Search Results (51)

Long-term monoculture of poplar plantations for industrial material production has been widely reported to cause severe soil degradation, while the presence of understory vegetation might enhance soil nitrogen (N) transformation and supply. This study employed a field experiment using a randomized block design with three blocks and four understory treatments, including understory removal, N-fixing species planting, single-species retention, and diverse vegetation retention, in poplar plantations on a mid-latitude alluvial plain in China over 6 years to assess the effects of different species and richness of understory on soil N transformation and related microbial traits via ¹⁵N assays and shotgun metagenomics. The results showed that understory removal significantly reduced soil N transformation rates, bacterial abundance, and gene abundance associated with N transformation. Compared to a single-species understory, retaining a diverse understory with high species richness significantly increased soil gross N transformation rate of mineralization by 149%, nitrification by 221%, and immobilization by 85%; comprehensively enriched dominant bacterial phyla; and elevated gene abundances of gdh_K15371, ureB, hao, and amoA_B associated with N transformation. No significant difference in N transformation rates existed between N-fixing species planting treatment and single-species retention treatment, while N-fixing species planting treatment specifically promoted the soil bacterial phyla Nitrospirae and Chloroflexi, and increased the gene abundances of gdh_K15371 and hao. These findings demonstrate that both introducing N-fixing species and an increase in species richness of the understory effectively promoted soil N transformation but that different underlying mechanisms existed. Planting N-fixing species selectively increased the soil bacterial phyla of Nitrospirae and Chloroflexi, whereas the increase in species richness broadly enriched soil bacterial diversity, thereby inducing the enrichment of the functional genes and enhancing soil N transformation. In conclusion, both planting N-fixing species and retaining diverse understory vegetation were effective strategies for maintaining sustainable management of poplar plantations by increasing soil N availability. Full article

Background/Objectives: Hailey–Hailey disease (HHD) is an uncommon genodermatosis with autosomal dominant inheritance caused by loss-of-function mutations in the ATP2C1 gene, which lead to disruption in keratinocyte adhesion and intraepidermal acantholysis. The chronic nature of the disease, its frequent recurrences and the lack of specific treatment pose real challenges in the long-term management of these patients. Recent studies have evaluated the effect of dupilumab, a human monoclonal antibody that blocks interleukin-4 and -13 receptor in refractory HHD, with very promising results. The aim of this study was to review the published data on the use of dupilumab for the treatment of HHD, to present our own experience in the field, and to discuss the mechanisms underlying dupilumab’s beneficial effects in HHD and the future treatment perspectives. Methods: A search of the medical literature on the use of dupilumab in the treatment of HHD was conducted. The terms “Hailey–Hailey disease”, “benign familial pemphigus”, “benign chronic pemphigus”, and “dupilumab” were searched across multiple databases (Medline, Chrocane Library, EMBASE) from inception until 30 September 2024. Results: To date, six manuscripts describing 11 refractory HHD cases treated with dupilumab have been published. All the patients experienced significant clinical improvement. The authors reported sustained disease quiescence in seven patients (64%), monitored for 5 to 24 months. None of the patients experienced adverse effects related to dupilumab. To the existing evidence, we add a new case of recalcitrant HHD successfully treated with dupilumab. Conclusions: Mounting evidence indicates dupilumab as a safe and efficient therapeutic alternative in patients with severe, refractory HHD. However, the long-term efficacy of dupilumab and the optimal therapeutic regimen for HHD are yet to be determined. Full article

