Search Results (452)

Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to 45 °C), and drought (DR group: 7 to 13 days). Through multi-algorithm evaluation (GeNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder) of eleven candidates, condition-specific optimal genes were established as ACT16 (Actin), SAL92 (IT4 phosphatase-associated protein), SSU32 (Ssu72-like family protein), and TSB05 (Tryptophan synthase beta-subunit 2) for the LT group; ACT16 and NRP13 (Asparagine-rich protein) for the HT group; and ACT16, SKP27 (S-phase kinase), and NRP13 for the DR group, with ACT16, NRP13, WLIM96 (LIM domain-containing protein), SSU32, SKP27, SAL92, and UBC22 (ubiquitin-conjugating enzyme E2) demonstrating cross-stress stability (global group). DHDPS96 (dihydrodipicolinate synthase) and EF03 (translation elongation factor) showed minimal stability. Validation using stress-responsive markers—COR72 (LT), HSP44 (HT), COR413-PM (LT), and DREB12 (DR)—confirmed reliability; COR72 and COR413-PM exhibited oscillatory cold response patterns, HSP44 peaked at 43 °C before declining, and DREB12 showed progressive drought-induced upregulation. Crucially, normalization with unstable genes (DHDPS96 and EF03) distorted expression profiles. This work provides validated reference standards for quinoa transcriptomics under abiotic stresses. Full article

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting protein translation, these targeted agents disrupt this oncoprotein via multiple axes distinct from mere protein synthesis inhibition. Whereas the oncogenic mechanisms of eEF1A has been well documented, there lacks a systemic survey of the eEF1A-targeting agents in terms of their mechanisms. Accordingly, the present work aims to examine their multifaceted modes of action more than just blocking protein synthesis. By unveiling these insights, our deepened knowledge of these eEF1A-binding inhibitors will inform the development of future eEF1A-targeted drugs for cancer treatment. Full article

Metarhizium (M.) granulomatis and M. viride have previously been described as pathogens causing hyalohyphomycosis in various species of captive chameleons and bearded dragons (Pogona vitticeps). Previous studies yielded different genotypes of M. granulomatis and M. viride based on sequencing of the internal transcribed spacer 1-5.8S rDNA (ITS-1-5.8S) and a fragment of the large subunit of the 28S rDNA (LSU). The aim of this study was to clarify the relationships between these genotypes and obtain a more accurate phylogenetic classification by sequencing two different loci of the RNA polymerase II second largest subunit (NRPB2), referred to as RPB1 and RPB2, and the translation elongation factor 1 alpha (EF1α). A total of 23 frozen isolates from 21 lizards, including the first isolates of M. granulomatis and M. viride from Parson’s chameleons (Calumma parsonii), were available for phylogenetic analysis. A total of 13 isolates belonged to the M. granulomatis complex and 10 isolates belonged to the M. viride complex. Following the amplification and sequencing of the protein-coding genes, the resulting nucleotide sequences were analyzed, trimmed and assembled. These were further analyzed with regard to differences in single-nucleotide polymorphisms (SNPs) and amino acid structure. In consideration of the results of the present analyses, a phylogenetic reclassification is recommended. Three different genotypes of M. granulomatis can be distinguished, which can be phylogenetically addressed as subspecies. Six subspecies can be distinguished regarding M. viride. Full article

With the ongoing development of lightweight automobiles, research on new aluminum alloys and welding technology has gained significant attention. Friction stir welding (FSW) is a solid-state joining technique for welding aluminum alloys without melting. In this study, novel squeeze-cast Al-Si-Mg-Fe-Zn alloys with different Zn contents (0, 3.4, 6.5, and 8.3 wt%) were friction stir welded (FSWed) at a translational speed of 200 mm/min and a rotational speed of 800 rpm. These parameters were chosen based on the observations of visually sound welds, defect-free and fine-grained microstructures, homogeneous secondary phase distribution, and low roughness. Zn can affect the microstructure of Al-Si-Mg-Fe-Zn alloys, including the grain size and the content of secondary phases, leading to different mechanical and corrosion behavior. Adding different Zn contents with Mg forms the various amount of MgZn₂, which has a significant strengthening effect on the alloys. Softening observed in the weld zones of the alloys with 0, 3.4, and 6.5 wt% Zn is primarily attributed to the reduction in Kernel Average Misorientation (KAM) and a decrease in the Si phase and MgZn₂. Consequently, the mechanical strengths of the FSWed joints are lower as compared to the base material. Conversely, the FSWed alloy with 8.3 wt% Zn exhibited enhanced mechanical properties, with hardness of 116.3 HV_0.2, yield strength (YS) of 184.4 MPa, ultimate tensile strength (UTS) of 226.9 MP, percent elongation (EL%) of 1.78%, and a strength coefficient exceeding 100%, indicating that the joint retains the strength of the as-cast one, due to refined grains and more uniformly dispersed secondary phases. The highest corrosion resistance of the FSWed alloy with 6.5%Zn is due to the smallest grain size and KAM, without MgZn₂ and the highest percentage of {111} texture (24.8%). Full article

