Direction-dependent dynamics of colloidal particle pairs and the Stokes-Einstein relation in quasi-two-dimensional fluids.

Hydrodynamic interactions are important for diverse fluids, especially those with low Reynolds number such as microbial and particle-laden suspensions, and proteins diffusing in membranes. Unfortunately, while far-field (asymptotic) hydrodynamic interactions are fully understood in two- and three-dimensions, near-field interactions are not, and thus our understanding of motions in dense fluid suspensions is still lacking. In this contribution, we experimentally explore the hydrodynamic correlations between particles in quasi-two-dimensional colloidal fluids in the near-field. Surprisingly, the measured displacement and relaxation of particle pairs in the body frame exhibit direction-dependent dynamics that can be connected quantitatively to the measured near-field hydrodynamic interactions. These findings, in turn, suggest a mechanism for how and when hydrodynamics can lead to a breakdown of the ubiquitous Stokes-Einstein relation (SER). We observe this breakdown, and we show that the direction-dependent breakdown of the SER is ameliorated along directions where hydrodynamic correlations are smallest. In total, the work uncovers significant ramifications of near-field hydrodynamics on transport and dynamic restructuring of fluids in two-dimensions.

Depletion-driven antiferromagnetic, paramagnetic, and ferromagnetic behavior in quasi-two-dimensional buckled colloidal solids.

We investigate quasi-two-dimensional buckled colloidal monolayers on a triangular lattice with tunable depletion interactions. Without depletion attraction, the experimental system provides a colloidal analog of the well-known geometrically frustrated Ising antiferromagnet [Y. Han et al., Nature 456, 898-903 (2008)]. In this contribution, we show that the added depletion attraction can influence both the magnitude and sign of an Ising spin coupling constant. As a result, the nearest-neighbor Ising "spin" interactions can be made to vary from antiferromagnetic to para- and ferromagnetic. Using a simple theory, we compute an effective Ising nearest-neighbor coupling constant, and we show how competition between entropic effects permits for the modification of the coupling constant. We then experimentally demonstrate depletion-induced modification of the coupling constant, including its sign, and other behaviors. Depletion interactions are induced by rod-like surfactant micelles that change length with temperature and thus offer means for tuning the depletion attraction in situ. Buckled colloidal suspensions exhibit a crossover from an Ising antiferromagnetic to paramagnetic phase as a function of increasing depletion attraction. Additional dynamical experiments reveal structural arrest in various regimes of the coupling-constant, driven by different mechanisms. In total, this work introduces novel colloidal matter with "magnetic" features and complex dynamics rarely observed in traditional spin systems.

Ratchetlike motion of helical bilayers induced by boundary constraints.

We show that application of boundary constraints generates unusual folding behaviors in responsive (swellable) helical bilayer strips. Unlike the smooth folding trajectories typical of free helical bilayers, the boundary-constrained bilayers exhibit intermittent folding behaviors characterized by rapid, steplike movements. We experimentally study bilayer strips as they swell and fold, and we propose a simple model to explain the emergence of ratchetlike behavior. Experiments and model predictions are then compared to simulations, which enable calculation of elastic energy during swelling. We investigate the dependence of this steplike behavior as a function of elastic boundary condition strength, strip length, and strip shape; interestingly, "V-shape" strips with the same boundary conditions fold smoothly.

Trisomy 21, transposition of the great arteries and abnormal myelopoiesis.

Down syndrome is a well-recognised genetic condition associated with several comorbidities. Although CHD is common in Down syndrome, transposition of the great arteries is exceptionally rare. We describe a neonate with Down syndrome who presented with transient abnormal myelopoiesis and transposition of the great arteries. Down syndrome may accelerate pulmonary hypertension in transposition of the great arteries and is associated with poor outcomes.

Rods in a lyotropic chromonic liquid crystal: emergence of chirality, symmetry-breaking alignment, and caged angular diffusion.

