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Biomedical subjects

Jianhua Zhu

Publications and source records attributed to Jianhua Zhu.

At least 19 recordsLinked to original sources
PubMed2026

Genome editing generates high oleic soybean and eliminates beany flavors.

Soybeans serve as excellent sources of vegetable oil, protein, and other valuable nutrients for human consumption, materials for diverse industries, including the cosmetics and medical industries, and feedstocks for animals. Nevertheless, some people do not favor soy oil or other various food products derived from soybeans, due to inadequate levels of oleic acid in the oil and the presence of undesirable grassy and beany flavors associated with oxidation products of polyunsaturated fatty acids in the seeds. In this study, we developed soybean cultivars with very high levels of oleic acid in the seeds, and without grassy and beany flavors. We achieved this by using CRISPR-Cas-SF01 to edit genes in the elite cultivar Xudou 18 (XD18), targeting two microsomal Δ-12 fatty acid desaturase 2 (GmFAD2-1A and GmFAD2-1B) and three lipoxygenase (GmLOX1, GmLOX2, and GmLOX3) genes. Our findings showed that fad2-1a/b and fad2-1a/b/lox1/2/3 plants performed similarly to XD18 plants in the field, indicating no obvious growth penalties. Overall, this research has demonstrated that the development of soybean germplasms with high levels of oleic acid and without undesirable beany flavors through gene-editing of multiple relevant genes is effective, and this endeavor can contribute to the health of a broader global consumer population.

Gene Editing↗
PubMed2025

A genotype-independent and highly efficient Agrobacterium-mediated soybean genetic transformation system.

A stable and efficient transformation system is crucial for functional genomics and trait improvement in soybean. This study developed a tissue culture based genetic transformation system incorporating dual selection (Spectinomycin and RUBY). This system significantly enhances transformation efficiency, shortens the transformation cycle, and demonstrates broad genotype independence, providing a powerful tool for soybean research and breeding.

Glycine max↗
PubMed2007

The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis.

The Arabidopsis DNA glycosylase/lyase ROS1 participates in active DNA demethylation by a base-excision pathway. ROS1 has been shown to be required for demethylating a transgene promoter. To determine the function of ROS1 in demethylating endogenous loci, we carried out bisulfite-sequencing analysis of several transposons and other genes in the ros1 mutant. In the wild-type, although CpG sites at the majority of these loci are heavily methylated, many of the CpXpG and CpXpX sites have low levels of methylation or are not at all methylated. However, these CpXpG and CpXpX sites become heavily methylated in the ros1 mutant. Associated with this increased DNA methylation, these loci show decreased expression in the ros1 mutant. Our results suggest that active DNA demethylation is important in pruning the methylation patterns of the genome, and even the normally "silent" transposons are under dynamic control by both methylation and demethylation. This dynamic control may be important in keeping the plant epigenome plastic so that it can efficiently respond to developmental and environmental cues.

Arabidopsis↗
PubMed2006

Tissue type-specific modulation of ER transcriptional activity by NFAT3.

NFAT3 belongs to the NFAT family of transcription factors playing important roles in the development of several organ systems and was found to act as a transcriptional coactivator of estrogen receptors (ERalpha and ERbeta) in breast cancer cells. Since some cofactors of transcription factors show cell or tissue type-specific effects on transcriptional regulation, we investigated the effect of NFAT3 on the transcriptional activity of ERs in different cell lines originated from kidney. Surprisingly, overexpression of NFAT3 in these cell types decreased dose-dependently both ERalpha and ERbeta transcriptional activities in a ligand-independent manner. Knockdown of endogenous NFAT3 using NFAT3 small interfering RNA (siRNA) increased ER transcriptional activities. NFAT3 deletion mutants lacking the ER-binding sites completely abolished the NFAT3 repression of ERalpha and ERbeta transcriptional activities. Replacement of Ser168 and Ser170, the amino acid residues on which NFAT3 can be phosphorylated, with Ala did not change the ability of NFAT3 to inhibit the transcriptional activity of ERalpha and ERbeta. Taken together, these results demonstrate that NFAT3 is a new kind of cofactor that displays dual transcription modulation mode dependent on tissue types.

Amino Acid Sequence↗
PubMed2006

The plasma membrane Na+/H+ antiporter SOS1 interacts with RCD1 and functions in oxidative stress tolerance in Arabidopsis.

