Biology subjects

Zhao, Z.

Publications and source records attributed to Zhao, Z..

At least 181 records · Page 10Linked to original sources

bioRxiv2025

Super-Resolution Diffusivity Mapping Reveals Spatial Correlations Between Lateral Mobility and Structural Heterogeneities on Cellular Membranes

Cellular membranes orchestrate critical processes such as molecular transport and signal transduction, both regulated by the lateral mobility of lipids and proteins. However, resolving nanoscale diffusional heterogeneities and elucidating their underlying mechanisms remains a formidable challenge due to the membranes intricate architecture and compositional diversity. Here, we present point-cloud single-molecule diffusivity mapping (pc-SMdM), a cutting-edge super-resolution technique that offers a point-cloud data format with enhanced spatial resolution for diffusivity mapping. Using pc-SMdM, we visualize nanoscale diffusion slowdown clusters with [~]50 nm in diameter on plasma membranes. These clusters are predominantly governed by cholesterol content, alongside contributions from membrane protein assemblies and topographical features. Leveraging two-color pc-SMdM, we concurrently imaged multiple lipids and membrane probes, revealing distinct "fingerprint" diffusivity maps shaped by their interactions within lipid bilayers. Our findings position pc-SMdM as a transformative tool for spatially resolving molecular interactions and membrane dynamics in live cells, offering new insights into the underlying mechanisms that govern membrane mobility at the nanoscale.

biophysics↗

bioRxiv2025

Genetic architecture of the S-locus supergene revealed in a tetraploid distylous species

SummaryO_LIHeterostyly is a polymorphic floral adaptation controlled by supergenes and maintained in populations by disassortative mating. The molecular basis of distyly has been investigated in several unrelated families. Previous studies have been limited to diploid species and have not included Rubiaceae, which has the highest number of heterostylous species. C_LIO_LIHere, we investigate the genetic architecture of tetraploid Schizomussaenda henryi (Rubiaceae) to identify candidate style-length genes, evidence for hemizygosity and the potential role of gene duplication in the evolution of the S-locus. Chromosome-level genome assemblies and transcriptomic approaches identified the S-locus region comprised of four hemizygous genes. C_LIO_LIThe candidate gene SchzAUX22 may regulate style length and filament growth by acting in the auxin signaling pathway. Comparative studies of the two sub-genomes of S. henryi indicated strong similarities and no significant sub-genome dominance, as expected from autotetraploidy. Evidence from haplotype-resolved assemblies of a short-styled plant indicated that it possessed the ssSS genotype, consistent with autotetraploidy, which was estimated to have originated [~]3.6 Mya. Analysis of Ks values between S-locus genes and their paralogs indicated that the S-locus likely originated through stepwise duplication. C_LIO_LIOur study provides comprehensive genomic analysis of distyly in a polyploid and demonstrates that despite whole genome doubling the S-locus supergene remains intact and functional as an outbreeding mechanism. Our results contrast with many other heterostylous lineages where polyploidy is associated with breakdown of the polymorphism and transitions to self-fertilization. C_LI

plant biology↗

bioRxiv2025

Evolutionary responses and genomic consequences of polyploidization in natural populations of Orychophragmus

Polyploidization has occurred throughout the tree of life and is particularly common in plants. Despite its ubiquity, our understanding of the short- and long-term effects and consequences of genome doubling in natural populations remains incomplete. In this study, we identified a novel ploidy-variable species system within the ornamental and industrial oilseed genus Orychophragmus (Brassicaceae), which comprises six species, including diploid and tetraploid cytotypes of O. taibaiensis. By integrating population-scale genomic and transcriptomic datasets across the species in this genus, we constructed a robust phylogenetic framework and investigated the divergence and demographic history of O. taibaiensis in comparison to its relatives. Specifically, we characterized the geographical distribution patterns of diploids and tetraploids in natural populations of O. taibaiensis, confirmed the autopolyploid origin of tetraploids, and inferred their origin time relative to diploid counterparts. Our findings further revealed that, following genome doubling, tetraploids accumulated a higher genetic load of deleterious mutations, likely due to relaxed purifying selection facilitated by allelic redundancy. Additionally, genome doubling was associated with pronounced changes in gene expression patterns, with differentially expressed genes evolving under relaxed selective constraints. These results highlight that the initial masking of deleterious mutations, changes in expression regulation, and divergent efficacy of selection likely all contribute to shaping the establishment and evolutionary potential of polyploids.

