Exploring Evolutionary Pathways and Abiotic Stress Responses through Genome-Wide Identification and Analysis of the Alternative Oxidase (AOX) Gene Family in Common Oat (Avena sativa).

The alternative oxidase (AOX), a common terminal oxidase in the electron transfer chain (ETC) of plants, plays a crucial role in stress resilience and plant growth and development. Oat (Avena sativa), an important crop with high nutritional value, has not been comprehensively studied regarding the AsAOX gene family. Therefore, this study explored the responses and potential functions of the AsAOX gene family to various abiotic stresses and their potential evolutionary pathways. Additionally, we conducted a genome-wide analysis to explore the evolutionary conservation and divergence of AOX gene families among three Avena species (Avena sativa, Avena insularis, Avena longiglumis) and four Poaceae species (Avena sativa, Oryza sativa, Triticum aestivum, and Brachypodium distachyon). We identified 12 AsAOX, 9 AiAOX, and 4 AlAOX gene family members. Phylogenetic, motif, domain, gene structure, and selective pressure analyses revealed that most AsAOXs, AiAOXs, and AlAOXs are evolutionarily conserved. We also identified 16 AsAOX segmental duplication pairs, suggesting that segmental duplication may have contributed to the expansion of the AsAOX gene family, potentially preserving these genes through subfunctionalization. Chromosome polyploidization, gene structural variations, and gene fragment recombination likely contributed to the evolution and expansion of the AsAOX gene family as well. Additionally, we hypothesize that AsAOX2 may have potential function in resisting wounding and heat stresses, while AsAOX4 could be specifically involved in mitigating wounding stress. AsAOX11 might contribute to resistance against chromium and waterlogging stresses. AsAOX8 may have potential fuction in mitigating ABA-mediated stress. AsAOX12 and AsAOX5 are most likely to have potential function in mitigating salt and drought stresses, respectively. This study elucidates the potential evolutionary pathways of the AsAOXs gene family, explores their responses and potential functions to various abiotic stresses, identifies potential candidate genes for future functional studies, and facilitates molecular breeding applications in A. sativa.

Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase.

The posttranslational regulation of the neuronal proteome is critical for brain homeostasis but becomes dysregulated in the aged or diseased brain, in which abnormal posttranslational modifications (PTMs) are frequently observed. While the full extent of modified substrates that comprise the "PTM-ome" are slowly emerging, how the upstream enzymes catalyzing these processes are regulated themselves is not well understood, particularly in the context of neurodegeneration. Here, we describe the reciprocal regulation of a kinase, the microtubule affinity-regulating kinase 2 (MARK2), and an acetyltransferase, CREB-binding protein (CBP), two enzymes known to extensively modify tau proteins in the progression of Alzheimer's disease. We found that MARK2 negatively regulates CBP and, conversely, CBP directly acetylates and inhibits MARK2 kinase activity. These findings highlight a reciprocal negative feedback loop between a kinase and an acetyltransferase, which has implications for how PTM interplay is coordinated on substrates including tau. Our study suggests that PTM profiles occur through the posttranslational control of the master PTM remodeling enzymes themselves.

Resource islands of Salix cupularis facilitating seedling emergence of the companion herbs in the restoration process of desertified alpine meadow, the Tibetan Plateau.

Salix cupularis is a common shrub for ecological restoration of the desertified alpine meadow on the Tibetan Plateau. However, the effect of S. cupularis on spatial heterogeneity of soil resources (i.e., resource islands effect) has not been systematically evaluated, and the influence of shrub patches on the rehabilitation of understory herbs has also been unknown. In this study, we randomly selected S. cupularis individuals in the early restoration stage of desertified alpine meadow, where the three native forages (Elymus nutans, Elymus sibiricus and Festuca sinensis) were sown at different microsites around S. cupularis to explore the effects of S. cupularis on soil resources and emergence rates of the native forages. The results showed that S. cupularis significantly increased SWC (soil water content), C (carbon) and N (nitrogen) nutrients (p < 0.01) and enzyme activities (p < 0.05) under canopy compared with the bare land, and the improvement performed better in the topsoil (0-5 cm) than in the subtop-soil (5-15 cm). Moreover, the soil properties were affected significantly by microsites around S. cupularis, resulting in regular changes of SWC, nutrients and enzyme activities in different microsites (Shrub center > Middle of canopy radius > Bare land). In addition, there are significant regression relationships between emergence rates and enriching soil water, C and N nutrients, so the emergence rates of native forages under canopy may be improved significantly with the enriched soil resources, especially for E. nutans. As a result, S. cupularis is a suitable pioneer shrub for the vegetation restoration of desertified alpine meadow on the Tibetan Plateau, because it could not only shape the enrichment of soil resources under canopy, but also facilitate emergence of companion forages in the process of vegetation restoration.