The adverse effects of high salt on plants include Na(+) toxicity and hyperosmotic and oxidative stresses. The plasma membrane-localized Na(+)/H(+) antiporter SOS1 functions in the extrusion of toxic Na(+) from cells and is essential for plant salt tolerance. We report here that, under salt or oxidative stress, SOS1 interacts through its predicted cytoplasmic tail with RCD1, a regulator of oxidative-stress responses. Without stress treatment, RCD1 is localized in the nucleus. Under high salt or oxidative stress, RCD1 is found not only in the nucleus but also in the cytoplasm. Like rcd1 mutants, sos1 mutant plants show an altered sensitivity to oxidative stresses. The rcd1mutation causes a decrease in salt tolerance and enhances the salt-stress sensitivity of sos1 mutant plants. Several genes related to oxidative-stress tolerance were found to be regulated by both RCD1 and SOS1. These results reveal a previously uncharacterized function of a plasma membrane Na(+)/H(+) antiporter in oxidative-stress tolerance and shed light on the cross-talk between the ion-homeostasis and oxidative-stress detoxification pathways involved in plant salt tolerance.

Arabidopsis↗
PubMed2006

STABILIZED1, a stress-upregulated nuclear protein, is required for pre-mRNA splicing, mRNA turnover, and stress tolerance in Arabidopsis.

In plants, many gene transcripts are very unstable, which is important for the tight control of their temporal and spatial expression patterns. To identify cellular factors controlling the stability of unstable mRNAs in plants, we used luciferase imaging in Arabidopsis thaliana to isolate a recessive mutant, stabilized1-1 (sta1-1), with enhanced stability of the normally unstable luciferase transcript. The sta1-1 mutation also causes the stabilization of some endogenous gene transcripts and has a range of developmental and stress response phenotypes. STA1 encodes a nuclear protein similar to the human U5 small ribonucleoprotein-associated 102-kD protein and to the yeast pre-mRNA splicing factors Prp1p and Prp6p. STA1 expression is upregulated by cold stress, and the sta1-1 mutant is defective in the splicing of the cold-induced COR15A gene. Our results show that STA1 is a pre-mRNA splicing factor required not only for splicing but also for the turnover of unstable transcripts and that it has an important role in plant responses to abiotic stresses.

Arabidopsis↗
PubMed2006

Methods and concepts in quantifying resistance to drought, salt and freezing, abiotic stresses that affect plant water status.

The abiotic stresses of drought, salinity and freezing are linked by the fact that they all decrease the availability of water to plant cells. This decreased availability of water is quantified as a decrease in water potential. Plants resist low water potential and related stresses by modifying water uptake and loss to avoid low water potential, accumulating solutes and modifying the properties of cell walls to avoid the dehydration induced by low water potential and using protective proteins and mechanisms to tolerate reduced water content by preventing or repairing cell damage. Salt stress also alters plant ion homeostasis, and under many conditions this may be the predominant factor affecting plant performance. Our emphasis is on experiments that quantify resistance to realistic and reproducible low water potential (drought), salt and freezing stresses while being suitable for genetic studies where a large number of lines must be analyzed. Detailed protocols for the use of polyethylene glycol-infused agar plates to impose low water potential stress, assay of salt tolerance based on root elongation, quantification of freezing tolerance and the use of electrolyte leakage experiments to quantify cellular damage induced by freezing and low water potential are also presented.

Adaptation, Physiological↗
PubMed2006

Study of the correlation between blood lipid levels and the severity of coronary atherosclerosis in a Chinese population sample.

OBJECTIVE: To investigate the relationship between blood lipid levels with severity of coronary artery atherosclerosis in a Chinese population sample. METHODS AND RESULTS: According to coronary angiography results, 363 patients (287 men and 76 women) with coronary artery atherosclerosis were divided into four groups: the single-vessel group (I, n = 125), the double-vessel group (II, n = 113), the triple-vessel group (III, n = 107) and the multi-vessel group (IV, n = 18). The severity of coronary artery atherosclerosis was quantified with a modified Gensini score on the basis of angiographic imaging. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C) were measured before angiography in all groups. Levels of serum TC, LDL-C and non-HDL-C of the II, III and IV group were significantly higher than those of the I group (4.78 +/- 0.82 mmol/L and 4.87 +/- 1.50 mmol/L and 4.73 +/- 0.99 mmol/L vs. 4.38 +/- 0.93 mmol/L, 2.91 +/- 0.68 mmol/L and 2.74 +/- 1.23 mmol/L and 2.64 +/- 0.84 mmol/L vs. 2.30 +/- 0.77 mmol/L, 3.58 +/- 0.75 mmol/L and 3.59 +/- 1.41 mmol/L and 3.43 +/- 0.94 mmol/L vs. 3.17 +/- 0.91 mmol/L; p < 0.05); the mean levels of TC, LDL-C and non-HDL-C associated positively with the Gensini score. CONCLUSION: Serum lipid levels correlate positively with the severity of coronary artery atherosclerosis in a Chinese population sample. Patients with higher levels of serum TC, LDL-C and non-HDL-C have more severe coronary atherosclerosis, compared with those with low levels of serum TC, LDL-C and non-HDL-C.

