ABSTRACT
KEY MESSAGE: We developed an array of Zea-Tripsacum tri-hybrid allopolyploids with multiple ploidies. We unveiled that changes in genome dosage due to the chromosomes pyramiding and shuffling of three species effects karyotypic heterogeneity, reproductive diversity, and phenotypic variation in Zea-Tripsacum allopolyploids. Polyploidy, or whole genome duplication, has played a major role in evolution and speciation. The genomic consequences of polyploidy have been extensively studied in many plants; however, the extent of chromosomal variation, genome dosage, phenotypic diversity, and heterosis in allopolyploids derived from multiple species remains largely unknown. To address this question, we synthesized an allohexaploid involving Zea mays, Tripsacum dactyloides, and Z. perennis by chromosomal pyramiding. Subsequently, an allooctoploid and an allopentaploid were obtained by hybridization of the allohexaploid with Z. perennis. Moreover, we constructed three populations with different ploidy by chromosomal shuffling (allopentaploid × Z. perennis, allohexaploid × Z. perennis, and allooctoploid × Z. perennis). We have observed 3 types of sexual reproductive modes and 2 types of asexual reproduction modes in the tri-species hybrids, including 2n gamete fusion (2n + n), haploid gamete fusion (n + n), polyspermy fertilization (n + n + n) or 2n gamete fusion (n + 2n), haploid gametophyte apomixis, and asexual reproduction. The tri-hybrids library presents extremely rich karyotype heterogeneity. Chromosomal compensation appears to exist between maize and Z. perennis. A rise in the ploidy of the trihybrids was linked to a higher frequency of chromosomal translocation. Variation in the degree of phenotypic diversity observed in different segregating populations suggested that genome dosage effects phenotypic manifestation. These findings not only broaden our understanding of the mechanisms of polyploid formation and reproductive diversity but also provide a novel insight into genome pyramiding and shuffling driven genome dosage effects and phenotypic diversity.
Subject(s)
Poaceae , Zea mays , Zea mays/genetics , Karyotype , Haploidy , Polyploidy , Biological Variation, PopulationABSTRACT
OBJECTIVES: To investigate the role of the oral and gut microbiome related to systemic metabolism and clinical parameters in various types of kidney stone disease. PATIENTS AND METHODS: We conducted a case-control study by analyzing 16S rRNA and untargeted metabolomics profiling of 76 fecal, 68 saliva, 73 urine, and 43 serum samples from 76 participants aged 18-75 years old. The participants included 15 patients with uric acid stones, 41 patients with calcium oxalate stones, and 20 healthy controls. Correlations among microbiome, metabolism, and clinical parameters were identified through Spearman's correlation analysis. (Clinical trial No. ChiCTR2200055316). RESULTS: Patients with uric acid stones exhibited reduced richness and diversity in their microbiome, as well as altered composition in both oral and gut microbiome. Furthermore, their fecal samples showed lower relative abundances of Bacteroides and Lachnospiraceae, while their saliva samples showed higher relative abundances of Porphyromonas and Neisseria. Predicted KEGG metabolism pathways, including amino acid and fatty acid metabolisms, were significantly altered in subjects with uric acid stones. Oral, gut microbiota, and metabolism were also associated with low water intake and urine pH. The area under the curve (AUC) of the specific microbiota and metabolite prediction models was over 0.85. CONCLUSION: The structure and composition of the oral and gut microbiome in different types of kidney stone disease, the correlations between oral and gut microbiome, and the associations among oral and gut microbiota, systemic metabolism and clinical parameters imply an important role that the oral and gut microbiome may play in kidney stone disease.