molecular biology↗

bioRxiv2025

A method for the detection and enrichment of endogenous cereblon substrates

C-Terminal cyclic imides are posttranslational modifications on proteins that are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN). Despite the observation of these modifications across the proteome by mass spectrometry-based proteomics, an orthogonal and generalizable method to visualize the C-terminal cyclic imide would enhance detection, sensitivity, and throughput of endogenous CRBN substrate characterization. Here we develop an antibody-like reagent, termed "cerebody," for visualizing and enriching C-terminal cyclic imide-modified proteins. We describe the engineering of CRBN derivatives to produce cerebody and use it to identify CRBN substrates by Western blot and enrichment from whole cell and tissue lysates. CRBN substrates identified by cerebody enrichment are mapped, validated, and further characterized for dependence on the C-terminal cyclic imide modification. These methods will accelerate the characterization of endogenous CRBN substrates and their regulation.

biochemistry↗

bioRxiv2025

PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates

The E3 ligase substrate adapter cereblon (CRBN), the primary target of clinical agents thalidomide and lenalidomide, recognizes endogenous substrates bearing the C-terminal cyclic imide modification. Although C-terminal cyclic imides can form spontaneously, an enzyme that regulates the formation of these modifications and thereby promotes a biological pathway connecting substrates to CRBN is unknown. Here, we report that protein carboxymethyltransferase (PCMT1) promotes formation of the C-terminal cyclic imide on C-terminal asparagine residues of CRBN substrates. PCMT1 and CRBN co-regulate the levels of metabolic enzymes glutamine synthetase (GLUL) and inorganic pyrophosphatase 1 (PPA1) in vitro, in cells, and in vivo, and this regulation is associated with the proepileptic phenotype of CRBN knockout mouse models. The discovery of an enzyme that regulates CRBN substrates through the C-terminal cyclic imide modification reveals a previously unknown biological pathway that is perturbed by thalidomide derivatives and provides a biochemical basis for the connection between multiple biological processes and CRBN.

biochemistry↗

bioRxiv2025

Cerebellin-2 positive (Cbln2+) Neurons in the Parafascicular Thalamic Nucleus Regulate Self-Grooming Behavior

Self-grooming represents a stereotyped repetitive behavior which is commonly observed in various neuropsychiatric disorders. Deep brain stimulation (DBS) targeting the centromedian / parafascicular complex (CM/PF) has been shown to alleviate obsessive-compulsive disorder/behavior (OCD/OCB) symptoms in human. However, little is known about the neural circuits of the PF that are involved in the regulation of self-grooming behavior in rodents. Here, we report that cerebellin-2 positive (Cbln2+) neurons in PF bidirectionally encode self-grooming. Chemogenetic activation of Cbln2+ PF neurons significantly reduces both physiological and pathological self-grooming, and chemogenetic inhibition of Cbln2+ PF neurons increases physiological self-grooming. Moreover, activating synaptic excitatory inputs to Cbln2+ PF neurons inhibits self-grooming, while synaptic inhibitory inputs enhance it. Cbln2+ PF neurons independently transmit neural signals to the dorsal and ventral striatum. Activation of PF-dorsal striatum and PF-ventral striatum pathways both inhibit self-grooming behavior. Most excitingly, we alleviate excessive grooming in OCD mice by the activation of PF neurons using non-invasive ultrasound stimulation. Together, these data reveal that Cbln2+ PF neurons are integral components of a brain network involved in self-grooming behavior and highly promising targets in the non-invasive therapy of OCD.

neuroscience↗

bioRxiv2025

High-Quality Cell Capture Reveals Transcriptomic Changes After Single-Axon Injury of Mauthner Cells

In vivo single-cell capture methods based on micropipettes are essential for correlating morphological characteristics with transcriptomic profiling under physiological conditions. However, they often suffer from significant contamination of off-target cells. Consequently, we developed Hip-seq, which significantly reduces heavily contaminated cells, decreases contamination levels, improves cell reproducibility, and enhances data analysis accuracy compared to patch-seq. Using Hip-seq, we found that axon regeneration failure could be due to abnormal activation of translation and the circadian clock. Axon-regenerable central neurons reactivated axon development-related genes during regeneration. And one-to-one associated analysis helped identify pro-regenerative genes.

