The sharp increase of plant genome and transcriptome data provide valuable resources to investigate evolutionary consequences of gene duplication in a range of taxa, and unravel common principles ...underlying duplicate gene retention.
We survey 141 sequenced plant genomes to elucidate consequences of gene and genome duplication, processes central to the evolution of biodiversity. We develop a pipeline named DupGen_finder to identify different modes of gene duplication in plants. Genes derived from whole-genome, tandem, proximal, transposed, or dispersed duplication differ in abundance, selection pressure, expression divergence, and gene conversion rate among genomes. The number of WGD-derived duplicate genes decreases exponentially with increasing age of duplication events-transposed duplication- and dispersed duplication-derived genes declined in parallel. In contrast, the frequency of tandem and proximal duplications showed no significant decrease over time, providing a continuous supply of variants available for adaptation to continuously changing environments. Moreover, tandem and proximal duplicates experienced stronger selective pressure than genes formed by other modes and evolved toward biased functional roles involved in plant self-defense. The rate of gene conversion among WGD-derived gene pairs declined over time, peaking shortly after polyploidization. To provide a platform for accessing duplicated gene pairs in different plants, we constructed the Plant Duplicate Gene Database.
We identify a comprehensive landscape of different modes of gene duplication across the plant kingdom by comparing 141 genomes, which provides a solid foundation for further investigation of the dynamic evolution of duplicate genes.
Implant and blood-contacting biomaterials are challenged by biofouling and thrombus formation at their interface. Zwitterionic polymer brush coating can achieve excellent hemocompatibility, but the ...preparation often involves tedious, expensive, and complicated procedures that are designed for specific substrates. Here, we report a facile and universal strategy of creating zwitterionic polymer brushes on variety of materials by polydopamine (PDA)-assisted and surface-initiated activators regenerated by electron transfer atom-transfer radical polymerization (PDA-SI-ARGET-ATRP). A PDA adhesive layer is first dipcoated on a substrate, followed by covalent immobilization of 3-trimethoxysilyl propyl 2-bromo-2-methylpropionate (SiBr, ATRP initiator) on the PDA via condensation. Meanwhile, the trimethoxysilyl group of SiBr also cross-links the PDA oligomers forming stabilized PDA/SiBr complex coating. Finally, SI-ARGET-ATRP is performed in a zwitterionic monomer solution catalyzed by the parts per million level of CuBr2 without deoxygenization. The conveniently fabricated zwitterionic polymer brush coatings are demonstrated to have stable, ultralow fouling, and extremely blood compatible and functionalizable characteristics. This facile, versatile, and universal surface modification strategy is expected to be widely applicable in various advanced biomaterials and devices.
Potassium and nitrogen are essential macronutrients for plant growth and have a positive impact on crop yield. Previous studies have indicated that the absorption and translocation of K+ and NO3
− ...are correlated with each other in plants; however, the molecular mechanism that coordinates K+ and NO3
− transport remains unknown. In this study, using a forward genetic approach, we isolated a low-K+-sensitive Arabidopsis thaliana mutant, lks2, that showed a leaf chlorosis phenotype under low-K+ conditions. LKS2 encodes the transporter NRT1.5/NPF7.3, a member of the NRT1/PTR (Nitrate Transporter 1/Peptide Transporter) family. The lks2/nrt1.5 mutants exhibit a remarkable defect in both K+ and NO3
− translocation from root to shoot, especially under low-K+ conditions. This study demonstrates that LKS2 (NRT1.5) functions as a proton-coupled H+/K+ antiporter. Proton gradient can promote NRT1.5-mediated K+ release out of root parenchyma cells and facilitate K+ loading into the xylem. This study reveals that NRT1.5 plays a crucial role in K+ translocation from root to shoot and is also involved in the coordination of K+/NO3
− distribution in plants.
