Publications by authors named "Siddhartha Das"

162 Publications

Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity.

Turk Patoloji Derg 2021 ;37(3):212-218

Department of Pathology, Indira Gandhi Medical College and Research Institute, PUDUCHERRY, INDIA.

Objective: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast.

Material And Method: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers.

Results: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning.

Conclusion: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.
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http://dx.doi.org/10.5146/tjpath.2021.01532DOI Listing
January 2021

Wood Ionic Cable.

Small 2021 Sep 8:e2008200. Epub 2021 Sep 8.

Department of Materials Science and Engineering, University of Maryland College Park, College Park, MD, 20742, USA.

The combination of good stability, biocompatibility, and high mechanical strength is attractive for bio-related material applications, but it remains challenging to simultaneously achieve these properties in a single, ionically conductive material. Here a "wood" ionic cable, made of aligned wood nanofibrils, demonstrating a combination of biocompatibility, high mechanical strength, high ionic conductivity, and excellent stability is reported. The wood ionic cable possesses excellent flexibility and exhibits high tensile strength up to 260 MPa (in the dry state) and ≈80 MPa (in the wet state). The nanochannels within the highly aligned cellulose nanofibrils and the presence of negative charges on the surfaces of these nanochannels, originating from the cellulose hydroxyl groups, provide new opportunities for ion regulation at low salt concentrations. Ion regulation in turn enables the wood ionic cable to have unique nanofluidic ionic behaviors. The Na ion conductivity of the wood ionic cable can reach up to ≈1.5 × 10 S cm at low Na ion concentration (1.0 × 10 mol L ), which is an order of magnitude higher than that of bulk NaCl solution at the same concentration. The scalable, biocompatible wood ionic cable enables novel ionic device designs for potential ion-regulation applications.
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http://dx.doi.org/10.1002/smll.202008200DOI Listing
September 2021

"Viscotaxis"- directed migration of mesenchymal stem cells in response to loss modulus gradient.

Acta Biomater 2021 Aug 29. Epub 2021 Aug 29.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India. Electronic address:

Directed cell migration plays a crucial role in physiological and pathological conditions. One important mechanical cue, known to influence cell migration, is the gradient of substrate elastic modulus (E). However, the cellular microenvironment is viscoelastic and hence the elastic property alone is not sufficient to define its material characteristics. To bridge this gap, in this study, we investigated the influence of the gradient of viscous property of the substrate, as defined by loss modulus (G) on cell migration. We cultured human mesenchymal stem cells (hMSCs) on a collagen-coated polyacrylamide gel with constant storage modulus (G) but with a gradient in the loss modulus (G). We found hMSCs to migrate from high to low loss modulus. We have termed this form of directional cellular migration as "Viscotaxis". We hypothesize that the high loss modulus regime deforms more due to creep in the long timescale when subjected to cellular traction. Such differential deformation drives the observed Viscotaxis. To verify our hypothesis, we disrupted the actomyosin contractility with myosin inhibitor blebbistatin and ROCK inhibitor Y27632, and found the directional migration to disappear. Further, such time-dependent creep of the high loss material should lead to lower traction, shorter lifetime of the focal adhesions, and dynamic cell morphology, which was indeed found to be the case. Together, findings in this paper highlight the importance of considering the viscous modulus while preparing stiffness-based substrates for the field of tissue engineering. STATEMENT OF SIGNIFICANCE: While the effect of substrate elastic modulus has been investigated extensively in the context of cell biology, the role of substrate viscoelasticity is poorly understood. This omission is surprising as our body is not elastic, but viscoelastic. Hence, the role of viscoelasticity needs to be investigated at depth in various cellular contexts. One such important context is cell migration. Cell migration is important in morphogenesis, immune response, wound healing, and cancer, to name a few. While it is known that cells migrate when presented with a substrate with a rigidity gradient, cellular behavior in response to viscoelastic gradient has never been investigated. The findings of this paper not only reveal a completely novel cellular taxis or directed migration, it also improves our understanding of cell mechanics significantly.
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http://dx.doi.org/10.1016/j.actbio.2021.08.039DOI Listing
August 2021

Traumatic herniation of intestine through ruptured skin at the ankle.

Forensic Sci Med Pathol 2021 Jul 9. Epub 2021 Jul 9.

Department of Forensic Medicine and Toxicology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Dhanvantari Nagar, Puducherry 605006, India.

Vehicular runover of pedestrians is a commonly reported occurrence in literature. The usual presentations at autopsy are avulsion of the intra-abdominal viscera, solid organ crushing, hemorrhage, fracture of pelvic bone and vertebra, and herniation of the abdominal contents. There are reports of many cases where the abdominal and thoracic viscera have herniated out of their respective compartment following rupture of the diaphragm. Herniation of the intestine through natural orifices or other anatomical openings of the body has also been reported. This herniation occurs following a reduction in the anteroposterior diameter and acute increase in intra-abdominal pressure, displacing the abdominal contents out of their normal position through some natural anatomical openings inside the body following the path of least resistance. We report an interesting case of vehicular runover where the intestinal coils have come out of the body at the ankle. The authors describe the plausible mechanism and the route through which the intestine could have traversed.
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http://dx.doi.org/10.1007/s12024-021-00399-5DOI Listing
July 2021

Overscreening, Co-Ion-Dominated Electroosmosis, and Electric Field Strength Mediated Flow Reversal in Polyelectrolyte Brush Functionalized Nanochannels.

ACS Nano 2021 Apr 2;15(4):6507-6516. Epub 2021 Apr 2.