The microtubule-associated protein tau plays an essential role in regulating the dynamic assembly of microtubules and is implicated in axonal elongation and maturation, axonal transport, synaptic plasticity regulation, and genetic stability maintenance. Nevertheless, the assembly of tau into neurofibrillary tangles in neurons is a pathological hallmark of a group of neurodegenerative diseases known as tauopathies. Despite enormous efforts and rapid advancements in the field, effective treatment remains lacking for these diseases. In this review, we provide an overview of the structure and phase transition of tau protein. In particular, we focus on the involvement of liquid–liquid phase separation in the biology and pathology of tau. We then discuss several potential strategies for combating tauopathies in the context of phase separation: (i) modulating the formation of tau condensates, (ii) delaying the liquid-to-solid transition of tau condensates, (iii) reducing the enrichment of aggregation-prone species into tau condensates, and (iv) suppressing abnormal post-translational modifications on tau inside condensates. Deciphering the structure–activity relationship of tau phase transition modulators and uncovering the conformational changes in tau during phase transitions will aid in developing therapeutic agents targeting tau in the context of phase separation. Full article

Fanconi anemia (FA) is a DNA repair deficiency disorder associated with genomic and chromosomal instability and a high cancer risk. In a small percentage of cases, FA is caused by biallelic pathogenic variants (PVs) in the BRCA2/FANCD1 gene, defining the FA-D1 subtype. Experimental and epidemiologic data indicate that the complete absence of BRCA2 is incompatible with viability. Therefore, cells from individuals affected with FA caused by biallelic BRCA2 PVs must have a residual BRCA2 function. This activity may be maintained through hypomorphic missense mutations, translation termination–reinitiation associated with a translational stop mutation, or other non-canonical or uncommon translation initiation and elongation events. In some cases, however, residual BRCA2 function is provided by alternatively or aberrantly spliced BRCA2 transcripts. Here, we review and debate aspects of the contribution of splicing in the 5′ segment to BRCA2 functions in the context of PVs affecting this largely intrinsically disordered protein region, with a focus on recent findings in individuals with FA-D1. In this Perspective, we also discuss some of the broader biological implications and open questions that arise from considering 5′-terminal BRCA2 splicing in light of old and new findings from FA-D1 patients and beyond. Full article

Rubber tree (Hevea brasiliensis Muell. Arg.) is a major tropical cash crop in southern China, with Hainan and Yunnan provinces being the main planting areas. In July 2023, bark cracking and gumming were observed on the trunks of mature rubber trees in Haikou City, Hainan Province, leading to xylem rot, which severely impacted the healthy growth of the rubber trees. The present study was conducted to confirm the pathogenicity of the patho-gen associated with stem gummosis disease, characterize it using morphological and mo-lecular tools, and devise field management strategies. Pathogenicity testing showed that this strain induced symptoms similar to those of natural outdoor infestation. Based on morphological study and molecular analyses of internal transcribed spacer (ITS), transla-tion elongation factor 1 alpha (TEF1-α), and β-tubulin 2 (TUB2) sequences, the causal agent was identified as Lasiodiplodia theobromae. Field trials demonstrated that an inte-grated fungicide approach—combining trunk application of Bordeaux mixture with root irrigation using citric acid–copper 6.4% + chelated copper-ammonium 15% at both 0.1% and 0.2% concentration—effectively suppressed stem gummosis disease incidence in rub-ber trees. To the best of our knowledge, this is the first report of L. theobromae causing stem gummosis on rubber tree in China. The findings of this study can provide valuable infor-mation for the management strategies and understanding of this disease. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as DPH1, DPH2, and DPH5, result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in DPH5, encoding a methyltransferase required for diphthamide synthesis. Methods: Clinical, neurological, and dysmorphological evaluations were performed by a multidisciplinary team. Brain MRI was acquired on a 3T scanner. Craniofacial abnormalities were assessed using the GestaltMatcher phenotyping tool. Whole exome sequencing (WES) was conducted on leukocyte-derived DNA with a trio-based approach. Bioinformatic analyses included variant annotation, filtering, and pathogenicity prediction using established databases and tools. Results: The affected subject carried a previously reported missense change, p.His260Arg, suggesting the occurrence of genotype–phenotype correlations and a hypomorphic behavior of the variant, likely explaining the overall milder phenotype compared to the previously reported patients with DPH5-related diphthamide deficiency syndrome. Conclusions: Overall, the co-occurrence of short stature, relative macrocephaly, congenital heart defects, variable DD/ID, minor skeletal and ectodermal features, and consistent craniofacial features suggests a differential diagnosis with Noonan syndrome and related phenotypes. Full article

