Biology subjects

Shi, G.

Publications and source records attributed to Shi, G..

71 records · Page 4Linked to original sources

bioRxiv2020

Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.

neuroscience↗

bioRxiv2020

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

genomics↗

bioRxiv2020

Transcranial in vivo detection of Aβ at single plaque resolution with large-field multifocal illumination fluorescence microscopy

The abnormal deposition of beta-amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimers disease. Currently available intravital microscopy techniques for high-resolution plaque visualization commonly involve highly invasive procedures and are limited to a small field-of-view within the rodent brain. Here, we report the transcranial detection of amyloid-beta deposits at the whole brain scale with 20 m resolution in APP/PS1 and arcA{beta} mouse models of Alzheimers disease amyloidosis using a large-field multifocal (LMI) fluorescence microscopy technique. Highly sensitive and specific detection of amyloid-beta deposits at a single plaque level in APP/PS1 and arcA{beta} mice was facilitated using luminescent conjugated oligothiophene HS-169. Immunohistochemical staining with HS-169, anti-A{beta} antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections further showed that HS-169 resolved compact parenchymal and vessel-associated amyloid deposits. The novel imaging platform offers new prospects for in vivo studies into Alzheimers disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.

neuroscience↗

bioRxiv2019

NADPH diaphorase neuronal dystrophy in gracile nucleus, cuneatus nucleus and spinal trigeminal nucleus in aged rat

NADPH-diaphorase (N-d) activity is commonly used to identify NOS-ergic neurons. In our previous study, N-d positive neuritic dystrophy and spheroid termed aging-related N-d Body is discovered in the lumbosacral spinal cord in the normal aging rats. Histological studies also reveal that N-d positive neurodegenerative changes occur in the gracile nucleus. We re-examined N-d activity in gracile nucleus in aged rat. We found N-d positive neuritic dystrophy and spheroid also occurred in the cuneatus nucleus and spinal trigeminal nucleus. Besides regular coronal section, longitudinal oriented dystrophic neurites were detected in the sagittal and horizontal section in gracile nucleus and dorsal column. We fziurther examined the medullary oblongata with regular classical histology including Golgi staining, immunocytochemistry of NOS and phosphorylated tau protein, neuronal tracing method with wheat germ agglutinin conjugated alexa-fluor-488 through sciatic nerve, and spinal cord transection at thoracic level. Most of N-d positive neuritic dystrophy and spheroid did not showed colocalization with NOS or phosphorylated tau protein. Neuronal tracing and spinal cord transection revealed that N-d dystrophic neurites in gracile nucleus originated from terminal of sensory projection from spinal cord and peripheral somatic input. The results suggested that aging-related N-d dystrophy in the gracile nucleus was unique morphological feature. In conclusion, it was postulated that the N-d dystrophy as a morphological marker of aging degenerative damage in normal aged organisms.

neuroscience↗

bioRxiv2019

Endoplasmic reticulum associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity

Many tissue-specific stem cells require quiescence to sustain stem cell pool and maintain lifelong tissue integrity. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis and metabolic activities are significantly reduced. Here, we report that endoplasmic reticulum associated degradation (ERAD) is required to preserve the function of quiescent hematopoietic stem cells (HSC). The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyper-proliferation which leads to reduced self-renewal and HSC depletion. ERAD deficiency induces a non-apoptotic ER stress and activates unfolded protein response (UPR). Furthermore, Sel1L knockout leads to mTOR activation, and mTOR inhibition rescues the HSC defects in Sel1L knockout mice. Protein quality control is, therefore, tightly regulated and actively engaged in quiescent HSCs. Sel1L/Hrd1 ERAD maintains HSC quiescence and self-renewal via restricting mTOR activity.