Department of Mechanical Engineering, University of Maryland, College Park, Maryland 20742, United States.

Controlling the direction and strength of nanofluidic electrohydrodyanmic transport in the presence of an externally applied electric field is extremely important in a number of nanotechnological applications. Here, we employ all-atom molecular dynamics simulations to discover the possibility of changing the direction of electroosmotic (EOS) liquid flows by merely changing the electric field strength in a nanochannel functionalized with polyelectrolyte (PE) brushes. In exploring this, we have uncovered three facets of nanoconfined PE brush behavior and resulting EOS transport. First, we identify the onset of an overscreening effect: such overscreening refers to the presence of more counterions (Na) within the brush layer than needed to neutralize the negative brush charges. Accordingly, as a consequence of the overscreening, in the bulk liquid outside the brush layer, there is a greater number of co-ions (Cl) than counterions in the presence of an added salt (NaCl). Second, this specific ion distribution ensures that the overall EOS flow is along the direction of motion of the co-ions. Such co-ion-dictated EOS transport directly contradicts the notion that EOS flow is always dictated by the motion of the counterions. Finally, for large-enough electric fields, the brush height reduces significantly, causing some of the excess overscreening-inducing counterions to squeeze out of the PE brush layer into the brush-free bulk. As a result, the overscreening effect disappears and the number of co-ions and counterions outside the PE brush layer become similar. Despite that there is an EOS transport, this EOS transport, unlike the standard EOS transport that occurs due to the imbalance of the co-ions and counterions, occurs since a larger residence time of the water molecules in the first solvation shell of the counterions (Na) ensures a water transport in the direction of motion of the counterions. The net effect is the reversal of the direction of the EOS transport by merely changing the strength of the electric field.
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http://dx.doi.org/10.1021/acsnano.0c09248DOI Listing
April 2021

The βγ subunit of heterotrimeric G proteins interacts with actin filaments during neuronal differentiation.

Biochem Biophys Res Commun 2021 04 2;549:98-104. Epub 2021 Mar 2.

Department of Biological Sciences, University of Texas, El Paso, TX, 79968, USA; Border Biomedical Research Center, University of Texas, El Paso, TX, 79968, USA. Electronic address:

The βγ subunit of heterotrimeric G proteins, a key molecule in the G protein-coupled receptors (GPCRs) signaling pathway, has been shown to be an important factor in the modulation of the microtubule cytoskeleton. Gβγ has been shown to bind to tubulin, stimulate microtubule assembly, and promote neurite outgrowth of PC12 cells. In this study, we demonstrate that in addition to microtubules, Gβγ also interacts with actin filaments, and this interaction increases during NGF-induced neuronal differentiation of PC12 cells. We further demonstrate that the Gβγ-actin interaction occurs independently of microtubules as nocodazole, a well-known microtubule depolymerizing agent did not inhibit Gβγ-actin complex formation in PC12 cells. A confocal microscopic analysis of NGF-treated PC12 cells revealed that Gβγ co-localizes with both actin and microtubule cytoskeleton along neurites, with specific co-localization of Gβγ with actin at the distal end of these neuronal processes. Furthermore, we show that Gβγ interacts with the actin cytoskeleton in primary hippocampal and cerebellar rat neurons. Our results indicate that Gβγ serves as an important modulator of the neuronal cytoskeleton by interacting with both microtubules and actin filaments, and is likely to participate in various aspects of neuronal differentiation including axon and growth cone formation.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.095DOI Listing
April 2021

Ultrathin and Ultrasensitive Printed Carbon Nanotube-Based Temperature Sensors Capable of Repeated Uses on Surfaces of Widely Varying Curvatures and Wettabilities.

ACS Appl Mater Interfaces 2021 Mar 17;13(8):10257-10270. Epub 2021 Feb 17.

Department of Mechanical Engineering, University of Maryland, College Park, Maryland 20742, United States.

In this paper, we demonstrate the ability to fabricate temperature sensors by using our newly developed carbon nanotube-graphene oxide (CNT-GO) ink to print temperature-sensitive traces on highly flexible, thin, and adhesive PET (polyethylene terephthalate) tapes, which in turn are integrated on surfaces of different curvatures and wettabilities. Therefore, the strategy provides a facile, low-cost, and environmentally friendly method to deploy printed temperature sensors on surfaces of widely varying curvatures and wettabilities. The temperature sensing occurs through a thermally induced change in the resistance of the printed traces and we quantify the corresponding negative temperature coefficient of resistance (α) for different conditions of curvatures and wettabilities. In addition, we identify that at low temperatures (below 15 °C), the printed traces show an α value that can be as large (in magnitude) as 60 × 10/°C, which is several times higher than the typical α values reported for temperature sensors fabricated with CNT or other materials. Furthermore, we achieve the printing of traces that are only 1-3 μm thick on a 50 μm-thick PET film: therefore, our design represents an ultrathin additively fabricated temperature sensor that can be easily integrated for wearable electronic applications. Finally, we show that despite being subjected to repeated temperature cycling, there is little degradation of the CNT-GO microarchitectures, making these printed traces capable of repeated uses as potential temperature sensors.
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http://dx.doi.org/10.1021/acsami.0c18095DOI Listing
March 2021

Viscoelastic substrate decouples cellular traction force from other related phenotypes.

Biochem Biophys Res Commun 2021 03 25;543:38-44. Epub 2021 Jan 25.