Subject(s)
Gastrointestinal Microbiome , Kidney Calculi , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Gastrointestinal Microbiome/genetics , Case-Control Studies , Uric Acid , RNA, Ribosomal, 16S/genetics , Kidney Calculi/urineABSTRACT
BACKGROUND: The 1RS arm of wheat-rye 1BL.1RS translocations contains several subtelomeric tandem repeat families. To study the effect of the difference in the composition of these tandem repeats on the meiotic recombination of 1RS arms can help to enrich the genetic diversity of 1BL.1RS translocation chromosomes. RESULTS: Five wheat-rye 1BL.1RS translocation cultivars/lines were used to build two cross combinations including group 1 (20T401 × Zhou 8425B, 20T401 × Lovrin 10 and 20T401 × Chuannong 17) and group 2 (20T360-2 × Zhou 8425B, 20T360-2 × Lovrin 10 and 20T360-2 × Chuannong 17). Oligonucleotide (oligo) probes Oligo-s120.3, Oligo-TR72, and Oligo-119.2-2 produced the same signal pattern on the 1RS arms in lines 20T401 and 20T360-2, and another signal pattern in the three cultivars Zhou 8425B, Lovrin 10 and Chuannong 17. The Oligo-pSc200 signal disappeared from the 1RS arms of the line 20T401, and the signal intensity of this probe on the 1RS arms of the line 20T360-2 was weaker than that of the three cultivars. The five cultivars/lines had the same signal pattern of the probe Oligo-pSc250. The recombination rate of 1RS arms in group 1 was significantly lower than that in group 2. In the progenies from group 1, unequal meiotic recombination in the subtelomeric pSc119.2 and pSc250 tandem repeat regions, and a 1BL.1RS with inversion of 1RS segment between the pSc200 and the nucleolar organizer region were found. CONCLUSIONS: This study provides a visual tool to detect the meiotic recombination of 1RS arms. The meiotic recombination rate of 1RS arms was affected by the variation of pSc200 tandem repeat, indicating the similar composition of subtelomeric tandem repeats on these arms could increase their recombination rate. These results indicate that the 1RS subtelomeric structure will affect its recombination, and thus the localization of genes on 1RS by means of meiotic recombination might also be affected.
Subject(s)
Secale , Triticum , Humans , Triticum/genetics , Secale/genetics , Chromosomes, Plant/genetics , Translocation, Genetic , Telomere/geneticsABSTRACT
BACKGROUND: Tripsacum dactyloides (2n = 4x = 72) and Zea perennis (2n = 4x = 40) are tertiary gene pools of Zea mays L. and exhibit many abiotic adaptations absent in modern maize, especially salt tolerance. A previously reported allopolyploid (hereafter referred to as MTP, 2n = 74) synthesized using Zea mays, Tripsacum dactyloides, and Zea perennis has even stronger salt tolerance than Z. perennis and T. dactyloides. This allopolyploid will be a powerful genetic bridge for the genetic improvement of maize. However, the molecular mechanisms underlying its salt tolerance, as well as the key genes involved in regulating its salt tolerance, remain unclear. RESULTS: Single-molecule real-time sequencing and RNA sequencing were used to identify the genes involved in salt tolerance and reveal the underlying molecular mechanisms. Based on the SMRT-seq results, we obtained 227,375 reference unigenes with an average length of 2300 bp; most of the unigenes were annotated to Z. mays sequences (76.5%) in the NR database. Moreover, a total of 484 and 1053 differentially expressed genes (DEGs) were identified in the leaves and roots, respectively. Functional enrichment analysis of DEGs revealed that multiple pathways responded to salt stress, including "Flavonoid biosynthesis," "Oxidoreductase activity," and "Plant hormone signal transduction" in the leaves and roots, and "Iron ion binding," "Acetyl-CoA carboxylase activity," and "Serine-type carboxypeptidase activity" in the roots. Transcription factors, such as those in the WRKY, B3-ARF, and bHLH families, and cytokinin negatively regulators negatively regulated the salt stress response. According to the results of the short time series-expression miner analysis, proteins involved in "Spliceosome" and "MAPK signal pathway" dynamically responded to salt stress as salinity changed. Protein-protein interaction analysis revealed that heat shock proteins play a role in the large interaction network regulating salt tolerance. CONCLUSIONS: Our results reveal the molecular mechanism underlying the regulation of MTP in the response to salt stress and abundant salt-tolerance-related unigenes. These findings will aid the retrieval of lost alleles in modern maize and provide a new approach for using T. dactyloides and Z. perennis to improve maize.