Aggregation of the nucleic acid-binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation.

TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein, and its aggregation represents the defining pathology in amyotrophic lateral sclerosis (ALS) and related proteinopathies. Recent studies implicate cytoplasmic stress granules (SGs) as hubs that may facilitate TDP-43 aggregation. Here, using cellular fractionation, biochemical analyses, and histological assays, we show that TDP-43 targeted to the cytoplasm has multiple fates. Whereas a TDP-43 subpopulation is indeed recruited to SGs, mature aggregated TDP-43, produced with aggregate-prone TDP-43 variants or exposure to oxidative stress, generates distinct TDP-43 inclusions that are surprisingly devoid of SGs. Consistent with this observation, we found that SG components are predominantly excluded from TDP-43 pathology in motor neurons from individuals with ALS. We generated de novo SGs by expressing the fragile X protein (FMRP) and found that rather than directly engaging TDP-43 aggregates, SGs can sequester the proteostasis factor histone deacetylase 6 (HDAC6) and thereby impede TDP-43 clearance from cells. These findings indicate that SGs form distinct cytoplasmic structures that can indirectly enhance TDP-43 aggregation. Therapeutic approaches that inhibit SG formation may therefore be effective at suppressing TDP-43-mediated toxicity in patients with ALS and related TDP-43 proteinopathies.

A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation.

Abnormal intracellular accumulation of aggregated tau is a hallmark feature of Alzheimer's disease and other tauopathies. Pathological tau can undergo a range of post-translational modifications (PTMs) that are implicated as triggers of disease pathology. Recent studies now indicate that tau acetylation, in particular, controls both microtubule binding and tau aggregation, thereby acting as a central regulator of tau's biochemical properties and providing avenues to exploit for potential therapies. Here, using cell-based assays and tau transgenic mice harboring an acetylation-mimic mutation at residue Lys-280 (K280Q), we evaluated whether this substitution modifies the neurodegenerative disease pathology associated with the aggregate-prone tau P301S variant. Strikingly, the addition of a K280Q-substituted variant altered P301S-mediated tau conformation and reduced tau hyperphosphorylation. We further evaluated neurodegeneration markers in K280Q acetylation-mimic mice and observed reduced neuroinflammation as well as restored levels of N-methyl-d-aspartate receptors and post-synaptic markers compared with the parental mice. Thus, substituting a single lysine residue in the context of a P301S disease-linked mutation produces a unique tau species that abrogates some of the cardinal features of tauopathy. The findings of our study indicate that a complex tau PTM code likely regulates tau pathogenesis, highlighting the potential utility of manipulating and detoxifying tau strains through site-specific tau-targeting approaches.

Pten Mutations Alter Brain Growth Trajectory and Allocation of Cell Types through Elevated ß-Catenin Signaling.

Abnormal patterns of head and brain growth are a replicated finding in a subset of individuals with autism spectrum disorder (ASD). It is not known whether risk factors associated with ASD and abnormal brain growth (both overgrowth and undergrowth) converge on common biological pathways and cellular mechanisms in the developing brain. Heterozygous mutations in PTEN (PTEN(+/-)), which encodes a negative regulator of the PI3K-Akt-mTOR pathway, are a risk factor for ASD and macrocephaly. Here we use the developing cerebral cortex of Pten(+/-) mice to investigate the trajectory of brain overgrowth and underlying cellular mechanisms. We find that overgrowth is detectable from birth to adulthood, is driven by hyperplasia, and coincides with excess neurons at birth and excess glia in adulthood. ß-Catenin signaling is elevated in the developing Pten(+/-) cortex, and a heterozygous mutation in Ctnnb1 (encoding ß-catenin), itself a candidate gene for ASD and microcephaly, can suppress Pten(+/-) cortical overgrowth. Thus, a balance of Pten and ß-catenin signaling regulates normal brain growth trajectory by controlling cell number, and imbalance in this relationship can result in abnormal brain growth. SIGNIFICANCE STATEMENT: We report that Pten haploinsufficiency leads to a dynamic trajectory of brain overgrowth during development and altered scaling of neuronal and glial cell populations. ß-catenin signaling is elevated in the developing cerebral cortex of Pten haploinsufficient mice, and a heterozygous mutation in ß-catenin, itself a candidate gene for ASD and microcephaly, suppresses Pten(+/-) cortical overgrowth. This leads to the new insight that Pten and ß-catenin signaling act in a common pathway to regulate normal brain growth trajectory by controlling cell number, and disruption of this pathway can result in abnormal brain growth.

Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington's disease.

Huntington's disease (HD) is caused by an expansion of glutamine repeats in the huntingtin protein (mHtt) that invokes early and prominent damage of the striatum, a region that controls motor behaviors. Despite its ubiquitous expression, why certain brain regions, such as the cerebellum, are relatively spared from neuronal loss by mHtt remains unclear. Previously, we implicated the striatal-enriched GTPase, Rhes (Ras homolog enriched in the striatum), which binds and SUMOylates mHtt and increases its solubility and cellular cytotoxicity, as the cause for striatal toxicity in HD. Here, we report that Rhes deletion in HD mice (N171-82Q), which express the N-terminal fragment of human Htt with 82 glutamines (Rhes(-/-)/N171-82Q), display markedly reduced HD-related behavioral deficits, and absence of lateral ventricle dilatation (secondary to striatal atrophy), compared to control HD mice (N171-82Q). To further validate the role of GTPase Rhes in HD, we tested whether ectopic Rhes expression would elicit a pathology in a brain region normally less affected in HD. Remarkably, ectopic expression of Rhes in the cerebellum of N171-82Q mice, during the asymptomatic period led to an exacerbation of motor deficits, including loss of balance and motor incoordination with ataxia-like features, not apparent in control-injected N171-82Q mice or Rhes injected wild-type mice. Pathological and biochemical analysis of Rhes-injected N171-82Q mice revealed a cerebellar lesion with marked loss of Purkinje neuron layer parvalbumin-immunoreactivity, induction of caspase 3 activation, and enhanced soluble forms of mHtt. Similarly reintroducing Rhes into the striatum of Rhes deleted Rhes(-/-)Hdh(150Q/150Q) knock-in mice, elicited a progressive HD-associated rotarod deficit. Overall, these studies establish that Rhes plays a pivotal role in vivo for the selective toxicity of mHtt in HD.

Physiologically based pharmacokinetic models for predicting lamotrigine exposure and dose optimization in pediatric patients receiving combination therapy with carbamazepine or valproic acid.

INTRODUCTION: Lamotrigine (LTG) is an antiepileptic drug that has been used in pediatric epilepsy as a combination therapy or monotherapy after stabilization in recent years. However, there are significant drug-drug interactions (DDI) between LTG and combined drugs such as carbamazepine (CBZ) and valproic acid (VPA). It is particularly important to consider the risk of DDI in combination therapy for intractable epilepsy in pediatric patients. Therefore, it is necessary to adjust the dosage of LTG accordingly. The aim of this study was to establish and validate a pediatric physiologically based pharmacokinetic (PBPK) model for predicting LTG exposure. The model is designed to explore the potential for quantifying pharmacokinetic (PK) DDI of LTG when administered concurrently with CBZ or VPA in pediatric patients. METHOD: Adult and pediatric PBPK models for LTG and VPA were developed using PK-Sim® software in combination with physiological information and drug-specific parameters, and a DDI model was developed in combination with the published CBZ model. The models were validated against available PK data. RESULTS: Predictive and observational results in adults, children, and the DDI model were in good agreement. The recommended doses of LTG for preschool children (2-6 years) and school-aged children (6-12 years) in the absence of drug interactions were 1.47 and 1.2 times higher than those for adults, respectively; 3.1 and 2.6 times higher than those for adults in combination with CBZ; and 0.67 and 0.57 times lower than those for adults in combination with VPA. In addition, plasma exposures in adolescents (12-18 years) were similar to those in adults at the same doses. CONCLUSION: We have successfully developed PBPK models and DDI models for LTG in adults and children, which provide a reference for rational drug use in the pediatric population.

