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Zhao, L.

Publications and source records attributed to Zhao, L..

At least 253 records · Page 14Linked to original sources

Effective infection with dengue virus in experimental neonate and adult mice through intranasal route

As a member of the family Flaviviridae, the dengue virus is transmitted to humans through mosquito vectors. The virus causes dengue fever with flu-like symptoms, life-threatening dengue hemorrhagic fever, and dengue shock syndrome that affects four billion people in 128 countries. It can also be transmitted through atypical routes, such as needle stick injury, vertical transmission, and the receipt of contaminated blood or organs. Although sporadic cases cannot be classified as atypical transmission routes and raise respiratory exposure concerns, the risks remain unclear. Here, we analyzed the respiratory infectivity of the dengue virus in BALB/c suckling and A6 adult mice using the dengue virus serotype 2 and intranasal inoculation. The results showed that the clinical symptoms of intranasally infected mice included excitement, emaciation, malaise, and death, and histopathological changes and viremia dynamics were observed in multiple tissues, including the brain, liver, and spleen. Notably, the DENV serotype 2 showed clear brain tropism after intranasal infection, and viral loads peaked at seven days post-inoculation. Furthermore, the virus was isolated from mouse brains, and the sequence homology between the viral stock and dengue virus isolates was 99.99%. Similar results were observed in adult IFN-/{beta} receptor-deficient mice. Taken together, our results suggest that the DENV serotype 2 can infect suckling mice and adult immune-deficient mice via the nasal route. The results of our study broaden our perception of atypical dengue transmission routes and may help explain dengue virus infections that occur without the presence of mosquito vectors. ImportanceDengue is transmitted mainly via mosquito vectors. Flu-like dengue fever or life-threatening severe dengue threatens four billion people in 128 countries. Non-vector dengue cases have occurred occasionally since 1990. These cases cannot be classified as atypical transmission routes and are suspected to have arisen via sexual or respiratory transmission. Recently, the sexual transmission of dengue has been confirmed in humans. The respiratory infectivity of other members of the Flaviviridae family, such as Zika and Japanese encephalitis viruses, has been determined under experimental conditions. The potential for respiratory infection with the dengue virus has not yet been confirmed. In this study, we analyzed the respiratory infectivity of the dengue virus in suckling mice and adult immunodeficient mice via intranasal inoculation, thereby exploring the potential for respiratory transmission in cases with non-vector dengue infection, especially for patients who were exposed to dengue virus contaminants.

microbiology↗

Arbidol inhibits esophageal squamous cell carcinoma growth in vitro and in vivo through suppressing ataxia telangiectasia and Rad3-related protein kinase

BackgroundEsophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma. Based upon a screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of esophageal squamous cell carcinoma in vitro and in vivo. MethodWe first conducted a series of cell-based assays and found that Arbidol treatment inhibited the proliferation and colony formation ability of ESCC cells and promoted G1 phase cell cycle arrest. Phospho-proteomics experiments and in vitro kinase assays were subsequently performed using cell lysates derived from Arbidol-treated cells in order to identify the underlying growth inhibitory mechanism. Finally, a PDX model was used to verify the inhibitory effect of Arbidol in vivo. FindingArbidol inhibits proliferation of ESCC in vitro and in vivo through the DNA replication pathway and is associated with the cell cycle. InterpretationArbidol is a potential ATR inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of MCM2 at Ser108. FundingThis research was supported by the National Natural Science Foundation of China (grant number 81872335), the National Natural Science Youth Foundation (grant number 81902486), and the Natural Science Foundation of Henan (grant number 161100510300).

cancer biology↗

Vector competence and transcriptional response of Aedes aegypti for Ebinur Lake virus, a newly mosquito-borne orthobunyavirus