Department of Chemical Engineering, Indian Institute of Technology Bombay (IITB), Mumbai, 400076, India. Electronic address:

Survival and maintenance of normal physiological functions depends on continuous interaction of cells with its microenvironment. Cells sense the mechanical properties of underlying substrate by applying force and modulate their behaviour in response to the resistance offered by the substrate. Most of the studies addressing cell-substrate mechanical interactions have been carried out using elastic substrates. Since tissues within our body are viscoelastic in nature, here we explore the effect of substrate's viscoelasticity on various properties of mesenchymal stem cells. Here, we used two sets of polyacrylamide substrates having similar storage modulus (G' = 1.1-1.6 kPa) but different loss modulus (G" = 45 Pa and 300 Pa). We report that human mesenchymal stem cells spread more but apply less force on the viscoelastic substrate (substrate with higher loss modulus). We further investigated the effect of substrate viscoelasticity on the expression of other contractility-associated proteins such as focal adhesion (FA) proteins (Vinculin, Paxillin, Talin), cytoskeletal proteins (actin, mysion, intermediate filaments, and microtubules) and mechano-sensor protein Yes-Associated Protein (YAP). Our results show that substrate viscoelasticity decouples cellular traction from other known traction related phenotypes.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.027DOI Listing
March 2021

Acute perturbation strategies in interrogating RNA polymerase II elongation factor function in gene expression.

Genes Dev 2021 02 14;35(3-4):273-285. Epub 2021 Jan 14.

Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

The regulation of gene expression catalyzed by RNA polymerase II (Pol II) requires a host of accessory factors to ensure cell growth, differentiation, and survival under environmental stress. Here, using the auxin-inducible degradation (AID) system to study transcriptional activities of the bromodomain and extraterminal domain (BET) and super elongation complex (SEC) families, we found that the CDK9-containing BRD4 complex is required for the release of Pol II from promoter-proximal pausing for most genes, while the CDK9-containing SEC is required for activated transcription in the heat shock response. By using both the proteolysis targeting chimera (PROTAC) dBET6 and the AID system, we found that dBET6 treatment results in two major effects: increased pausing due to BRD4 loss, and reduced enhancer activity attributable to BRD2 loss. In the heat shock response, while auxin-mediated depletion of the AFF4 subunit of the SEC has a more severe defect than AFF1 depletion, simultaneous depletion of AFF1 and AFF4 leads to a stronger attenuation of the heat shock response, similar to treatment with the SEC inhibitor KL-1, suggesting a possible redundancy among SEC family members. This study highlights the usefulness of orthogonal acute depletion/inhibition strategies to identify distinct and redundant biological functions among Pol II elongation factor paralogs.
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http://dx.doi.org/10.1101/gad.346106.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849361PMC
February 2021

Lipid flip-flop and desorption from supported lipid bilayers is independent of curvature.

PLoS One 2020 30;15(12):e0244460. Epub 2020 Dec 30.

Department of Mechanical Engineering, University of Maryland, College Park, Maryland, United States of America.

Flip-flop of lipids of the lipid bilayer (LBL) constituting the plasma membrane (PM) plays a crucial role in a myriad of events ranging from cellular signaling and regulation of cell shapes to cell homeostasis, membrane asymmetry, phagocytosis, and cell apoptosis. While extensive research has been conducted to probe the lipid flip flop of planar lipid bilayers (LBLs), less is known regarding lipid flip-flop for highly curved, nanoscopic LBL systems despite the vast importance of membrane curvature in defining the morphology of cells and organelles and in maintaining a variety of cellular functions, enabling trafficking, and recruiting and localizing shape-responsive proteins. In this paper, we conduct molecular dynamics (MD) simulations to study the energetics, structure, and configuration of a lipid molecule undergoing flip-flop and desorption in a highly curved LBL, represented as a nanoparticle-supported lipid bilayer (NPSLBL) system. We compare our findings against those of a planar substrate supported lipid bilayer (PSSLBL). Our MD simulation results reveal that despite the vast differences in the curvature and other curvature-dictated properties (e.g., lipid packing fraction, difference in the number of lipids between inner and outer leaflets, etc.) between the NPSLBL and the PSSLBL, the energetics of lipid flip-flop and lipid desorption as well as the configuration of the lipid molecule undergoing lipid flip-flop are very similar for the NPSLBL and the PSSLBL. In other words, our results establish that the curvature of the LBL plays an insignificant role in lipid flip-flop and desorption.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244460PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773258PMC
March 2021

Coarse-grained modelling of DNA plectoneme pinning in the presence of base-pair mismatches.

Nucleic Acids Res 2020 11;48(19):10713-10725

Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Damaged or mismatched DNA bases result in the formation of physical defects in double-stranded DNA. In vivo, defects in DNA must be rapidly and efficiently repaired to maintain cellular function and integrity. Defects can also alter the mechanical response of DNA to bending and twisting constraints, both of which are important in defining the mechanics of DNA supercoiling. Here, we use coarse-grained molecular dynamics (MD) simulation and supporting statistical-mechanical theory to study the effect of mismatched base pairs on DNA supercoiling. Our simulations show that plectoneme pinning at the mismatch site is deterministic under conditions of relatively high force (>2 pN) and high salt concentration (>0.5 M NaCl). Under physiologically relevant conditions of lower force (0.3 pN) and lower salt concentration (0.2 M NaCl), we find that plectoneme pinning becomes probabilistic and the pinning probability increases with the mismatch size. These findings are in line with experimental observations. The simulation framework, validated with experimental results and supported by the theoretical predictions, provides a way to study the effect of defects on DNA supercoiling and the dynamics of supercoiling in molecular detail.
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http://dx.doi.org/10.1093/nar/gkaa836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641772PMC
November 2020

Theoretical study on the massively augmented electro-osmotic water transport in polyelectrolyte brush functionalized nanoslits.