Identifying major blast resistance genes in Oryza sativa L. genotypes is key to enhancing and maintaining the resistance. Observing rice varieties with durable resistance to blast has become a potential target in rice breeding programs. In this study, an evaluation was conducted during 2020 and 2021 on ten Egyptian and introduced varieties. First, a field experiment was conducted in a randomized complete block design with three replications, and it was found that the Egyptian cultivar Sakha 101 had the highest crop grain yields (53.27 g). The Spanish varieties Hispagrán and Puebla were the earliest (110 and 108 days, respectively) as well as the highest in 1000-grain yield, giving them priority as donors for these traits; however, they had the lowest mean values in the number of panicles. Second, these cultivars were subjected to eighteen isolates from five strains of Pyricularia oryzae (IH, IC, ID, IE, and II). The Egyptian varieties Giza 177, Giza 179, Sakha 106, Giza 182, GZ1368-5-5-4, and GZ6296 were 100% resistant, while Hispagrán’s resistance was 16.6%, followed by Sakha 101 with 27.8%. To gain insight into the ten varieties, we used STS, SCAR, and CAPS markers to detect and mine alleles for major blast broad-spectrum resistance genes Pi2, Pi9, and Pita2. In the context of considering gene pyramiding as an effective strategy for achieving broad durable spectrum resistance to blast, molecular profiling was also conducted on eighteen F2 single plants obtained from the hybridization of Giza 177 (resistant) × Puebla (susceptible) varieties. Also, eighteen F2 single plants were obtained from Giza 177 × Hispagrán (highly susceptible) varieties. Conducting a molecular scan with STS dominant marker YL153/YL154 was performed on ten cultivars to detect the presence of the Pita2 gene, which conferred a unique band in Puebla. By doing a scan of the 18 second-generation plants derived from Giza 177 × Puebla, 11 individual plants of the 18 plants obtained a band, which was transferred from Puebla. F2 plants obtained from Giza 177 × Puebla amplified with CAPS marker RG64-431/RG64-432 had higher numbers of Pi2 alleles, while F2 plants of Giza 177 × Hispagrán cross-amplified with SCAR marker linked to Pi9 exceeded their parents more. Our results have revealed that molecular markers played an essential role in determining the direction of evolution for blast resistance traits. Full article

The white poplar (Populus alba) is a dioecious woody plant with significant potential for the phytoremediation of soils. To realize this potential, it is necessary to utilize growth-promoting microorganisms. One potential source of such beneficial microorganisms is the rhizosphere community of wild-growing trees. However, the structure, dynamics, and metabolism of the rhizosphere community of wild-growing white poplar remain poorly understood. To ascertain seasonal dynamics, species diversity, and metabolic potential, we sequenced 16S rRNA genes in metagenomes derived from 165 soil samples collected in spring and autumn from the root surfaces of 102 trees situated in disparate geographical locations. The three most prevalent phyla across all samples are Proteobacteria, Actinobacteriota, and Acidobacteriota. At the order level, the most prevalent orders are Sphingomonadales and Rhizobiales. Accordingly, the families Sphingomonadaceae and Rhizobiaceae were identified as dominant. The rhizospheric microbiome exhibited substantial inter-seasonal variation. Six families, including Caulobacteraceae, Xanthomonadaceae, Chitinophagaceae, Chthoniobacteraceae, Sphingomonadaceae, and Rhizobiaceae, exhibited alterations (spring-to-autumn) across all geographical locations under study. Members of the Rhizobiaceae family, which includes nitrogen-fixing bacteria, can provide poplar with plant-available forms of nitrogen such as nitrate and ammonium. The rhizosphere microbiome may facilitate the conversion of inorganic sulfur into sulfur-containing amino acids, cysteine and methionine, that are bioavailable to plants. Furthermore, the rhizosphere microbiome is capable of synthesizing amino acids, organic acids (including Krebs cycle acids), and some lipids and sugars. Consequently, the rhizosphere community can stimulate poplar growth by providing it with readily available forms of nitrogen and sulfur, as well as building blocks for the synthesis of proteins, nucleic acids, and other macromolecules. Many of these pathways, including nitrogen fixation, were subjected to seasonal changes. Full article

Background: Oncogenic mutations in the KRAS gene are detected in >90% of pancreatic cancers (PC). In genetically engineered mouse models of PC, oncogenic KRAS drives the formation of precursor lesions and their progression to invasive PC. The Yes-associated Protein (YAP) is a transcriptional coactivator required for transformation by the RAS oncogenes and the development of PC. In Ras-driven tumors, YAP can also substitute for oncogenic KRAS to drive tumor survival after the repression of the oncogene. Ras oncoproteins exert their transforming properties through their downstream effectors, including the PI3K kinase, Rac1 GTPase, and MAPK pathways. Methods: To identify Ras effectors that regulate YAP, YAP levels were measured in PC cells exposed to inhibitors of oncogenic K-Ras and its effectors. Results: In PC cells, the inhibition of Rac1 leads to a time-dependent decline in YAP protein, which could be blocked by proteosome inhibitor MG132. This YAP degradation after Rac1 inhibition was observed in a range of cell lines using different Rac1 inhibitors, Rac1 siRNA, or expression of dominant negative Rac1^T17N mutant. Several E3 ubiquitin ligases, including SCF^βTrCP, regulate YAP protein stability. To be recognized by this ligase, the βTrCP degron of YAP (amino acid 383–388) requires its phosphorylation by casein kinase 1 at Ser384 and Ser387, but these events must first be primed by the phosphorylation of Ser381 by LATS1/2. Using Flag-tagged mutants of YAP, we show that YAP degradation after Rac1 inhibition requires the integrity of this degron and is blocked by the silencing of βTrCP1/2 and by the inhibition of casein kinase 1. Unexpectedly, YAP degradation after Rac1 inhibition was still observed after the silencing of LATS1/2 or in cells carrying a LATS1/2 double knockout. Conclusions: These results reveal Rac1 as an oncogenic KRAS effector that contributes to YAP stabilization in PC cells. They also show that this regulation of YAP by Rac1 requires the SCF^βTrCP ligase but occurs independently of the LATS1/2 kinases. Full article