The global impact of mosquito-borne diseases is increasing in the last decades. The newly classified orthobunyavirus, Ebinur Lake virus (EBIV) has been verified with highly virulent pathogenic to adult laboratory mice, and antibodies against EBIV have been detected in humans. As a potential emerging virus, it is necessary to assess the vector capacity of mosquitoes for EBIV to predicting its risk to public health. Herein, Aedes aegypti, the gradually important vector in China, was used as a model to evaluate the vector competence for EBIV. It was showed that EBIV can be transmitted by Ae. aegypti through oral feeding and the transmission rates could get to 11.8% at 14 days post infection (dpi). The highest infection rate, dissemination rate and ovary infection rate were 70%, 42.9%, and 29.4%, respectively. Through intrathoracic infection, Ae. aegypti was highly susceptible to EBIV and the transmission rates could get to 90% at 10 dpi. Moreover, the infection rate, dissemination rate and ovary infection rate were all 100%. Transcriptome analysis demonstrated EBIV can alter expressions of mosquito genes related to immune-related process and metabolism-related process. Defensin-C and chitinase 10 had been continuously down-regulated in the mosquitoes infected by intrathoracic inoculation. Our studies made the comprehensive analysis of the vector competence and transcriptional response of Ae. aegypti for EBIV, which implied the potential risk of EBIV to public health. Moreover, these findings indicated a complex interplay between EBIV and the mosquito immune system to affect the vector transmission capability.

molecular biology↗

Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

immunology↗

Chromatin reprogramming and transcriptional regulation orchestrate embryogenesis in hexaploid wheat

Embryogenesis represents the beginning of life cycle, but our understanding of the regulatory circuitry in plants is far lagged to animals. Here, we draw a transcriptome trajectory and chromatin landscape profile during embryogenesis of most cultivated crop hexaploid wheat, highlighting large-scale chromatin reconfiguration and distinct proximal and distal transcriptional regulation in defining cell fate transition. Upon fertilization, H3K27ac and H3K4me3 resetting were correlated with maternal genome silence, while de novo building of chromatin accessibility activated zygotic genome. Global depletion of H3K27me3 in pre-embryo results in a permissive chromatin environment with gain-of-chromatin accessibility, allowing subsequent hierarchical cis- and trans-regulation network mediated by key factors, such as LEC1, MYB, ZHD, LEC2, governing embryo pattern formation. By contrast, H3K27me3 restoration coordinating with chromatin compaction in developmental genes attenuated totipotency and prohibited extensive organogenesis during embryo maturation. In addition, dynamic biased expression of homeolog triads and diverse expression profiles after polyploidization were observed. This is correlated with asymmetric transposon elements insertion in accessible proximal and distal regions. Thus, our study revealed a plant-specific chromatin reprogramming process in facilitating the hierarchical transcription regulation circuits mediated "inverse hourglass model" and unveiled epigenetic regulation of evolutionary divergence among different sub-genome in shaping embryogenesis in polyploidy wheat.

plant biology↗

The effector protein CgNLP1 of Colletotrichum gloeosporioides from Hevea brasiliensis disrupts nuclear localization of necrosis-induced transcription factor HbMYB8-like to suppress plant defense signaling

O_LIColletotrichum gloeosporioides is the dominant causal agent of rubber tree anthracnose and leads to serious loss of natural rubber production. Fungi secrete numerous effectors to modulate host defense systems. Understanding the molecular mechanisms by which fungal effectors regulate plant defense is of great importance for the development of novel strategies for disease control. C_LIO_LIHere, we identified an NLP effector gene, CgNLP1, which contributed to virulence of C. gloeosporioides to rubber tree. Transient expression of CgNLP1 in the leaves of Nicotiana benthamiana induced ethylene production in plants. Ectopic expression of CgNLP1 in Arabidopsis significantly enhanced the resistance to Botrytis cinerea and A. brassicicola. C_LIO_LICgNLP1 was shown to target a R2R3 type transcription factor HbMYB8-like in rubber tree, which localized on nucleus and induced necrosis in N. benthamiana. CgNLP1 disrupted nuclear accumulation of HbMYB8-like and suppressed necrosis induced by HbMYB8-like mediated SA signal pathway. C_LIO_LIThis work suggested a strategy whereby C. gloeosporioides exploited CgNLP1 effector to suppress host defense to facilitate infection by disrupting the subcellular compartment of a host defense regulator HbMYB8-like. C_LI

pathology↗

Improving the Identification Coverage of Protein Interactome by Enhancing the Click Chemistry-based Cross-linking Enrichment Efficiency