cell biology↗

bioRxiv2019

Solution of the FISH-Hi-C paradox for Human Interphase Chromosomes

Hi-C experiments are used to infer the contact probabilities between loci separated by varying genome lengths. Contact probability should decrease as the spatial distance between two loci increases. However, studies comparing Hi-C and FISH data show that in some cases the distance between one pair of loci, with larger Hi-C readout, is paradoxically larger compared to another pair with a smaller value of the contact probability. Here, we show that the FISH-Hi-C paradox can be resolved using a theory based on a Generalized Rouse Model for Chromosomes (GRMC). The FISH-Hi-C paradox arises because the cell population is highly heterogeneous, which means that a given contact is present in only a fraction of cells. Insights from the GRMC is used to construct a theory, without any adjustable parameters, to extract the distribution of subpopulations from the FISH data, which quantitatively reproduces the Hi-C data. Our results show that heterogeneity is pervasive in genome organization at all length scales, reflecting large cell-to-cell variations.

biophysics↗

bioRxiv2019

Changes in the Physicochemical Properties and Microbial Communities of Rhizospheric Soil after Cassava/Peanut Intercropping

Cassava/peanut intercropping is a popular cultivation method in southern China and has the advantages of apparently increased yield and economic efficiency compared with monoculture, however, the ecological benefits of this method are poorly understood. This study aimed to investigate the effects of intercropping on the physicochemical properties and microbial community structures of soil. Field trials were performed to determine the effects of cassava/peanut intercropping on rhizospheric soil nutrient content, enzyme activities, microbial quantity and microbial community structure. The microbial community was characterized by 16S rRNA tag-based high-throughput sequencing on the Illumina MiSeq platform. Results showed that cassava/peanut intercropping could improve the physicochemical properties of rhizospheric soil by increasing the available nutrient content, pH, bacterial quantity, and some enzyme activities and by altering the microbial community structure. 16S rRNA gene sequencing demonstrated that the microbial community structure varied between the intercropping and monoculture systems. Nitrospirae, Verrucomicrobia and Gemmatimonadetes were more abundant in the intercropping system than in the monocultures. Redundancy analysis (RDA) revealed that the abundances of DA101, Pilimelia and Ramlibacter were positively correlated with environmental parameters such as available nitrogen and pH, and these were dominant genera in the rhizospheric soil of the intercropped peanut plants.

ecology↗

bioRxiv2019

SynQuant: An Automatic Tool to Quantify Synapses from Microscopy Images

MotivationSynapses are essential to neural signal transmission. Therefore, quantification of synapses and related neurites from images is vital to gain insights into the underlying pathways of brain functionality and diseases. Despite the wide availability of synapse imaging data, several issues prevent satisfactory quantification of these structures by current tools. First, the antibodies used for labeling synapses are not perfectly specific to synapses. These antibodies may exist in neurites or other cell compartments. Second, the brightness for different neurites and synapses is heterogeneous due to the variation of antibody concentration and synapse-intrinsic differences. Third, images often have low signal to noise ratio (SNR) due to constraints of experiments and availability of sensitive antibodies. The combination of these issues makes the detection of synapses challenging and necessitates developing a new tool to accurately and reliably quantify synapses. ResultsWe present an automatic probability-principled synapse detection algorithm and integrate it into our synapse quantification tool SynQuant. Derived from the theory of order statistics, our method controls the false discovery rate and improves the power of detecting synapses. Through extensive experiments on both synthetic and real images in the presence of severe antibody diffusion, high heterogeneity, and large noise, our method was demonstrated to outperform peer specialized synapse detection tools as well as generic spot detection methods by a large margin. Finally, we show SynQuant reliably uncovers statistically significant differences between disease and control conditions in a neuron-astrocyte co-culture based model of Down Syndrome. AvailabilityThe Java source code, Fiji plug-in, and test data are available at https://github.com/yu-lab-vt/SynQuant. Contactyug@vt.edu

neuroscience↗

bioRxiv2019

Dual forms of aging-related NADPH diaphorase neurodegeneration in the sacral spinal cord of aged non-human primates