Phys Rev E 2020 Jul;102(1-1):013103

Department of Mechanical Engineering, University of Maryland, College Park, Maryland 20742, USA.

We demonstrate that functionalizing nanoslits with pH-responsive polyelectrolyte brushes can lead to extremely fast electro-osmotic (EOS) water transport, where the maximum centreline velocity and the volume flow rate can be an order of magnitude larger than these quantities in identically charged brush-free nanochannels for a wide range of system parameters. Such an enhancement is most remarkable given that the brushes have been known to retard the transport by imparting additional drag on the fluid flow. We argue that this enhancement stems from the localization of the charge density of the brush-induced electric double layer (and, hence, the EOS body force) away from the nanochannel wall (or the location of the wall-induced drag force). This ensures a much larger impact of the EOS body force triggering such fast water transport. Finally, the calculated flux values for the present brush-grafted nanochannels are found to be significantly larger than those for a wide range of nanofluidic membranes and channels, suggesting that the brush functionalization can be considered as a mechanism for enabling such superfast nanofluidic transport.
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http://dx.doi.org/10.1103/PhysRevE.102.013103DOI Listing
July 2020

All-atom molecular dynamics simulations of weak polyionic brushes: influence of charge density on the properties of polyelectrolyte chains, brush-supported counterions, and water molecules.

Soft Matter 2020 Aug;16(33):7808-7822

Department of Mechanical Engineering, University of Maryland, 4298 Campus Drive, College Park, MD 20742, USA.

All atom molecular dynamics (MD) simulations of planar Na+-counterion-neutralized polyacrylic acid (PAA) brushes are performed for varying degrees of ionization (and thereby varying charge density) and varying grafting density. Variation in the PE charge density (or degree of ionization) and grafting density leads to massive changes of the properties of the PE molecules (quantified by the changes in the height and the mobility of the PE brushes) as well as the local arrangement and distribution of the brush-supported counterions and water molecules within the brushes. The effect on the counterions is manifested by the corresponding variation of the counterion mobility, counterion concentration, extent of counterion binding to the charged site of the PE brushes, water-in-salt-like structure formation, and counterion-water-oxygen radial distribution function within the PE brushes. On the other hand, the effect on water molecules is manifested by the corresponding variation of water-oxygen-water-oxygen RDF, local water density, water-water and water-PE functional group hydrogen bond networks, static dielectric constant of water molecules, orientational tetrahedral order parameter, and water mobility. Enforcing such varying degree of ionization of weak polyelectrolytes is possible by changing the pH of the surrounding medium. Thus, our results provide insights into the changes in microstructure (at the atomistic level) of weak polyionic brushes at varying pH. We anticipate that this knowledge will prove to be vital for the efficient design of several nano-scale systems employing PE brushes such as nanomechanical gates, current rectifiers, etc.
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http://dx.doi.org/10.1039/d0sm01000fDOI Listing
August 2020

Quantifying Water Friction in Misaligned Graphene Channels under Ångström Confinements.

ACS Appl Mater Interfaces 2020 Aug 22;12(31):35757-35764. Epub 2020 Jul 22.

Micro & Nano-Scale Transport Laboratory, Waterloo Institute for Nanotechnology, Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

Two-dimensional (2D) materials, such as graphene (GE), hold great potential to be employed as the fundamental building blocks of novel nanofluidic devices for a wide range of applications. Recent advances in experimental techniques are materializing such prospects by enabling the assembly of 2D material-based fluidic channels with heights as small as few Ångströms. Here, we conduct molecular dynamics simulations to probe the effect of the relative misalignment between the walls of the GE fluidic channel with Ångströms height on the resistance to water transport through the channel. Two types of misalignments are studied, namely, translational and rotational misalignments. Our results show that the relative misalignment of the GE lattices can lead to a substantial reduction in the friction between water and the channel walls. Moreover, a dependence of the friction on the degree of misalignment and flow direction is found for the cases with translational misalignment. In contrast, the resistance exerted by the channels with rotational misalignment is found to be independent of the rotation angle (θ) for 0° < θ < 60° but always lower than the perfectly aligned case. We associate such lowering of the resistance to water transport to the corrugation and the anisotropy in the corresponding potential energy landscape associated with each degree of misalignment. The findings, therefore, point to an unprecedented possibility of significantly enhancing the water transport in Ångströms height GE channels by engineering the misalignments of the GE channel walls.
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http://dx.doi.org/10.1021/acsami.0c10445DOI Listing
August 2020

Coordinated regulation of cellular identity-associated H3K4me3 breadth by the COMPASS family.

Sci Adv 2020 Jun 24;6(26):eaaz4764. Epub 2020 Jun 24.

Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Set1A and Set1B, two members of the COMPASS family of methyltransferases that methylate the histone H3 lysine 4 (H3K4) residue, have been accredited as primary depositors of global H3K4 trimethylation (H3K4me3) in mammalian cells. Our previous studies in mouse embryonic stem cells (ESCs) demonstrated that deleting the enzymatic SET domain of Set1A does not perturb bulk H3K4me3, indicating possible compensatory roles played by other COMPASS methyltransferases. Here, we generated a series of ESC lines harboring compounding mutations of COMPASS methyltransferases. We find that Set1B is functionally redundant to Set1A in implementing H3K4me3 at highly expressed genes, while Mll2 deposits H3K4me3 at less transcriptionally active promoters. While Set1A-B/COMPASS is responsible for broad H3K4me3 peaks, Mll2/COMPASS establishes H3K4me3 with narrow breadth. Additionally, Mll2 helps preserve global H3K4me3 levels and peak breadth in the absence of Set1A-B activity. Our results illustrate the biological flexibility of such enzymes in regulating transcription in a context-dependent manner to maintain stem cell identity.
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http://dx.doi.org/10.1126/sciadv.aaz4764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314515PMC
June 2020

Strong stretching theory for pH-responsive polyelectrolyte brushes in large salt concentrations.

