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Biology subjects

LI, Z.

Publications and source records attributed to LI, Z..

16 recordsLinked to original sources

Viewing geometry and pattern type shape the detectability of snakes

Protective coloration can reduce predation risk by altering how prey are detected, recognised, or attacked. High-contrast markings may function as warning signals, camouflage, or both. In snakes, dorsal colour patterns are highly variable but the function remains debated, particularly because their appearance to an observer may change with viewing distance and angle. This study tested whether the function and efficacy of common snake pattern types (blotches, spots, diamonds, zig-zags and bands) is observer-view dependent, mediated by viewing distance and angle. Artificial snake models marked with these different pattern types that are broadly common across snake taxa, were placed in woodland habitat with a mixed shrub and grass understorey in Cornwall, UK, with photographs taken for evaluating levels of predicted camouflage and contrast against the background. Next, human volunteers searched for models, and we recorded detection distances and angles. Field results showed no significant difference in overall detection rates between pattern types; however, zigzag-patterned models were more likely to be detected at significantly shorter distances than blotch-patterned models, with a marginal trend towards shorter distances than diamond-patterned models, indicating effective longer-range camouflage. Detection risk did not alter gradually as volunteers approached but increased abruptly, correlating with image analyses showing that levels of predicted disruptive camouflage decreased with reduced distance. When detection was analysed using viewing angle, an advantage of zigzag patterns was robust to geometric scale, and observer height may further shape detection through viewing geometry. These findings suggest that snake dorsal patterns could potentially serve dual roles in reducing detection from afar, while being more conspicuous at close range. In addition, the results highlight the need to consider three-dimensional viewing geometry, including distance and visual angle, when evaluating the ecological function of animal coloration.

animal behavior and cognition↗

Camouflage functions of juvenile giant panda colouration in forest environments

The contrasting black-and-white coloration of the giant panda (Ailuropoda melanoleuca) has long attracted attention. Recent works suggest this contrasting pattern may generate camouflage-relevant visual effects. However, most previous studies have focused on adult pandas, whereas juveniles may face greater predation risk and may therefore represent a more ecologically relevant life stage for testing concealment hypotheses. We investigated whether juvenile panda coloration provides the potential for camouflage through background matching or disruptive coloration, and how this potential is shaped by vegetation cover, illumination and background position. We used life-sized juvenile panda models with natural and experimentally modified coloration by adjusting the relative proportions and spatial arrangement of white, black, and grey patches. Models were photographed in temperate woodland environments at ground level and against canopy backgrounds, under sunny and cloudy conditions, with and without vegetation occlusion. We quantified colour and luminance contrast, as well as edge-disruption metrics, using dichromatic canid and felid visual models. Natural juvenile panda coloration influences target-background contrast and edge-disruption, although these effects varies with vegetation, lighting, background height and visual model. Vegetation cover significantly reduced contrast and increased edge disruption metrics, while bright light condition only increased the metrics of edge disruption. Background position affected camouflage-relevant metrics in a context- and observer-dependent manner: under vegetation occlusion, canopy placement reduced chromatic contrast under felid-like vision, whereas ground-level placement reduced luminance contrast under both visual models. Alterations to patch extent and boundary arrangement modified camouflage-relevant metrics under specific environmental conditions, suggesting that the natural arrangement of pelage boundaries may enhance concealment under specific conditions. Overall, our findings support the hypothesis that juvenile giant panda coloration can produce visual effects consistent with potential camouflage, while highlighting the importance of habitat structure and viewing context in shaping camouflage.

animal behavior and cognition↗

Molecular Mechanism of pH Sensing and Activation in GPR4 Reveals Proton-Mediated GPCR Signaling