The Maculipennis subgroup of malaria mosquitoes includes both dominant malaria vectors and non-vectors in Eurasia. Understanding the genetic factors, particularly chromosomal inversions, that differentiate Anopheles species can provide valuable insights for vector control strategies. Although autosomal inversions between the species in this subgroup have been characterized based on the chromosomal banding patterns, the number and positions of rearrangements in the X chromosome remain unclear due to the divergent banding patterns. Here, we identified two large X chromosomal inversions, approximately 13 Mb and 10 Mb in size, using fluorescence in situ hybridization. The inversion breakpoint regions were mapped by hybridizing 53 gene markers with polytene chromosomes of An. messeae. The DNA probes were designed based on gene sequences from the annotated An. atroparvus genome. The two nested inversions resulted in five syntenic blocks. Only two small syntenic blocks, which encompass 181 annotated genes in the An. atroparvus genome, changed their position and orientation in the X chromosome. The analysis of the An. atroparvus genome revealed an enrichment of gene ontology terms associated with immune system and mating behavior in the rearranged syntenic blocks. Additionally, the enrichment of DNA transposons was found in sequences homologous to three of the four breakpoint regions. This study demonstrates the successful application of the physical genome mapping approach to identify rearrangements that differentiate species in insects with polytene chromosomes. Full article

Rehmannia glutinosa is one of the most important medicinal plants in China and is affected by viral diseases. In this study, a new virus tentatively named Rehmannia Allexivirus virus (ReAV) was identified through high-throughput sequencing, reverse-transcription polymerase chain reaction (RT-PCR), and Sanger sequencing. The complete genome length was 7297 nt and it contained five open reading frames (ORFs) encoding replicase, triple gene block 1(TGB1), TGB2, TGB3, and coat protein (CP). The replicase and CP presented nucleotide homology ranges of 59.9–65.2% and 47.5–55.5% between the nine ReAV isolates and the other 12 species of the genus Allexivirus. In the nine isolates, ReAV-20 and ReAV-31 isolates showed breakpoints in the replicase and CP regions, respectively. The other isolates shared 87.2–96.5% nt with the whole genome nucleotide identity. The phylogenetic tree showed that seven ReAV isolates based on replicase, CP, and whole genome sequences were clustered in the same branch and were related to the genus Allexivirus. The ReAV detection rates for 60 R. glutinosa samples were 73.3–81.7% through RT-PCR using primers targeting the replicase or CP genes. These results demonstrate that ReAV is the dominant virus in R. glutinosa. This study provides important evidence for understanding viruses infecting R. glutinosa and for establishing efficient strategies to prevent viral spread. Full article

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small vessel disease, caused by a mutation in the NOTCH3 gene on chromosome 19. The main clinical features include migraine (often with aura), early onset, recurrent subcortical ischemic strokes, mood disturbances, and cognitive impairment, frequently leading to dementia and disability with a reduction in life expectancy. Cerebral chronic global hypoperfusion, due to impaired cerebrovascular reactivity, seems to play a primary role in CADASIL. Migraine is the most common early feature of the disease, and to date, there are no consensus guidelines for treatment. Given the vasomodulatory influence of many antimigraine drugs, there is concern about their use in this disease. In particular, the calcitonin gene-related peptide (CGRP) system serves as a vasodilatory protective mechanism during cerebral and cardiac ischemia. Blocking this system could exacerbate ischemic events. Herein, we describe two CADASIL patients who were treated with the calcitonin gene-related peptide (CGRP) receptor antagonist erenumab for chronic migraine, reporting a significant reduction in the frequency of attacks and intensity of pain, and an improvement in quality of life without adverse effects. Full article