Subject(s)
Salt Tolerance , Zea mays , Gene Expression Regulation, Plant , Poaceae/genetics , Polyploidy , Salt Tolerance/genetics , Sequence Analysis, RNA , Zea mays/metabolismABSTRACT
Acupuncture is an important part of Chinese medicine that has been widely used in the treatment of inflammatory diseases. During the coronavirus disease 2019 (COVID-19) epidemic, acupuncture has been used as a complementary treatment for COVID-19 in China. However, the underlying mechanism of acupuncture treatment of COVID-19 remains unclear. Based on bioinformatics/topology, this paper systematically revealed the multi-target mechanisms of acupuncture therapy for COVID-19 through text mining, bioinformatics, network topology, etc. Two active compounds produced after acupuncture and 180 protein targets were identified. A total of 522 Gene Ontology terms related to acupuncture for COVID-19 were identified, and 61 pathways were screened based on the Kyoto Encyclopedia of Genes and Genomes. Our findings suggested that acupuncture treatment of COVID-19 was associated with suppression of inflammatory stress, improving immunity and regulating nervous system function, including activation of neuroactive ligand-receptor interaction, calcium signaling pathway, cancer pathway, viral carcinogenesis, Staphylococcus aureus infection, etc. The study also found that acupuncture may have additional benefits for COVID-19 patients with cancer, cardiovascular disease and obesity. Our study revealed for the first time the multiple synergistic mechanisms of acupuncture on COVID-19. Acupuncture may play an active role in the treatment of COVID-19 and deserves further promotion and application. These results may help to solve this pressing problem currently facing the world.
Subject(s)
Acupuncture , COVID-19/therapy , Computational Biology/methods , COVID-19/physiopathology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification , Treatment OutcomeABSTRACT
KEY MESSAGE: Two candidate genes (ZmbZIP113 and ZmTSAH1) controlling low-temperature germination ability were identified by QTL-seq and integrative transcriptomic analyses. The functional verification results showed that two candidate genes positively regulated the low-temperature germination ability of IB030. Low-temperature conditions cause slow maize (Zea mays L.) seed metabolism, resulting in slow seedling emergence and irregular seedling emergence, which can cause serious yield loss. Thus, improving a maize cultivar's low-temperature germination ability (LTGA) is vital for increasing yield production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant of cold stress and can thus be used to improve the LTGA of maize. In a previous study, the genetic bridge MTP was constructed (from maize, T. dactyloides, and Z. perennis) and used to obtain a highly LTGA maize introgression line (IB030) by backcross breeding. In this study, IB030 (Strong-LTGA) and Mo17 (Weak-LTGA) were selected as parents to construct an F2 offspring. Additionally, two major QTLs (qCS1-1 and qCS10-1) were mapped. Then, RNA-seq was performed using seeds of IB030 and the recurrent parent B73 treated at 10 °C for 27 days and 25 °C for 7 days, respectively, and two candidate genes (ZmbZIP113 and ZmTSAH1) controlling LTGA were located using QTL-seq and integrative transcriptomic analyses. The functional verification results showed that the two candidate genes positively regulated LTGA of IB030. Notably, homologous cloning showed that the source of variation in both candidate genes was the stable inheritance of introgressed alleles from Z. perennis. This study was thus able to analyze the LTGA mechanism of IB030 and identify resistance genes for genetic improvement in maize, and it proved that using MTP genetic bridge confers desirable traits or phenotypes of Z. perennis and tripsacum essential to maize breeding systems.
