A programmable platform for probing cell migration and proliferation.

The advent of advanced robotic platforms and workflow automation tools has revolutionized the landscape of biological research, offering unprecedented levels of precision, reproducibility, and versatility in experimental design. In this work, we present an automated and modular workflow for exploring cell behavior in two-dimensional culture systems. By integrating the BioAssemblyBot (BAB) robotic platform and the BioApps™ workflow automater with live-cell fluorescence microscopy, our workflow facilitates execution and analysis of migration and proliferation assays.

Biomarker Selection for Adaptive Systems.

Biomarkers enable objective monitoring of a given cell or state in a biological system and are widely used in research, biomanufacturing, and clinical practice. However, identifying appropriate biomarkers that are both robustly measurable and capture a state accurately remains challenging. We present a framework for biomarker identification based upon observability guided sensor selection.

A unified approach of detecting phase transition in time-varying complex networks.

Deciphering the non-trivial interactions and mechanisms driving the evolution of time-varying complex networks (TVCNs) plays a crucial role in designing optimal control strategies for such networks or enhancing their causal predictive capabilities. In this paper, we advance the science of TVCNs by providing a mathematical framework through which we can gauge how local changes within a complex weighted network affect its global properties. More precisely, we focus on unraveling unknown geometric properties of a network and determine its implications on detecting phase transitions within the dynamics of a TVCN.

A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity.

Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM phenotype dynamics. We integrated single-cell RNA-Seq, spatial transcriptomics, and imaging of murine adipose tissue in a time course study of diet-induced obesity.

Validity and reliability of the Sinhalese version of the perceived stress scale questionnaire among Sri Lankans.

Introduction: Despite the availability of validated psychometrics tools to assess depression, there has not been any validated and reliable tool established to test perceived stress among Sri Lankans. The objective of this study is to test the validity and reliability of the Sinhalese Version of the Sheldon Cohen Perceived Stress Scale.

Materials And Methods: Standard and systematic procedures were adopted to translate the original English version of the Perceived Stress Scale-10 questionnaire into Sinhalese.

HAT: Hypergraph analysis toolbox.

Recent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely represent and analyze multi-way interactions. Here we present the Hypergraph Analysis Toolbox (HAT), a software package for visualization and analysis of multi-way interactions in complex systems.

Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm.

The paradoxical action of insulin on hepatic glucose metabolism and lipid metabolism in the insulin-resistant state has been of much research interest in recent years. Generally, insulin resistance would promote hepatic gluconeogenesis and demote hepatic lipogenesis. The underlying major drivers of these mechanisms were insulin-dependent, FOXO-1-mediated gluconeogenesis and SREBP1c-mediated lipogenesis.

Therapeutic Potential of miRNAs for Type 2 Diabetes Mellitus: An Overview.

MicroRNA(miRNA)s have been identified as an emerging class for therapeutic interventions mainly due to their extracellularly stable presence in humans and animals and their potential for horizontal transmission and action. However, treating Type 2 diabetes mellitus using this technology has yet been in a nascent state. MiRNAs play a significant role in the pathogenesis of Type 2 diabetes mellitus establishing the potential for utilizing miRNA-based therapeutic interventions to treat the disease.

Deciphering multi-way interactions in the human genome.

Chromatin architecture, a key regulator of gene expression, can be inferred using chromatin contact data from chromosome conformation capture, or Hi-C. However, classical Hi-C does not preserve multi-way contacts. Here we use long sequencing reads to map genome-wide multi-way contacts and investigate higher order chromatin organization in the human genome.

Rearrangement of T Cell genome architecture regulates GVHD.

WAPL, cohesin's DNA release factor, regulates three-dimensional (3D) chromatin architecture. The 3D chromatin structure and its relevance to mature T cell functions is not well understood. We show that lymphopenic expansion, and alloantigen-driven proliferation, alters the 3D structure and function of the genome in mature T cells.

The Pattern of Substance Use and Characteristics of the Individuals Enrolled in Residential Treatment at Selected Rehabilitation Centers in Sri Lanka: A Descriptive Cross-Sectional Study.

Introduction: Substance use becomes censorious when it leads to harmful effects on individuals, their families, and the community. The nature of substance use in Sri Lankan context is poorly understood and empirical evidences are sparse. The study aimed to describe patterns of substance use and characteristics of the individuals enrolled in residential treatment at selected rehabilitation centers in Sri Lanka.

Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters.