Deciphering the molecular basis of heterosis would yield genes and markers for designing improved maize-hybrid varieties. In this study, 481 BC₁F₃ lines derived from Zheng58 and PH4CV were genotyped with 15,386 polymorphic SNPs markers and testcrossed with two testers (Chang7-2 and PH6WC) to generate 962 testcross lines. The yield of these testcross lines and their parental lines was evaluated across multiple environments. Genetic analysis revealed that dominance is the primary contributor to heterosis. Mapping of midparent heterosis (MPH) identified two dominant QTL, six additive-by-additive interactions, eighteen additive-by-dominance interactions, and fifty-four dominance-by-dominance interactions. These interactions encompassed 104 genetic blocks, including 24 genetic blocks that explained >1% of phenotypic variances for both MPH and hybrid performance. We compared the locations of the allele-specific expression genes (ASEGs) identified from the expression data of two hybrid lines and their parental lines with those of the 24 genetic blocks and found 15 ASEGs related to yield or biomass regulation, including two known genes BT2 and ZmNF-YC4. Fisher’s exact test analysis indicated a significant enrichment of these ASEGs in the 24 blocks, affirming the reliability of the MPH-mapping results. The co-expression network of six ASEGs, including BT2 and ZmNF-YC4, contained many genes related to yield or biomass regulation. This study unravels potential candidate genes and regulatory networks associated with maize heterosis. Full article

To discover potential cytotoxic agents, new semi-synthetic phenoxy acetamide derivatives, compound I and compound II, were synthesized, characterized, and screened for their cytotoxic activity against breast cancer (MCF-7) and liver cancer (HepG2) cell lines. The two compounds were more promising against HepG2 than the MCF-7 cell line according to IC₅₀ values. When tested against the HepG2 cell line, compound I, and compound II both had significantly increased cytotoxic activity when compared to the reference medication 5-Fluorouracil (5-FU), with IC₅₀ values of 1.43 M, 5.32 M, and 6.52 M for compound 1, 5-FU and compound II, respectively. Also, compound I displayed a degree of selectivity towards cancer cells compared to normal cells. Compound I significantly enhanced HepG2 total apoptotic cell death by about a 24.51-fold increase. According to cell cycle analysis, compound I induced the arrest of the cell cycle phases G1/S and blocked the progression of the HepG2 cells. Applying the RT-PCR technique achieved a highly significant upregulation in pro-apoptotic genes. The anti-apoptotic gene was significantly downregulated. There was an intrinsic and extrinsic pathway, but the intrinsic pathway was the dominant one. Tumor growth suppression as measured by tumor weight and volume and other hematological, biochemical, and histopathological analyses confirmed the efficacy of compound I as an anticancer agent in vivo examination. Finally, the molecular docking study revealed that compound I was properly docked inside the binding site of PARP-1 protein with stable binding energies and interactive binding modes. Therefore, compound I shows promise as a selective anti-cancer derivative for the treatment of liver cancer after more investigations and clinical studies. This selectivity is a favorable characteristic in the developing cytotoxic agents for cancer treatment, as it indicates a potential for reduced harm to health tissues. Full article

The plant mirid bug Apolygus lucorum is an omnivorous pest that can cause considerable economic damage. The steroid hormone 20-hydroxyecdysone (20E) is mainly responsible for molting and metamorphosis. The adenosine monophosphate-activated protein kinase (AMPK) is an intracellular energy sensor regulated by 20E, and its activity is regulated allosterically through phosphorylation. It is unknown whether the 20E-regulated insect’s molting and gene expression depends on the AMPK phosphorylation. Herein, we cloned the full-length cDNA of the AlAMPK gene in A. lucorum. AlAMPK mRNA was detected at all developmental stages, whereas the dominant expression was in the midgut and, to a lesser extent, in the epidermis and fat body. Treatment with 20E and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AlCAR) or only AlCAR resulted in activation of AlAMPK phosphorylation levels in the fat body, probed with an antibody directed against AMPK phosphorylated at Thr172, enhancing AlAMPK expression, whereas no phosphorylation occurred with compound C. Compared to compound C, 20E and/or AlCAR increased the molting rate, the fifth instar nymphal weight and shortened the development time of A. lucorum in vitro by inducing the expression of EcR-A, EcR-B, USP, and E75-A. Similarly, the knockdown of AlAMPK by RNAi reduced the molting rate of nymphs, the weight of fifth-instar nymphs and blocked the developmental time and the expression of 20E-related genes. Moreover, as observed by TEM, the thickness of the epidermis of the mirid was significantly increased in 20E and/or AlCAR treatments, molting spaces began to form between the cuticle and epidermal cells, and the molting progress of the mirid was significantly improved. These composite data indicated that AlAMPK, as a phosphorylated form in the 20E pathway, plays an important role in hormonal signaling and, in short, regulating insect molting and metamorphosis by switching its phosphorylation status. Full article