Subject(s)
Transcriptome , Zea mays , Zea mays/genetics , Temperature , Plant Breeding , Quantitative Trait Loci , Poaceae/genetics , Phenotype , GerminationABSTRACT
Chilling injury owing to low temperatures severely affects the growth and development of maize (Zea mays.L) seedlings during the early and late spring seasons. The existing maize germplasm is deficient in the resources required to improve maize's ability to tolerate cold injury. Therefore, it is crucial to introduce and identify excellent gene/QTLs that confer cold tolerance to maize for sustainable crop production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant to cold and can be used to improve the cold tolerance of maize. In a previous study, a genetic bridge among maize that utilized Z. perennis and T. dactyloides was created and used to obtain a highly cold-tolerant maize introgression line (MIL)-IB030 by backcross breeding. In this study, two candidate genes that control relative electrical conductivity were located on MIL-IB030 by forward genetics combined with a weighted gene co-expression network analysis. The results of the phenotypic, genotypic, gene expression, and functional verification suggest that two candidate genes positively regulate cold tolerance in MIL-IB030 and could be used to improve the cold tolerance of cultivated maize. This study provides a workable route to introduce and mine excellent genes/QTLs to improve the cold tolerance of maize and also lays a theoretical and practical foundation to improve cultivated maize against low-temperature stress.
Subject(s)
Seedlings , Zea mays , Seedlings/genetics , Transcriptome , Plant Breeding , Chromosome Mapping , Cold TemperatureABSTRACT
Excitationemission-spectral unmixing-based fluorescence resonance energy transfer (ExEm-spFRET) microscopy exhibits excellent robustness in living cells. We here develop an automatic ExEm-spFRET microscope with 3.04 s of time resolution for a quantitative FRET imaging. The user-friendly interface software has been designed to operate in two modes: administrator and user. Automatic background recognition, subtraction, and cell segmentation were integrated into the software, which enables FRET calibration or measurement in a one-click operation manner. In administrator mode, both correction factors and spectral fingerprints are only calibrated periodically for a stable system. In user mode, quantitative ExEm-spFRET imaging is directly implemented for FRET samples. We implemented quantitative ExEm-spFRET imaging for living cells expressing different tandem constructs (C80Y, C40Y, C10Y, and C4Y, respectively) and obtained consistent results for at least 3 months, demonstrating the stability of our microscope. Next, we investigated Bcl-xL-Bad interaction by using ExEm-spFRET imaging and FRET two-hybrid assay and found that the Bcl-xL-Bad complexes exist mainly in Bad-Bcl-xL trimers in healthy cells and Bad-Bcl-xL2 trimers in apoptotic cells. We also performed time-lapse FRET imaging on our system for living cells expressing Yellow Cameleon 3.6 (YC3.6) to monitor ionomycin-induced rapid extracellular Ca2+ influx with a time interval of 5 s for total 250 s.
ABSTRACT
Heat shock transcription factors (HSF) are divided into classes A, B and C. Class A transcription factors are generally recognized as transcriptional activators, while functional characterization of class B and C heat shock transcription factors have not been fully developed in most plant species. We isolated and characterized a novel HSF transcription factor gene, TrHSFB2a (a class B HSF) gene, from the drought stress-sensitive forage crop species, white clover (Trifolium repens). TrHSFB2a was highly homologous to MtHSFB2b, CarHSFB2a, AtHSFB2b and AtHSFB2a. The expression of TrHSFB2a was strongly induced by drought (PEG6000 15% w/v), high temperature (35 °C) and salt stresses (200 mM L-1 NaCl) in white clover, while subcellular localization analysis showed that it is a nuclear protein. Overexpression of the white clover gene TrHSFB2a in Arabidopsis significantly reduced fresh and dry weight, relative water contents (RWC), maximum photosynthesis efficiency (Fv/Fm) and performance index on the absorption basis (PIABS), while it promoted leaf senescence, relative electrical conductivity (REC) and the contents of malondialdehyde (MDA) compared to a wild type under drought, heat and salt stress conditions of Arabidopsis plants. The silencing of its native homolog (AtHSFB2a) by RNA interference in Arabidopsis thaliana showed opposite trends by significantly increasing fresh and dry weights, RWC, maximum photosynthesis efficiency (Fv/Fm) and performance index on the absorption basis (PIABS) and reducing REC and MDA contents under drought, heat and salt stress conditions compared to wild type Arabidopsis plants. These phenotypic and physiological indicators suggested that the TrHSFB2a of white clover functions as a negative regulator of heat, salt and drought tolerance. The bioinformatics analysis showed that TrHSFB2a contained the core B3 repression domain (BRD) that has been reported as a repressor activator domain in other plant species that might repress the activation of the heat shock-inducible genes required in the stress tolerance process in plants. The present study explores one of the potential causes of drought and heat sensitivity in white clover that can be overcome to some extent by silencing the TrHSFB2a gene in white clover.