Phys Chem Chem Phys 2020 Jun;22(24):13536-13553

Department of Mechanical Engineering, University of Maryland, College Park, MD-20742, USA.

In this paper, we develop a theory for describing the thermodynamics, configuration, and electrostatics of strongly-stretched, pH-responsive polyelectrolyte (PE) brushes in the presence of large salt concentrations. The aim of the paper, therefore, is to study the properties of a PE brush in a salt concentration regime (namely, large concentrations of several molars) that has been hitherto unexplored theoretically in the context of PE brushes but can be routinely encountered in molecular scale simulations of the problem. The brushes are modelled using our recently developed augmented Strong Stretching Theory (SST), while the effect of the presence of the large salt concentration is accounted for by including the contributions of three different types of non-Poisson-Boltzmann (non-PB) effects to the free energy description of the PE brush induced electric double layer (EDL). These non-PB effects are ionic non-mean-field ion-ion correlations, solvent polarization, and the finite size effect of the ions and water dipoles. We study the individual influences of these different effects and show that the ion-ion correlations and solvent polarization effect reduce the brush height which consequently enhances the monomer density and leads to an electrostatic potential distribution of the brush induced EDL that has a larger magnitude at near-wall locations and becomes zero at shorter distances from the wall. The finite size effect, on the other hand, increases the brush height and therefore, weakens the monomer density and leads to a smaller near-wall magnitude of the EDL potential that becomes zero at larger distances from the wall. Eventually, we consider the impact of all the three non-PB effects simultaneously and show that the ion-ion correlations and solvent polarization effect dominate the size effects and dictate the overall brush configuration and the EDL electrostatics. We also point out that the influence of all the three non-PB effects becomes the largest for a larger salt concentration and a smaller bulk pH. Finally, we compare our theoretical predictions with those obtained from our recently developed all-atom MD simulation model and obtain an excellent match.
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http://dx.doi.org/10.1039/d0cp02099kDOI Listing
June 2020

The Diagnosis of a Case of Household Cleaner Fatality.

Am J Forensic Med Pathol 2020 Sep;41(3):203-206

Forensic Sciences Department, Chennai, India.

Household cleaners are an unavoidable entity in our routine domestic life. They are available either in company-labeled bottles or locally made unlabeled bottles especially in the developing countries. In this report, we are discussing a case of fatal ingestion of household cleaner, which was stored in an unlabeled bottle. The deceased developed features of gastrointestinal irritation, such as vomiting and pain in throat and abdomen. He also had features of aspiration such as cough and chest crepitation. Finally, he developed metabolic acidosis, gastric perforation, respiratory failure, and died within a day. The autopsy features such as teeth discoloration, corrosion of mouth and lips, and histopathological findings helped us in concluding that the ingredients contained some corrosive mineral acid. This case highlights the importance of histopathological examination of viscera in alleged cases of household cleaner poisoning where toxicological analysis of viscera gives negative results.
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http://dx.doi.org/10.1097/PAF.0000000000000566DOI Listing
September 2020

Formation and Properties of a Self-Assembled Nanoparticle-Supported Lipid Bilayer Probed through Molecular Dynamics Simulations.

Langmuir 2020 05 12;36(20):5524-5533. Epub 2020 May 12.

Department of Mechanical Engineering, University of Maryland, 4298 Campus Drive, College Park, Maryland 20742, United States.

We have carried out coarse-grained molecular dynamics (MD) simulations to study the self-assembly procedure of a system of randomly placed lipid molecules, water beads, and a nanoparticle (NP). The self-assembly results in the formation of the nanoparticle-supported lipid bilayer (NPSLBL), with the self-assembly mechanism being driven by events such as the formation of small lipid clusters, merging of the lipid clusters in the vicinity of the NP to form NP-embedded vesicle with a pore, and collapsing of that pore to eventually form the equilibrated NPSLBL system overcoming a large free-energy barrier. Subsequently, we quantify the properties and the configurations of this NPSLBL system. We reveal that unlike our proposition of an equal number of lipid molecules occupying the inner and outer leaflets in a recent report studying the properties of a preassembled lipid bilayer, the equilibrated self-assembled NPSLBL system demonstrates a much larger number of lipid molecules occupying the outer leaflet as compared to the inner leaflet. Second, the thickness of the water layer entrapped between the NP and the inner leaflet shows similar values as predicted by experiments and our previous study. Finally, we reveal that, similar to our previous study, the diffusivity of the lipid molecules in the outer leaflet is larger than that in the inner leaflet but, due to higher temperature employed during our simulations, are even larger than that predicted by our previous study.
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http://dx.doi.org/10.1021/acs.langmuir.0c00593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494177PMC
May 2020

Rhabdomyolysis associated acute renal failure - Report of two fatal cases and a brief review of literature.

J Forensic Leg Med 2020 Apr 12;71:101941. Epub 2020 Mar 12.

Department of Forensic Medicine & Toxicology, JIPMER, Puducherry, India.