In lyotropic chromonic liquid crystals (LCLCs), twist distortion of the nematic director costs much less energy than splay or bend distortion. This feature leads to novel mirror-symmetry breaking director configurations when the LCLCs are confined by interfaces or contain suspended particles. Spherical colloids in an aligned LCLC nematic phase, for example, induce chiral director perturbations ("twisted tails"). The asymmetry of rod-like particles in an aligned LCLC offer a richer set of possibilities due to their aspect ratio (α) and mean orientation angle (〈θ〉) between their long axis and the uniform far-field director. Here we report on the director configuration, equilibrium orientation, and angular diffusion of rod-like particles with planar anchoring suspended in an aligned LCLC. Video microscopy reveals, counterintuitively, that two-thirds of the rods have an angled equilibrium orientation (〈θ〉 ≠ 0) that decreases with increasing α, while only one-third of the rods are aligned (〈θ〉 = 0). Polarized optical video-microscopy and Landau-de Gennes numerical modeling demonstrate that the angled and aligned rods are accompanied by distinct chiral director configurations. Angled rods have a longitudinal mirror plane (LMP) parallel to their long axis and approximately parallel to the substrate walls. Aligned rods have a transverse and longitudinal mirror plane (TLMP), where the transverse mirror plane is perpendicular to the rod's long axis. Effectively, the small twist elastic constant of LCLCs promotes chiral director configurations that modify the natural tendency of rods to orient along the far-field director. Additional diffusion experiments confirm that rods are angularly confined with strength that depends on α.

Epigallocatechin-3-Gallate Allosterically Activates Protein Kinase C-α and Improves the Cognition of Estrogen Deficiency Mice.

Protein kinase C (PKC) isozymes play essential roles in biological processes, and activation of PKC is proposed to alleviate the symptoms of a variety of diseases. It would be of great significance to find effective pharmacological modulators of PKC isozymes that can be translated for clinical use. Here, using in vitro activity assay, we demonstrated that green tea extract (-)-epigallocatechin-3-gallate (EGCG) dose-dependently activated PKCα with a half effective concentration (EC50) of 0.49 µM. We also performed surface plasmon resonance analysis and found that EGCG binds PKCα with an equilibrium dissociation constant (KD) value of 4.11 × 10-6 mol/L. Further computational flexible docking analysis revealed that EGCG interacted with the catalytic C3-C4 domain of PKCα (PDB: 4RA4) through establishing polar hydrogen bonds with V420, T401, E387, and K368 of PKCα, and the benzene ring group of EGCG hydrophobically interacted with the hydrophobic pocket formed by L345, M470, I479, and V353 of PKCα. Interestingly, the PKCα-selective blocker Ro-32-0432 could compete with EGCG for the same substrate-binding pocket of PKCα. Moreover, we found that EGCG dose-dependently improved the spatial memory, object recognition ability, and hippocampal long-term potentiation of ovariectomized mice, which was offset by Ro-32-0432. Collectively, our findings reveal a novel PKCα agonist and open the way to a new perspective on PKCα pharmacology and the treatment of PKCα-related diseases, including cognitive impairment.

Structural and short-time vibrational properties of colloidal glasses and supercooled liquids in the vicinity of the re-entrant glass transition.

We investigate the short-time vibrational properties and structure of two-dimensional, bidisperse, colloidal glasses and supercooled liquids in the vicinity of the re-entrant glass transition, as a function of interparticle depletion attraction strength. The long-time spatiotemporal dynamics of the samples are measured to be non-monotonic, confirming that the suspensions evolve from repulsive glass to supercooled liquid to attractive glass with increasing depletion attraction. Here, we search for vibrational signatures of the re-entrant behavior in the short-time spatiotemporal dynamics, i.e., dynamics associated with particle motion inside its nearest-neighbor cage. Interestingly, we observe that the anharmonicity of these in-cage vibrations varies non-monotonically with increasing attraction strength, consistent with the non-monotonic long-time structural relaxation dynamics of the re-entrant glass. We also extract effective spring constants between neighboring particles; we find that spring stiffness involving small particles also varies non-monotonically with increasing attraction strength, while stiffness between large particles increases monotonically. Last, from study of depletion-dependent local structure and vibration participation fractions, we gain microscopic insight into the particle-size-dependent contributions to short-time vibrational modes in the glass and supercooled liquid states.

