Topological metric detects hidden order in disordered media

Recent advances in microscopy techniques make it possible to study the growth, dynamics, and response of complex biophysical systems at single-cell resolution, from bacterial communities to tissues and organoids. In contrast to ordered crystals, it is less obvious how one can reliably distinguish two amorphous yet structurally different cellular materials. Here, we introduce a topological earth mover's (TEM) distance between disordered structures that compares local graph neighborhoods of the microscopic cell-centroid networks. Leveraging structural information contained in the neighborhood motif distributions, the TEM metric allows an interpretable reconstruction of equilibrium and non-equilibrium phase spaces and embedded pathways from static system snapshots alone. Applied to cell-resolution imaging data, the framework recovers time-ordering without prior knowledge about the underlying dynamics, revealing that fly wing development solves a topological optimal transport problem. Extending our topological analysis to bacterial swarms, we find a universal neighborhood size distribution consistent with a Tracy-Widom law.Comment: 23 pages, 25 figures. Fly wing analysis extended; new bacterial swarming example added; co-authors adde

The role of dietary fatty acids in predicting myocardial structure in fat-fed rats

<p>Abstract</p> <p><it>Background</it></p> <p>Obesity increases the risk for development of cardiomyopathy in the absence of hypertension, diabetes or myocardial ischemia. Not all obese individuals, however, progress to heart failure. Indeed, obesity may provide protection from cardiovascular mortality in some populations. The fatty acid milieu, modulated by diet, may modify obesity-induced myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy in obese individuals.</p> <p><it>Methods</it></p> <p>Adult male Sprague-Dawley rats were fed 1 of the following 4 diets for 32 weeks: control (CON); 50% saturated fat (SAT); 40% saturated fat + 10% linoleic acid (SAT+LA); 40% saturated fat + 10% α-linolenic acid (SAT+ALA). Serum leptin, insulin, glucose, free fatty acids and triglycerides were quantitated. <it>In vivo </it>cardiovascular outcomes included blood pressure, heart rate and echocardiographic measurements of structure and function. The rats were sacrificed and myocardium was processed for fatty acid analysis (TLC-GC), and evaluation of potential modifiers of myocardial structure including collagen (Masson's trichrome, hydroxyproline quantitation), lipid (Oil Red O, triglyceride quantitation) and myocyte cross sectional area.</p> <p><it>Results</it></p> <p>Rats fed SAT+LA and SAT+ALA diets had greater cranial LV wall thickness compared to rats fed CON and SAT diets, in the absence of hypertension or apparent insulin resistance. Treatment was not associated with changes in myocardial function. Myocardial collagen and triglycerides were similar among treatment groups; however, rats fed the high-fat diets, regardless of composition, demonstrated increased myocyte cross sectional area.</p> <p><it>Conclusions</it></p> <p>Under conditions of high-fat feeding, replacement of 10% saturated fat with either LA or ALA is associated with thickening of the cranial LV wall, but without concomitant functional changes. Increased myocyte size appears to be a more likely contributor to early LV thickening in response to high-fat feeding. These findings suggest that myocyte hypertrophy may be an early change leading to gross LV hypertrophy in the hearts of "healthy" obese rats, in the absence of hypertension, diabetes and myocardial ischemia.</p

Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity

Vibrio cholerae remains a major global health threat, disproportionately impacting parts of the world without adequate infrastructure and sanitation resources. In aquatic environments, V. cholerae exists both as planktonic cells and as biofilms, which are held together by an extracellular matrix. V. cholerae biofilms have been shown to be hyperinfective, but the mechanism of hyperinfectivity is unclear. Here we show that biofilm-grown cells, irrespective of the surfaces on which they are formed, are able to markedly outcompete planktonic-grown cells in the infant mouse. Using an imaging technique designed to render intestinal tissue optically transparent and preserve the spatial integrity of infected intestines, we reveal and compare three-dimensional V. cholerae colonization patterns of planktonic-grown and biofilm-grown cells. Quantitative image analyses show that V. cholerae colonizes mainly the medial portion of the small intestine and that both the abundance and localization patterns of biofilm-grown cells differ from that of planktonic-grown cells. In vitro biofilm-grown cells activate expression of the virulence cascade, including the toxin coregulated pilus (TCP), and are able to acquire the cholera toxin-carrying CTXФ phage. Overall, virulence factor gene expression is also higher in vivo when infected with biofilm-grown cells, and modulation of their regulation is sufficient to cause the biofilm hyperinfectivity phenotype. Together, these results indicate that the altered biogeography of biofilm-grown cells and their enhanced production of virulence factors in the intestine underpin the biofilm hyperinfectivity phenotype