Background: Rhabdomyolysis is a potentially fatal condition which occurs due to skeletal muscle injury and classically presents with myalgia and red-brown coloured urine. Presence of excess myoglobin in the glomerular filtrate forms myoglobin casts which causes severe obstruction and necrosis of the tubules leading to acute renal failure.

Methods: We report two fatal cases of rhabdomyolysis associated acute renal failure. The first victim died in police custody and the second victim died due to severe physical exertion.

Results: In both the cases, creatine kinase levels were elevated and myoglobin was detected in urine in the second case. Myoglobin immunohistochemistry detected the presence of myoglobin cast in the glomerular tubules of kidney in both the cases.

Conclusions: Myoglobin immunohistochemistry of renal tissues, serum creatine kinase, urine myoglobin analysis and muscle histopathology are the laboratory tests that should be considered at autopsy where rhabdomyolysis is suspected.
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http://dx.doi.org/10.1016/j.jflm.2020.101941DOI Listing
April 2020

Triazoxins: Novel nucleosides with anti-Giardia activity.

Bioorg Med Chem Lett 2020 06 7;30(12):127175. Epub 2020 Apr 7.

Center for Drug Design, College of Pharmacy, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address:

Novel nucleoside analogues named "triazoxins" were synthesized. Of these, two analogues were found to be highly effective against Giardia lamblia, an intestinal parasite and a major cause of waterborne infection, worldwide. While compound 7 reduced the growth of trophozoites in culture (IC, ~5 μM), compound 21 blocked the in vitro cyst production (IC ~5 μM). Compound 21 was also effective against trophozoites (IC, ~36 μM). A third analogue (compound 8) was effective against both trophozoites (IC, ~36 μM) and cysts (IC, ~20 μM) although at higher concentration. Thus triazoxin analogues are unique and exhibit morphology (i.e., trohozoites or cysts) -specific effects against Giardia.
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http://dx.doi.org/10.1016/j.bmcl.2020.127175DOI Listing
June 2020

On the wetting translucency of hexagonal boron nitride.

Phys Chem Chem Phys 2020 Apr;22(15):7710-7718

Micro & Nano-Scale Transport Laboratory, Waterloo Institute for Nanotechnology, Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

When a liquid drop sits on an atomically thin layer of a 2D van der Waals (vdW) solid (like graphene) supported by a hydrophilic material, it is possible that the drop demonstrates an equilibrium contact angle that is influenced by this underlying hydrophilic material and hence is different from that observed on the bulk 2D material (e.g., graphite) surface. Such a behavior is known as the wetting translucency effect. While the wetting translucency effect of graphene has been extensively studied, the wetting translucency of hexagonal boron nitride (hBN) remains largely unexplored despite significant similarities in structural properties between these materials. In this study, we probe the wetting translucency of hBN. For this purpose, we conduct molecular dynamics simulations of water droplets and water films on hBN layers supported on a gold-like hydrophilic substrate. Our results show that for a substrate coated by monolayer hBN ("coated substrate"), depending on the contact distance between underlying substrate and hBN, an increase in the hydrophilicity of the underlying surface causes a monotonic increase in the overall adhesion energy between water and the coated substrate and a monotonic decrease in the contact angle of a drop on the coated substrate. For an increasing number of stacked hBN layers, the wettability of coated substrate becomes independent of the wettability of the underlying solid. Accordingly, our results confirm a distinct wetting translucency nature of hBN very similar to that observed in graphene.
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http://dx.doi.org/10.1039/d0cp00200cDOI Listing
April 2020

Coating for preventing nonspecific adhesion mediated biofouling in salty systems: Effect of the electrostatic and van der waals interactions.

Electrophoresis 2020 05 12;41(9):657-665. Epub 2020 Mar 12.

Department of Mechanical Engineering, University of Maryland, College Park, MD, 20742, USA.

Development of anti-biofouling coating has attracted immense attention for reducing the massively detrimental effects of biofouling in systems ranging from ship hulls and surgical instruments to catheters, implants, and stents. In this paper, we propose a model to quantify the role of electrostatic and van der Waals (vdW) forces in dictating the efficacy of dielectric coating for preventing the nonspecific adhesion mediated biofouling in salty systems. The model considers a generic charged lipid-bilayer encapsulated vesicle-like structure representing the bio-organism. Also, we consider the fouling caused by the nonspecific adhesion of the bio-organism on the substrate, without accounting for the explicit structures (e.g., pili, appendages) or conditions (e.g., surface adhesins secreted by the organisms) involved in the adhesion of specific microorganism. The model is tested by considering the properties of actual coating materials and biofouling causing microorganisms (bacteria, fungi, algae). Results show that while the electrostatic-vdW effect can be significant in anti-biofouling action for cases where the salt concentration is relatively low (e.g., saline solution for surgical instruments), it might not be effective for marine environment where the salt concentration is much higher. The findings, therefore, point to a hitherto unexplored driving mechanism of anti-biofouling action of the coating. Such an identification will also enable the appropriate choices of the coating materials (e.g., possible dielectric material with volume charge) and other system parameters (e.g., salinity of the solution for storing the surgical instruments) that will significantly improve the efficiency of the coatings in preventing the nonspecific adhesion mediated biofouling.
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http://dx.doi.org/10.1002/elps.201900348DOI Listing
May 2020

Wettability of nanostructured hexagonal boron nitride surfaces: molecular dynamics insights on the effect of wetting anisotropy.

Phys Chem Chem Phys 2020 Jan 15;22(4):2488-2497. Epub 2020 Jan 15.