Chemical cross-linking coupled with mass spectrometry has emerged as a powerful strategy which enables global profiling of protein interactome with direct interaction interfaces in complex biological systems. The alkyne-tagged enrichable cross-linkers are preferred to improve the coverage of low-abundance cross-linked peptides, combined with click chemistry for biotin conjugation to allow the cross-linked peptides enrichment. However, a systematic evaluation on the efficiency of click approaches (protein-based or peptide-based) and diverse cleavable click chemistry ligands (acid, reduction, photo) for cross-linked peptides enrichment and release is lacking. Herein, together with in vivo chemical cross-linking by alkyne-tagged cross-linker, we explored the click chemistry-based enrichment approaches on protein and peptide level with three cleavable click chemistry ligands, respectively. By comparison, the approach of protein-based click chemistry conjugation with acid-cleavable tag was demonstrated to permit the most cross-linked peptides identification. The advancement of this strategy enhanced the proteome-wide cross-linking analysis, permitting a detection of 5,017 protein-protein interactions among 1,909 proteins across all subcellular compartments with wide abundance distribution in cell. Therefore, all these results demonstrated a guideline value of our work for efficient cross-linked peptides enrichment, thus facilitated the in-depth profiling of protein interactome for functional analysis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/475819v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1a7ae4forg.highwire.dtl.DTLVardef@1a4d6d2org.highwire.dtl.DTLVardef@113a0eborg.highwire.dtl.DTLVardef@1a9c193_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Spatially resolved profiling of protein conformation and interactions by biocompatible chemical cross-linking in living cells

The protein structures and interactions that maintain and regulate cellular processes in different subcellular organelles are heterogeneous and dynamic. However, it remains challenging to characterize the subcellular specificity and translocation of protein complexes in terms of conformation and interactions. Herein, we developed a spatially resolved protein complex profiling approach by biocompatible chemical cross-linking in living cells (SPACX) to monitor the dynamics of protein conformation, interactions and translocation. The advancement of fast capturing protein complexes in the physiological state, coupled with efficient enrichment of the cross-linked peptides, ensured deep-coverage analysis of the protein interactome in living cells. By ensemble structure refinement with cross-linking restraints, subcellular-specific conformation heterogeneity was identified for PTEN. PTEN displayed a broader range of dynamic conformation changes on the dual specificity domains in the nucleus than in the cytoplasm. Moreover, based on conformational differences, different interacting assemblies involving 25 cytoplasm-exclusively and 18 nucleus-exclusively PTEN-interacting proteins were found to account for diverse biological functions. Upon ubiquitin-proteasome system (UPS) stress, the assembly of PTEN and its interacting partners changed obviously during translocation. We newly identified 36 PTEN-interacting proteins, which were found to be highly enriched in functional pathways closely related to cell apoptosis. Inspiringly, the interactions among PTEN isoforms and their interacting proteins were accessible by the determination of sequence-unique cross-linking interfaces for direct interactions. All these results indicate the promise of SPACX to elucidate the functional heterogeneity of proteins in individual subcellular sociology.

biochemistry↗

Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of Fragile X Syndrome

BackgroundFragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic form of autism, is caused by a loss of FMRP translational regulator 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects. MethodsWe treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying persistent effects of Nutlin-3, we analyzed proliferation and differentiation of neural stem cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice. ResultsWe found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6-month of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to extracellular matrix, secreted factors, and cell membrane proteins in FMR1-deficient hippocampus. ConclusionsOur data indicates that transient Nutlin-3 treatment in young adults leads to long-lasting neurogenic and behavioral changes through modulating adult neurogenic niche rather than intrinsic properties of adult neural stem cells. Our results demonstrate that cognitive impairments in FXS may be prevented by an early intervention through Nutlin-3 treatment.

neuroscience↗

Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance anti-HIV activity in vitro

HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4+ T cells that express virus either spontaneously or after intentional latency reversal. However, the T-cell exhaustion and the patient-specific autologous paradigm of CAR-T hurdled the clinical application. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 CAR (3BE CAR) construct that enables the expression of PD-1 blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). In comparison with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater anti-HIV potency with stronger proliferation capability, higher killing efficiency (up to ~75%) and enhanced cytokine secretion in the presence of HIV envelope glycoprotein-expressing cells. Furthermore, our approach achieved high levels (over 97%) of the TCR-deficient 3BE CAR-T cells with the functional inactivation of endogenous TCR to avoid graft-versus-host disease without compromising their antiviral activity relative to standard anti-HIV CAR-T cells. These data suggest that we have provided a feasible approach to large-scale generation of "off-the-shelf" anti-HIV CAR-T cells in combination with antibody therapy of PD-1 blockade, which can be a powerful therapeutic candidate for the functional cure of HIV.

