Biology subjects

Srivastava, L. K.

Publications and source records attributed to Srivastava, L. K..

3 recordsLinked to original sources

bioRxiv2024

Effects of prenatal maternal immune activation and exposure to circadian disruption during adolescence: exploring the two-hit model of neurodevelopmental disorders

BackgroundAround 80% of individuals with neurodevelopmental disorders (NDDs) such as schizophrenia and autism spectrum disorders experience disruptions in sleep/circadian rhythms. We explored whether prenatal infection, an established risk factor for NDDs, and environmental circadian disruption synergistically induced sex-specific deficits in mice. MethodsA maternal immune activation (MIA) protocol was used by injecting pregnant mice (at E9.5) with a viral mimic poly IC or saline. Then, juvenile/adolescent offspring (3-7 weeks old) were subjected to either standard lighting (12:12LD) or constant light (LL). ResultsWe found interactions of the two factors on behaviors related to cognition, anxiety, and sociability. Also, poly IC exposure led to a more activated profile of hippocampal microglia in males only, while LL diminished these effects. Using RNA sequencing in the dorsal hippocampus, we found that poly IC exposure led to many differentially expressed genes in males (but not females), and fewer differentially expressed genes were observed after LL exposure. Using the WGCNA analysis, we found several significant gene modules positively associated with poly IC (in comparison to saline exposure) and LL (in comparison to LD exposure) in males, and less so in females. Interestingly, many of the identified hub bottleneck genes were homologous to human genes associated with both sleep/circadian rhythms and neurodevelopmental disorders as identified by GWA studies. ConclusionsOur work demonstrates that in a mouse model of prenatal infection, disruptions in circadian rhythms induced by LL play a role in modulating the effects of MIA at behavioral, cellular, and molecular levels.

neuroscience↗

bioRxiv2020

Pattern-based Contractility Screening (PaCS), a reference-free traction force microscopy methodology, reveals contractile differences in breast cancer cells

The sensing and generation of cellular forces are essential aspects of life. Traction Force Microscopy (TFM) has emerged as a standard broadly applicable methodology to measure cell contractility and its role in cell behavior. While TFM platforms have enabled diverse discoveries, their implementation remains limited in part due to various constraints, such as time-consuming substrate fabrication techniques, the need to detach cells to measure null force images, followed by complex imaging and analysis, and the unavailability of cells for post-processing. Here we introduce a reference-free technique to measure cell contractile work in real-time, with basic substrate fabrication methodologies, simple imaging, and analysis with the availability of the cells for post-processing. In this technique, we confine the cells on fluorescent adhesive protein micropatterns of a known area on compliant silicone substrates and use the cell deformed pattern area to calculate cell contractile work. We validated this approach by comparing this Pattern-based Contractility Screening (PaCS) to conventional bead-displacement TFM and show quantitative agreement between the methodologies. Using this platform, we measure the contractile work of highly metastatic MDA-MB-231 breast cancer cells is significantly higher than non-invasive MCF-7 cells. PaCS enables the broader implementation of contractile work measurements in diverse quantitative biology and biomedical applications.

biophysics↗

bioRxiv2019

Spatial distribution of lamin A determines nuclear stiffness and stress-mediated deformation

The nucleus is the largest organelle and information center of the cell; while diverse cellular components have been identified as mechanotransduction elements, the deformation of the nucleus itself is emerging as a critical mechanosensory mechanism, suggesting that the nuclear stiffness is essential in determining responses to intracellular and extracellular stresses. The nuclear membrane protein, lamin A, is known to be a dominant component in nuclear stiffening; however, the quantitative relationship between lamin A expression and nuclear deformation is still unclear. Here we measure the nuclear moduli as a function of lamin A expression and applied stress, revealing a linear dependence of bulk modulus on lamin A expression. We also find that the bulk modulus is anisotropic, with the vertical axis of the nucleus being more compliant than the minor and major axis. To examine how lamin A influences nuclear mechanics at the sub-micron scale we correlated the spatial distribution of lamin A with 3D nuclear envelope deformation, revealing that local areas of the nuclear envelope with higher expression levels of lamin A have correspondingly lower local deformations, and that increased lamin A expression levels result in a narrower distribution of smaller deformations. These findings describe the complex dispersion of nuclear deformations as a function of lamin A expression and distribution and implicate a role in mechanotransduction.

bioengineering↗