Subject(s)
Arabidopsis , Trifolium , Droughts , Arabidopsis/metabolism , Trifolium/genetics , Trifolium/metabolism , Heat Shock Transcription Factors/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Stress, Physiological/genetics , Salt Stress , Transcription Factors/genetics , Transcription Factors/metabolism , Medicago/metabolismABSTRACT
Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of α-synuclein (α-syn)-containing neuronal protein aggregates. Although the exact mechanism of α-syn-mediated cell death remains elusive, recent research suggests that α-syn-induced alterations in neuronal excitability contribute to cell death in PD. Because the fragile X mental retardation protein (FMRP) controls the expression and function of numerous neuronal genes related to neuronal excitability and synaptic function, we here investigated the role of FMRP in α-syn-associated pathological changes in cell culture and mouse models of PD as well as in post-mortem human brain tissue from PD patients. We found FMRP to be decreased in cultured DA neurons and in the mouse brain in response to α-syn overexpression. FMRP was, furthermore, lost in the SNc of PD patients and in patients with early stages of incidental Lewy body disease (iLBD). Unlike fragile X syndrome (FXS), FMR1 expression in response to α-syn was regulated by a mechanism involving Protein Kinase C (PKC) and cAMP response element-binding protein (CREB). Reminiscent of FXS neurons, α-syn-overexpressing cells exhibited an increase in membrane N-type calcium channels, increased phosphorylation of ERK1/2, eIF4E and S6, increased overall protein synthesis, and increased expression of Matrix Metalloproteinase 9 (MMP9). FMRP affected neuronal function in a PD animal model, because FMRP-KO mice were resistant to the effect of α-syn on striatal dopamine release. In summary, our results thus reveal a new role of FMRP in PD and support the examination of FMRP-regulated genes in PD disease progression.
Subject(s)
Fragile X Mental Retardation Protein/metabolism , Parkinson Disease/etiology , Parkinson Disease/pathology , alpha-Synuclein/metabolism , Aged , Aged, 80 and over , Animals , Cell Culture Techniques , Disease Models, Animal , Female , Fragile X Mental Retardation Protein/genetics , Humans , Male , Mice , Middle Aged , Parkinson Disease/metabolism , PhenotypeABSTRACT
In this study, the chromosome number and composition of a novel perennial forage crop, 'Yucao No. 6' (Yu6), was revealed by chromosome spread and McGISH (multicolor genomic in situ hybridization) techniques to clarify its genitor origin. Cytogenetic analysis showed that Yu6, which has 56 chromosomes, is an aneuploid representing 12, 17 and 27 chromosomes from Zea mays ssp. mays L. (Zm, 2n = 2x = 20), Tripsacum dactyloides L. (Td, 2n = 4x = 72), and Z. perennis (Hitchc.) Reeves & Mangelsd. (Zp, 2n = 4x = 40), respectively. This finding indicates that Yu6 is the product of a reduced egg (n = 36 = 12Zm + 17Td + 7Zp) of MTP (a near-allohexaploid hybrid, 2n = 74 = 20Zm + 34Td + 20Zp) fertilized by a haploid sperm nucleus (n = 20Zp) of Z. perennis. Moreover, 3 translocated chromosomes consisting of the maize-genome chromosome with the segment of Z. perennis were observed. These results suggest that it is practical to develop perennial forage maize by remodeling the chromosomal architecture of MTP offspring with Z. perennis as a pollen parent. Finally, the overview of forage breeding in the Zea and Tripsacum genera was discussed.