Micro & Nano-Scale Transport Laboratory, Waterloo Institute for Nanotechnology, Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

Nanostructured van der Waals (vdW) layered materials hold great potential for achieving smart surfaces with controllable wettability. Inspired by this possibility, we conduct Molecular Dynamics (MD) simulations of the wetting of nanostructured hexagonal boron nitride (hBN) surfaces. The nanostructure consists of periodically placed nanopillars made of hBN nanoribbons. We demonstrate that the polarity effect of the nanoribbon edges triggers wetting anisotropy of the nanoribbons: the vertical edges of the nanoribbons demonstrate a different wetting behavior as compared to the flat surfaces of the nanoribbons. Depending on the nature of the edge of the nanoribbon (armchair or zigzag), these vertical edges can be more hydrophilic for the zigzag edges or more hydrophobic for the armchair edges than the flat part. Such differences ensure that the nanostructured hBN surfaces become more hydrophilic (hydrophobic) as compared to the flat non-nanostructured hBN surfaces for cases where the edges of the nanoribbon are more hydrophilic (hydrophobic) than the flat part. Overall, the present study develops a most remarkable design space where by introducing nanopillars/nanoribbons on hBN and by merely changing the nature of the edges of these nanopillars, one can ensure atomistically thin coating of hBN with a wide range of wettability.
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http://dx.doi.org/10.1039/c9cp06708fDOI Listing
January 2020

Demographic and clinical profile of youth onset diabetes patients in India-Results from the baseline data of a clinic based registry of people with diabetes in India with young age at onset-[YDR-02].

Pediatr Diabetes 2021 02 6;22(1):15-21. Epub 2020 Feb 6.

Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.

Background: We here report the demographic and clinical profile of the patients enrolled in the Indian Council of Medical Research funded Registry of people with diabetes in India with young age at onset (YDR) from 1 January 2000 to 31 July 2011.

Methods: The YDR registry recruits all diabetes cases (newly diagnosed or treated) reporting on or after 1 January 2000 with age of diagnosis ≤25 years, and residing within the assigned geographical area of the reporting centres. A baseline proforma was used to obtain information on demographic and clinical details at registration.

Results: The registry has enrolled 5546 patients (49.5% male; 50.5% female) with youth onset diabetes from 205 reporting centres linked to 8 regional collaborating centres (RCC) across India. T1DM (63.9%; n = 3545) and T2DM (25.3%; n = 1401) were the commonest variants of youth onset diabetes, though their relative proportion varied across RCCs. The mean (SD) age at diagnosis for T1DM was 12.9 (6.5) years, while that for T2DM was 21.7 (3.7) years. Nearly half the T1DM patients were registered within 6 months of the onset of disease. Most cases of T2DM (47.3%) were registered after 3 years from their date of diagnosis. 56.1% of patients had at least one episode of hospitalization at registration.

Conclusion: The observations from YDR registry indicate the need to establish a surveillance system in India to monitor diabetes in youth, not only to understand its complex etiology and natural history but also due to its detrimental socio economic impact.
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http://dx.doi.org/10.1111/pedi.12973DOI Listing
February 2021

Accentuated osseointegration in osteogenic nanofibrous coated titanium implants.

Sci Rep 2019 12 9;9(1):17638. Epub 2019 Dec 9.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, 400076, Maharashtra, India.

Anchoring of endosseous implant through osseointegration continues to be an important clinical need. Here, we describe the development of superior endosseous implant demonstrating enhance osseointegration, achieved through surface modification via coating of osteogenic nanofibres. The randomized bio-composite osteogenic nanofibres incorporating polycaprolactone, gelatin, hydroxyapatite, dexamethasone, beta-glycerophosphate and ascorbic acid were electrospun on titanium implants mimicking bone extracellular matrix and subsequently induced osteogenesis by targeting undifferentiated mesenchymal stem cells present in the peri-implant niche to regenerate osseous tissue. In proof-of-concept experiment on rabbit study models (n = 6), micro-computed tomography (Micro-CT), histomorphometric analysis and biomechanical testing in relation to our novel osteogenic nanofibrous coated implants showed improved results when compared to uncoated controls. Further, no pathological changes were detected during gross examination and necropsy on peri-implant osseous tissues regenerated in response to such coated implants. The findings of the present study confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and favours the dynamics of osseointegration.
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http://dx.doi.org/10.1038/s41598-019-53884-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901521PMC
December 2019

Shape-driven arrest of coffee stain effect drives the fabrication of carbon-nanotube-graphene-oxide inks for printing embedded structures and temperature sensors.

Nanoscale 2019 Dec 3;11(48):23402-23415. Epub 2019 Dec 3.

Department of Mechanical Engineering, University of Maryland, College Park, MD 20742, USA.

Carbon nanotube (CNT) based binder-free, syringe-printable inks, with graphene oxide (GO) being used as the dispersant, have been designed and developed. We discovered that the printability of the ink is directly attributed to the uniform deposition of the GO-CNT agglomerates, as opposed to the 'coffee-staining' despite these aggregates being micron-sized. The ellipsoidal nature of the micron-scale GO-CNT agglomerates/particles enables these particles to severely perturb the air-water interface, triggering a large long-range capillary interaction that causes the uniform deposition by overcoming the "coffee-stain"-forming forces from the evaporation-mediated flows. We evaluated the properties of this ink and identified a temperature-dependent resistance with a negative temperature coefficient of resistance (TCR) α ranging from ∼-10 to -10/°C depending on ink compositions. Finally, the printing is conducted on flat and curved surfaces, for developing polymer-ink embedded structures that might serve as precursors to syringe-printable CNT-based nanocomposites, and for fabricating sensor-like patterns that for certain ink compositions demonstrate α∼-10/°C with a large averaged resistance drop (per unit temperature) of -3.5 Ω°C.
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http://dx.doi.org/10.1039/c9nr08450aDOI Listing
December 2019

Ionic current in nanochannels grafted with pH-responsive polyelectrolyte brushes modeled using augmented strong stretching theory.