bioengineering↗

Microscopic and ultramicroscopic anatomical characteristics of root nodules in Podocarpus macrophyllus during development

To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, mature, and senescent stages. Optical microscopy and transmission electron microscopy (SEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well-developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as P. macrophyllus. The conclusions of this study can provide a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts. HighlightsWe discuss from the perspective of cell developmental biology, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as Podocarpus macrophyllus.

developmental biology↗

SpotLink enables sensitive and precise identification of site non-specific cross-links at the proteome scale

We developed SpotLink software for identifying site non-specific cross-links at the proteome scale. Contributed by the dual pointer dynamic pruning (DPDP) algorithm and the quality control of cross-linking sites, SpotLink identified more than 3000 cross-links from human proteome database with rich site information in a few days. We demonstrated that SpotLink outperformed other approaches in terms of sensitivity and precision on a simulated dataset and a protein complexes dataset with known structures. Additionally, we discovered some valuable protein-protein interaction (PPI) information contained in the protein complexes dataset and HeLa dataset, indicating the unique identification advantages of site non-specific cross-linking. The excellent performance of SpotLink will increase the usage of site non-specific cross-linking in the near future. SpotLink is publicly available on GitHub [https://github.com/DICP1810/SpotLink].

bioinformatics↗

Parasite defensive limb movements enhance signal attraction in male little torrent frogs: insight into the evolution of multimodal signals

Many animals rely on complex sexual signals that target multiple senses to attract mates and repel rivals. These multimodal mating displays can however also attract unintended receivers, which can be an important driver of signal complexity. Despite being taxonomically widespread, we often lack insight into how multimodal signals evolve from unimodal signals and in particular what roles unintended eavesdroppers play. Here we assess whether the physical movements of parasite defense behavior increase the complexity and attractiveness of an acoustic sexual signal in the little torrent frog (Amolops torrentis). Calling males of this species often display limb movements in order to defend against blood-sucking parasites such as frog-biting midges that eavesdrop on their acoustic signal. Through mate choice tests we show that some of these midge-evoked movements influence female preference for acoustic signals. Our data suggest that midge-induced movements may be incorporated into a sexual display, targeting both hearing and vision in the intended receiver. Females may play an important role in incorporating these multiple components because they prefer signals which combine multiple programs. Our results thus help to understand the relationship between ecological and sexual selection pressure operating on signalers and how in turn this may influence multimodal signal evolution.

evolutionary biology↗

Transcriptional and mutational signatures of the aging germline

Aging is a complex biological process that is accompanied by changes in gene expression and mutational load. In many species, including humans, older fathers pass on more paternally-derived de novo mutations; however, the cellular basis and cell types driving this pattern are still unclear. To explore the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissues from the same flies. We found that early germ cells from old and young flies enter spermatogenesis with similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. Mutations in old cells may also increase during spermatogenesis. Our data reveal that old and young flies have distinct mutational biases. Many classes of genes show increased post-meiotic expression in the germlines of older flies. Late spermatogenesis-enriched genes have higher dN/dS than early spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is a source of evolutionary innovation. Surprisingly, young fly enriched genes show higher dN/dS than old fly enriched genes. Our results provide novel insights into the role of the germline in de novo mutation.

evolutionary biology↗

Determining the architecture of nuclear ring of Xenopus laevis nuclear pore complex using integrated approaches

The nuclear pore complexes (NPCs) are large protein assemblies as a physical gate to regulate nucleocytoplasmic transport. Here, using integrated approaches including cryo-electron microscopy, hybrid homology modeling and cell experiment, we determined the architecture of the nuclear ring (NR) from Xenopus laevis oocytes NPC at subnanometer resolution. In addition to the improvement of the Y complex model, eight copies of Nup205 and ELYS were assigned in NR. Nup205 connects the inner and outer Y complexes and contributes to the assembly and stability of the NR. By interacting with both the inner Nup160 and the nuclear envelope (NE), the N-terminal {beta}-propeller and -solenoid domains of ELYS were found to be essential for accurate assembly of the NPC on the NE.

molecular biology↗

Persistent CAD activity in memory CD8+ T cells supports rRNA synthesis and ribosomal biogenesis required at rechallenge