Peripheral nerve injuries (PNIs) present a significant clinical challenge due to the inherently limited regenerative capacity of the adult nervous system. Conventional therapeutic strategies, such as nerve autografting and systemic pharmacological interventions, are often limited by donor site morbidity, restricted graft availability, and suboptimal drug bioavailability. In this context, gelatin-based hydrogels have emerged as a promising class of biomaterials due to their excellent biocompatibility, biodegradability, and structural similarity to the native extracellular matrix. These hydrogels could offer a highly tunable platform capable of supporting cellular adhesion, promoting axonal elongation, and enabling localized and sustained release of therapeutic agents. This narrative review synthesizes recent advances in the application of gelatin-based hydrogels for peripheral nerve regeneration, with a particular focus on their use as delivery vehicles for neurotrophic factors, stem cells, and pharmacologically active compounds. Additionally, this review provides a foundation for extending our ongoing preclinical study, evaluating the neuroregenerative effects of alpha-lipoic acid, B-complex vitamins, and a deproteinized hemoderivative in a murine PNI model. Although systemic administration has demonstrated promising neuroprotective effects, limitations related to local drug availability and off-target exposure highlight the need for site-specific delivery strategies. In this regard, gelatin hydrogels might represent an excellent candidate for localized, controlled drug delivery. The review concludes by discussing formulation techniques, manufacturing considerations, biological performance, and key translational and regulatory aspects. Full article

Vibrio harveyi, a pathogenic vibrio, is ubiquitous and the most prevalent disease infecting tropical and subtropical mariculture animals in marine and estuarine environments. It presents a major risk to mariculture companies worldwide and can cause serious disease problems in aquaculture. Recent studies have shown that various pathogens employ post-translational modifications (PTMs) to regulate cellular processes. One of the major PTMs is lysine succinylation, which is widespread in eukaryotic and prokaryotic cells. Many basic biological functions of bacteria are associated with the regulation of lysine (K) succinylation (Ksuc). However, little is known about the role of lysine succinylation in V. harveyi pathogenesis. Here, we performed LC-MS/MS analysis of 1271 proteins from V. harveyi to identify 4252 Ksuc modification sites. The modification of S-ribosylhomocysteine lyase (LuxS) and transcription elongation factor GreA proteins by Ksuc was confirmed through immunoprecipitation combined with Western blot, further validating our proteomics results. Bioinformatics study revealed that the identified Ksuc proteins play roles in multiple cellular processes and vital metabolic pathways, including LuxS, biofilm exopolysaccharide biosynthesis protein EpsG, and the general secretory system (Sec systems), and are proteins that regulate bacterial virulence. Generally, this scientific study serves as the basis for additional research on the pathogenic nature of Ksuc in V. harveyi and reveals potential targets that would accelerate the manufacturing of attenuated vaccines. Full article

Translational control is crucial for maintaining cellular homeostasis, yet the distinct features and regulatory requirements governing protein synthesis during erythropoiesis remain unclear. Here, we reveal that erythroid cells exhibit an extraordinarily high demand for protein synthesis, which is required for their differentiation but also implies the need for tight regulation to prevent excessive erythropoiesis. Notably, we identify significant phosphorylation of eukaryotic elongation factor 2 (eEF2) at threonine 56 during erythroid differentiation, which reduces protein synthesis and acts as a molecular brake to limit unchecked erythropoiesis. This is evidenced by elevated red blood cell counts in peripheral blood and increased incidence of blood hyperviscosity and thrombosis in eEF2_T56M mice, which are deficient in eEF2 phosphorylation. Mechanistic studies demonstrate that eEF2 phosphorylation selectively regulates the translation of a subset of proteins, including NFE2, which partially mediates the effects of eEF2 modification. Collectively, our findings highlight a previously unappreciated role for translational control in achieving efficient and balanced erythropoiesis, with eEF2 phosphorylation serving as a critical protective mechanism against hyperactive erythropoiesis and offering a potential therapeutic target for hematologic disorders such as polycythemia vera. Full article

