bioRxiv Science⌕ Search

Biology subjects

Venkatraman, L.

Publications and source records attributed to Venkatraman, L..

4 recordsLinked to original sources

Magnetic compass orientation behaviour of Eurasian blackcaps at the predicted 110-120 MHz upper cut-off frequency for radiofrequency-field effects

Night-migratory songbirds use the Earths magnetic field to guide their migratory journeys. Most evidence suggests that the magnetic compass sensor is a flavin-tryptophan radical pair whose operation is disrupted by broadband radiofrequency (RF) fields at frequencies up to [~]116 MHz. Here, we test whether broadband 110-120 MHz RF fields affect the magnetic orientation behaviour of night-migratory Eurasian blackcaps (Sylvia atricapilla). We found that the birds oriented in their expected migratory direction in the natural geomagnetic field (NMF) control condition and that they turned their orientation [~]120{degrees} when the field was rotated 120{degrees} horizontally (changed magnetic field, CMF). When they were exposed to broadband 110-120 MHz RF fields, the birds continued to orient in the appropriate direction in the NMF. In the CMF, we found orientation behaviour that was not consistent with the expected direction. We conclude that the birds could still orient when exposed to 110-120 MHz fields, but speculate that their magnetic orientation capabilities might have been somewhat reduced compared to the control condition. We suggest that 110-120 MHz could represent a grey zone of reduced magnetic orientation capability centred at the cut-off frequency predicted for a flavin-based radical pair (probably in the flavoprotein cryptochrome).

animal behavior and cognition↗

Pre-determined macromolecular leakage sites with dynamic properties establish endothelial intra-vessel heterogeneity

Endothelial cells display heterogeneous properties based on location and function. How this heterogeneity influences endothelial barrier stability both between and within vessel subtypes is unexplored. We find here that endothelial cells exhibit heterogeneous barrier properties on inter-organ and intra-vessel levels. Using intravital microscopy and sequential stimulation of the ear dermis with vascular endothelial growth factor-A and/or histamine, we observe distinct, reappearing sites, common for both agonists, where leakage preferentially takes place. Further, through repetitive stimulation of the diaphragm and trachea, we find inter-organ conservation of such leakage sites. Qualitatively, pre-determined sites display distinct leakage properties and enhanced barrier breakdown compared to less susceptible regions. Mechanistically, pre-determined sites exhibit lower laminin 5 deposition, which correlates with reduced junctional vascular endothelial (VE)-Cadherin. These data thus highlight functional intra-vessel heterogeneity that defines pre-determined sites which display distinct leakage properties and which may have great impact on pathological vascular leakage and drug delivery.

cell biology↗

Mouse retinal cell behaviour in space and time using light sheet fluorescence microscopy

As the general population ages and the incidence of diabetes increases epidemically, more people are affected by eye diseases, such as retinopathies. It is therefore critical to improve imaging of eye disease mouse models. Here, we demonstrate that 1) rapid, quantitative 3D and 4D (time lapse) imaging of cellular and subcellular processes in the murine eye is feasible, with and without tissue clearing, using light-sheet fluorescent microscopy (LSFM) and 2) LSFM readily reveals new features of even well studied eye disease mouse models, such as the Oxygen-Induced Retinopathy (OIR) model. Through correlative LSFM-Confocal imaging we find that flat-mounting retinas for confocal microscopy significantly distorts tissue morphology. The minimized distortion with LSFM dramatically improved analysis of pathological vascular tufts in the OIR model revealing \"knotted\" morphologies, leading to a proposed new tuft nomenclature. Furthermore, live-imaging of OIR tuft formation revealed abnormal cell motility and altered filopodia dynamics. We conclude that quantitative 3D/4D LSFM imaging and analysis has the potential to advance our understanding of pathological processes in the eye, in particular neuro-vascular degenerative processes.

developmental biology↗

Positive-feedback defines the timing and robustness of angiogenesis

Blood vessel formation by angiogenesis is critical for tissue development, homeostasis and repair, and is frequently dysregulated in disease[1-3]. Angiogenesis is triggered by vascular endothelial growth factor receptor-2/3 (VEGFR) signalling, which induces motile endothelial cell (ECs) tip identity[4,5]. Tip cells lead new branching vessels, but also coordinate collective EC movement by repressing tip identity in adjacent ECs via Delta-Like 4 (DLL4)-Notch-mediated down-regulation of VEGFR activity[6-13]. Hence, angiogenesis is driven by lateral inhibition-mediated competition of ECs for migratory status. Recent work reveals that temporal modulation of this DLL4-Notch-mediated lateral inhibition circuit fundamentally shapes both normal and pathological angiogenesis[14-17]. However, the core regulatory network defining the timing and dynamics of EC decision-making is unclear. Here, by integrating computational modeling with in-vivo experimentation, we uncover a unique ultrasensitive switch that temporally defines EC lateral inhibition and ultimately determines the timing, magnitude and robustness of angiogenic responses. We reveal that positive-feedback to Vegfr via the atypical tetraspanin, tm4sf18, amplifies Vegfr activity and expedites EC decision-making in-vivo. Moreover, this Tm4sf18-mediated positive-feedback confers robustness to angiogenesis against changeable environmental conditions by invoking bistable-like behavior. Consequently, mutation of tm4sf18 in zebrafish delays motile EC selection, generates hypoplastic vessels, sensitizes ECs to fluctuations in pro-angiogenic signal and disrupts angiogenesis. We propose that positive-feedback transforms the normally protracted process of lateral inhibition into a quick, adaptive and robust decision-making mechanism, suggestive of a general framework for temporal modulation of cell fate specification in development and disease.

developmental biology↗