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Diabetic retinopathy is one of the serious complications of diabetes, is currently the world's second largest blinding disease. Early epidemiological data showed that the development is related to blood sugar level, diabetes duration, blood lipids, and other factors. In recent years, the correlation of gene polymorphism with DR received widespread attention. Accurately grasp the genetic mechanism in the process of development in the DR and the differences of expression, is of great significance to DR early diagnosis and prevention. So in this article, the progress of gene of DR were reviewed.

Background: Prostate cancer (PCa) was one of the most common malignancies among men, while the prognosis for PCa patients was poor, especially for patients with recurrent and advanced diseases. Materials and methods: Five PCa cohorts were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and the biochemical recurrence (BCR)-related chemokine genes were identified by LASSO-Cox regression. The chemokine-related prognostic gene signature (CRPGS) was established, and its association with PCa patients' clinical, pathological and immune characteristics was analyzed. The association between CRPGS and PCa patients' responses to androgen deprivation therapy (ADT) and immunotherapy was analyzed. The CRPGS was compared with other previously published molecular signatures, and the CRPGS was externally validated in our real-world AHMU-PC cohort. Results: Four recurrence-free survival (RFS)-related chemokine genes (CXCL14, CCL20, CCL24, and CCL26) were identified, and the CRPGS was established based on the four identified chemokine genes, and TCGA-PRAD patients with high riskscores exhibited poorer RFS, which was validated in the GSE70768 cohort. The CRPGS was associated with the clinical, pathological, and immune characteristics of PCa patients. Low-risk PCa patients were predicted to respond better to ADT and immunotherapy. By comparing with other molecular signatures, the CRPGS could classify PCa patients into two risk groups well, and the CRPGS was associated with the m6A level, as well as TP53 and SPOP mutation status of PCa patients. In the AHMU-PC cohort, the CRPGS was associated with the advanced pathology stage and Gleason score. Conclusions: The identified chemokine genes and CRPGS were associated with the prognosis of PCa, which could predict PCa patients' responses to antiandrogen and immunotherapies. [ABSTRACT FROM AUTHOR]

Hypoxia spontaneously forms in the interior of glioma tissues and regulates the expression of various genes. However, the status of hypoxia-driven genes in glioma tissues is not completely known. In the current study, RNA-seq data of 695 glioma tissues in The Cancer Genome Atlas (TCGA) were set as a discovery cohort and were used to identify hypoxia-driven genes and construct a novel gene signature. The prognostic values of that signature were verified in data from the TCGA and the Chinese Glioma Genome Atlas (CGGA). The expression and diagnostic values of hypoxia-driven genes were analyzed using immunohistochemistry and receiver operator characteristic curves. Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay. A total of 169 hypoxia-driven genes were identified, which were associated with a poor outcome in glioma patients. Among them, 22 genes had a degree score =10 and 6 genes (WT1, HOXA2, HOXC6, MMP9, SHOX2 and MYOD1) were selected to construct a signature to classify glioma patients into low- or high-risk groups. That signature had a remarkable prognostic value for glioma patients in TCGA and CGGA. The expression of HOXC6, MMP9, SHOX2 and MYOD1 was associated with hypoxia degree in glioma tissues and in recurrent cases, had a remarkable diagnostic value and a significant relationship with disease free survival in glioma patients. Moreover, SHOX2 was highly expressed in glioma tissues with O-6-methylguanine-DNA methyltransferase (MGMT)- unmethylation and temozolomide (TMZ) resistant glioma cell lines, and associated with MGMT expression. Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia. [ABSTRACT FROM AUTHOR]

High-density planting is a major way to improve crop yields. However, shade-avoidance syndrome (SAS) is a major factor limiting increased planting density. First Green Revolution addressed grass lodging problem by using dwarf/semi-dwarf genes. However, it is not suitable for soybean, which bear seeds on stalk and whose seed yield depends on plant height. Hence, mining shade-tolerant germplasms and elucidating the underlying mechanism could provide meaningful resources and information for high-yield breeding. Here, we report a high-plant density-tolerant soybean cultivar, JiDou 17, which exhibited an inactive SAS (iSAS) phenotype under high-plant density or low-light conditions at the seedling stage. A quantitative trait locus (QTL) mapping analysis using a recombinant inbred line (RIL) population showed that this iSAS phenotype is related to a major QTL, named shade-avoidance response 1 (qSAR1), which was detected. The mapping region was narrowed by a haplotype analysis into a 554 kb interval harboring 44 genes, including 4 known to be key regulators of the SAS network and 4 with a variance response to low-light conditions between near isogenic line (NIL) stems. Via RNA-seq, we identified iSAS-specific genes based on one pair of near isogenic lines (NILs) and their parents. The iSAS-specific genes expressed in the stems were significantly enriched in the “proteasomal protein catabolic” process and the proteasome pathway, which were recently suggested to promote the shade-avoidance response by enhancing PIF7 stability. Most iSAS-specific proteasome-related genes were downregulated under low-light conditions. The expression of genes related to ABA, CK, and GA significantly varied between the low- and normal-light conditions. This finding is meaningful for the cloning of genes that harbor beneficial variation(s) conferring the iSAS phenotype fixed in domestication and breeding practice. [ABSTRACT FROM AUTHOR]