neuroscience↗

bioRxiv2025

Synergistic neuroprotective and cognitive-enhancing effects of Walnut Peptide and Theanine in human brain organoid and mouse stress models

Stress is a prevalent mental health concern emerging predominantly in late adolescence or early adulthood. Since 2007, the Food and Drug Administration (FDA) has not approved any novel anxiolytic pharmaceuticals, fueling interest in nutritional supplements as alternative therapies for stress management. Building on prior zebrafish research, this study investigates the synergistic effects of Theanine (Th) and Walnut Peptide (WP) on stress mitigation and cognitive enhancement. Utilizing the human brain organoid stress (BO-stress) model, WP+ Th were observed to reduce stress and regulate expression of neurotransmitters, including Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), and acetylcholine (Ach), as well as brain-derived neurotrophic factor (BDNF) and serotonin transporter (SERT). Subsequent in vivo study using C57BL/6J mouse-stress model demonstrated that the treatment (Th 85 mg/mL + WP 200 mg/mL), or administrated with vehicles, significantly improved their performance in stress and cognitive assessments, partially normalized neurotransmitter imbalances by modulating SERT and BDNF expression. These findings highlighted the potential of using WP + Th, particularly when delivered with vehicles (eg: powder/yogurt/milk), as a novel combined therapeutic approach for stress management and cognitive enhancement. We performed a correlation analysis between BO-stress model and mouse-stress model, revealing a alignement in the SERT levels.In addition, SERT was highly correlated with other markers in the mouse hippocampus and may represent a key target for modulating the balance between stress and cognition. Significance StatementThis study established an innovative human brain organoid-stress model and, in conjunction with mouse-stress model, elucidated the synergistic actions of Theanine and Walnut Peptide in mitigating stress and augmenting cognitive function. Their beneficial effects were mediated through the regulation of SERT and BDNF, presenting a promising non-pharmacological avenue for mental health care. In addition, species differences between humans and mice were also examined through correlation analysis of brain organoids and mouse models. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/640260v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1a81886org.highwire.dtl.DTLVardef@e2281dorg.highwire.dtl.DTLVardef@1b7b167org.highwire.dtl.DTLVardef@dff9aa_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

Autophagy Suppresses CCL2 to Preserve Appetite and Prevent Lethal Cachexia

Macroautophagy (autophagy hereafter) captures intracellular components and delivers them to lysosomes for degradation and recycling1. In adult mice, autophagy sustains metabolism to prevent wasting by cachexia and to survive fasting, and also suppresses inflammation, liver steatosis, neurodegeneration, and lethality2,3. Defects in autophagy contribute to metabolic, inflammatory and degenerative diseases, however, the specific mechanisms involved were unclear 4. Here we profiled metabolism and inflammation in adult mice with conditional, whole-body deficiency in an essential autophagy gene and found that autophagy deficiency altered fuel usage, and reduced ambulatory activity, energy expenditure, and food intake, and elevated circulating GDF15, CXCL10, and CCL2. While deletion of Gdf15 or Cxcl10 provided no or mild benefit, deletion of Ccl2 restored food intake, suppressed cachexia and rescued lethality of autophagy-deficient mice. To test if appetite suppression by CCL2 was responsible for lethal cachexia we performed single nucleus RNA sequencing of the hypothalamus, the center of appetite control in the brain. Notably, we found that autophagy deficiency was specifically toxic to PMCH and HCRT neurons that produce orexigenic neuropeptides that promote food intake, which was rescued by deficiency in CCL2. Finally, the restoration of food intake via leptin deficiency prevented lethal cachexia in autophagy-deficient mice. Our findings demonstrate a novel mechanism where autophagy prevents induction of a cachexia factor, CCL2, which damages neurons that maintain appetite, the destruction of which may be central to degenerative wasting conditions. Key points of paper1) Autophagy-deficient mice have reduced food intake, systemic inflammation, and cachexia 2) CCL2, but not GDF15 or CXCL10, induces lethal cachexia caused by autophagy defect 3) Autophagy-deficient mice have CCL2-dependent destruction of appetite-promoting neurons in the hypothalamus 4) Leptin deficiency restores appetite and rescues lethal cachexia in autophagy-deficient mice 5) Autophagy-deficient mice die from cachexia mediated by appetite loss 6) Degenerative conditions due to impaired autophagy are caused by the inflammatory response to the damage 7) Targeting CCL2 may be a viable approach to prevent degenerative wasting disorders

molecular biology↗

bioRxiv2025

Investigating Gene Expression Noise Reduction by MicroRNAs and MiRISC Reinforcement by Self-Feedback Regulation of mRNA Degradation