We discovered two different anomalous NADPH diaphorase (NADPH-d) positive alterations, which were expressed as aging-related NADPH-d positive spheroidal bodies and megaloneurites specially distributed in the superficial dorsal horn, dorsal gray commissure (DGC), lateral collateral pathway (LCP) and sacral parasympathetic nucleus (SPN) in the aged monkeys sacral spinal cord, compared with the cervical, thoracic and lumbar segments. In the gracile nucleus of aged monkeys, only aging-related spheroidal bodies were observed and no megaloneurites occurred. The dense, abnormal NADPH-d positive megaloneurites, extremely different from regular NADPH-d positive fibers, were prominent in the sacral segments and occurred in extending from Lissauers tract (LT) through lamina I along the lateral boundary of the dorsal horn to the region of the SPN. Meanwhile, large diameter punctate NADPH-d activity occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone (DREZ) at the same level of NADPH-d abnormality in the gray matters. Those dot-like NADPH-d alterations were examined by horizontal sectioning and indicated ascending or descending oriental fibers. These NADPH-d megaloneurites had the same composition as the punctate NADPH-d alterations and were co-localized with the VIP immunoreaction, while the ANBs did not coexist with the VIP immunoreaction. Both ANBs and megaloneurites provide consistent evidence that the anomalous neuritic alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.

neuroscience↗

bioRxiv2018

A generalist pathogen view of plant evolution

Botrytis cinerea is a polyphagous fungal pathogen that causes necrotic disease on more than a thousand known hosts widely spread across the plant kingdom. While it is known that quantitative resistance in the host and quantitative virulence in the pathogen largely mediate this pathosystem, how this pathogen interacts with the extensive host diversity is unknown. Does this pathogen have quantitative virulence efficiency on all hosts or individual solutions for each host? To address this question, we generated an infectivity matrix of 98 strains of Botrytis cinerea on 90 genotypes representing eight host plants. This experimental infectivity matrix showed that the predominant sources of quantitative variation are between host species and among pathogen strains. Furthermore, the eight eudicot hosts interacted individually with Botrytis cinerea strains independently of the evolutionary relatedness between hosts. An additive quantitative model can explain the complexity of these interactions in which Botrytis host specificity and general virulence have distinct polygenic architectures.

plant biology↗

bioRxiv2018

Study on physicochemical properties and microbial diversity of flammulina velutipes residue during rapid fermentation

In order to investigate the effects of different mass ratios of corn straw, super absorbent resin (SAR) and cellulose decomposing strains on fermentation of flammulina velutipes residue, the cellulose degradation rate, germination index, bacterial diversity, urease activity, cellulase activity and other indicators were evaluated comprehensively so as to determine the optimal fermentation parameters. The research results indicated that the three factors of corn straw, high water-absorbent resin (SAR), and cellulose-decomposing strains have the tendency to enhance fermentation in the process. In the orthogonal test, the treatment with the highest cellulose degradation rate was T6. By 24 days, all the treated seeds germination Indices (GIs) were higher than 80%, which indicated that they were basically harmless to crops. The cellulase activity and urease activity of each treatment showed the characteristics of first rising and then decreasing as the fermentation time prolonged. In general, the T6 (the added amount of corn straw was 10%, the amount of super absorbent resin was 0.15%, and the amount of cellulose-decomposing strains was 2%) was the suitable mass ratio of additives in the fermentation which provided a certain theoretical support for resource utilization of flammulina velutipes residue.

plant biology↗

bioRxiv2018

5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed -fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.

cancer biology↗

bioRxiv2018

Diverse Mechanisms of Resistance in Carbapenem-Resistant Enterobacteriaceae at a Health Care System in Silicon Valley, California

