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.

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.

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.

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.

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.

RNA sequencing and weighted gene co-expression network analysis uncover the hub genes controlling cold tolerance in Helictotrichon virescens seedlings.

Helictotrichon virescens is a perennial herbaceous plant with a life expectancy of about 10 years. It has high cold and heat resistance and can successfully survive over winter in the habitats with a temperature range of -25 to 25°C. Therefore, this study aimed to identify the key genes regulating low-temperature stress responses in H. virescens and analyze cold tolerant at molecular level. This study used RNA sequencing (RNA-Seq) and weighted gene co-expression network analysis (WGCNA) to identify the hub genes associated with cold tolerance in H. virescens. RT-PCR was conducted, homologous genes were identified, and related bioinformatics were analyzed to verify the identified hub genes. Moreover, WGCNA analysis showed that only the brown module had the highest correlation with the active-oxygen scavenging enzymes [peroxide (POD), superoxide dismutase (SOD), and catalase (CAT)]. The expression levels of three hub genes in the brown module (Cluster-37118.47362, cluster-37118.47713, and cluster-37118.66740) were significantly higher under low-temperature stress than those under control conditions. Furthermore, gene ontology (GO) and KEGG annotations showed that the three hub genes were mainly enriched in the metabolism pathways of sphingolipids, selenocompounds, glyoxylate, and dicarboxylate, carotenoids biosynthesis, and other biological pathways. The results of this study also showed that the subcellular localization prediction results showed that the cold tolerance hub genes were all localized to the plasma membrane. By constructing a protein interaction network, it was found that the hub gene Cluster-37118.66740 interacted with Sb09g003460.1 and Sb04g020180.1 proteins in Sorghum bicolor. By constructing phylogenetic trees of the four species of H. virescens, Sorghum bicolo, Oryza sativa Japonica, and Arabidopsis thaliana, the results showed that, the hub gene Cluster 37118.66740 (of H. virescens) and Os03g0340500 (of Oryza sativa Japonica) belonged to the same ancestral branch and were in the same subfamily. Thus, this study provides methodology and guidance to identify the cold tolerance genes for other herbage and their cold tolerant molecular mechanisms at molecular level.

Characterization of disinfection byproduct formation potential in 13 source waters in China.

The formation potential of four trihalomethanes (THMFP) and seven haloacetic acids (HAA7FP) in 13 source waters taken from four major water basin areas in China was evaluated using the simulated distribution system (SDS) chlorination method. The specific ultraviolet absorbance (SUVA254: the ratio of UV254 to dissolved organic carbon (DOC)), which ranged between 0.9 and 5.0 L/(mg x m), showed that the organic compounds in different source waters exhibited different reactivities with chlorine. The HAA7FP of source waters ranged from 20 to 448 microg/L and the THMFP ranged from 29 to 259 microg/L. The HAA7FP concentrations were higher than the THMFP concentrations in all but one of the samples. Therefore, the risks of haloacetic acids (HAAs) should be of concern in some source waters. TCM (chloroform) and BDCM (bromodichloromethane) were the major THM constituents, while TCAA (trichloroacetic acid) and DCAA (dichloroacetic acid) were the major HAA species. Br-THM (brominated THM species) were much higher than Br-HAA (brominated HAA species), and the formation of Br-DBP (Br-THM and Br-HAA) should be of concern when the bromide concentration is over 100 microg/L.

Specific Rhizobacteria Responsible in the Rhizosheath System of Kengyilia hirsuta.

The rhizosheath is a critical interface supporting the exchange of resources between plants and their associated environment of soil. Favorable microenvironment of rhizosphere soil provides the rhizosheath formed and then promotes desert plant survival. However, it remains unclear how rhizosheath benefits the colonization of pioneer plants in alpine desert under changing environment. In this study, we investigated the effect of different soil moisture and sterilization treatments (three moisture levels and unsterilized or sterilized soil) on rhizosheath forming process of Kengyilia hirsuta (K. hirsuta), a sand-inhabiting and drought-resistant pioneer plant of the Tibetan Plateau desert. The results showed that in both unsterilized and sterilized soil, increasing soil moisture first increased and then decreased rhizosheath weight, with the highest value is 25%. During rhizosheath formation, developing rhizosheaths were selectively enriched in the bacterial genera Massilia and Arthrobacter. These suggest the existence of a highly specialized signal recognition system during rhizosheath formation that involves the accumulation of bacteria. These bacterial species exhibited different roles in the process of rhizosheath formation and is an advantageous strategy for K. hirsuta.

