the treated lungs are related to microstructural remodeling and network phenomena at the level of the alveolar walls.

Animals↗

Fluid transport in branched structures with temporary closures: a model for quasistatic lung inflation.

We analyze the problem of fluid transport through a model system relevant to the inflation of a mammalian lung, an asymmetric bifurcating structure containing random blockages that can be removed by the pressure of the fluid itself. We obtain a comprehensive description of the fluid flow in terms of the topology of the structure and the mechanisms which open the blockages. We show that when calculating averaged flow properties of the fluid, the tree structure can be partitioned into a linear superposition of one-dimensional chains. In particular, we relate the pressure-volume P-V relationship of the fluid to the distribution Pi(n) of the generation number n of the tree's terminal branches, a structural property. We invert this relation to obtain a statistical description of the underlying branching structure of the lung, by analyzing experimental pressure-volume data from dog lungs. The Pi(n) extracted from the experimental P-V data agrees well with available data on lung branching structure. Our general results are applicable to any physical system involving transport in bifurcating structures with removable closures.

Animals↗

Physiology: Dynamic instabilities in the inflating lung.

In lung diseases such as asthma, expiratory flow becomes limited, airways can collapse and the vital exchange of gases is compromised. Here we model the inflation of collapsed regions of the lung during inspiration in terms of avalanches propagating through a bifurcating network of airways, and find that the accompanying cascade of dynamic pressure instabilities -- avalanche 'shocks' -- manifests as negative elastic resistance of the lung. Our analysis of this apparent thermodynamic paradox provides a better understanding of aeration in the deep regions of the lung, which may find application in medical conditions in which gas exchange is impaired.

Animals↗