[Display omitted] • 113 members of the AP2/ERF family were identified for the first time in mango. • Transient overexpression of MiERF4 in tobacco and mango improves defense against bacteria. • MiERF4 increases ETH and MeJA content and enhances plant resistance. An important regulatory role for ethylene-responsive transcription factors (ERFs) is in plant growth and development, stress response, and hormone signaling. However, AP2/ERF family genes in mango have not been systematically studied. In this study, a total of 113 AP2/ERF family genes were identified from the mango genome and phylogenetically classified into five subfamilies: AP2 (28 genes), DREB (42 genes), ERF (33 genes), RAV (6 genes), and Soloist (4 genes). Of these, the ERF family, in conjunction with Arabidopsis and rice, forms a phylogenetic tree divided into seven groups, five of which have MiERF members. Analysis of gene structure and cis -elements showed that each MiERF gene contains only one AP2 structural domain, and that MiERF genes contain a large number of cis -elements associated with hormone signaling and stress response. Collinearity tests revealed a high degree of homology between MiERF s and CsERF s. Tissue-specific and stress-responsive expression profiling revealed that MiERF genes are primarily involved in the regulation of reproductive growth and are differentially and positively expressed in response to external hormones and pathogenic bacteria. Physiological results from a gain-of-function analysis of MiERF4 transiently overexpressed in tobacco and mango showed that transient expression of MiERF4 resulted in decreased colony count and callose deposition, as well as varying degrees of response to hormonal signals such as ETH, JA, and SA. Thus, MiERF4 may be involved in the JA/ETH signaling pathway to enhance plant defense against pathogenic bacteria. This study provides a basis for further research on the function and regulation of MiERF genes and lays a foundation for the selection of disease-resistant genes in mango. [ABSTRACT FROM AUTHOR]

The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases. In this study, we investigated the relationship between obesity and diseases from Online Mendelian Inheritance in Man (OMIM) databases on the protein-protein interaction (PPI) network. The obesity genes and genes of one OMIM disease were mapped onto the network, and the interaction scores between the two gene sets were investigated on the basis of the PPI of individual gene pairs, thereby inferring the relationship between obesity and this disease. Results suggested that diseases related to nutrition and endocrine are the top two diseases that are closely associated with obesity. This finding is consistent with our general knowledge and indicates the reliability of our obtained results. Moreover, we inferred that diseases related to psychiatric factors and bone may also be highly related to obesity because the two diseases followed the diseases related to nutrition and endocrine according to our results. Numerous obesity-disease associations were identified in the literature to confirm the relationships between obesity and the aforementioned four diseases. These new results may help understand the underlying molecular mechanisms of obesity-disease co-occurrence and provide useful insights for disease prevention and intervention. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle is one of the most important economic traits in agricultural animals, especially in pigs. In the modern pig industry, lean type pigs have undergone strong artificial selection for muscle growth, which has led to remarkable phenotypic variations compared with fatty type pigs, making these different breeds an ideal model for comparative studies. Results: Here, we present comprehensive gene expression profiling for the white (longissimus dorsi muscle) and the red (psoas major muscle) skeletal muscles among male and female fatty Rongchang, feral Tibetan and lean Landrace pigs, using a microarray approach. We identified differentially expressed genes that may be associated the phenotypic differences of porcine muscles among the breeds, between the sexes and the anatomical locations. We also used a clustering method to identify sets of functionally coexpressed genes that are linked to different muscle phenotypes. We showed that, compared with the white muscles, which primarily modulate metabolic processes, the red muscles show a tendency to be a risk factor for inflammation and immune-related disorders. Conclusions: This analysis presents breed-, sex- and anatomical location-specific gene expression profiles and further identified genes that may be associated with the phenotypic differences in porcine muscles among breeds, between the sexes and the anatomical locations. [ABSTRACT FROM AUTHOR]

