Biology subjects

Zhang, S.-J.

Publications and source records attributed to Zhang, S.-J..

10 recordsLinked to original sources

bioRxiv2024

Uncovering Ancient DNA in Petroleum: Insights into Earth Hidden Life Events and Geological History

Specific macromolecules in petroleum, preserved through geological processes from ancient organisms, are recognized as molecular fossils or geochemical markers (GMs). Our selected GMs indicate that the source rocks of Nanyang Oilfield formed in an anoxic, saline, and stratified lacustrine environment with marine influence. Contrary to science fiction notions that oil originates from ancient large animals, mainstream academia has consistently asserted that oil is derived from the organic matter of lower life forms, formed over extended geological processes, with intact DNA no longer persisting in oil post-formation. However, this study successfully extracted 3,159,020 DNA fragments from the petroleum samples using the nanoparticle affinity bead technology, followed by sequencing and classification via the mega screen method. These fragments, categorized as original in situ DNA (oriDNA), recent environmental DNA (preDNA), and paleo-environmental DNA (paeDNA), exhibit a "Genome Accumulated over Time" (GAT) pattern of "old-less, new-many". This aligns with findings from GMs while offering more specific genetic information. The analysis reveals evidence of historical events, including animal extinctions, marine invasions, ancient bird species presence, Asian Homo erectus activities, and modern human influences in preDNA. Notably, the mitogenomic data positions Asian Homo erectus closer to modern humans than to chimpanzees at the maternal basis. The absence of deamination in petroleum ancient DNA (aDNA) fragments is likely due to the anaerobic, anhydrous environment and the screening process that excludes degraded fragments. Consequently, the authenticity criteria and scope of application of traditional aDNA methods require reevaluation. Surprisingly, the near-absence of oriDNA has impeded our efforts to determine the specific biological origins of the oil. These findings position petroleum as a novel, non-skeletal source of aDNA, offering insights into ancient animal activities, geological changes, and human origins while underscoring its potential as an untapped resource for studying genetic preservation across geological timescales.

paleontology↗

bioRxiv2024

Determinants of de novo mutations in extended pedigrees of 43 dog breeds

Intensive breeding of dogs has had dramatic effects on genetic variants underlying phenotypes. To investigate whether this also affected mutation rates, we deep-sequenced pedigrees from 43 different dog breeds representing 404 trios. We find that the mutation rate is remarkably stable across breeds and is predominantly influenced by variation in parental ages. The effect of paternal age per year on mutation rates is approximately 1.5 times greater in dogs than humans, suggesting that the elevated yearly mutation rate in dogs is only partially attributed to earlier reproduction. While there is no significant effect of breeds on the overall mutation rate, larger breeds accumulate proportionally more mutations earlier in development than small breeds. Interestingly, we find a 2.6 times greater mutation rate in CG Islands (CGIs) compared to the remaining genome in dogs, unlike humans, where there is no difference. Our estimated rate of mutation by recombination in dogs is more than 10 times larger than estimates in humans. We ascribe these to the fact that canids have lost PRDM9-directed recombination and draw away recombination from CGIs. In conclusion, our study sheds light on stability of mutation processes and disparities in mutation accumulation rates reflecting the influence of differences in growth patterns among breeds, and the impact of PRDM9 gene loss on the de novo mutations of canids.

evolutionary biology↗

bioRxiv2023

Progesterone is an Inducement of Heritable Pulmonary Arterial Hypertension with BMPR2 Mutation

BackgroundBone morphogenetic protein type II receptor (BMPR2) gene mutation accounts for 80% of patients with heritable pulmonary artery hypertension (HPAH), and female mutation carriers have significantly higher penetrance rate than males. The inducement of HPAH penetrance and the mechanism of sex differential penetrance are still elusive. MethodsWe infected or transfected pulmonary artery smooth muscle cells (PASMCs) with shBMPR2 lentivirus or siBMPR2 to simulate the pathologic condition of BMPR2 heterozygous mutation and treated them with progesterone. The HPAH patient-derived induced pluripotent stem cells (iPSCs) were induced into vascular smooth muscle cells (VSMCs) to further verify the cellular phenotype. Wild-type flox+/- female mice and SM22-cre BMPR2 flox+/- female mice (CKO mice) were administered with 1-month progesterone, and their phenotype of PAH was evaluated by right heart catheterization and histopathological examination. ResultsProgesterone promoted the proliferation of PASMCs with BMPR2-knockdownby activating ERK pathway via progesterone receptor (PGR). Activated ERK not only upregulated the phosphorylation and elevation of cMYC, but also induced the transcription of endothelin (EDN1) by promoting the nuclear entry of c-JUN and combination on the its promoter region. Similar results were confirmed by iPSCs-VSMCs experiment. CKO mice developed PAH spontaneously and had increased expression of EDN1, which was further aggravated by exogenous progesterone. ConclusionsProgesterone might be an inducement of HPAH penetrance caused by BMPR2 mutation, accounting for sex differential penetrance.