Microbiome and response surface methodology analyses reveal Acetobacter pasteurianus as the core bacteria responsible for aerobic spoilage of corn silage (Zea mays) in hot and humid areas.

Introduction: Weak aerobic stability is a notable challenge for whole-plant corn silage, particularly in hot and humid regions. Acetobacter is commonly regarded as an indicator of aerobic deterioration in silage, yet its precise role in fermentation and during aerobic exposure, as well as the factors that promote its growth, remain insufficiently understood. Methods: In this study, whole-plant corn silage was prepared using a bagged method with controlled dry matter (DM) content at 20%, 25%, and 30%, and initial concentrations of A. pasteurianus at 40%, 50%, and 60%. The silage was stored for 60 days under varying temperatures (20°C, 30°C, and 40°C). Following the anaerobic storage phase, the silage was exposed to air at room temperature (20-25°C) for 7 days, both with and without A. pasteurianus inoculation. Results: The results demonstrated that A. pasteurianus did not impact the nutritional value of the silage during anaerobic fermentation, maintaining a low pH (< 3.80). However, during aerobic exposure, the presence of A. pasteurianus significantly reduced the aerobic stability of the silage. The microbial community shifted from primarily Klebsiella species initially to Lactobacillus and Acetobacter species post-ensiling. During the aerobic exposure phase, A. pasteurianus and A. fabarum became the dominant species. Response Surface Methodology (RSM) analysis identified optimal conditions for the proliferation of A. pasteurianus during the aerobic phase, which occurred at 28°C, 25% DM, and 52% initial concentration at 3 ml/kg. Discussion: These findings confirm that A. pasteurianus plays a critical role in reducing the aerobic stability of whole-plant corn silage. Additionally, the study identifies the optimal conditions that favor the proliferation of A. pasteurianus, offering valuable insights for the development of strategies to prevent and control this bacterium, thereby improving the aerobic stability of silage in hot and humid regions.

The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study.

Background: Atypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles. Results: Our analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses. Conclusion: This is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

Physiologically based pharmacokinetic model of brivaracetam to predict the exposure and dose exploration in hepatic impairment and elderly populations.

Brivaracetam (BRV) is a new third-generation antiseizure medication for the treatment of focal epileptic seizures. Its use has been increasing among epileptic populations in recent years, but pharmacokinetic (PK) behavior may change in hepatic impairment and the elderly populations. Due to ethical constraints, clinical trials are difficult to conduct and data are limited. This study used PK-Sim® to develop a physiologically based pharmacokinetic (PBPK) model for adults and extrapolate it to hepatic impairment and the elderly populations. The model was evaluated with clinical PK data, and dosage explorations were conducted. For the adult population with mild hepatic impairment, the dose is recommended to be adjusted to 70 % of the recommended dose, and to 60 % for moderate and severe hepatic impairment. For the elderly population with mild hepatic impairment under 80 years old, it is recommended that the dose be adjusted to 60 % of the recommended dose and to 50 % for moderate and severe conditions. The elderly population with hepatic impairment over 80 years old is adjusted to 50 % of the recommended dose for all stages. Healthy elderly do not need to adjust. The BRV PBPK model was successfully developed, studying exposure in hepatic impairment and elderly populations and optimizing dosing regimens.

Comparative physiological and transcriptomic analyses reveal genotype specific response to drought stress in Siberian wildrye (Elymus sibiricus).

Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC-MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops.

The melanosomal protein PMEL17 as a target for antibody drug conjugate therapy in melanoma.

Melanocytes uniquely express specialized genes required for pigment formation, some of which are maintained following their transformation to melanoma. Here we exploit this property to selectively target melanoma with an antibody drug conjugate (ADC) specific to PMEL17, the product of the SILV pigment-forming gene. We describe new PMEL17 antibodies that detect the endogenous protein. These antibodies help define the secretory fate of PMEL17 and demonstrate its utility as an ADC target. Although newly synthesized PMEL17 is ultimately routed to the melanosome, we find substantial amounts accessible to our antibodies at the cell surface that undergo internalization and routing to a LAMP1-enriched, lysosome-related organelle. Accordingly, an ADC reactive with PMEL17 exhibits target-dependent tumor cell killing in vitro and in vivo.