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a major health threat in North America. The mechanism of resistance to carbapenems has therapeutic and public health implications. We comprehensively characterized the underlying mechanisms of carbapenem resistance in CRE isolates recovered between 2013 and 2016 at a health system in Northern California. Genotypic methods were used to detect carbapenemases and plasmid-encoded cephalosporinases, and mass spectrometry was used to quantify relative porin levels for OmpC and OmpF and their analogs. MICs for imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and ceftolozane-tazobactam were measured. Whole genome sequencing was used for strain typing. A carbapenemase gene encoding blaOXA-48 like, blaNDM, blaKPC, blaSME, blaIMP, and blaVIM was detected in 38.7% (24/62) of CRE isolates. Porin levels was down at least 2-fold in 91.9% (57/62) of isolates. Including carbapenemase genes and porin loss, the mechanism of resistance was identified in 95.2% (59/62) of CRE isolates. Of the carbapenemase gene-positive isolates, blaKPC -positive isolates were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and blaSME-positive isolates were 100% susceptible to meropenem-vaborbactam and ceftolozane-tazobactam. 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) of carbapenemase gene-negative CRE isolates were susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were genetically identical. In conclusion, at this health system in Silicon Valley, carbapenemase-producing CRE occurred sporadically and were mediated by diverse mechanisms. Nucleic acid testing for blaOXA-48 like, blaNDM, blaKPC, blaIMP, and blaVIM was sufficient to distinguish between carbapenemase-producing and non-producing CRE and accurately predicted susceptibility to ceftazidime-avibactam, meropenem-vaborbactam and imipenem-relebactam.

microbiology↗

bioRxiv2018

Crop domestication and pathogen virulence: Interactions of tomato and Botrytis genetic diversity

Human selection during crop domestication alters numerous traits, including disease resistance. Studies of qualitative resistance to specialist pathogens typically find decreased resistance in domesticated crops in comparison to their wild relatives. However, less is known about how crop domestication affects quantitative interactions with generalist pathogens. To study how crop domestication impacts plant resistance to generalist pathogens, and correspondingly how this interacts with the pathogens genetics, we infected a collection of wild and domesticated tomato accessions with a genetically diverse population of the generalist pathogen Botrytis cinerea. We quantified variation in lesion size of 97 B. cinerea genotypes (isolates) on 6 domesticated Solanum lycopersicum and 6 wild S. pimpinellifolium genotypes. This showed that lesion size was significantly controlled by plant domestication, plant genetic variation, and the pathogens genotype. Overall, resistance was slightly elevated in the wild germplasm in comparison to domesticated tomato accessions. Genome-wide association (GWA) mapping in B. cinerea identified a highly polygenic collection of genes. This suggests that breeding against this pathogen would need to utilize a diversity of isolates to capture all possible mechanisms. Critically, we identified a discrete subset of B. cinerea genes where the allelic variation was linked to altered virulence against the wild versus domesticated tomato accessions. This indicates that this generalist pathogen already has the necessary allelic variation in place to handle the introgression of wild resistance mechanisms into the domesticated crop. Future studies are needed to assess how these observations extend to other domesticated crops and other generalist pathogens.

plant biology↗

bioRxiv2018

Aberrant calcium signaling in astrocytes inhibits neuronal excitability in a human Down syndrome stem cell model

Down syndrome (DS) is a devastating genetic disorder causing severe cognitive impairment. The staggering array of effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We developed an in vitro system to examine the interplay of neurons and astrocytes in a fully recapitulated HSA21 trisomy model differentiated from DS patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we utilized this system to investigate the functional defects of DS astroglia and their effects on neuronal excitability. We found that, compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. DS astrocytes exerted this effect on both DS and healthy neurons. Neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated astrocyte-neuron signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100{beta}, a calcium binding protein coded on HSA21. Our results suggest a novel mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability. Furthermore, our study establishes an all-optical neurophysiological platform for studying human neuron-astrocyte interactions associated with neurological disorders.\n\nSignificant statementDown syndrome (DS) is the most common genetic disorder caused by trisomy of chromosome 21 (HSA21). Problems with cognitive impairment, have not been properly addressed due to the inability to fully recapitulate HSA21, which is further confounded by the snapshot views of morphological changes of brain cells in isolation obtained from current studies. The brain develops neural networks consisting of neurons and glial cells that work together. To understand how DS affects the neural networks, we used DS patient-derived stem cells and calcium imaging to investigate functional defects of DS astrocytes and their effects on neuronal excitability. Our study has significant implication in understanding functional defects during brain development underlying DS.