China↗
PubMed2006

Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population.

BACKGROUND AND AIMS: Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1beta gene (C(-511)-->T) have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. MATERIALS AND METHODS: One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. RESULTS: The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (Ra*1 allele) in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1beta -511 genotype and the allele distribution between the two groups. CONCLUSIONS: Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.

Aged↗
PubMed2005

Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis.

In higher eukaryotes, miRNAs and siRNAs guide translational inhibition, mRNA cleavage, or chromatin regulation. We found that the antisense overlapping gene pair of Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH), a stress-related gene, and SRO5, a gene of unknown function, generates two types of siRNAs. When both transcripts are present, a 24-nt siRNA is formed by a biogenesis pathway dependent on DCL2, RDR6, SGS3, and NRPD1A. Initial cleavage of the P5CDH transcript guided by the 24-nt siRNA establishes a phase for the subsequent generation of 21-nt siRNAs by DCL1 and further cleavage of P5CDH transcripts. The expression of SRO5 is induced by salt, and this induction is required to initiate siRNA formation. Our data suggest that the P5CDH and SRO5 proteins are also functionally related, and that the P5CDH-SRO5 gene pair defines a mode of siRNA function and biogenesis that may be applied to other natural cis-antisense gene pairs in eukaryotic genomes.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed2005

Stimulatory cross-talk between NFAT3 and estrogen receptor in breast cancer cells.

Estrogen receptors (ERalpha and ERbeta) are ligand-regulated transcription factors that play critical roles in the development and progression of breast cancer by regulating target genes involved in cellular proliferation. The transcriptional activity of ERalpha and ERbeta is known to be modulated by cofactor proteins. We used a yeast two-hybrid system and identified NFAT3 as a novel ERbeta-binding protein. NFAT3 interacted with ERalpha and ERbeta both in vitro and in mammalian cells in a ligand-independent fashion. NFAT3 bound specifically to the ERbeta region containing the activation function-1 domain, a ligand-independent transactivation domain. Overexpression of NFAT3 enhanced both ERalpha and ERbeta transcriptional activities in a ligand-independent manner and up-regulated downstream estrogen-responsive genes including pS2 and cathepsin D. Reduction of endogenous NFAT3 with NFAT3 small interfering RNA or overexpression of NFAT3 deletion mutants that lack the ER-binding sites reduced the NFAT3 coactivation of ERalpha and ERbeta. NFAT3 increased binding of ERalpha to the estrogen-responsive element and was recruited to endogenous estrogen-responsive promoters. NFAT3 was expressed differentially in many breast cancer cell lines and overexpressed in a subset of breast cancer patients. Knockdown of endogenous NFAT3 reduced the growth of human breast cancer ZR75-1 cells in a ligand-independent manner. Taken together, these results suggest that NFAT3 may play important roles in ER signaling and represent a novel target for breast cancer therapy.

Binding Sites↗
PubMed2005

HOS10 encodes an R2R3-type MYB transcription factor essential for cold acclimation in plants.

We report the identification and characterization of an Arabidopsis mutant, hos10-1 (for high expression of osmotically responsive genes), in which the expression of RD29A and other stress-responsive genes is activated to higher levels or more rapidly activated than in wild-type by low temperature, exogenous abscisic acid (ABA), or salt stress (NaCl). The hos10-1 plants are extremely sensitive to freezing temperatures, completely unable to acclimate to the cold, and are hypersensitive to NaCl. Induction of NCED3 (the gene that encodes the rate-limiting enzyme in ABA biosynthesis) by polyethylene glycol-mediated dehydration and ABA accumulation are reduced by this mutation. Detached shoots from the mutant plants display an increased transpiration rate compared with wild-type plants. The hos10-1 plants exhibit several developmental alterations, such as reduced size, early flowering, and reduced fertility. The HOS10 gene encodes a putative R2R3-type MYB transcription factor that is localized to the nucleus. Together, these results indicate that HOS10 is an important coordinating factor for responses to abiotic stress and for growth and development.

Abscisic Acid↗
PubMed2005

FAST: a novel protein structure alignment algorithm.

We present a novel algorithm named FAST for aligning protein three-dimensional structures. FAST uses a directionality-based scoring scheme to compare the intra-molecular residue-residue relationships in two structures. It employs an elimination heuristic to promote sparseness in the residue-pair graph and facilitate the detection of the global optimum. In order to test the overall accuracy of FAST, we determined its sensitivity and specificity with the SCOP classification (version 1.61) as the gold standard. FAST achieved higher sensitivities than several existing methods (DaliLite, CE, and K2) at all specificity levels. We also tested FAST against 1033 manually curated alignments in the HOMSTRAD database. The overall agreement was 96%. Close inspection of examples from broad structural classes indicated the high quality of FAST alignments. Moreover, FAST is an order of magnitude faster than other algorithms that attempt to establish residue-residue correspondence. Typical pairwise alignments take FAST less than a second with a Pentium III 1.2GHz CPU. FAST software and a web server are available at http://biowulf.bu.edu/FAST/.