Maintaining pH homeostasis is critical for cellular function across all living organisms. Proton-sensing G protein-coupled receptors (GPCRs), particularly GPR4, play a pivotal role in cellular responses to pH changes, yet the molecular mechanisms underlying their proton sensing and activation remain incompletely understood. Here we present high-resolution cryo-electron microscopy structures of GPR4 in complex with G proteins under physiological and acidic pH conditions. Our structures expose an intricate proton-sensing mechanism driven by a sophisticated histidine network in the receptors extracellular domain. Upon protonation of key histidines under acidic conditions, a remarkable conformational cascade is initiated, propagating from the extracellular region to the intracellular G protein-coupling interface. This dynamic process involves precise transmembrane helix rearrangements and conformational shifts of conserved motifs, mediated by strategically positioned water molecules. Notably, we discovered a bound bioactive lipid, lysophosphatidylcholine, which has positive allosteric effects on GPR4 activation. These findings provide a comprehensive framework for understanding proton sensing in GPCRs and the interplay between pH sensing and lipid regulation, offering insights into cellular pH homeostasis and potential therapies for pH-related disorders.

molecular biology↗

Iridescent structural coloration in a crested Cretaceous enantiornithine bird from Jehol Biota

A combination of sectioning and microscopy techniques, along with the application of finite-difference-time-domain modeling on a fossil feather, results in the novel estimation of the range of iridescent colors from the fossilized melanosome type and organization preserved in the elongate head crest feathers of a new Cretaceous enantiornithine bird. The densely packed rod-like melanosomes are estimated to have yielded from red to deep blue iridescent coloration of the head feathers. The shape and density of these melanosomes also may have further increased the feathers structural strength. This occurrence on a likely male individual is highly suggestive of both a signaling function of the iridescent crest, and a potential behavioral role in adjusting the angle of light incidence to control the display of this iridescent structural coloration.

evolutionary biology↗

Aging limits stemness and tumorigenesis in the lung by reprogramming iron homeostasis

Aging is associated with a decline in the number and fitness of adult stem cells1-4. Aging-associated loss of stemness is posited to suppress tumorigenesis5,6, but this hypothesis has not been tested in vivo. Here, using physiologically aged autochthonous genetically engineered mouse models and primary cells7,8, we demonstrate aging suppresses lung cancer initiation and progression by degrading stemness of the alveolar cell of origin. This phenotype is underpinned by aging-associated induction of the transcription factor NUPR1 and its downstream target lipocalin-2 in the cell of origin in mice and humans, leading to a functional iron insufficiency in the aged cells. Genetic inactivation of the NUPR1--lipocalin-2 axis or iron supplementation rescue stemness and promote tumorigenic potential of aged alveolar cells. Conversely, targeting the NUPR1-- lipocalin-2 axis is detrimental to young alveolar cells via induction of ferroptosis. We find that aging-associated DNA hypomethylation at specific enhancer sites associates with elevated NUPR1 expression, which is recapitulated in young alveolar cells by inhibition of DNA methylation. We uncover that aging drives a functional iron insufficiency, which leads to loss of stemness and tumorigenesis, but promotes resistance to ferroptosis. These findings have significant implications for the therapeutic modulation of cellular iron homeostasis in regenerative medicine and in cancer prevention. Furthermore, our findings are consistent with a model whereby most human cancers initiate in young individuals, revealing a critical window for such cancer prevention efforts.

cancer biology↗

Circulating Microparticles: Optimization and Standardization of Isolation Protocols and Reassessment of Their Characteristics and Functions

Microparticles (MPs) are convenient for clinical diagnosis, and have functional roles in signal transduction. Although the importance of MPs is being increasingly recognized, the diversity of isolated protocols for MPs results in a heterogeneous population of their unknown origins, even expands to uncertain functions. Here we systematically studied the composition of MPs at different centrifugal speed intervals, and found that 3000g was a critical centrifugation speed in determining new MPs composition. The platelet-derived particles accounted for more than 80% under 3000g, while only about 20% in MPs obtained over 3000g. Furthermore, we found that the function of new MPs was significantly different from that of traditional ones, such as procoagulation activity, anti-inflammation and clinical diagnosis etc. Thus, our work optimized the method of MPs isolation, clarified some characteristics and physiological functions that should belong to platelets rather than MPs, which will derive new conceptual MPs for its composition and function.

cell biology↗

Organoid-based single-cell spatiotemporal gene expression landscape of human embryonic development and hematopoiesis

