Intra-cellular transport of single-headed molecular motors KIF1A

Motivated by experiments on single-headed kinesin KIF1A, we develop a model of intra-cellular transport by interacting molecular motors. It captures explicitly not only the effects of ATP hydrolysis, but also the ratchet mechanism which drives individual motors. Our model accounts for the experimentally observed single molecule properties in the low density limit and also predicts a phase diagram that shows the influence of hydrolysis and Langmuir kinetics on the collective spatio-temporal organization of the motors. Finally, we provide experimental evidence for the existence of domain walls in our {\it in-vitro} experiment with fluorescently labeled KIF1A.Comment: 4 pages, REVTEX, 5 EPS figures; Accepted for Publication in Phys. Rev. Let

Stochastic kinetics of ribosomes: single motor properties and collective behavior

Synthesis of protein molecules in a cell are carried out by ribosomes. A ribosome can be regarded as a molecular motor which utilizes the input chemical energy to move on a messenger RNA (mRNA) track that also serves as a template for the polymerization of the corresponding protein. The forward movement, however, is characterized by an alternating sequence of translocation and pause. Using a quantitative model, which captures the mechanochemical cycle of an individual ribosome, we derive an {\it exact} analytical expression for the distribution of its dwell times at the successive positions on the mRNA track. Inverse of the average dwell time satisfies a ``Michaelis-Menten-like'' equation and is consistent with the general formula for the average velocity of a molecular motor with an unbranched mechano-chemical cycle. Extending this formula appropriately, we also derive the exact force-velocity relation for a ribosome. Often many ribosomes simultaneously move on the same mRNA track, while each synthesizes a copy of the same protein. We extend the model of a single ribosome by incorporating steric exclusion of different individuals on the same track. We draw the phase diagram of this model of ribosome traffic in 3-dimensional spaces spanned by experimentally controllable parameters. We suggest new experimental tests of our theoretical predictions.Comment: Final published versio

Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding

Ribosome is a molecular machine that polymerizes a protein where the sequence of the amino acid residues, the monomers of the protein, is dictated by the sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that serves as the template. The ribosome is a molecular motor that utilizes the template mRNA strand also as the track. Thus, in each step the ribosome moves forward by one codon and, simultaneously, elongates the protein by one amino acid. We present a theoretical model that captures most of the main steps in the mechano-chemical cycle of a ribosome. The stochastic movement of the ribosome consists of an alternating sequence of pause and translocation; the sum of the durations of a pause and the following translocation is the time of dwell of the ribosome at the corresponding codon. We derive the analytical expression for the distribution of the dwell times of a ribosome in our model. Whereever experimental data are available, our theoretical predictions are consistent with those results. We suggest appropriate experiments to test the new predictions of our model, particularly, the effects of the quality control mechanism of the ribosome and that of their crowding on the mRNA track.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at DOI:10.1088/1478-3975/8/2/02600

Competition of coarsening and shredding of clusters in a driven diffusive lattice gas

We investigate a driven diffusive lattice gas model with two oppositely moving species of particles. The model is motivated by bi-directional traffic of ants on a pre-existing trail. A third species, corresponding to pheromones used by the ants for communication, is not conserved and mediates interactions between the particles. Here we study the spatio-temporal organization of the particles. In the uni-directional variant of this model it is known to be determined by the formation and coarsening of ``loose clusters''. For our bi-directional model, we show that the interaction of oppositely moving clusters is essential. In the late stages of evolution the cluster size oscillates because of a competition between their `shredding' during encounters with oppositely moving counterparts and subsequent "coarsening" during collision-free evolution. We also establish a nontrivial dependence of the spatio-temporal organization on the system size

Flow properties of driven-diffusive lattice gases: theory and computer simulation

We develop n-cluster mean-field theories (0 < n < 5) for calculating the flow properties of the non-equilibrium steady-states of the Katz-Lebowitz-Spohn model of the driven diffusive lattice gas, with attractive and repulsive inter-particle interactions, in both one and two dimensions for arbitrary particle densities, temperature as well as the driving field. We compare our theoretical results with the corresponding numerical data we have obtained from the computer simulations to demonstrate the level of accuracy of our theoretical predictions. We also compare our results with those for some other prototype models, notably particle-hopping models of vehicular traffic, to demonstrate the novel qualitative features we have observed in the Katz-Lebowitz-Spohn model, emphasizing, in particular, the consequences of repulsive inter-particle interactions.Comment: 12 RevTex page

Can follow-up examination of tuberculosis patients be simplified? A study in Chhattisgarh, India

Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely

Footprint traversal by ATP-dependent chromatin remodeler motor

ATP-dependent chromatin remodeling enzymes (CRE) are bio-molecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, adenosine triphosphate (ATP). CREs actively participate in many cellular processes that require accessibility of specific segments of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp $\sim$ 50 nm of a double stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. The helical path of histone-DNA contact on a nucleosome is also called "footprint". We investigate the mechanism of footprint traversal by a CRE that translocates along the dsDNA. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechano-chemical cycle of each ATP-dependent CRE. We calculate the mean time of traversal. Our predictions on the ATP-dependence of the mean traversal time can be tested by carrying out {\it in-vitro} experiments on mono-nucleosomes.Comment: 11 pages, 12 figures; minor revision of tex

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Entity Augmentation for Efficient Classification of Vertically Partitioned Data with Limited Overlap

Vertical Federated Learning (VFL) is a machine learning paradigm for learning from vertically partitioned data (i.e. features for each input are distributed across multiple "guest" clients and an aggregating "host" server owns labels) without communicating raw data. Traditionally, VFL involves an "entity resolution" phase where the host identifies and serializes the unique entities known to all guests. This is followed by private set intersection to find common entities, and an "entity alignment" step to ensure all guests are always processing the same entity's data. However, using only data of entities from the intersection means guests discard potentially useful data. Besides, the effect on privacy is dubious and these operations are computationally expensive. We propose a novel approach that eliminates the need for set intersection and entity alignment in categorical tasks. Our Entity Augmentation technique generates meaningful labels for activations sent to the host, regardless of their originating entity, enabling efficient VFL without explicit entity alignment. With limited overlap between training data, this approach performs substantially better (e.g. with 5% overlap, 48.1% vs 69.48% test accuracy on CIFAR-10). In fact, thanks to the regularizing effect, our model performs marginally better even with 100% overlap.Comment: GLOW @ IJCAI 2024 (12 pages + 2 page bibliography. 15 figures.