Genome-wide identification and characterization of abiotic stress responsive GRAS family genes in oat (Avena sativa).

Background: GRAS transcription factors play a variety of functions in plant growth and development and are named after the first three transcription factors GAI (GIBBERRELLICACIDINSENSITIVE), RGA (REPRESSOROFGAI), and SCR (SCARECROW) found in this family. Oat (Avena sativa) is one of the most important forage grasses in the world. However, there are few reports on the GRAS gene family in oat. Methods: In order to understand the information and expression pattern of oat GRAS family members, we identified the GRAS members and analyzed their phylogenetic relationship, gene structure, and expression pattern in oat by bioinformatics technology. Results: The results showed that the oat GRAS family consists of 30 members, and most of the AsGRAS proteins were neutral or acidic proteins. The phylogenetic tree divided the oat GRAS members into four subfamilies, and each subfamily has different conservative domains and functions. Chromosome location analysis suggested that 30 GRAS genes were unevenly distributed on five chromosomes of oat. The results of real-time quantitative reverse transcription-PCR (qRT-PCR) showed that some AsGRAS genes (AsGRAS12, AsGRAS14, AsGRAS21, and AsGRAS24) were all up-regulated with increasing stress treatment time.The results of this study provide a theoretical basis for further research into the corresponding stress of oat. Therefore, further studies concentrating on these AsGRAS genes might reveal the many roles played by GRAS genes in oat.

Transcriptomics integrated with metabolomics provides a new strategy for mining key genes in response to low temperature stress in Helictotrichon virescens.

H. virescens is a perennial herbaceous plant with highly tolerant to cold weather, but the key genes that respond to low temperature stress still remain unclear. Hence, RNA-seq was performed using leaves of H. virescens treated at 0 °C and 25 °C for 12 h, 36 h, and 60 h, respectively, and a total of 9416 DEGs were significantly enriched into seven KEGG pathways. The LC-QTRAP platform was performed using leaves of H. virescens leaves at 0 °C and 25 °C for 12 h, 36 h, and 60 h, respectively, and a total of 1075 metabolites were detected, which were divided into 10 categories. Additionally, 18 major metabolites, two key pathways, and six key genes were mined using a multi-omics analytical strategy. The RT-PCR results showed that with the extension of treatment time, the expression levels of key genes in the treatment group gradually increased, and the difference between the treatment group and the control group was extremely significant. Notably, the functional verification results showed that the key genes positively regulated cold tolerance of H. virescens. These results can lay a foundation for the in-depth analysis of the mechanism of response of perennial herbs to low temperature stress.

Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity.

Tau-mediated toxicity is associated with cognitive decline and Alzheimer's disease (AD) progression. In particular, tau post-translational modifications (PTMs) are thought to generate aberrant tau species resulting in neuronal dysfunction. Despite being well characterized in postmortem AD brain, it is unclear how caspase-mediated C-terminal tau cleavage promotes neurodegeneration, as few studies have developed the models to dissect this pathogenic mechanism. Here, we show that proteasome impairment results in cleaved tau accumulation at the post-synaptic density (PSD), a process that is modulated by neuronal activity. Cleaved tau (at residue D421) impairs neuronal firing and causes inefficient initiation of network bursts, consistent with reduced excitatory drive. We propose that reduced neuronal activity, or silencing, is coupled to proteasome dysfunction, which drives cleaved tau accumulation at the PSD and subsequent synaptotoxicity. Our study connects three common themes in the progression of AD: impaired proteostasis, caspase-mediated tau cleavage, and synapse degeneration.

RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.

TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic acid-binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed endogenous models of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43K145Q resulted in stress-induced nuclear TDP-43 foci and loss of TDP-43 function in primary mouse and human-induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of human FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies.

Responses of photosynthetic characteristics of oat flag leaf and spike to drought stress.