Detection of three pandemic causing coronaviruses from non-respiratory samples: systematic review and meta-analysis.

SARS-CoV-2 has posed an unprecedented challenge to the world. Pandemics have been caused previously by viruses of this family like Middle East Respiratory Corona Virus (MERS CoV), Severe Acute Respiratory Syndrome Corona Virus (SARS CoV). Although these viruses are primarily respiratory viruses, but they have been isolated from non-respiratory samples as well. Presently, the detection rate of SARS-CoV-2 RNA from different clinical specimens using Real Time Reverse Transcriptase Polymerized Chain Reaction (qRT-PCR) after onset of symptoms is not yet well established. Therefore, the aim of this systematic review was to establish the profile of detecting SARS-CoV-2, MERS CoV, SARS CoV from different types of clinical specimens other than the respiratory using a standard diagnostic test (qRT-PCR). A total of 3429 non-respiratory specimens were recorded: SARS CoV (total sample-802), MERS CoV (total sample-155), SARS CoV-2 (total sample-2347). Out of all the samples studied high positive rate was seen for saliva with 96.7% (14/14; 95% CI 87.6-100.0%) for SARS CoV and 57.5% (58/250; 95% CI - 1.2 to 116.2%) for SARS CoV-2, while low detection rate in urine samples for SARS CoV-2 with 2.2% (8/318; 95% CI 0.6-3.7%) and 9.6% (12/61; 95% CI - 0.9 to 20.1%) for SARS CoV but there was relatively higher positivity in urine samples for MERS CoV with detection rate of 32.4% (2/38; 95% CI - 37.3 to 102.1%). In Stool sample positivity was 54.9% (396/779; 95% CI 41.0-68.8%), 45.2% (180/430; 95% CI 28.1-62.3%) and 34.7% (4/38; 95% CI - 29.5 to 98.9%) for SARS CoV-2, MERS CoV, and SARS CoV, respectively. In blood sample the positivity was 33.3% (7/21; 95% CI 13.2-53.5%), 23.7% (42/277; 95% CI 10.5-36.9%) and 2.5% (2/81; 95% CI 0.00-5.8%) for MERS CoV, SARS CoV-2 and SARS CoV respectively. SARS-CoV-2 along with previous two pandemic causing viruses from this family, were highly detected stool and saliva. A low positive rate was recorded in blood samples. Viruses were also detected in fluids along with unusual samples like semen and vaginal secretions thus highlighting unique pathogenic potential of SARS-CoV-2.

Lentivirus-Carried microRNA-195 Rescues Memory Deficits of Alzheimer's Disease Transgenic Mouse by Attenuating the Generation of Amyloid Plaques.