The microRNA (miRNA) induced silencing complex (miRISC) is the targeting apparatus and arguably the rate-limiting step of the miRNA-mediated regulatory subsystem - a major noise reducing, though metabolically costly, mechanism. Recently, we reported that miRISC channels miRNA-mediated regulatory activity back onto its own mRNAs to form negative self-feedback loops, a noise-reduction technique in engineering and synthetic/systems biology. In this paper, our mathematical modeling predicts that mRNA expression noise exhibits a negative correlation with the degradation rate (Kdeg) and is attenuated by self-feedback control of degradation. We also calculated Kdeg and expression noise of mRNAs detected in a total-RNA single-cell RNA-seq (scRNA-seq) dataset. As predicted, miRNA-targeted mRNAs exhibited higher Kdeg values accompanied by reduced inter-cell expression noise, confirming the operational trade-off between noise suppression and the increased metabolic/energetic costs associated with producing these mRNAs subjected to accelerated degradation and translational inhibition. Moreover, consistent with the Kdeg self-feedback control model, miRISC mRNAs (AGO1/2/3 and TNRC6A/B/C) exhibited further reduced expression noise. In summary, mathematical-modeling and total-RNA scRNA-seq data-analyses provide evidence that negative self-feedback regulation of mRNA degradation reinforces miRISC, the core machinery of the miRNA-mediated noise-reduction subsystem. To our knowledge, this is the first study to concurrently analyze mRNA degradation dynamics and expression noise, and to demonstrate noise reduction by self-feedback regulation of mRNA degradation.

systems biology↗

bioRxiv2025

HKU5 bat merbecoviruses use divergent mechanisms to engage bat and mink ACE2 as entry receptors

Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy (cryo-EM) analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

microbiology↗

bioRxiv2024

The Basal Ciliary but not Cytosol PKA Specifically Regulates HH Pathway Downstream of Smoothened

Effectors of the vertebrate Hedgehog (HH) signaling pathway are organized through primary cilia (PC) that grow and retract in lockstep with the cell cycle in response to extracellular signals. Protein kinase A (PKA), a kinase with ubiquitous distribution in most cells, functions as a specific negative regulator of the HH pathway. Its functional specificity in the HH pathway has been suggested to be controlled by cAMP in the PC. However, the regulation of PKA and its functions in PC remain unclear, in part due to the lack of observation of PKA localization in PC during HH resting state as well as conflicting reports of the dynamic changes of cAMP in cilia and HH pathway activity. To address this issue, we have developed a ciliary-localized FRET-based A-kinase activity probe (Nphp3N-AKAR2-CR) as an improved biosensor for monitoring real-time PKA activity in the PC of both cultured cells and living zebrafish embryos. Although the PKA catalytic subunit (PKA-C) was not observed in PC, basal PKA activity in cells could be detected with this probe. In addition, we have found that only ciliary-targeted PKA and not cytosolic PKA, can modulate the HH pathway, even when the integrity of the PC is disrupted. Notably, ciliary PKA activity was barely changed either by inhibition or activation of the HH pathway at the level of Smoothened (SMO), the obligate HH signal transducer. Moreover, we found that even low concentration of the adenylyl cyclase agonist forskolin (FSK) can efficiently inhibit the HH pathway in the presence of the constitutively active variant SMOA1, suggesting that the activation of the HH pathway by SMO may not be due solely to direct regulation of PKA activity in the PC.

cell biology↗

bioRxiv2024

A new class of penicillin-binding protein inhibitors to address drug-resistant Neisseria gonorrhoeae

{beta}-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to {beta}-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) Neisseria gonorrhoeae strains possessing altered penA alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic. Here we disclose a novel benzoxaborinine-based penicillin-binding protein inhibitor series (boro-PBPi) that is envisioned to address penA-mediated resistance while offering protection against evolution and expansion of {beta}-lactamases. Optimization of boro-PBPi led to the identification of compound 21 (VNRX-14079) that exhibits potent antibacterial activity against MDR N. gonorrhoeae achieved by high affinity binding to the PBP2 target. Boro-PBPi/PBP2 complex structures confirmed covalent interaction of the boron atom with Ser310 and the importance of the {beta}3-{beta}4 loop for improved affinity. 21 elicits bactericidal activity, a low frequency of resistance, a good safety profile, suitable pharmacokinetic properties, and in vivo efficacy in a murine infection model against ceftriaxone-resistant N. gonorrhoeae. 21 is a promising anti-gonorrhea agent poised for further advancement.