Memory CD8+ T cells are characterized by their ability to persist long after the initial antigen encounter and their ability to generate a rapid recall response. Recent studies have identified a role for metabolic reprogramming and mitochondrial function in promoting the longevity of memory T cells. However, detailed mechanisms involved in promoting the rapid recall response are incompletely understood. Here we identify a novel role for the initial and continued activation of the trifunctional rate-limiting enzyme of the de novo pyrimidine synthesis pathway CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) as critical in promoting the rapid recall response of previously-activated CD8+ T cells. CAD is rapidly phosphorylated upon T cell activation in an mTORC1-dependent manner yet remains phosphorylated long after initial activation. Previously-activated CD8+ T cells display continued de novo pyrimidine synthesis in the absence of mitogenic signals and interfering with this pathway diminishes the speed and magnitude of cytokine production upon rechallenge. Inhibition of CAD does not affect cytokine transcript levels, but diminishes available pre-rRNA, the polycistronic rRNA precursor whose synthesis is the rate-limiting step in ribosomal biogenesis. CAD inhibition additionally decreases levels of detectable ribosomal proteins in previously-activated CD8+ T cells. Overexpression of CAD improves both the cytokine response and proliferation of memory T cells. Overall, our studies reveal a novel and critical role for CAD-induced pyrimidine synthesis and ribosomal biogenesis in promoting the rapid recall response characteristic of memory T cells. One Sentence SummaryPyrimidine synthesis fuels ribosomal biogenesis to facilitate rapid recall responses in CD8+ T cells

immunology↗

Dominant species determine ecosystem stability across scales in Inner Mongolian grassland

There is an urgent need to extend knowledge on ecosystem temporal stability to larger spatial scales because presently available local-scale studies generally do not provide effective guide for management and conservation decisions at the level of an entire region with diverse plant communities. We investigated temporal stability of plant biomass production across spatial scales and hierarchical levels of community organization and analyzed impacts of dominant species, species diversity and climatic factors using a multi-site survey of Inner Mongolian grassland. We found that temporal stability at a large spatial scale, i.e. a large area aggregating multiple local communities, was related to temporal stability of and asynchrony among spatially separated local communities and large-scale population dynamics of dominant species, yet not to species richness. Additionally, a lower mean and higher variation of yearly precipitation destabilized communities at local and large scales by destabilizing dominant species population dynamics. We argue that, for semi-arid temperate grassland, dynamics and precipitation responses of dominant species and asynchrony among local communities stabilize ecosystems at large spatial scales. Our results indicate that reduced amounts and increased variation of precipitation may present key threats to the sustainable provision of biological products and services to human well-being in this region.

ecology↗

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

Sexual and asexual reproduction is ubiquitous in eukaryotes. PI3K/AKT signaling pathway can modulate sexual reproduction in mammals. However, this signaling pathway modulating sexual and asexual reproduction in fungi is scarcely understood. SeASF1, a SeH4 chaperone, could manipulate sexual and asexual reproduction of Stemphylium eturmiunum. SeDJ-1, screened from Se{Delta}asf1 transcriptome, was confirmed to regulate sexual and asexual development by RNAi, of which the mechanism was demonstrated by detecting transcriptional levels and protein interactions of SeASF1, SeH4 and SeDJ-1 by qRT-PCR, and Y2H, Co-IP and Pull-down, respectively. SeASF1 coupling SeH4 bound SeDJ-1 to arouse the sexual and asexual activity. In S. eturmiunum genome, SeDJ-1 was upstream while SeGSK3 was downstream in PI3K/AKT signaling pathway. Moreover, SeDJ-1 interacted with SePI3K or SeGSK3 in vivo and in vitro. Significantly, SeDJ-1 or SePI3K could effectively stimulate sexual activity alone, but SePI3K could recover the sexual development of SiSeDJ-1. Meanwhile, SeDJ-1-M6 was a critical segment for interaction of SeDJ-1 with SePI3K. SeDJ-1-M6 played a critical role in irritating sexual reproduction in SiSePI3K, which further uncovered the regulated mechanism of SeDJ-1. Summarily, SeASF1 coupling SeH4 motivates SeDJ-1 to arouse SePI3K involved in sexual reproduction. Thus, SeASF1 can activate PI3K/AKT signaling pathway to regulate sexual and asexual development in filamentous ascomycete.

microbiology↗