Electrophoresis 2020 04 7;41(7-8):554-561. Epub 2019 Oct 7.

Department of Mechanical Engineering, University of Maryland, College Park, MD, USA.

In this paper, we provide a theory to quantify the ionic current ( ) in nanochannels grafted with pH-responsive polyelectrolyte (PE) brushes. We consider the PE brushes to be modeled by our recently proposed augmented strong stretching theory (SST) model that improves the existing SST models by incorporating the effects of excluded volume interactions and an extended mass action law. Use of such augmented SST for this problem implies that this is the first study on computing in PE brush-grafted nanochannels accounting for the appropriate coupled configuration-electrostatic description of the PE brushes. is obtained as functions of PE brush grafting density, medium pH and salt concentration ( ), and the density of polyelectrolyte chargeable sites (PECS). For large , increases linearly with (as for such , becomes independent of the PE charge and is dominated by the bulk mobility and number density of the electrolyte ions), whereas is independent of at small (where the electric double layer electrostatics and the total number of ions in the system is dominated by the hydrogen ions). We further witness an enhancement of for smaller pH and larger grafting density at low and moderate , while there is little to no effect of the PECS density on the ionic current except for weakly grafted brushes at low . We anticipate that this study will serve as a theoretical foundation for a large number of applications that are based on the brush-induced modification of the ionic current in a nanochannel.
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http://dx.doi.org/10.1002/elps.201900248DOI Listing
April 2020

Extendibility Limits the Performance of Quantum Processors.

Phys Rev Lett 2019 Aug;123(7):070502

ICREA & Física Teòrica: Informació i Fenòmens Quàntics, Departament de Física, Universitat Autònoma de Barcelona, ES-08193 Bellaterra (Barcelona), Spain.

Resource theories in quantum information science are helpful for the study and quantification of the performance of information-processing tasks that involve quantum systems. These resource theories also find applications in other areas of study; e.g., the resource theories of entanglement and coherence have found use and implications in the study of quantum thermodynamics and memory effects in quantum dynamics. In this paper, we introduce the resource theory of unextendibility, which is associated with the inability of extending quantum entanglement in a given quantum state to multiple parties. The free states in this resource theory are the k-extendible states, and the free channels are k-extendible channels, which preserve the class of k-extendible states. We make use of this resource theory to derive nonasymptotic, upper bounds on the rate at which quantum communication or entanglement preservation is possible by utilizing an arbitrary quantum channel a finite number of times, along with the assistance of k-extendible channels at no cost. We then show that the bounds obtained are significantly tighter than previously known bounds for quantum communication over both the depolarizing and erasure channels.
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http://dx.doi.org/10.1103/PhysRevLett.123.070502DOI Listing
August 2019

A Targeted Mass Spectrometric Analysis Reveals the Presence of a Reduced but Dynamic Sphingolipid Metabolic Pathway in an Ancient Protozoan, .

Front Cell Infect Microbiol 2019 24;9:245. Epub 2019 Jul 24.

Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX, United States.

, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, has adapted a "minimalistic" life style, as it becomes dependent on available resources of the small intestine. Because expresses fewer sphingolipid (SL) genes-and glycosphingolipids are critical for encystation-we investigated the SL metabolic cycle in this parasite. A tandem mass spectrometry (MS/MS) analysis reveals that major SLs in include sphingomyelins, sphingoid bases, ceramides, and glycosylceramides. Many of these lipids are obtained by from the growth medium, remodeled at their fatty acyl chains and end up in the spent medium. For instance, ceramide-1-phosphate, a proinflammatory molecule that is not present in the culture medium, is generated from sphingosine (abundant in the culture medium) possibly by remodeling reactions. It is then subsequently released into the spent medium. Thus, the secretion of ceramide-1-phospate and other SL derivatives by could be associated with inflammatory bowel disease observed in acute giardiasis. Additionally, we found that the levels of SLs increase in encysting and are differentially regulated throughout the encystation cycle. We propose that SL metabolism is important for this parasite and, could serve as potential targets for developing novel anti-giardial agents.
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http://dx.doi.org/10.3389/fcimb.2019.00245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668603PMC
July 2020

Colon Perforation by Compressed Air: A Case Report and Short Review of Literature.

Am J Forensic Med Pathol 2019 Dec;40(4):376-380

Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Barotrauma-associated perforation of the colon is not common and usually occurs due to the passage of compressed air through the anus. Most of the cases are accidental and done for fun often at the victim's workplace. Therefore, it is necessary that the workers should be made aware of the dangers of the equipment they regularly use at their workplace. Here, we describe one such case where a rice mill worker died when compressed air through an air pump pipe entered his rectum. His chief complaint was abdominal pain and breathing difficulty. Computed tomography scan of the abdomen and thorax showed pneumoperitoneum, pneumomediastinum, and soft tissue emphysema. There was a complete tear in the rectosigmoid junction of the colon. The mucosa was deeply hemorrhagic and congested. Histopathology of this segment showed hemorrhagic necrosis of the mucosa.
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http://dx.doi.org/10.1097/PAF.0000000000000499DOI Listing
December 2019
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