microbiology↗

bioRxiv2024

LINC00599 Promotes Pulmonary Hypertension via LLPS with G3BP1 and MYH9

BACKGROUNDPulmonary hypertension (PH) represents a significant cardiovascular disorder marked by both functional and structural alterations within the pulmonary vasculature. Long non-coding RNAs (lncRNAs) have been closely associated with the pathogenesis and progression of PH. Nonetheless, the precise mechanisms by which lncRNAs interact with its downstream target molecules to modulate the disease remain inadequately elucidated. METHODSThe expression levels of LINC00599 were quantified in the lung tissues of mice and pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions. The involvement of LINC00599 in the progression of PH and vascular remodeling was evaluated through in vivo studies. To investigate the mechanisms by which LINC00599 influences the proliferation of human PASMCs, small interfering RNA and overexpression plasmids were employed. RESUITSThe expression of LINC00599 is upregulated in the medial layer of pulmonary arteries in experimental models of PH and in hypoxic PASMCs. Administration of a single dose of lentivirus-mediated shRNA targeting LINC00599 effectively reverses hypoxic PH in murine models. LINC00599 plays a critical role in PASMC proliferation by modulating stress granule formation through N6-methyladenosine (m6A) modification and promoting proliferation via liquid-liquid phase separation with myosin heavy chain 9. Furthermore, the expression of LINC00599 is regulated by a super-enhancer, which is mediated by the transcription factor ZNF263. CONCLUSIONSThese findings demonstrate for the first time that LINC00599, involved in liquid-liquid phase separation, facilitates the progression of pulmonary hypertension by enhancing the proliferation of pulmonary artery smooth muscle cells. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/629439v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@7ac192org.highwire.dtl.DTLVardef@13a88b3org.highwire.dtl.DTLVardef@1e4c761org.highwire.dtl.DTLVardef@ddd105_HPS_FORMAT_FIGEXP M_FIG C_FIG What Is New?This study identified LINC00599 as a critical regulator of liquid-liquid phase separation through m6A modification and as a pivotal target in promoting the progression of PH. What Is Relevant?LncRNAs are intricately associated with the pathogenesis and progression of PH through the modulation of downstream target molecules. However, it remains unclear whether lncRNAs contribute to PH by forming specific subcellular structures with these target molecules. Furthermore, some studies have suggested that the increased presence of stress granules in PASMCs is implicated in the pathogenesis of pulmonary arterial hypertension. In this study, we provide evidence that LINC00599 promotes the development of PH by forming stress granules with its target proteins. Our findings indicate that the binding of LINC00599, modified with m6A, to G3BP1 and MYH9 in PASMCs suggests that the regulation of liquid-liquid phase separation by lncRNA m6A modification may represent a significant pathological mechanism underlying PH. What Are the Pathophysiological Implications?We found that LINC00599 levels were elevated in hypoxic PASMCs and experimental PH models. Knockout LINC00599 effectively prevented PH, indicating its potential as both a bomarker and therapeutic target for PH.

physiology↗

bioRxiv2024

YibN, a bona fide interactor of YidC with implications in membrane protein insertion and membrane lipid production

YidC, a prominent member of the Oxa1 superfamily, is essential for the biogenesis of the bacterial inner membrane, significantly influencing its protein composition and lipid organization. It interacts with the Sec translocon, aiding the proper folding of multi-pass membrane proteins. It also functions independently, serving as an insertase and lipid scramblase, augmenting the insertion of smaller membrane proteins while contributing to the organization of the bilayer. Despite the wealth of structural and biochemical data available, how YidC operates remains unclear. To investigate this, we employed proximity-dependent biotin labeling (BioID), leading to the identification of YibN as a crucial component within the YidC protein environment. We then demonstrated the association between YidC and YibN by affinity purification-mass spectrometry assays conducted on native membranes, with further confirmation using on-gel binding assays with purified proteins. Co-expression studies and in vitro assays indicated that YibN enhances the production and membrane insertion of YidC substrates, such as M13 and Pf3 phage coat proteins, ATP synthase subunit c, and various small membrane proteins like SecG. Additionally, the overproduction of YibN was found to stimulate membrane lipid production and promote inner membrane proliferation, perhaps by interfering with YidC lipid scramblase activity. Consequently, YibN emerges as a significant physical and functional interactor of YidC, influencing membrane protein insertion and lipid organization.