ABSTRACT
MAIN CONCLUSION: Tripsacum dactyloides is closely related to Zea mays since Zea perennis and the MTP tri- species hybrid have four possible reproductive modes. Eastern gamagrass (Tripsacum dactyloides L.) and tetraploid perennial teosinte (Zea perennis) are well known to possess genes conferring resistance against biotic and abiotic stresses as well as adaptation to flood and aluminum toxic soils. However, plant breeders have been hampered to utilize these and other beneficial traits for maize improvement due to sterility in their hybrids. By crossing a tetraploid maize-inbred line × T. dactyloides, a female fertile hybrid was produced that was crossed with Z. perennis to yield a tri-genomic female fertile hybrid, which was backcrossed with diploid maize to produce BC1 and BC2. The tri-genomic hybrid provided a new way to transfer genetic material from both species into maize by utilizing conventional plant breeding methods. On the basis of cytogenetic observations using multi-color genomic in situ hybridization, the progenies were classified into four groups, in which chromosomes could be scaled both up and down with ease to produce material for varying breeding and genetic purposes via apomixis or sexual reproduction. In the present study, pathways were found to recover maize and to obtain specific translocations as well as a speedy recovery of the T. dactyloides-maize addition line in a second backcross generation. However, phenotypes of the recovered maize were in most cases far from maize as a result of genetic load from T. dactyloides and Z. perennis, and could not be directly used as a maize-inbred line but could serve as an intermediate material for maize improvement. A series of hybrids was produced (having varying chromosome number, constitution, and translocations) with agronomic traits from all three parental species. The present study provides an application of overcoming the initial interspecific barriers among these species. Moreover, T. dactyloides is closely related to Z. mays L. ssp. mays since Z. perennis and the MTP tri- species hybrid have four possible reproductive modes.
Subject(s)
Chromosomes, Plant/genetics , Gene Flow , Genetic Speciation , Genome, Plant/genetics , Poaceae/genetics , Zea mays/genetics , Apomixis , Chimera , Chromosome Segregation , In Situ Hybridization , Phenotype , Plant Breeding , Polyploidy , Reproduction , Translocation, GeneticABSTRACT
Deafness is a common human disease, which is mainly caused by irreversible damage to hair cells and spiral ganglion neurons (SGNs) in the mammalian cochlea. At present, replacement of damaged or missing hair cells and SGNs by stem cell transplantation therapy is an effective treatment. However, the survival rate of stem cell transplantation is low, with uncontrollable differentiation hindering its application. Most researchers have focused on biochemical factors to regulate the growth and differentiation of stem cells, whereas little study has been performed using physical factors. This review intends to illustrate the current problems in stem cell-based treatment against deafness and to introduce electric field stimulation as a physical factor to regulate stem cell behavior and facilitate stem cell therapy to treat hearing loss in the future.