molecular biology↗

bioRxiv2022

Excitatory-Inhibitory Recurrent Dynamics Produce Robust Visual Grids and Stable Attractors

Spatially modulated grid cells has been recently found in the rat secondary visual cortex (V2) during activation navigation. However, the computational mechanism and functional significance of V2 grid cells remain unknown, and a theory-driven conceptual model for experimentally observed visual grids is missing. To address the knowledge gap and make experimentally testable predictions, here we trained a biologically-inspired excitatory-inhibitory recurrent neural network (E/I-RNN) to perform a two-dimensional spatial navigation task with multisensory (e.g., velocity, acceleration, and visual) input. We found grid-like responses in both excitatory and inhibitory RNN units, and these grid responses were robust with respect to the choices of spatial cues, dimensionality of visual input, activation function, and network connectivity. Dimensionality reduction analysis of population responses revealed a low-dimensional torus-like manifold and attractor, showing the stability of grid patterns with respect to new visual input, new trajectory and relative speed. We found that functionally similar receptive fields with strong excitatory-to-excitatory connection appeared within fully connected as well as structurally connected networks, suggesting a link between functional grid clusters and structural network. Additionally, multistable torus-like attractors emerged with increasing sparsity in inter- and intra-subnetwork connectivity. Finally, irregular grid patterns were found in a convolutional neural network (CNN)-RNN architecture while performing a visual sequence recognition task. Together, our results suggest new computational mechanisms of V2 grid cells in both spatial and non-spatial tasks. HighlightsO_LIGrid patterns emerge in trained RNNs with multisensory inputs C_LIO_LIGrid patterns are robust to the RNN input and network connectivity C_LIO_LIPopulation responses show emergent ring-like manifolds and attractors C_LIO_LIGrid-like patterns persist in RNNs while performing a non-spatial task. C_LI

neuroscience↗

bioRxiv2021

Protective effect of peroxisome proliferator-activated receptor- in regulating the early inflammation response to extended hepatectomy from a comparative transcriptomic analysis

The regulation mechanism of small-for-size syndrome remains unclear. Thus, we aimed to analyze the molecular profiles following extended hepatectomy and identify the therapeutic target. Major hepatectomy and extended hepatectomy were performed in the rat model, and the remnant livers were obtained dynamically for the high-throughput transcriptome analysis to identify the differentially expressed genes (DEGs). The general framework for weighted gene co-expression network analysis (WGCNA) was employed to explore the expression patterns of DEGs. As result, WGCNA identified 10 distinct gene co-expression modules according to the correlation between module eigengene and different postoperative time-points. The magenta module (gene count: 289) and the lightcyan module (gene count: 484) were found positively correlated with major hepatectomy instead of extended hepatectomy. In the lightcyan module, peroxisome proliferator-activated receptor- (PPAR) was selected and found the down-regulation in the remnant liver following extended (marginal) hepatectomy in rats and humans. Besides, administration of PPAR agonist attenuated hepatic inflammation injury while PPAR antagonist increased liver inflammation injury after extended hepatectomy in rats, marked by the significantly changed aminotransferases, tumor necrosis factor- and interleukin-6 levels in the plasm, and histological Suzuki criteria. Consequently, DEGs and their molecular profiles after extended hepatectomy were identified, and PPAR might be a potential therapy target for small-for-size syndrome.

genomics↗

bioRxiv2021

Bimodal Remapping of Visual Grids

Spatially modulated neurons from the rat secondary visual cortex (V2) show grid-like firing patterns during freely foraging in open-field enclosures. However, the remapping of the V2 grid cells is not well understood. Here we report two classes of V2 grid cell populations with distinct remapping properties: one regular class with invariant grid field patterns, and the other bimodal class that has remapping induced by environmental manipulations such as changes in enclosure shape, size, orientation and lighting in a familiar environment. The bimodal V2 grid cell pattern remains stable regardless of the follow-up manipulations, but restores to the original firing pattern upon animals re-entry into the familiar environment on the next day or from the novel environment. The bimodal V2 grid cells are modulated with theta frequency during the course of remapping and stabilize quickly. We also found conjunctive bistable V2 grid cells with invariant head directional tuning. Overall, our results suggest a new grid cell mechanism in V2 that is different from the medial entorhinal cortex (MEC) grid cells. HighlightsO_LIBistable V2 grid cells display bimodal or bistable remapping C_LIO_LIV2 grid cell firing patterns are not disrupted in darkness C_LIO_LIV2 grid cells preserve theta frequency modulation during remapping C_LI

