NAC转录因子在植物生长发育中的调控作用

NAC转录因子是植物特异转录因子,是植物中最大的转录因子家族之一,其N端含大约150个高度保守的氨基酸组成的NAC结构域。NAC转录因子通过与DNA结合、直接或间接与其它蛋白的互作。参与植物生物和非生物胁迫应答、激素信号途径的转导、机体的凋亡等过程,在植物的生长发育过程中起重要作用。综述了NAC转录因子在植物细胞次生壁的形成、植物的衰老、侧根的发育、茎、叶和种子的形成等过程中的重要调控作用及机理,指出了今后NAC转录因子研究的方向。     

A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10.     

WRKY转录因子在植物生长发育中的调控作用

植物在生长发育过程中,形成了一系列具有调控作用的转录因子。其中,WRKY家族是近年来研究较为广泛的植物所特有的转录因子。WRKY转录因子具有多种生理功能,在植物种子萌发、形态建设、繁殖和衰老等过程中具有重要调控作用。对WRKY转录因子的结构及其在植物生长发育过程中的调控作用进行了综述。     

A Potential Involvement of Anandamide in the Modulation of HO/NOS Systems: Women,Menopause, and “Medical Cannabinoids”

Endocannabinoids and their receptors are present in the cardiovascular system; however, their actions under different pathological conditions remain controversial. The aim of our study was to examine the effects of anandamide (AEA) on heme oxygenase (HO) and nitric oxide synthase (NOS) systems in an estrogen-depleted rat model. Sham-operated (SO) and surgically induced estrogen-deficient (OVX) female Wistar rats were used. During a two-week period, a group of OVX rats received 0.1 mg/kg estrogen (E₂) per os, while AEA-induced alterations were analyzed after two weeks of AEA treatment at the dose of 1.0 mg/kg. At the end of the experiment, cardiac activity and expression of HO and NOS enzymes, content of cannabinoid 1 receptor, as well as concentrations of transient potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) were measured. Our results show that estrogen withdrawal caused a significant decrease in both NOS and HO systems, and a similar tendency was observed regarding the TRPV1/CGRP pathway. Two weeks of either AEA or E₂ treatment restored the adverse changes; however, the combined administration of these two molecules did not result in a further improvement. In light of the potential relationship between AEA and HO/NOS systems, AEA-induced upregulation of HO/NOS enzymes may be a therapeutic strategy in estrogen-deficient conditions.     

The “Hitchhiker’s Guide to the Galaxy” of Endothelial Dysfunction Markers in Human Fertility

Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and represents the first step in the pathogenesis of cardiovascular diseases. The evaluation of endothelial health is fundamental in clinical practice and several direct and indirect markers have been suggested so far to identify any alterations in endothelial homeostasis. Alongside the known endothelial role on vascular health, several pieces of evidence have demonstrated that proper endothelial functioning plays a key role in human fertility and reproduction. Therefore, this state-of-the-art review updates the endothelial health markers discriminating between those available for clinical practice or for research purposes and their application in human fertility. Moreover, new molecules potentially helpful to clarify the link between endothelial and reproductive health are evaluated herein.     

Control of Plant Defense Mechanisms and Fire Blight Pathogenesis through the Regulation of 6‐Thioguanine Biosynthesis in Erwinia amylovora

Fire blight is a devastating disease of Rosaceae plants, such as apple and pear trees. It is characterized by necrosis of plant tissue, caused by the phytopathogenic bacterium Erwinia amylovora. The plant pathogen produces the well‐known antimetabolite 6‐thioguanine (6TG), which plays a key role in fire blight pathogenesis. Here we report that YcfR, a member of the LTTR family, is a major regulator of 6TG biosynthesis in E. amylovora. Inactivation of the regulator gene (ycfR) led to dramatically decreased 6TG production. Infection assays with apple plants (Malus domestica cultivar Holsteiner Cox) and cell cultures of Sorbus aucuparia (mountain ash, rowan) revealed abortive fire blight pathogenesis and reduced plant response (biphenyl and dibenzofuran phytoalexin production). In the presence of the ΔycfR mutant, apple trees were capable of activating the abscission machinery to remove infected tissue. In addition to unveiling the regulation of 6TG biosynthesis in a major plant pathogen, we demonstrate for the first time that this antimetabolite plays a pivotal role in dysregulating the plant response to infection.     