neuroscience↗

bioRxiv2017

Architecture of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci

By incorporating the information of human chromosome inferred from Hi-C experiments into a heteropolymer model of chromatin chain, we generate a conformational ensemble to investigate its spatiotemporal dynamics. The heterogeneous loci interactions result in hierarchical organization of chromatin chain, which obeys compact space-filling (SF) statistics at intermediate length scale. Remarkably, the higher order architecture of the chromatin, characterized by the single universal Flory exponent ({nu} = 1/3) for condensed homopolymers, provides quantitative account of the dynamical properties of the chromosome. The local chromosome structures, exemplified by topologically associated domains (~ 0.1 - 1 Mb), display dynamics with fast relaxation time ([lsim] 50 sec), whereas the long-range spatial reorganization of the entire chromatin [Formula] occurs on a much longer time scale ({gtrsim} hour), suggestive of glass-like behavior. This key finding provides the dynamic basis of cell-to-cell variability. Active forces, modeled using stronger isotropic white noises, accelerate the relaxation dynamics of chromatin domain described by the low frequency modes. Surprisingly, they do not significantly change the local scale dynamics from those under passive condition. By linking the spatiotemporal dynamics of chromosome with its organization, our study highlights the importance of physical constraints in chromosome architecture on the sluggish dynamics.\n\nSignificance StatementChromosomes are giant chain molecules made of hundreds of megabase-long DNA intercalated with proteins. Structure and dynamics of interphase chromatin in space and time hold the key to understanding the cell type-dependent gene regulation. In this study, we establish that the crumpled and space-filling organization of chromatin fiber in the chromosome territory, characterized by a single universal exponent used to describe polymer sizes, is sufficient to explain the complex spatiotemporal hierarchy in chromatin dynamics as well as the subdiffusive motion of the chromatin loci. While seemingly a daunting problem at a first glance, our study shows that relatively simple principles, rooted in polymer physics, can be used to grasp the essence of dynamical properties of the interphase chromatin.

biophysics↗

bioRxiv2017

Interphase Human Chromosome Exhibits Out of Equilibrium Glassy Dynamics

The structural organization of the condensed chromosomes is being revealed using chromosome conformation capture experiments and super-resolution imaging techniques. Fingerprints of their three-dimensional organization on length scale from about hundred kilo base pairs to millions of base pairs have emerged using advances in Hi-C and super-resolution microscopy. To determine the poorly understood dynamics of human interphase chromosomes, we created the Chromosome Copolymer Model (CCM) by representing the chromosomes as a self-avoiding polymer with two loci types corresponding to euchromatin and heterochromatin. Using advanced clustering algorithms we establish quantitatively that the simulated contact maps for chromosomes 5 and 10 and those inferred from Hi-C experiments are in agreement. Ward Linkage Matrix (WLM), constructed from spatial distance information, shows that the Topologically Associated Domains (TADs) and compartments predicted from simulations are in agreement with inferred WLM computed using data from super-resolution microscopy experiments. Glassy dynamics is manifested in the stretched exponential relaxation of the structure factor and caging in the mean square displacement of individual loci, {triangleup}i(t) [~] t with 0 < < 1. Remarkably, the distribution of , is extremely broad suggestive of highly heterogeneous dynamics, which is also reflected in the large cell-to-cell variations in the contact maps. Chromosome organization is hierarchical involving the formation of chromosome droplets (CDs) on short genomic scale followed by coalescence of the CDs, reminiscent of Ostwald ripening. We propose that glassy landscapes for the condensed active chromosomes might provide a balance between genomic conformational stability and biological functions.

biophysics↗