Subject(s)
Deafness/therapy , Electric Stimulation Therapy/methods , Stem Cell Transplantation/methods , Animals , Combined Modality Therapy , Deafness/physiopathology , Hair Cells, Auditory/physiology , Humans , Regeneration/physiologyABSTRACT
Magnesium (Mg(2+)) is an essential macronutrient for plant growth and development, and the CorA/MRS2/MGT-type Mg(2+) transporters play important roles in maintaining Mg(2+) homeostasis in plants. Although the MRS2/MGT genes have been identified in two model plant species, Arabidopsis and rice, a comprehensive analysis of the MRS2/MGT gene family in other plants is lacking. In this work, 12 putative MRS2/MGT genes (ZmMGT1- ZmMGT12) were identified in maize and all of them were classified into five distinct subfamilies by phylogenetic analysis. A complementation assay in the Salmonella typhimurium MM281 strain showed that five representatives of the 12 members possess Mg(2+) transport abilities. Inhibition of ZmMGT protein activity using the hexaamminecobalt (III) (Co-Hex) inhibitor indicated that the ZmMGT protein mediated both low-affinity and high-affinity Mg(2+) transport in maize. A semi-quantitative reverse transcription-PCR (RT-PCR) analysis revealed that eight genes were constitutively expressed in all of the detected tissues, with one being specifically expressed in roots and three having no detectable expression signals. A quantitative RT-PCR analysis showed that some ZmMGT members displayed differential responses to Mg(2+) deficiency and aluminum (Al) stress. Furthermore, root growth inhibition and Mg(2+) accumulation analyses in two maize inbred lines, which conferred different levels of Al tolerance, revealed that ZmMGT proteins contributed to the Al resistance of the Al tolerance genotype. We hypothesize that ZmMGT family members function as Mg(2+) transporters and may play a role in linking Mg(2+) deficiency and Al stress responses. Our results will be valuable in a further analysis of the important biological functions of ZmMGT members in maize.
Subject(s)
Gene Expression Regulation, Plant , Magnesium/metabolism , Membrane Transport Proteins/genetics , Multigene Family , Plant Proteins/genetics , Zea mays/genetics , Adaptation, Physiological/drug effects , Adaptation, Physiological/genetics , Aluminum/toxicity , Amino Acid Sequence , Arabidopsis/genetics , Chromosomes, Plant/genetics , Gene Duplication , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , Genes, Plant , Genetic Complementation Test , Genotype , Inbreeding , Membrane Transport Proteins/metabolism , Mutation/genetics , Oryza/genetics , Phylogeny , Plant Proteins/chemistry , Plant Proteins/metabolism , Sequence Alignment , Stress, Physiological/drug effects , Stress, Physiological/genetics , Zea mays/drug effects , Zea mays/physiologyABSTRACT
BACKGROUND: Intracranial pressure (ICP) monitoring is widely used in the management of patients with severe traumatic brain injury (TBI). However, there is limited evidence about the efficacy of ICP monitoring in older subjects (aged ≥65 years). This study evaluated the effect of intraventricular ICP monitoring on the outcome of older adults suffering from a severe TBI. METHODS: This prospective, observational study included 166 older TBI patients (aged ≥65 years) with Glasgow Coma scale (GCS) scores lower than 9 at admission. The study cohort was divided into two groups, intraventricular ICP monitoring and non-ICP monitoring. The primary outcome was in-hospital mortality. The secondary outcomes included the Glasgow Outcome Scale (GOS) score 6 months after injury, the ICU and total hospital lengths of stay, and mechanical ventilation days. RESULTS: There were 80 patients in the intraventricular ICP monitoring group and 86 patients in non-ICP monitoring group. There was no statistical difference between groups in demographics and severity of head injury. Patients treated with intraventricular ICP monitoring had lower in-hospital mortality (33.8 % vs 51.2 %, P < 0.05), a higher 6-month GOS score (3.0 ± 1.4 vs 2.5 ± 1.2 P < 0.05), and a lower dosage (514 ± 246 g vs 840 ± 323 g, P < 0.0001) and shorter duration (7.2 ± 3.6 days vs 8.4 ± 4.3 days, P < 0.01) of mannitol use. However, the ICU length of stay (14.3 ± 6.4 days vs 11.6 ± 5.8 days, P < 0.01) and mechanical ventilation days (6.7 ± 3.5 days vs 5.6 ± 2.4 days, P < 0.05) were longer in the ICP monitoring group. The total length of hospital stay did not differ between the two groups (28.5 ± 12.1 days vs 26.1 ± 13.5 days, P = 0.23). CONCLUSIONS: Intraventricular ICP monitoring may have beneficial effects on the decreased in-hospital mortality and improved 6-month outcome of older patients with severe TBI. However, given that this was an observational study conducted in a single institution, further well-designed randomized control trials are needed to evaluate the effect of intraventricular ICP monitoring on the outcome of older severe TBI patients.