biochemistry↗

bioRxiv2024

Evolution of Salmonella Chromosomes and Its Influence on Gene Expression and Chromosomal Conformation

Salmonella is one of the most important bacterial pathogens in the world, causing an estimated 120 million infections each year. There is considerable diversity, with [~]2,600 serovars, but it remains unclear how the genomes have evolved as the species and subspecies of Salmonella differentiate. Here, we have reconstructed the ancient orthologous chromosomes of each major Salmonella lineage and traced their evolutionary process. In total, 911 rearrangement events were identified, with 64% of events occurring in a locus-specific way. Using RNA sequencing and multi-strain association analysis, we demonstrate that genetic rearrangements have a significant effect on gene expression across Salmonella lineages. Moreover, we perform chromosome conformation capture (3C) sequencing analysis, which demonstrates large variations for the organization of ter chromosomal interaction domains among Salmonella lineages. In conclusion, our work delineates the evolutionary trajectory of Salmonella chromosomes, and demonstrates the influence of rearrangements on gene expression profiles and chromosomal conformation. ImportanceThis study reconstructed the ancient orthologous chromosomes of the Salmonella genus, species and well-recognized subspecies, by which the trajectory of gene flow caused by genetic rearrangements was delineated chronologically. The rearrangements show apparent hotspot distribution property and are enriched with genes important for bacterial fitness. Correlation analysis further disclosed the general influence of the rearrangements on gene expression and the organization and conformation of chromosome interaction domains. The results provide new insights on the evolution of Salmonella chromosomes, especially the genetic rearrangements and their epigenetic consequences.

microbiology↗

bioRxiv2024

Magnetically induced magnetosome chain (MAGiC):A biogenic magnetic-particle-imaging tracer with high performance and navigability

Magnetic particle imaging (MPI) enables real-time, sensitive and quantitative visualization of magnetic tracers spatial distribution, augmenting the capability of in vivo imaging technologies. Previous tracer studies in MPI have primarily focused on superparamagnetic nanoparticles; however, their non-ideal sigmoidal magnetization response limits the spatial resolution. Here we demonstrate the utilization of magnetically induced magnetosome chain (MAGiC) as a novel superferromagnetic MPI tracer, exhibiting a 25-fold improvement in resolution and a 91-fold enhancement in signal intensity compared to the commercial tracer VivoTrax+. The spatial resolution of MPI was pushed to an unprecedented 80 m under a 4 T/m gradient field. Additionally, MAGiC can be precisely controlled using magnetic fields, enabling it to function as a MPI trackable microrobot. We provided a theoretical model elucidating MAGiCs unique properties, and validated its imaging and actuation performance through phantom studies and in vivo experiments. As a high-performance MPI tracer and magnetic microrobot with exceptional capabilities, MAGiC holds tremendous potential for diverse applications including cell tracking, targeted drug delivery as well as therapeutic interventions.

bioengineering↗

bioRxiv2024

Ultrasensitive tuning of cytoplasmic viscosity via active noise

The mechanical properties of cytoplasm are crucial for cellular functions. While active processes significantly alter cytoplasmic viscoelasticity, the physical mechanisms remain elusive. Here, we model the cytoplasm as a colloidal suspension subject to passive and active noise, coarse-grained as an effective temperature. We show that a jammed cytoplasm transitions from a solid to a liquid phase at a critical effective temperature. Intriguingly, the simulated complex shear modulus at the critical state exhibits a 1/2 power-law scaling with frequency and quantitatively matches the experimental data of live cells without fitting parameters, given that the cytoplasmic volume fraction is slightly above the jamming transition. We further reveal the biological significance for the cytoplasm to be slightly above jamming: it is a regime in which the viscosity is ultrasensitive to changes in the effective temperature. Our results suggest that cells actively regulate their volume fractions in the sensitive regime in which they can tune cytoplasmic viscosity efficiently via active processes.

biophysics↗