neuroscience↗

bioRxiv2021

Egocentric Asymmetric Coding in Sensory Cortical Border Cells

Both egocentric and allocentric representations of space are essential to spatial navigation. Although some studies of egocentric coding have been conducted within and around the hippocampal formation, externally anchored egocentric spatial representations have not yet been fully explored. Here we record and identify two subtypes of border cell in the rat primary somatosensory cortex (S1) and secondary visual cortex (V2). Subpopulations of S1 and V2 border cells exhibit rotation-selective asymmetric firing fields in an either clockwise (CW) or counterclockwise (CCW) manner. CW- and CCW-border cells increase their firing rates when animals move unidirectionally along environmental border(s). We demonstrate that both CW- and CCW-border cells fire in an egocentric reference frame relative to environmental borders, maintain preferred directional tunings in rotated, stretched, dark as well as novel arenas, and switch their directional firings in the presence of multi-layer concentric enclosures. These findings may provide rotation-selective egocentric reference frames within a larger spatial navigation system, and point to a common computational principle of spatial coding shared by multiple sensory cortical areas. HighlightsO_LIEgocentric border cells are present in rat S1 and V2 C_LIO_LISubtypes of border cells display egocentric asymmetric coding C_LIO_LIEgocentric and allocentric streams coexist in sensory cortices C_LIO_LIRotation-selective asymmetric firing is robust with environmental manipulations C_LI

neuroscience↗

bioRxiv2021

A compact spatial map in V2 visual cortex

Vision plays a critical role in guiding spatial navigation. A traditional view of the visual cortex is to compute a world-centered map of visual space, and visual neurons exhibit diverse tunings to simple or complex visual features. The neural representation of spatio-visual map in the visual cortex is thought to be transformed from spatial modulation signals at the hippocampal-entorhinal system. Although visual thalamic and cortical neurons have been shown to be modulated by spatial signals during navigation, the exact source of spatially modulated neurons within the visual circuit has never been identified, and the neural correlate underpinning a visuospatial or spatio-visual map remains elusive. To search for direct visuospatial and visuodirectional signals, here we record in vivo extracellular spiking activity in the secondary visual cortex (V2) from freely foraging rats in a naturalistic environment. We identify that V2 neurons forms a complete spatio-visual map with a wide range of spatial tunings, which resembles the classical spatial map that includes the place, head-direction, border, grid and conjunctive cells reported in the hippocampal-entorhinal network. These spatially tuned V2 neurons display stable responses to external visual cues, and are robust with respect to non- spatial environmental changes. Spatially and directionally tuned V2 neuronal firing persists in darkness, suggesting that this spatio-visual map is not completely dependent on visual inputs. Identification of functionally distinct spatial cell types in visual cortex expands its classical role of information coding beyond a retinotopic map of the eye-centered world.

neuroscience↗

bioRxiv2020

Sharp tuning of head direction by somatosensory fast-spiking interneurons

Head direction (HD) information is intricately linked to spatial navigation and cognition. We recently reported the co-existence of all currently recognized spatial cell types can be found in the hindlimb primary somatosensory cortex (S1HL). In this study, we carried out an in-depth characterization of HD cells in S1HL. We show fast-spiking (FS), putative inhibitory neurons are over-represented in and sharply tuned to HD compared to regular-spiking (RS), putative excitatory neurons. These FS HD cells are non-conjunctive, rarely theta modulated, not locally connected and are enriched in layer 4/5a. Their co-existence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the S1HL presents a previously unreported organization of spatial circuits. These findings challenge the notion that FS, putative inhibitory interneurons are weakly tuned to external stimuli in general and present a novel local network configuration not reported in other parts of the brain.

neuroscience↗

bioRxiv2018

A novel somatosensory spatial navigation system outside the hippocampal formation

Spatially selective firing in the forms of place cells, grid cells, boundary vector/border cells and head direction cells are the basic building blocks of a canonical spatial navigation system centered on the hippocampal-entorhinal complex. While head direction cells can be found throughout the brain, spatial tuning outside the hippocampal formation are often non-specific or conjunctive to other representations such as a reward. Although the precise mechanism of spatially selective activities is not understood, various studies show sensory inputs (particularly vision) heavily modulate spatial representation in the hippocampal-entorhinal circuit. To better understand the contribution from other sensory inputs in shaping spatial representation in the brain, we recorded from the primary somatosensory cortex in foraging rats. To our surprise, we were able to identify the full complement of spatial activity patterns reported in the hippocampal-entorhinal network, namely, place cells, head direction cells, boundary vector/border cells, grid cells and conjunctive cells. These newly identified somatosensory spatial cell types form a spatial map outside the hippocampal formation and support the hypothesis that location information is necessary for body representation in the somatosensory cortex, and may be analogous to spatially tuned representations in the motor cortex relating to the movement of body parts. Our findings are transformative in our understanding of how spatial information is used and utilized in the brain, as well as functional operations of the somatosensory cortex in the context of rehabilitation with brain-machine interfaces.

neuroscience↗