Mutations in the human desmin gene (DES) may cause both autosomal dominant and recessive cardiomyopathies leading to heart failure, arrhythmias and atrio-ventricular blocks, or progressive myopathies. Cardiac conduction disorders, arrhythmias and cardiomyopathies usually associated with progressive myopathy are the main manifestations of autosomal dominant desminopathies, due to mono-allelic pathogenic variants. The recessive forms, due to bi-allelic variants, are very rare and exhibit variable phenotypes in which premature sudden cardiac death could also occur in the first or second decade of life. We describe a further case of autosomal recessive desminopathy in an Italian boy born of consanguineous parents, who developed progressive myopathy at age 12, and dilated cardiomyopathy four years later and died of intractable heart failure at age 17. Next Generation Sequencing (NGS) analysis identified the homozygous loss-of-function variant c.634C>T; p.Arg212*, which was likely inherited from both parents. Furthermore, we performed a comparison of clinical and genetic results observed in our patient with those of cases so far reported in the literature. Full article

Wheat is one of the main cereals. At this time, the crucial difficulty in improving nutritional traits is the influence on genotypes of different environments. Selecting superior genotypes on the basis of a gene effects analysis for varying environments is demanded. In this study, 10 different genotypes of bread wheat (Triticum aestivum L.) were used. Parents, hybrids, and two standard checks were evaluated in a complete randomized block design with three replicates in four environments: E₁ and E₂ (normal and late sown, Rabi 2018-19) & E₃ and E₄ (normal and late sown, Rabi 2019-20). The analysis of the components of the gene effect revealed that most of the characters were governed by additive and dominant gene actions in the environments; for gluten, the wet gluten (E₂) and starch (E₃) content were the only dominant components (H₁ and H₂) with a significant gene effect. Overdominance, asymmetrical distribution of positive–negative and dominant–recessive genes, and narrow-sense heritability were observed in most of the characters in all environments. In a graphical analysis, the regression value b was observed to be in unity among protein content (E₁ and E₃), sedimentation value (E₁, E₂, and E₃), and starch content (E₁), indicating the absence of digenic interactions. Based on the intercept of the regression line on the Wr axis, the degree of dominance for protein content (E₁ and E₃), sedimentation value (E₁, E₂, and E₃), and starch content (E₁) was depicted as overdominance. Therefore, a given population may be improved to isolate superior recombinants for the development of desired parents in future breeding programs. Full article

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33 × 10⁻⁸ calculated with the Yates-corrected χ² test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWASs of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network, where BDNF is the most significant hub gene. This study indicates that several genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The study also reveals a central role of BDNF in the pathogenesis of AD. Full article

The areca nut (Areca catechu L.) and pandan (Pandanus amaryllifolius Roxb.) intercropping cultivation system has been widely practiced to improve economic benefits and achieve the development of sustainable agriculture in Hainan Province, China. However, there is a lack of research on the relationships among soil properties, soil enzyme activities, and microbes in this cultivation system. Therefore, a random block field experiment of pandan intercropped with areca nut was established to investigate the effects of environmental factors on the diversity and functions of soil microbial communities in Lingshui county, Hainan Province. The diversity and composition of soil microbial communities under different cropping modes were compared using Illumina sequencing of 16S rRNA (bacteria) and ITS-1 rRNA (fungi) genes, and FAPROTAX and FUNGuild were used to analyze and predict the bacteria and fungi community functions, respectively. Correlation analysis and redundancy analysis were used to explore the responses of soil microbial communities to soil environmental factors. The results showed that the bacterial community was more sensitive to the areca nut and pandan intercropping system than the fungal community. The functional predictions of fungal microbial communities by FAPROTAX and FUNGuild indicated that chemoheterotrophy, aerobic chemoheterotrophy, and soil saprotroph were the most dominant functional communities. The intercropping of pandan in the areca nut plantation significantly enhanced the soil bacterial Ace and Chao indices by reducing the soil organic carbon (SOC) and total phosphorus (TP) content. In the intercropping system, urease (UE) and acid phosphatase were the key factors regulating the soil microbial community abundance. The dominant bacterial and fungal phyla, such as Firmicutes, Methylomirabilota, Proteobacteria, Actinobacteria, Chloroflexi, Verrucomicrobia, and Ascomycota significantly responded to the change in planting modes. Soil properties, such as UE, total nitrogen, and SOC had a significant stimulating effect on Proteobacteria, Chloroflexi, and Ascomycota. In summary, soil bacteria responded more significantly to the change in cropping modes than soil fungi and better reflected the changes in soil environmental factors, suggesting that intercropping with pandan positively affects soil microbial homeostasis in the long-term areca nut plantation. Full article