Single-cell level characterization of embryonic development is a major benchmark of human developmental biology. Spatiotemporal analysis of stem-cell-derived embryos offers conceptual and technical advances in the field. Here, we defined the single-cell spatiotemporal gene expression landscape of human embryonic development with stem-cell-derived organoids. We established the human embryonic organoid (HEMO) from expanded potential stem cells and achieved both embryonic and extraembryonic tissues in the same organoid. Time-series single-cell RNA sequencing paired with single-cell resolution spatial revealed human embryonic development signatures such as extraembryonic placenta, yolk sac hematopoiesis neural crest, blood vessels, and cardiac mesoderm. Hematopoietic tissues eventually predominated HEMO with erythropoiesis, mekagaryopiesis, and myelopoiesis. Cell-cell communication network analysis demonstrated that trophoblast-like tissues supplied WNT signaling in neural crest cells to facilitate maturation and migration. Single-cell resolution spatial transcriptomics defined the yolk sac erythro-megakaryopoietic niche. Vitronectin-integrin signaling, a major contributor to megakaryocyte maturation, was predominant in the yolk sac niche in HEMO and to human fetal samples. Overall, our study advances the spatiotemporal analysis of human embryonic development in stem-cell-derived organoids. HighlightsO_LIModeling human embryonic development from stem cells C_LIO_LIUsed of both 10X Chromium and 10X Visium to define the gene expression landscape of embryonic development and hematopoiesis C_LIO_LIWNT signaling as a regulator of neural crest maturation and EMT C_LIO_LIVTN-ITGA2B as the main contributor to Mk maturation within the yolk sac erythro-megakaryopoietic niche C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=158 HEIGHT=200 SRC="FIGDIR/small/505700v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1710d00org.highwire.dtl.DTLVardef@10ca8e0org.highwire.dtl.DTLVardef@2310d1org.highwire.dtl.DTLVardef@252728_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

Cell-cell communication is a key aspect of dissecting the complex cellular microenvironment. Existing single-cell and spatial transcriptomics-based methods primarily focus on identifying cell-type pairs for a specific interaction, while less attention has been paid to the prioritisation of interaction features or the identification of interaction spots in the spatial context. Here, we introduce SpatialDM, a statistical model and toolbox leveraging a bivariant Morans statistic to detect spatially co-expressed ligand and receptor pairs, their local interacting spots (single-spot resolution), and communication patterns. By deriving an analytical null distribution, this method is scalable to millions of spots and shows accurate and robust performance in various simulations. On multiple datasets including melanoma, Ventricular-Subventricular Zone (SVZ), and intestine, SpatialDM reveals promising communication patterns and identifies differential interactions between conditions, hence enabling the discovery of context-specific cell cooperation and signalling.

bioinformatics↗

Dynamic characteristics and Functional Analysis Provide new insights into the role of GauERF105 in resistance against Verticillium wilt in Cotton

Verticillium wilt is the most devastating disease of cotton and it results in huge yield losses every year in the fields. The underlying mechanisms of VW in cotton are not well explored yet. In the current approach we used the transcriptome data from G. australe in response to Verticillium wilt attack to mine the ERF TFs and prove their potential role in resistance against VW attack in cotton. We identified 23 ERFs in total, and on the basis of expression at different time points i.e., 24h, 48h and 72h post inoculation and selected GauERF105 for further validation. We performed VIGS in cotton and over expression in Arabidopsis respectively. Moreover, DAB and trypan staining also suggests that the impact of disease was more in the wildtype as compared to transgene lines. On the basis of our results, we confirmed that GauERF105 is the key candidate and playing a key role for defending cotton against VW attack. Current finding might be helpful for generating resistance germplasm in cotton and it will be beneficial to recover the yield losses in field.