Although lots of new drugs are developed to treat Alzheimer's disease (AD), many clinical trials of monotherapy have failed to affect disease progression or symptoms compared with placebo. Recently, scientists believe that combination treatment is more promising than monotherapy. Previous studies found that microRNA-195 (miR-195) was down-regulated in the hippocampi and cortices of chronic brain hypoperfusion (CBH) rats and ApoE4(+/+) mice, and up-regulation of miR-195 can improve the declined cognitive function of ApoE4(+/+) mice and CBH rats by targeting multi-genes that are related to AD pathology, including amyloid precursor protein (APP) and ß-site APP cleaving enzyme 1 (BACE1) genes. However, whether the gain-of-function of miR-195 could improve the impaired learning and memory ability of APP/PS1 transgenic mouse has not been reported. In this study, we stereotaxically injected lentiviral-carried miR-195 into the bilateral hippocampus of 4-month-old (4M) APP/PS1 mice. Morris water maze (MWM) was performed to detect the effect of miR-195 on the cognitive function of APP/PS1 mice after 1M, 2M, and 3M treatment. Western blot was used to detect the expression of APP, BACE1, and AT8. Aß plagues were quantitatively assessed by immunofluorescence technique. We found that the declined cognitive phenotype of APP/PS1 mice occurred at the age of 6M, not at the age of 5M. And treatment of Lv-pre-miR-195 to APP/PS1 mice for 1M did not achieve any changes. Although Lv-pre-miR-195 treatment for 2M improved the declined learning ability of APP/PS1 mice, it did not affect the memory functions. However, Lv-pre-miR-195 treatment in APP/PS1 mice for 3M can effectively improve both the learning and memory ability of APP/PS1 mice at the age of 7M. Further studies demonstrated that gain-of-function of miR-195 by Lv-pre-miR-195 injection could inhibit the increased APP and AT8 expression of APP/PS1 mice but did not affect BACE1 level that was not changed in both hippocampus and cortex. By counting the number of Aß plaques of different sizes, we found that Lv-pre-miR-195 treatment mainly reduced the number of Aß plaques of less than 20 µm, but did not affect the number of Aß plaques of greater than 50 µm. Taken together, the gain-of -function of miR-195 in the hippocampus can improve the cognition of APP/PS1 mice, probably by blocking the formation of Aß plagues rather than clearing those that have already formed Aß plagues.

Cholinergic Dysfunction Involvement in Chronic Cerebral Hypoperfusion-Induced Impairment of Medial Septum-dCA1 Neurocircuit in Rats.

Chronic cerebral hypoperfusion (CCH) is considered a preclinical condition of mild cognitive impairment and thought to precede dementia. However, as the principal cholinergic source of hippocampus, whether the septo-hippocampal neurocircuit was impaired after CCH is still unknown. In this study, we established the CCH rat model by bilateral common carotid artery occlusion (2VO). Under anesthesia, the medial septum (MS) of rats was stimulated to evoke the field excitatory post-synaptic potential (fEPSP) in the pyramidal cell layer of dCA1. Consequently, we observed decreased amplitude of fEPSP and increased paired-pulse ratio (PPR) after 8-week CCH. After tail pinch, we also found decreased peak frequency and shortened duration of hippocampal theta rhythm in 2VO rats, indicating the dysfunction of septo-hippocampal neurocircuit. Besides, by intracerebroventricularly injecting GABAergic inhibitor (bicuculline) and cholinergic inhibitors (scopolamine and mecamylamine), we found that CCH impaired both the pre-synaptic cholinergic release and the post-synaptic nAChR function in MS-dCA1 circuits. These results gave an insight into the role of CCH in the impairment of cholinergic MS-dCA1 neurocircuits. These findings may provide a new idea about the CCH-induced neurodegenerative changes.

MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion.

BACKGROUND: Chronic brain hypoperfusion (CBH) is closely related to Alzheimer's disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear. METHODS: In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1-43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO). RESULTS: Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1-43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2'-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3' untranslated region (3'UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats. CONCLUSIONS: Overexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3'UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD. Video Abstract.

Cooperative particle rearrangements facilitate the self-organized growth of colloidal crystal arrays on strain-relief patterns.

Strain-relief pattern formation in heteroepitaxy is well understood for particles with long-range attraction and is a routinely exploited organizational principle for atoms and molecules. However, for particles with short-range attraction such as colloids and nanoparticles, which form brittle assemblies, the mechanism(s) of strain-relief is not known. Here, we found that for colloids with short-range attraction, monolayer films on substrates with square symmetry could accommodate large compressive misfit strains through locally dewetted hexagonally ordered stripes. Unexpectedly, over a window of compressive strains, cooperative particle rearrangements first resulted in a periodic strain-relief pattern, which then guided the growth of laterally ordered defect-free colloidal crystals. Particle-resolved imaging of monomer dynamics on strained substrates also helped uncover cooperative kinetic pathways for surface transport. These processes, which substantially influenced the film morphology, have remained unobserved in atomic heteroepitaxy studies hitherto. Leaning on our findings, we developed a heteroepitaxy approach for fabricating hierarchically ordered surface structures.