Tomato is a widely cultivated vegetable crop worldwide. It is susceptible to various phytopathogens, including fungi, bacteria, viruses, and nematodes. In 2024, an unknown leaf spot disease outbreak, characterized by distinct brown necrotic lesions on leaves, was observed in tomato plants in Yunnan Province, China. Through rigorous pathogen isolation and the fulfillment of Koch’s postulates, it was proved that the fungal isolate could infect tomato leaves and cause typical symptoms. The pathogen isolated from tomato leaves was identified as Nigrospora oryzae based on its morphology and using a multilocus sequence analysis method with the internal transcribed spacer gene (ITS1), beta-tubulin gene (TUB2), and translation elongation factor 1-alpha gene (TEF1-α). This represents the first documented case of N. oryzae infecting tomatoes in the world. Given the damage caused by N. oryzae to tomato plants, we explored biocontrol methods. Through a dual-culture assay on PDA plates, Bacillus velezensis B31 demonstrated significant biocontrol potential, exhibiting strong antagonistic activity toward N. oryzae. In addition, we developed a polyethylene glycol (PEG)-mediated transformation system that successfully introduced pYF11-GFP into the protoplasts of N. oryzae. This achievement provides a foundation for future genetic manipulation studies of N. oryzae. Full article

The eukaryotic translation elongation factor 1 (eEF1) family exhibits critical roles in RNA viral infection beyond its canonical function in protein synthesis. This review analyzes the structural characteristics of eEF1A and the eEF1B complex, and their regulatory mechanisms during viral infection. eEF1A impacts viral replication by stabilizing viral RNA-dependent RNA polymerase (RdRp) complexes, modulating genomic RNA synthesis, and facilitating viral assembly through cytoskeletal regulation. eEF1B subunits contribute through enhancing viral mRNA translation, regulating nuclear transport of viral components, and mediating post-translational modifications. The high conservation of eEF1 proteins across species and their involvement in multiple stages of viral replication establish them as promising broad-spectrum antiviral targets. Current eEF1-targeting compounds like plitidepsin demonstrate efficacy against diverse viral families, though therapeutic development faces challenges in balancing antiviral activity with host toxicity. This review provides a theoretical foundation for developing novel antiviral strategies targeting host–virus interaction interfaces and offers insights into addressing emerging infectious diseases. Full article

The fungal family Botryosphaeriaceae, which includes genera such as Diplodia, Dothiorella, and Phaeobotryon, comprises species commonly associated with woody plants such as endophytes, pathogens, and saprophytes. The Xizang Autonomous Region of China, known for its rich forest resources, harbors significant fungal diversity. However, limited research has been conducted on plant-disease-associated fungi in this region. In this study, we employed morphological characteristics and molecular phylogenetic analyses of the internal transcribed spacer region of rDNA (ITS), the ribosomal large subunit (LSU), the translation elongation factor 1-alpha (tef1) gene, and the partial beta-tubulin (tub2) gene to identify fungal species. As a result, two new species, Diplodia salicicola sp. nov. and Phaeobotryon xizangense sp. nov., are proposed and described herein. Additionally, Di. corticola, Di. mutila, Do. acericola, Do. magnoliae, Do. vidmadera, Do. yunnana comb. nov., and Do. zanthoxyli are reported for the first time in Xizang. Our findings contribute to advancing the knowledge of fungal biodiversity in Xizang’s high-altitude ecosystems. Full article

Hypocreales is one of the largest orders within the class Sordariomycetes and is renowned for its diversity of lifestyles, encompassing plant, insect, and human pathogens, as well as endophytes, parasites, and saprobes. In this study, we focused on saprobic hypocrealean fungi isolated from rice in northern Thailand. Species identification was conducted using morphological characteristics and multilocus phylogenetic analyses, including the internal transcribed spacer region (ITS), 28S large subunit nuclear ribosomal DNA (LSU), translation elongation factor 1–alpha (tef1-α), RNA polymerase II second-largest subunit (rpb2), and calmodulin (cmdA). This research confirmed the presence of 14 species of hypocrealean taxa, viz. Fusarium (9), Ochronectria (1), Sarocladium (2), Trichothecium (1), and Waltergamsia (1). Among these were two new species (Fusarium chiangraiense and F. oryzigenum), four new host records (Fusarium kotabaruense, Ochronectria thailandica, Sarocladium bactrocephalum, and Waltergamsia fusidioides), and three new geographical records (Fusarium commune, F. guilinense, and F. hainanese). Full article