The two hallmarks of Alzheimer's disease (AD) are amyloid‐β (Aβ) plaques and neurofibrillary tangles marked by phosphorylated tau. Increasing evidence suggests that aggregating Aβ drives tau ...accumulation, a process that involves synaptic degeneration leading to cognitive impairment. Conversely, there is a realization that non‐fibrillar (oligomeric) forms of Aβ mediate toxicity in AD. Fibrillar (filamentous) aggregates of proteins across the spectrum of the primary and secondary tauopathies were the focus of recent structural studies with a filament structure‐based nosologic classification, but less emphasis was given to non‐filamentous co‐aggregates of insoluble proteins in the fractions derived from post‐mortem human brains. Here, we revisited sarkosyl‐soluble and ‐insoluble extracts to characterize tau and Aβ species by quantitative targeted mass spectrometric proteomics, biochemical assays, and electron microscopy. AD brain sarkosyl‐insoluble pellets were greatly enriched with Aβ42 at almost equimolar levels to N‐terminal truncated microtubule‐binding region (MTBR) isoforms of tau with multiple site‐specific post‐translational modifications (PTMs). MTBR R3 and R4 tau peptides were most abundant in the sarkosyl‐insoluble materials with a 10‐fold higher concentration than N‐terminal tau peptides. This indicates that the major proportion of the enriched tau was the aggregation‐prone N‐terminal and proline‐rich region (PRR) of truncated mixed 4R and 3R tau with more 4R than 3R isoforms. High concentration and occupancies of site‐specific phosphorylation pT181 (~22%) and pT217 (~16%) (key biomarkers of AD) along with other PTMs in the PRR and MTBR indicated a regional susceptibility of PTMs in aggregated tau. Immunogold labelling revealed that tau may exist in globular non‐filamentous form (N‐terminal intact tau) co‐localized with Aβ in the sarkosyl‐insoluble pellets along with tau filaments (N‐truncated MTBR tau). Our results suggest a model that Aβ and tau interact forming globular aggregates, from which filamentous tau and Aβ emerge. These characterizations contribute towards unravelling the sequence of events which lead to end‐stage AD changes.
We revisited Alzheimer's Disease (AD) brain sarkosyl‐extraction to characterize tau and Amyloid‐β (Aβ) by biochemical assays and electron microscopy. Immunogold labelling revealed non‐filamentous globular co‐aggregates of tau and Aβ along with filamentous tau in the sarkosyl‐insoluble fractions. Quantitative proteomics showed equimolar amounts of Aβ and R1 tau, while the insoluble fraction was rich in MTBR 3R/4R mixed tau isoforms with multiple post‐translational modifications. Our results suggest a model that Aβ and tau interact forming globular aggregates, from which filamentous tau and Aβ may emerge. These results contribute towards unravelling the sequence of events which lead to end‐stage AD changes.
To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease, supportive biomarker ...information is necessary. The only validated methods for identifying amyloid-β deposition in the brain-the earliest pathological signature of Alzheimer's disease-are amyloid-β positron-emission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable. Despite much effort, to our knowledge, no study has validated the clinical utility of blood-based amyloid-β markers. Here we demonstrate the measurement of high-performance plasma amyloid-β biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-β precursor protein (APP)
/amyloid-β (Aβ)
and Aβ
/Aβ
ratios, and their composites, to predict individual brain amyloid-β-positive or -negative status was determined by amyloid-β-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using
C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-β burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-β-PET burden and levels of Aβ
in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-β burden at an individual level. These plasma biomarkers also have cost-benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.
In response to low K
+
stress, the
MYB59
transcription factor regulates both the expression of transporter gene
NRT1.5
/
NPF7.3
in Arabidopsis roots and the rate of root-to-shoot K
+
/NO
3
−
...transport.