Slaying (Yet Again) the Brain-Eating Zombie Called the “Isochore Theory”: A Segmentation Algorithm Used to “Confirm” the Existence of Isochores Creates “Isochores” Where None Exist

The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore families. The isochore theory, in all its reincarnations, has been repeatedly falsified in the literature, yet isochore proponents have persistently resurrected it by either redefining isochores or by proposing alternative means of testing the theory. Here, I deal with the latest attempt to salvage this seemingly immortal zombie—a sequence segmentation method called isoSegmenter, which was claimed to “identify” isochores while at the same time disregarding the main characteristic attribute of isochores—compositional homogeneity. I used a series of controlled, randomly generated simulated sequences as a benchmark to study the performance of isoSegmenter. The main advantage of using simulated sequences is that, unlike real data, the exact start and stop point of any isochore or homogeneous compositional domain is known. Based on three key performance metrics—sensitivity, precision, and Jaccard similarity index—isoSegmenter was found to be vastly inferior to isoPlotter, a segmentation algorithm with no user input. Moreover, isoSegmenter identified isochores where none exist and failed to identify compositionally homogeneous sequences that were shorter than 100−200 kb. Will this zillionth refutation of “isochores” ensure a final and permanent entombment of the isochore theory? This author is not holding his breath.     

The “Elastic Perspective” of SARS-CoV-2 Infection and the Role of Intrinsic and Extrinsic Factors

Elastin represents the structural component of the extracellular matrix providing elastic recoil to tissues such as skin, blood vessels and lungs. Elastogenic cells secrete soluble tropoelastin monomers into the extracellular space where these monomers associate with other matrix proteins (e.g., microfibrils and glycoproteins) and are crosslinked by lysyl oxidase to form insoluble fibres. Once elastic fibres are formed, they are very stable, highly resistant to degradation and have an almost negligible turnover. However, there are circumstances, mainly related to inflammatory conditions, where increased proteolytic degradation of elastic fibres may lead to consequences of major clinical relevance. In severely affected COVID-19 patients, for instance, the massive recruitment and activation of neutrophils is responsible for the profuse release of elastases and other proteolytic enzymes which cause the irreversible degradation of elastic fibres. Within the lungs, destruction of the elastic network may lead to the permanent impairment of pulmonary function, thus suggesting that elastases can be a promising target to preserve the elastic component in COVID-19 patients. Moreover, intrinsic and extrinsic factors additionally contributing to damaging the elastic component and to increasing the spread and severity of SARS-CoV-2 infection are reviewed.     

The Consequences of Mitochondrial T10432C Mutation in Cika Cattle: A “Potential” Model for Leber’s Hereditary Optic Neuropathy

While mitogenome mutations leading to pathological manifestations are rare, more than 200 such mutations have been described in humans. In contrast, pathogenic mitogenome mutations are rare in domestic animals and have not been described at all in cattle. In the small local Slovenian cattle breed Cika, we identified (next-generation sequencing) two cows with the T10432C mitogenome mutation in the ND4L gene, which corresponds to the human T10663C mutation known to cause Leber’s hereditary optic neuropathy (LHON). Pedigree analysis revealed that the cows in which the mutation was identified belong to two different maternal lineages with 217 individual cows born between 1997 and 2020. The identified mutation and its maternal inheritance were confirmed by Sanger sequencing across multiple generations, whereas no single analysis revealed evidence of heteroplasmy. A closer clinical examination of one cow with the T10432C mutation revealed exophthalmos, whereas histopathological examination revealed retinal ablations, subretinal oedema, and haemorrhage. The results of these analyses confirm the presence of mitochondrial mutation T10432C with homoplasmic maternal inheritance as well as clinical and histopathological signs similar to LHON in humans. Live animals with the mutation could be used as a suitable animal model that can improve our understanding of the pathogenesis of LHON and other mitochondriopathies.     

Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).     

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Macrophages act as immune scavengers and are important cell types in the homeostasis of various tissues. Given the multiple roles of macrophages, these cells can also be found as tissue resident macrophages tightly integrated into a variety of tissues in which they fulfill crucial and organ-specific functions. The lung harbors at least two macrophage populations: interstitial and alveolar macrophages, which occupy different niches and functions. In this review, we provide the latest insights into the multiple roles of alveolar macrophages while unraveling the distinct factors which can influence the ontogeny and function of these cells. Furthermore, we will highlight pulmonary diseases, which are associated with dysfunctional macrophages, concentrating on congenital diseases as well as pulmonary infections and impairment of immunological pathways. Moreover, we will provide an overview about different treatment approaches targeting macrophage dysfunction. Improved knowledge of the role of macrophages in the onset of pulmonary diseases may provide the basis for new pharmacological and/or cell-based immunotherapies and will extend our understanding to other macrophage-related disorders.     