Subject(s)
Brain Injuries, Traumatic/therapy , Intracranial Pressure , Monitoring, Physiologic/methods , Respiration, Artificial/statistics & numerical data , Aged , Aged, 80 and over , Brain Injuries, Traumatic/physiopathology , Female , Glasgow Coma Scale , Hospital Mortality , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Mannitol/administration & dosage , Prospective StudiesABSTRACT
PURPOSE: It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs). METHODS: We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs. RESULTS: Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region. CONCLUSION: The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.
Subject(s)
Brain Injuries, Traumatic/cerebrospinal fluid , Computational Biology , MicroRNAs/cerebrospinal fluid , Polymorphism, Single Nucleotide , Adult , Brain Injuries, Traumatic/genetics , Humans , Male , MicroRNAs/genetics , Middle Aged , Unconscious, PsychologyABSTRACT
The pseudo-trisaccharide allosamidin 1 is a potent inhibitor of all family-18 chitinases, and it is confirmed to have insecticidal and antifungal activities. But the synthesis of allosamidins is very difficult, and it is a challengeable subject. Allosamidins were synthesized in solid-liquid phase, total solid-phase and total liquid-phase, respectively. Solid-liquid phase method realizes the partial solid-phase synthesis of allosamidins. Total solid-phase method greatly simplifies the purification process. Total liquid-phase method shortens the synthetic steps of allosamidins. The insecticidal and antifungal activities of allosamidins were also reported herein.
Subject(s)
Acetylglucosamine/analogs & derivatives , Antifungal Agents/pharmacology , Enzyme Inhibitors/pharmacology , Insecticides/pharmacology , Trisaccharides/chemical synthesis , Trisaccharides/pharmacology , Acetylglucosamine/chemical synthesis , Acetylglucosamine/chemistry , Acetylglucosamine/pharmacology , Animals , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Bombyx/drug effects , Carbohydrate Conformation , Chitinases/antagonists & inhibitors , Chitinases/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Fungi/drug effects , Insecticides/chemical synthesis , Insecticides/chemistry , Spodoptera/drug effects , Trisaccharides/chemistryABSTRACT
BACKGROUND: Drought stress is one of the major limiting factors for maize production. With the availability of maize B73 reference genome and whole-genome resequencing of 15 maize inbreds, common variants (CV) and clustering analyses were applied to identify non-synonymous SNPs (nsSNPs) and corresponding candidate genes for drought tolerance. RESULTS: A total of 524 nsSNPs that were associated with 271 candidate genes involved in plant hormone regulation, carbohydrate and sugar metabolism, signaling molecules regulation, redox reaction and acclimation of photosynthesis to environment were detected by CV and cluster analyses. Most of the nsSNPs identified were clustered in bin 1.07 region that harbored six previously reported QTL with relatively high phenotypic variation explained for drought tolerance. Genes Ontology (GO) analysis of candidate genes revealed that there were 35 GO terms related to biotic stimulus and membrane-bounded organelle, showing significant differences between the candidate genes and the reference B73 background. Changes of expression level in these candidate genes for drought tolerance were detected using RNA sequencing for fertilized ovary, basal leaf meristem tissue and roots collected under drought stressed and well-watered conditions. The results indicated that 70% of candidate genes showed significantly expression changes under two water treatments and our strategies for mining candidate genes are feasible and relatively efficient. CONCLUSIONS: Our results successfully revealed candidate nsSNPs and associated genes for drought tolerance by comparative sequence analysis of 16 maize inbred lines. Both methods we applied were proved to be efficient for identifying candidate genes for complex traits through the next-generation sequencing technologies (NGS). These selected genes will not only facilitate understanding of genetic basis of drought stress response, but also accelerate genetic improvement through marker-assisted selection in maize.