Increased adipose tissue macrophages (ATMs) correlate with metabolic dysfunction in humans and are causal in development of insulin resistance in mice. Recent bulk and single-cell transcriptomics studies reveal a wide spectrum of gene expression signatures possible for macrophages that depends on context, but the signatures of human ATM subtypes are not well defined in obesity and diabetes. We profiled 3 prominent ATM subtypes from human adipose tissue in obesity and determined their relationship to type 2 diabetes.

Functional organization of the maternal and paternal human 4D Nucleome.

Every human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data from a B lymphoblastoid cell line, we investigate this relationship both globally and locally.

Understanding memory B cell selection.

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen.

Network dynamics of hypothalamic feeding neurons.

Mutations in the melanocortin 4 receptor (MC4R) result in hyperphagia and obesity and are the most common cause of monogenic obesity in humans. Preclinical rodent studies have determined that the critical role of the MC4R in controlling feeding can be mapped in part to its expression in the paraventricular nucleus of the hypothalamus (paraventricular nucleus [PVN]), where it regulates the activity of anorexic neural circuits. Despite the critical role of PVN MC4R neurons in regulating feeding, the in vivo neuronal activity of these cells remains largely unstudied, and the network activity of PVN MC4R neurons has not been determined.

4DNvestigator: time series genomic data analysis toolbox.

Data on genome organization and output over time, or the 4D Nucleome (4DN), require synthesis for meaningful interpretation. Development of tools for the efficient integration of these data is needed, especially for the time dimension. We present the '4DNvestigator', a user-friendly network-based toolbox for the analysis of time series genome-wide genome structure (Hi-C) and gene expression (RNA-seq) data.

TCF7L2 silencing results in altered gene expression patterns accompanied by local genomic reorganization.

Canonical Wnt signaling is crucial for intestinal homeostasis as TCF4, the major Wnt signaling effector in the intestines, is required for stem cell maintenance. The capability of TCF4 to maintain the stem cell phenotype is contingent upon β-catenin, a potent transcriptional activator, which interacts with histone acetyltransferases and chromatin remodeling complexes. We used RNAi to explore the influence of TCF4 on chromatin structure (Hi-C) and gene expression (RNA sequencing) across a 72-hour time series in colon cancer.

Cellular reprogramming: Mathematics meets medicine.

Generating needed cell types using cellular reprogramming is a promising strategy for restoring tissue function in injury or disease. A common method for reprogramming is addition of one or more transcription factors that confer a new function or identity. Advancements in transcription factor selection and delivery have culminated in successful grafting of autologous reprogrammed cells, an early demonstration of their clinical utility.

Doxycycline Usage for Prevention of Leptospirosis among Farmers and Reasons for Failure to Use Chemoprophylaxis: A Descriptive Study from Southern Sri Lanka.

Background: Leptospirosis causes substantial morbidity and mortality in Sri Lanka. Health authorities have implemented a chemoprophylaxis programme for prevention of disease for farmers who are at a high risk of leptospirosis. Only 39% of general population is aware of chemoprophylaxis.

Single Chromosome Aneuploidy Induces Genome-Wide Perturbation of Nuclear Organization and Gene Expression.

Chromosomal aneuploidy is a defining feature of carcinomas and results in tumor-entity specific genomic imbalances. For instance, most sporadic colorectal carcinomas carry extra copies of chromosome 7, an aneuploidy that emerges already in premalignant adenomas, and is maintained throughout tumor progression and in derived cell lines. A comprehensive understanding on how chromosomal aneuploidy affects nuclear organization and gene expression, i.

Biomaterial Scaffolds Recruit an Aggressive Population of Metastatic Tumor Cells .

For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic premetastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here, we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor (PT) cells, similar to cells derived from lung micrometastases (LUNG).

Genome Architecture Mediates Transcriptional Control of Human Myogenic Reprogramming.

Genome architecture has emerged as a critical element of transcriptional regulation, although its role in the control of cell identity is not well understood. Here we use transcription factor (TF)-mediated reprogramming to examine the interplay between genome architecture and transcriptional programs that transition cells into the myogenic identity. We recently developed new methods for evaluating the topological features of genome architecture based on network centrality.

Algorithm for cellular reprogramming.

The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior.

4D nucleome Analysis Toolbox: analysis of Hi-C data with abnormal karyotype and time series capabilities.

Motivation: The availability of powerful analysis tools will further understanding of genome organization and its relationship to phenotype in dynamical settings.

Results: The 4D Nucleome Analysis Toolbox (NAT) is a user-friendly and powerful MATLAB toolbox for time series analysis of genome-wide chromosome conformation capture (Hi-C) data and gene expression (RNA-seq). NAT can load and normalize data, define topologically associating domains, analyse translocations, produce visualization, and study time course data.