Potential PET tracers for imaging of tumor-associated macrophages

The increasing incidence of cancer over the years is one of the most challenging problems in healthcare. As cancer progresses, the recruitment of several immune cells is triggered. Infiltration of tumor-associated macrophages (TAMs) is correlated with poor patient prognosis. Since TAMs constitute a big portion of the tumor mass, targeting these cells seems to be an attractive approach for cancer immunotherapy. Additionally, TAM assessment using non-invasive imaging techniques, such as positron emission tomography (PET), might provide a better understanding of the role of TAMs in cancer, and a means for tumor profile characterization, patient selection for individualized immunotherapy and treatment monitoring. Imaging of TAMs using PET tracers is still in its infancy. TAMs have several characteristics that could be exploited as potential targets for imaging. Various PET tracers for these TAM biomarkers have been developed, although often in the context of (neuro)inflammatory diseases rather than cancer. Since macrophages in inflammatory diseases express similar biomarkers as TAMs, these PET tracers could potentially also be applied for the assessment of TAMs in the tumor microenvironment. Therefore, the present review provides an overview of the TAM biomarkers, for which potential PET tracers are available and discusses the status of these tracers

Search for Axionlike and Scalar Particles with the NA64 Experiment

We carried out a model-independent search for light scalar (s) and pseudoscalar axionlike (a) particles that couple to two photons by using the high-energy CERN SPS H4 electron beam. The new particles, if they exist, could be produced through the Primakoff effect in interactions of hard bremsstrahlung photons generated by 100 GeV electrons in the NA64 active dump with virtual photons provided by the nuclei of the dump. The a(s) would penetrate the downstream HCAL module, serving as shielding, and would be observed either through their $a(s)\to\gamma \gamma$ decay in the rest of the HCAL detector or as events with large missing energy if the a(s) decays downstream of the HCAL. This method allows for the probing the a(s) parameter space, including those from generic axion models, inaccessible to previous experiments. No evidence of such processes has been found from the analysis of the data corresponding to $2.84\times10^{11}$ electrons on target allowing to set new limits on the $a(s)\gamma\gamma$-coupling strength for a(s) masses below 55 MeV.Comment: This publication is dedicated to the memory of our colleague Danila Tlisov. 7 pages, 5 figures, revised version accepted for publication in Phys. Rev. Let

Search for Axionlike and Scalar Particles with the NA64 Experiment

We carried out a model-independent search for light scalar (s) and pseudoscalar axionlike (a) particles that couple to two photons by using the high-energy CERN SPS H4 electron beam. The new particles, if they exist, could be produced through the Primakoff effect in interactions of hard bremsstrahlung photons generated by 100 GeV electrons in the NA64 active dump with virtual photons provided by the nuclei of the dump. The a(s) would penetrate the downstream HCAL module, serving as a shield, and would be observed either through their a(s)→γγ decay in the rest of the HCAL detector, or as events with a large missing energy if the a(s) decays downstream of the HCAL. This method allows for the probing of the a(s) parameter space, including those from generic axion models, inaccessible to previous experiments. No evidence of such processes has been found from the analysis of the data corresponding to 2.84×10^{11} electrons on target, allowing us to set new limits on the a(s)γγ-coupling strength for a(s) masses below 55 MeV