Rickets with hypophosphatemia, hypokalemia and normal anion gap metabolic acidosis: not always an easy diagnosis.

Rickets other than those associated with advanced kidney disease, isolated distal renal tubular acidosis (dRTA) and hypophosphatasia (defective tissue non-specific alkaline phosphatase) are associated with hypophosphatemia due to abnormal proximal tubular reabsorption of phosphate. dRTA, however, at times is associated with completely reversible proximal tubular dysfunction. On the other hand, severe hypophosphatemia of different aetiologies may also interfere with both distal tubular acid excretion and proximal tubular functions giving rise to transient secondary renal tubular acidosis (distal and/or proximal). Hypophosphatemia and non-anion gap metabolic acidosis thus pose a diagnostic challenge occasionally. A definitive diagnosis and an appropriate management of the primary defect results in complete reversal of the secondary abnormality. A child with vitamin D resistant rickets was thoroughly evaluated and found to have primary dRTA with secondary proximal tubular dysfunction in the form of phosphaturia and low molecular weight proteinuria. The child was treated only with oral potassium citrate. A complete clinical, biochemical and radiological improvement was noticed in follow-up.

Long-wavelength fluctuations and anomalous dynamics in 2-dimensional liquids.

In 2-dimensional systems at finite temperature, long-wavelength Mermin-Wagner fluctuations prevent the existence of translational long-range order. Their dynamical signature, which is the divergence of the vibrational amplitude with the system size, also affects disordered solids, and it washes out the transient solid-like response generally exhibited by liquids cooled below their melting temperatures. Through a combined numerical and experimental investigation, here we show that long-wavelength fluctuations are also relevant at high temperature, where the liquid dynamics do not reveal a transient solid-like response. In this regime, these fluctuations induce an unusual but ubiquitous decoupling between long-time diffusion coefficient D and structural relaxation time τ, where [Formula: see text], with [Formula: see text] Long-wavelength fluctuations have a negligible influence on the relaxation dynamics only at extremely high temperatures in molecular liquids or at extremely low densities in colloidal systems.

Correlations between short- and long-time relaxation in colloidal supercooled liquids and glasses.

Spatiotemporal dynamics of short- and long-time structural relaxation are measured experimentally as a function of packing fraction, ϕ, in quasi-two-dimensional colloidal supercooled liquids and glasses. The relaxation times associated with long-time dynamic heterogeneity and short-time intracage motion are found to be strongly correlated and to grow by orders of magnitude with increasing ϕ toward dynamic arrest. We find that clusters of fast particles on the two timescales often overlap, and, interestingly, the distribution of minimum-spatial-separation between closest nonoverlapping clusters across the two timescales is revealed to be exponential with a decay length that increases with ϕ. In total, the experimental observations suggest short-time relaxation events are very often precursors to heterogeneous relaxation at longer timescales in glassy materials.

Dynamic Heterogeneities in Colloidal Supercooled Liquids: Experimental Tests of Inhomogeneous Mode Coupling Theory.

The dynamics in supercooled liquids slow enormously upon approaching the glass transition, albeit without significant change of liquid structure. This empirical observation has stimulated development of many theoretical models which attempt to elucidate microscopic mechanisms in glasses and glass precursors. Here, quasi-two-dimensional colloidal supercooled liquids and glasses are employed to experimentally test predictions of widely used models: mode coupling theory (MCT) and its important extension, inhomogeneous MCT (IMCT). We measure two-point dynamic correlation functions in the glass forming liquids to determine structural relaxation times, τα, and mode coupling exponents, a, b, and γ; these parameters are then used to extract the mode coupling dynamic crossover packing area-fraction, ϕ c. This information, along with our measurements of supercooled liquid spatiotemporal dynamics, permits characterization of dynamic heterogeneities in the samples and facilitates direct experimental tests of the scaling predictions of IMCT. The time scales at which dynamic heterogeneities are largest, and their spatial sizes, exhibit power law growth on approaching ϕ c. Within experimental error, the exponents of the measured power laws are close to the predictions of IMCT.