pathology↗

Bacterial origin of thymidylate and folate metabolism in Asgard Archaea

Little is known about the evolution and biosynthetic function of DNA precursor and the folate metabolism in the Asgard group of archaea. As Asgard occupy a key position in the archaeal and eukaryotic phylogenetic trees, we have exploited very recently emerged genome and metagenome sequence information to investigate these central metabolic pathways. Our genome-wide analyses revealed that the recently cultured Asgard archaeon Candidatus Prometheoarchaeum syntrophicum strain MK-D1 (Psyn) contains a complete folate-dependent network for the biosynthesis of DNA/RNA precursors, amino acids and syntrophic amino acid utilization. Altogether our experimental and computational data suggest that phylogenetic incongruences of functional folate-dependent enzymes from Asgard archaea reflect their persistent horizontal transmission from various bacterial groups, which has rewired the key metabolic reactions in an important and recently identified archaeal phylogenetic group. We also experimentally validated the functionality of the lateral gene transfer of Psyn thymidylate synthase ThyX. This enzyme uses bacterial-like folates efficiently and is inhibited by mycobacterial ThyX inhibitors. Our data raise the possibility that the thymidylate metabolism, required for de novo DNA synthesis, originated in bacteria and has been independently transferred to archaea and eukaryotes. In conclusion, our study has revealed that recent prevalent lateral gene transfer has markedly shaped the evolution of Asgard archaea by allowing them to adapt to specific ecological niches.

microbiology↗

Foot scales in the Early Cretaceous bird Gansus yumenensis from China

Most modern birds have scales covering the foot and feathers elsewhere. Discoveries of fossil feathers attached to the metatarsus in non-avian dinosaurs and basal birds suggests that the avian scales are secondarily derived from feathers. However, our knowledge of early avian scales and their taphonomy is still limited, due to the scarcity of fossil record. Here we employ multiple techniques to characterize the morphological and chemical details preserved and investigate how they are preserved in the skin of IVPP V15077, a referred specimen of the Early Cretaceous Gansus yumenensis. Results show that two types of scales, scutellate and interstitial scales, are preserved in IVPP V15077, which, in combination with previous discovery of scutate and reticulate scales in other Early Cretaceous birds, indicates that all four types of scales present in modern birds have appeared in the Early Cretaceous. SEM observations and Raman analysis suggest that the skin of Gansus yumenensis may be pigmented. Elemental mapping indicates that aluminosilicates and calcium phosphate are involved in the mineralization of the skin.

paleontology↗

Proteome-scale Analysis of Vertebrate Protein Thermoadaptation Modulated by Dynamic Allostery And Protein Solvation

Despite differences in behaviors and living conditions, vertebrate organisms share the great majority of proteins, often with subtle differences in amino acid sequence. Here, we present a simple way to analyze the difference in amino acid occurrence by comparing highly homologous proteins on a sub-proteome level between several vertebrate model organisms. Specifically, we use this method to identify a pattern of amino acid conservation as well as a shift in amino acid occurrence between homeotherms (warm-blooded species) and poikilotherms (cold-blooded species). Importantly, this general analysis and a specific example further establish a correlation, if not likely connection between the thermoadaptation of protein sequences and two of their physical features: a possible change in their protein dynamics and, even more strongly, in their solvation. For poikilotherms, such as frog and fish, the lower body temperature is expected to increase the association of proteins due to a decrease in protein internal dynamics. In order to prevent overly-sticky protein association at low temperatures, the use of amino acids suggests that poikilotherms enhance the solvation of their proteins by favoring polar groups on their proteins surface. This feature appears to dominate over possible changes in dynamics. The results suggest that a general trend for amino acid choice is part of the mechanism for thermoadaptation of vertebrate organisms at the molecular level.

biophysics↗

Plexin-Bs enhance their GAP activity with a novel activation switchloop

Plexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and find that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Importantly, we unveil an activation mechanism of Plexin-B1 by identifying a novel functional loop which partially blocks Rap1b entry to the plexin GAP domain. Consistent with the concept of allokairy developed for other systems, Plexin-B activity is increased by an apparent substrate mediated cooperative effect. Simulations and mutagenesis suggest the repositioned JM conformation is stabilized by the new activation switch loop when the active site is occupied, giving rise to faster enzymatic turnover and cooperative behavior. The biological implications, essentially of a threshold behavior for cell migration are discussed.

biophysics↗

Mathematical relations between measures of brain connectivity estimated from electrophysiological recordings for Gaussian distributed data