Raising crops production via improving photosynthesis has always been focused. Recently excavating and increasing the photosynthetic capacity of non-leaf organs becomes an important approach to crops yield increase. Here we studied the photosynthetic characteristics of the flag leaf and the non-leaf organs including the sheath, the glume and the lemma under greenhouse. The relative water content (RWC), the stomatal characteristics, the photosynthetic pigment contents, the enzyme activities in C3 and C4 pathway and the malate content of the flag leaf and the non-leaf organs on 7, 14, 21, and 28 days after anthesis (denoted by 7DAA, 14DAA, 21DAA, and 28DAA) were determined under well-watered (CK) and water-stressed (D) treatments. Drought stress significantly reduced the RWC of the flag leaf and the non-leaf organs, while the variation of RWC in the glume and the lemma was lower than in the flag leaf. The chlorophyll a content, the chlorophyll b content, the total chlorophyll content and the xanthophyll content in the flag leaf were significantly decreased under D. However, drought stress significantly increased the photosynthetic pigment contents in the glume at the late stage (21DAA and 28DAA). In addition, the induced activities of PEPC, NADP-MDH, NADP-ME, NAD-ME, and PPDK in non-leaf organs under drought stress suggested that the C4 photosynthetic pathway in non-leaf organs compensated the limited C3 photosynthesis in the flag leaf. Non-leaf organs, in particular the glume, showed the crucial function in maintaining the stable photosynthetic performance of oat.

The microbiota diversity of Festuca sinensis seeds in Qinghai-Tibet Plateau and their relationship with environments.

A total of 14 Festuca sinensis seed lots were collected from different geographical locations on the Qinghai-Tibet Plateau to study the seed microbiota and determine the abiotic (temperature, precipitation, and elevation) and biotic (Epichloë sinensis infection rate) factors likely to shape the seed microbiome. The 14 seed lots had different bacterial and fungal structures and significantly different diversities (p < 0.05). The α-diversity indices of the bacteria were significantly correlated with precipitation (p < 0.05), whereas those of the fungi were significantly correlated with temperature (p < 0.05). Microbiota analysis showed that Proteobacteria, Cyanobacteria, and Bacteroidetes were the most abundant bacteria at the phylum level in the seeds, and Ascomycota and Basidiomycota were the most abundant fungi. ß-diversity analysis suggested large differences in the microbial communities of each sample. Redundancy analysis showed that temperature and precipitation were the main environmental factors that drive variations in the microbial community, at the medium-high elevation (3,000-4,500 m), the impact of temperature and precipitation on microbial community is different, and the other elevations that effect on microbial community were basically identical. Spearman's correlation analysis showed that the relative abundances of the most abundant bacterial phyla were significantly correlated with temperature (p < 0.05), whereas those of the most abundant fungal phyla were significantly correlated with precipitation (p < 0.05). E. sinensis infection rates were significantly correlated with elevation and temperature (p < 0.05). These results suggest that temperature and precipitation are the key factors driving the microbial community, that temperature and elevation also had a great influence on the E. sinensis infection rate, and that environmental factors (temperature and elevation) may further affect the microbial community by regulating the E. sinensis infection rate.

Response characteristics of root to moisture change at seedling stage of Kengyilia hirsuta.

Kengyilia hirsuta is an important pioneer plant distributed on the desertified grassland of the Qinghai-Tibet Plateau. It has strong adaptability to alpine desert habitats, so it can be used as a sand-fixing plant on sandy alpine land. To study the response mechanisms of root morphological and physiological characteristics of K. hirsuta to sandy soil moisture, 10%, 25% and 40% moisture levels were set up through potted weighing water control method. The biomass, root-shoot ratio, root architecture parameters, and biochemical parameters malondialdehyde, free proline, soluble protein, indole-3-acetic acid, abscisic acid, cytokinin, gibberellin, relative conductivity and antioxidant enzyme activities were measured in the trefoil stage, and the response mechanisms of roots at different moisture levels were analyzed. The results showed that with the increase of soil moisture, root morphological indexes such as root biomass, total root length, total root volume and total root surface increased, while the root topological index decreased continuously. The malondialdehyde content, relative conductivity, superoxide dismutase activity, peroxidase activity, catalase activity, free proline content, soluble protein content, abscisic acid content and cytokinin content at the 25% and 40% moisture levels were significantly decreased compared with the 10% level (P< 0.05). Thus, the root growth of K. hirsuta was restricted by the 10% moisture level, but supported by the 25% and 40% moisture levels. An artificial neural network revealed that total root length, total root surface area, root link average length, relative conductivity, soluble protein, free proline and moisture level were the key factors affecting root development. These research results could contribute to future agricultural sustainability.