Site-specific colloidal crystal nucleation by template-enhanced particle transport.

The monomer surface mobility is the single most important parameter that decides the nucleation density and morphology of islands during thin-film growth. During template-assisted surface growth in particular, low surface mobilities can prevent monomers from reaching target sites and this results in a partial to complete loss of nucleation control. Whereas in atomic systems a broad range of surface mobilities can be readily accessed, for colloids, owing to their large size, this window is substantially narrow and therefore imposes severe restrictions in extending template-assisted growth techniques to steer their self-assembly. Here, we circumvented this fundamental limitation by designing templates with spatially varying feature sizes, in this case moiré patterns, which in the presence of short-range depletion attraction presented surface energy gradients for the diffusing colloids. The templates serve a dual purpose: first, directing the particles to target sites by enhancing their surface mean-free paths and second, dictating the size and symmetry of the growing crystallites. Using optical microscopy, we directly followed the nucleation and growth kinetics of colloidal islands on these surfaces at the single-particle level. We demonstrate nucleation control, with high fidelity, in a regime that has remained unaccessed in theoretical, numerical, and experimental studies on atoms and molecules as well. Our findings pave the way for fabricating nontrivial surface architectures composed of complex colloids and nanoparticles as well.

Shape of dynamical heterogeneities and fractional Stokes-Einstein and Stokes-Einstein-Debye relations in quasi-two-dimensional suspensions of colloidal ellipsoids.

We examine the influence of the shape of dynamical heterogeneities on the Stokes-Einstein (SE) and Stokes-Einstein-Debye (SED) relations in quasi-two-dimensional suspensions of colloidal ellipsoids. For ellipsoids with repulsive interactions, both SE and SED relations are violated at all area fractions. On approaching the glass transition, however, the extent to which this violation occurs changes beyond a crossover area fraction. Quite remarkably, we find that it is not just the presence of dynamical heterogeneities but their change in the shape from stringlike to compact that coincides with this crossover. On introducing a suitable short-range depletion attraction between the ellipsoids, associated with the lack of morphological evolution of dynamical heterogeneities, the extent to which the SE and SED relations are violated remains unchanged even for deep supercooling.

Dynamical facilitation governs glassy dynamics in suspensions of colloidal ellipsoids.

One of the greatest challenges in contemporary condensed matter physics is to ascertain whether the formation of glasses from liquids is fundamentally thermodynamic or dynamic in origin. Although the thermodynamic paradigm has dominated theoretical research for decades, the purely kinetic perspective of the dynamical facilitation (DF) theory has attained prominence in recent times. In particular, recent experiments and simulations have highlighted the importance of facilitation using simple model systems composed of spherical particles. However, an overwhelming majority of liquids possess anisotropy in particle shape and interactions, and it is therefore imperative to examine facilitation in complex glass formers. Here, we apply the DF theory to systems with orientational degrees of freedom as well as anisotropic attractive interactions. By analyzing data from experiments on colloidal ellipsoids, we show that facilitation plays a pivotal role in translational as well as orientational relaxation. Furthermore, we demonstrate that the introduction of attractive interactions leads to spatial decoupling of translational and rotational facilitation, which subsequently results in the decoupling of dynamical heterogeneities. Most strikingly, the DF theory can predict the existence of reentrant glass transitions based on the statistics of localized dynamical events, called excitations, whose duration is substantially smaller than the structural relaxation time. Our findings pave the way for systematically testing the DF approach in complex glass formers and also establish the significance of facilitation in governing structural relaxation in supercooled liquids.