A large variety of methods exist to estimate brain coupling in the frequency domain from electrophysiological data measured e.g. by EEG and MEG. Those data are to reasonable approximation, though certainly not perfectly, Gaussian distributed. This work is based on the well-known fact that for Gaussian distributed data, the cross-spectrum completely determines all statistical properties. In particular, for an infinite number of data, all normalized coupling measures at a given frequency are a function of complex coherency. However, it is largely unknown what the functional relations are. We here present those functional relations for six different measures: the weighted phase lag index, the phase lag index, the absolute value and imaginary part of the phase locking value (PLV), power envelope correlation, and power envelope correlation with correction for artifacts of volume conduction. With the exception of PLV, the final results are simple closed form formulas. We tested in simulations of linear and nonlinear dynamical systems and for empirical resting state EEG on sensor level to what extent a model, namely the respective function of coherency, can explain the observed couplings. For empirical data w e found that for measures of phase-phase coupling deviations from the model are in general minWor, while power envelope correlations systematically deviate from the model for all frequencies. For power envelope correlation with correction for artifacts of volume conduction the model cannot explain the observed couplings at all. We also analyzed power envelope correlation as a function of time and frequency in an event related experiment using a stroop reaction task and found significant event related deviations mostly in the alpha range.

neuroscience↗

Pattern, Pathways and Dynamics of EphA2 SAM and SHIP2 SAM Heterodimer Association Revealed by All-Atom Molecular Dynamics Simulation

Native protein-protein interactions (PPIs) are the cornerstone for understanding the structure, dynamics and mechanisms of function of protein complexes. In this study, we investigate the association of the SAM domains of the EphA2 receptor and SHIP2 enzyme by performing a combined total of 48 s all-atom molecular dynamics (MD) simulations. While the native SAM heterodimer is only predicted at a low rate of 6.7% with the original CHARMM36 force field, the yield is increased to 16.7% and to 18.3% by scaling the vdW solute-solvent interactions (better fitting the solvation free energy of amino acid side chain analogues) and by an increase of vdW radius of guanidinium interactions, and thus a dramatic reduction of electrostatic interaction between Arg and Glu/Asn in CHARMM36m, respectively. These modifications effectively improve the overly sticky association of proteins, such as ubiquitin, using the original potential function. By analyzing the 25 native SAM complexes formed in the simulations, we find that their formation involves a pre-orientation guided by electrostatic interaction, consistent with an electrostatic steering mechanism. The complex could then transform to the native protein interaction surfaces directly from a well pre-orientated position ({Delta}interface-RMSD < 5[A]). In other cases, modest (< 90{degrees}) orientational and/or translational adjustments are needed (5 [A] <{Delta}i-RMSD <10 [A]) to the native complex. Although the tendency for non-native complexes to dissociate has nearly doubled with the modified potential functions, a re-association to the correct complex structure is still rare. Instead a most non-native complexes are undergoing configurational changes/surface searching, which do not lead to native structures on a timescale of 250 ns. These observations provide a rich picture on mechanisms of protein-protein complex formation, and suggest that computational predictions of native complex protein-protein interactions could be improved further.

biophysics↗

A "Tug of War" maintains a dynamic protein-membrane complex: MD simulations of C-Raf RBD-CRD bound to K-Ras4B at an anionic membrane

Association of Raf kinase with activated Ras triggers downstream signaling cascades, towards regulating transcription in the cells nucleus. Dysregulation of Ras: Raf signaling stimulates cancers. We investigate the C-Raf RBD and CRD regions when bound to oncogenic K-Ras4B at the membrane. All-atom molecular dynamics simulations suggest that the membrane plays an integral role in regulating the configurational ensemble of the complex. Remarkably, the complex samples a few states dynamically, reflecting a competition between C-Raf CRD and K-Ras4B- membrane interactions. This competition arises because the interaction between the RBD and K-Ras is strong and the linker between the RBD and CRD is short. This study reveals a mechanism that maintains a modest binding for the overall complex at the membrane to facilitate fast signaling processes. It is likely a common mechanism for other multi-protein, if not multidomain proteins at membranes.

biophysics↗