Potassium and nitrogen are essential nutrients for plant growth and development. Plants can sense potassium nitrate (K
+
/NO
3
–
) levels in soils, and accordingly they adjust root-to-shoot K
+
/NO
3
–
transport to balance the distribution of these ions between roots and shoots. In this study, we show that the transcription factorMYB59 maintains this balance by regulating the transcription of the Arabidopsis (
Arabidopsis thaliana
)
Nitrate Transporter1.5
(
NRT1.5
)/
Nitrate Transporter/Peptide Transporter Family7.3
(
NPF7.3
) in response to low K
+
(LK) stress. The
myb59
mutant showed a yellow-shoot sensitive phenotype when grown on LK medium. Both the transcript and protein levels of
NPF7.3
were remarkably reduced in the
myb59
mutant. LK stress repressed transcript levels of both
MYB59
and
NPF7.3
. The
npf7.3
and
myb59
mutants, as well as the
npf7.3 myb59
double mutant, showed similar LK-sensitive phenotypes. Ion content analyses indicated that root-to-shoot K
+
/NO
3
–
transport was significantly reduced in these mutants under LK conditions. Moreover, chromatin immunoprecipitation and electrophoresis mobility shift assay assays confirmed that MYB59 bound directly to the
NPF7.3
promoter. Expression of
NPF7.3
in root vasculature driven by the
PHOSPHATE 1
promoter rescued the sensitive phenotype of both
npf7.3
and
myb59
mutants. Together, these data demonstrate that
MYB59
responds to LK stress and directs root-to-shoot K
+
/NO
3
–
transport by regulating the expression of
NPF7.3
in Arabidopsis roots.
Since the first dendrimer was reported in 1978 by Fritz Vögtle, dendrimer research has grown exponentially, from synthesis to application in the past four decades. The distinct structure ...characteristics of dendrimers include nanoscopic size, multi-functionalized surface, high branching, cavernous interior, and so on, making dendrimers themselves ideal drug delivery vehicles. This mini review article provides a brief overview of dendrimer's history and properties and the latest developments of dendrimers as drug delivery systems. This review focuses on the latest progress in the applications of dendrimers as drug and gene carriers, including 1) active drug release strategies to dissociate drug/gene from dendrimer in response to stimuli; 2) size-adaptive and charge reversal dendrimer delivery systems that can better take advantage of the size and surface properties of dendrimer; 3) bulk and micro/nano dendrimer gel delivery systems. The recent advances in dendrimer formulations may lead to the generation of new drug and gene products and enable the development of novel combination therapies.
Aging and Alzheimer's disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether ...continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.
BACE1 is responsible for β-secretase cleavage of the amyloid precursor protein (APP), which represents the first step in the production of amyloid β (Aβ) peptides. Previous reports, by us and others, ...have indicated that the levels of BACE1 protein and activity are increased in the brain cortex of patients with Alzheimer's disease (AD). The association between oxidative stress (OS) and AD has prompted investigations that support the potentiation of BACE1 expression and enzymatic activity by OS. Here, we have established conditions to analyse the effects of mild, non-lethal OS on BACE1 in primary neuronal cultures, independently from apoptotic mechanisms that were shown to impair BACE1 turnover. Six-hour treatment of mouse primary cortical cells with 10-40 µM hydrogen peroxide did not significantly compromise cell viability but it did produce mild oxidative stress (mOS), as shown by the increased levels of reactive radical species and activation of p38 stress kinase. The endogenous levels of BACE1 mRNA and protein were not significantly altered in these conditions, whereas a toxic H2O2 concentration (100 µM) caused an increase in BACE1 protein levels. Notably, mOS conditions resulted in increased levels of the BACE1 C-terminal cleavage product of APP, β-CTF. Subcellular fractionation techniques showed that mOS caused a major rearrangement of BACE1 localization from light to denser fractions, resulting in an increased distribution of BACE1 in fractions containing APP and markers for trans-Golgi network and early endosomes. Collectively, these data demonstrate that mOS does not modify BACE1 expression but alters BACE1 subcellular compartmentalization to favour the amyloidogenic processing of APP, and thus offer new insight in the early molecular events of AD pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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