Algorithms↗
PubMed2005

Regulation of connexin expression after balloon injury: possible mechanisms for antiproliferative effect of statins.

Statins, the 3-hydroxy-3-methylglutaryl-cooenzyme A (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect. Although this beneficial effect of statins has been suggested to be independent of lipid lowering properties, the possible mechanisms responsible for this action is largely unknown. Gap junctions, which serve as channels for direct intercellular exchange of ions, secondary messengers, and small signaling molecules, play an important role in tissue homeostasis and regulation of growth, differentiation, and development. This study was designed to test the hypothesis that expression of the component proteins of gap junctions, connexins 40 and 43 (Cx40 and Cx43), is upregulated in arteries subjected to balloon injury and that this upregulation can be suppressed by statin therapy. Male New Zealand white rabbits were subjected to injury in which an angioplasty catheter was introduced into the right iliac artery from the femoral artery under fluoroscopic guidance. Five groups of rabbits (n = 6 to 7) were treated for 2 weeks with one of the following: balloon injury (BL); BL+lovastatin (BL+L, 10 mg/kg/day); BL+fluvastatin (BL+F, 10 mg/kg/day); sham operation (Sham); and control (Con). Immunohistochemistry studies showed that Cx40 and Cx43 were expressed in normal smooth muscle cells (SMC) throughout the media. Reverse transcription-polymerase chain reaction and Western blot analysis showed that Cx40 and Cx43 mRNA and protein expression was elevated after injury (P < .001 for both proteins and both assays), and these elevations were suppressed by lovastatin and fluvastatin to a similar degree (P < .05 for both drugs and both assays). Immunostaining of Cx40 and Cx43 was consistently enhanced in the neointimal area after injury and lovastatin and fluvastatin reduced staining of these proteins in the lessened neointimal layer. Transmission electron microscopy revealed that there were abundant gap junctions between neointimal SMC as well as fewer and smaller gap junctions after statin treatment. Therefore, balloon injury causes upregulation of Cx40 and Cx43 in neointimal SMC. Lovastatin and fluvastatin suppress upregulated Cx40 and Cx43 expression and reduce neointimal proliferation, suggesting that Cx40 and Cx43 may play a role in statin-induced antiproliferative effect.

Animals↗
PubMed2005

Metastatic lung cancer in the cerebellopontine angles mimicking bilateral acoustic neuroma.

Bilateral cerebellopontine angle (CPA) tumors identified on MRI are considered bilateral acoustic neuromas, the definitive diagnostic criterion of neurofibromatosis 2 (NF-2). We report the case of a 67-year-old man with progressive bilateral hearing loss, vertigo, and imbalance. MRI revealed bilateral enhancing CPA lesions, which were suggestive of acoustic neuromas and a diagnosis of NF-2. However, autopsy showed metastatic adenocarcinoma of the lung. Therefore, metastatic carcinoma to the CPA can mimic bilateral acoustic neuromas; imaging studies alone may be insufficient to diagnose NF-2.

Adenocarcinoma↗
PubMed2004

A DEAD box RNA helicase is essential for mRNA export and important for development and stress responses in Arabidopsis.

An Arabidopsis thaliana mutant, cryophyte, was isolated and found to have an enhanced cold stress-induction of the master regulator of cold tolerance, C-repeat binding factor 2 (CBF2), and its downstream target genes. The mutant is more tolerant to chilling and freezing stresses but is more sensitive to heat stress. Under warm but not cold growth temperatures, the mutant has a reduced stature and flowers earlier. Under long day conditions, flowering of the mutant is insensitive to vernalization. The mutant is also hypersensitive to the phytohormone abscisic acid. The mutation was found in a DEAD box RNA helicase gene that is identical to the previously identified low expression of osmotically responsive genes 4 (LOS4) locus, which was defined by the los4-1 mutation that reduces cold regulation of CBFs and their target genes and renders Arabidopsis plants chilling sensitive. We show evidence suggesting that the CRYOPHYTE/LOS4 protein may be enriched in the nuclear rim. In situ poly(A) hybridization indicates that the export of poly(A)+ RNAs is blocked in the cryophyte/los4-2 mutant at warm or high temperatures but not at low temperatures, whereas the los4-1 mutation weakens mRNA export at both low and warm temperatures. These results demonstrate an important role of the CRYOPHYTE/LOS4 RNA helicase in mRNA export, plant development, and stress responses.

Acclimatization↗