Progress in Laser Ablation and Biological Synthesis Processes: “Top-Down” and “Bottom-Up” Approaches for the Green Synthesis of Au/Ag Nanoparticles

Because of their small size and large specific surface area, nanoparticles (NPs) have special properties that are different from bulk materials. In particular, Au/Ag NPs have been intensively studied for a long time, especially for biomedical applications. Thereafter, they played a significant role in the fields of biology, medical testing, optical imaging, energy and catalysis, MRI contrast agents, tumor diagnosis and treatment, environmental protection, and so on. When synthesizing Au/Ag NPs, the laser ablation and biosynthesis methods are very promising green processes. Therefore, this review focuses on the progress in the laser ablation and biological synthesis processes for Au/Ag NP generation, especially in their fabrication fundamentals and potential applications. First, the fundamentals of the laser ablation method are critically reviewed, including the laser ablation mechanism for Au/Ag NPs and the controlling of their size and shape during fabrication using laser ablation. Second, the fundamentals of the biological method are comprehensively discussed, involving the synthesis principle and the process of controlling the size and shape and preparing Au/Ag NPs using biological methods. Third, the applications in biology, tumor diagnosis and treatment, and other fields are reviewed to demonstrate the potential value of Au/Ag NPs. Finally, a discussion surrounding three aspects (similarity, individuality, and complementarity) of the two green synthesis processes is presented, and the necessary outlook, including the current limitations and challenges, is suggested, which provides a reference for the low-cost and sustainable production of Au/Ag NPs in the future.     

Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia.     

A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up.     

Function of Graphene Oxide as the “Nanoquencher” for Hg2+ Detection Using an Exonuclease I-Assisted Biosensor

Graphene oxide is well known for its excellent fluorescence quenching ability. In this study, positively charged graphene oxide (pGO25000) was developed as a fluorescence quencher that is water-soluble and synthesized by grafting polyetherimide onto graphene oxide nanosheets by a carbodiimide reaction. Compared to graphene oxide, the fluorescence quenching ability of pGO25000 is significantly improved by the increase in the affinity between pGO25000 and the DNA strand, which is introduced by the additional electrostatic interaction. The FAM-labeled single-stranded DNA probe can be almost completely quenched at concentrations of pGO25000 as low as 0.1 μg/mL. A simple and novel FAM-labeled single-stranded DNA sensor was designed for Hg²⁺ detection to take advantage of exonuclease I-triggered single-stranded DNA hydrolysis, and pGO25000 acted as a fluorescence quencher. The FAM-labeled single-stranded DNA probe is present as a hairpin structure by the formation of T–Hg²⁺–T when Hg²⁺ is present, and no fluorescence is observed. It is digested by exonuclease I without Hg²⁺, and fluorescence is recovered. The fluorescence intensity of the proposed biosensor was positively correlated with the Hg²⁺ concentration in the range of 0–250 nM (R² = 0.9955), with a seasonable limit of detection (3σ) cal. 3.93 nM. It was successfully applied to real samples of pond water for Hg²⁺ detection, obtaining a recovery rate from 99.6% to 101.1%.     

Partial Endothelial Nitric Oxide Synthase Deficiency Exacerbates Cognitive Deficit and Amyloid Pathology in the APPswe/PS1ΔE9 Mouse Model of Alzheimer’s Disease

Increasing evidence implicates endothelial dysfunction in the pathogenesis of Alzheimer’s disease (AD). Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is essential in maintaining cerebrovascular function and can modulate the production and clearance of amyloid beta (Aβ). APPswe/PSdE1 (APP/PS1) mice display age-related Aβ accumulation and memory deficits. In order to make the model more clinically relevant with an element of endothelial dysfunction, we generated APP/PS1/eNOS^+/− mice by crossing complete eNOS deficient (eNOS^−/−) mice and APP/PS1 mice. APP/PS1/eNOS^+/− mice at 8 months of age displayed a more severe spatial working memory deficit relative to age-matched APP/PS1 mice. Moreover, immunohistochemistry and immunoblotting revealed significantly increased Aβ plaque load in the brains of APP/PS1/eNOS^+/− mice, concomitant with upregulated BACE-1 (hence increased Aβ production), downregulated insulin-degrading enzyme (hence reduced Aβ clearance) and increased immunoreactivity and expression of microglia. The present study, for the first time, demonstrated that partial eNOS deficiency exacerbated behavioral dysfunction, Aβ brain deposition, and microglial pathology in APP/PS1 mice, further implicating endothelial dysfunction in the pathogenesis of AD. The present findings also provide the scientific basis for developing preventive and/or therapeutic strategies by targeting endothelial dysfunction.