Phenotypic Plasticity and Local Adaptation of Leaf Cuticular Waxes Favor Perennial Alpine Herbs under Climate Change.

Six perennial herbs (Plantago asiatica, Polygonum viviparum, Anaphalis lactea, Kobresia humilis, Leontopodium nanum and Potentilla chinensis) widely distributed in alpine meadows were reciprocally transplanted at two sites in eastern edge of Qinghai-Tibetan Plateau, Hongyuan (3434 m, 2.97 °C, 911 mm) and Qilian (3701 m, 2.52 °C, 472 mm), aiming to evaluate the responses of alpine plants to changing environments. When plants were transplanted from Hongyuan to Qilian, most plant species showed a decrease of total wax coverage in first year and reverse trend was observed for some plant species in second year. However, when plants were transplanted from Qilian to Hongyuan, the response of total wax coverage differed greatly between plant species. When compared with those in first year, plasticity index of average chain length of alkane decreased whereas carbon preference index of alkane increased at both Hongyuan and Qilian in second year. The total wax coverage differed between local and transplanted plants, suggesting both environmental and genetic factors controlled the wax depositions. Structural equation modeling indicated that co-variations existed between leaf cuticular waxes and leaf functional traits. These results suggest that alpine herbs adjust both wax depositions and chain length distributions to adapt to changing environment, showing climate adaptations.

Tau seeds are subject to aberrant modifications resulting in distinct signatures.

The prion-like spread of tau pathology could underlie a spectrum of clinical syndromes including Alzheimer's disease (AD). Although evidence indicates that tau is transmissible, it is unclear how pathogenic tau seeds are processed in neurons. Here, we analyze fibrillar wild-type and disease-associated P301L tau seeds by using in vitro and neuronal assays. We show that P301L seeds are uniquely modified by post-translational modifications (PTMs) within the microtubule-binding region (MTBR). Although these modifications do not alter tau seed trafficking or localization, acetylated tau variants show accelerated tau aggregation, enhanced tau PTM priming, and prion-like templating. To explain the enhanced tau seed acetylation, we demonstrate that P301L seeds undergo auto-acetylation. Moreover, tau acts generally to inhibit HDAC6 deacetylase activity by preventing HDAC6 phosphorylation, leading to increased substrate acetylation. Our study highlights complex post-translational regulation of transmissible tau seeds and provides insight into the biological properties of tau strains in AD and other tauopathies.

Double-edged effects of climate change on plant invasions: Ecological niche modeling global distributions of two invasive alien plants.

The prediction of the potential distribution of invasive alien species is key for the control of their proliferation. This study developed ensemble niche models to explore the distribution patterns of Cecropia peltata and Ulex europaeus under baseline and future conditions, as well as the factors that regulate them. The models were based on occurrence records as well as climate, land-use and topography datasets. Climatic factors played a stronger role than land-use and topographical factors in their distribution patterns. Additionally, temperature seasonality and temperature annual range were the optimal predictor for the global distributions of C. peltata and U. europaeus, respectively. Under the baseline-RCP 8.5 scenario in 2070, significant increases in habitat suitability for C. peltata were generally detected in tropical regions, while for U. europaeus under the same condition, significant increases in habitat suitability were generally observed in west coast of South America and Europe, suggesting the impacts of climate changes on species distribution may be species specific. The contrast changes of suitable habitat areas for U. europaeus under the baseline-2.6 and 8.5 scenarios may suggest that the scenarios of climate changes may modify its distribution patterns and variations in suitable habitats. The double-edged effects of global warming on plant invasions may be a result of the scenario specific climate change and the species-specific responses to changes in climate. Our findings highlight the importance of climate change scenario specific and species-specific research on the impact of climate change on plant invasions.