Reverse transcription quantitative real-time PCR (RT-qPCR), a sensitive technique for quantifying gene expression, depends on the stability of the reference gene(s) used for data normalization. Only a few studies on reference genes have been done in fruit trees and none in litchi. In the present study, seven frequently used candidate reference genes, including actin ( ACTIN), glyceraldehyde-3-phosphate-dehydrogenase ( GADPH), elongation factor 1-alpha ( EF- 1α), poly ubiquitin enzyme ( UBQ), α-tubulin ( TUA), β-tubulin ( TUB) and RNA polymerase-II transcription factor ( RPII), were evaluated for their expression stability in litchi. A total of 78 samples, including different varieties, tissues, organs, developmental stages and treatments, such as NAA, shading and girdling plus defoliation, were addressed in this analysis. Our results showed that GAPDH was the most suitable reference gene among all the tested samples, different organs and NAA treatment. ACTIN was stably expressed in varieties and fruit developmental stages. RPII and UBQ exhibited better expression stability in tissues. EF- 1α was the most stable gene in shading and girdling plus defoliation treatments. Moreover, using combination of two genes as reference genes might improve the reliability of gene expression by RT-qPCR in litchi. A better combination was GAPDH + EF- 1α or GAPDH + ACTIN for all the examined samples. In addition, the validated reference genes were further relied on to quantify the expression of an interested gene, LcARF13 under different experimental conditions. These results first provide guidelines for reference genes selection under different experimental conditions and also a foundation for more accurate and widespread use of RT-qPCR in litchi. [ABSTRACT FROM AUTHOR]

The harpin protein HrpN induces Arabidopsis resistance to the green peach aphid by activating the ethylene signalling pathway and by recruiting EIN2, an essential regulator of ethylene signalling, for a defence response in the plant. We investigated 37 ethylene-inducible Arabidopsis transcription factor genes for their effects on the activation of ethylene signalling and insect defence. Twenty-eight of the 37 genes responded to both ethylene and HrpN, and showed either increased or inhibited transcription, while 18 genes showed increased transcription not only by ethylene but also by HrpN. In response to HrpN, transcription levels of 22 genes increased, with AtMYB44 being the most inducible, six genes had decreased transcript levels, and nine remained unchanged. When Arabidopsis mutants previously generated by mutagenicity at the 37 genes were surveyed, 24 mutants were similar to the wild type plant while four mutants were more resistant and nine mutants were more susceptible than wild type to aphid infestation. Aphid-susceptible mutants showed a greater susceptibility for atmyb15, atmyb38 and atmyb44, which were generated previously by T-DNA insertion into the exon region of AtMYB15 and the promoter regions of AtMYB38 and AtMYB44. The atmyb44 mutant was the most susceptible to aphid infestation and most compromised in induced resistance. Resistance accompanied the expression of PDF1.2, an ethylene signalling marker gene that requires EIN2 for transcription in wild type but not in atmyb15, atmyb38, and atmyb44, suggesting a disruption of ethylene signalling in the mutants. However, only atmyb44 incurred an abrogation in induced EIN2 expression, suggesting a close relationship between AtMYB44 and EIN2. [ABSTRACT FROM AUTHOR]

Clustering is a popular technique for analyzing microarray data sets, with n genes and m experimental conditions. As explored by biologists, there is a real need to identify coregulated gene clusters, which include both positive and negative regulated gene clusters. The existing pattern-based and tendency-based clustering approaches cannot directly be applied to find such coregulated gene clusters, because they are designed for finding positive regulated gene clusters. In this paper, in order to cluster coregulated genes, we propose a coding scheme that allows us to cluster two genes into the same cluster if they have the same code, where two genes that have the same code can be either positive or negative regulated. Based on the coding scheme, we propose a new algorithm for finding maximal subspace coregulated gene clusters with new pruning techniques. A maximal subspace coregulated gene cluster clusters a set of genes on a condition sequence such that the cluster is not included in any other subspace coregulated gene clusters. We conduct extensive experimental studies. Our approach can effectively and efficiently find maximal subspace coregulated gene clusters. In addition, our approach outperforms the existing approaches for finding positive regulated gene clusters. [ABSTRACT FROM AUTHOR]

To seek more information on function of two-component regulatory systems (TCSs) in Streptomyces coelicolor, a dozen TCS-knockout mutants were generated, and phenotype changes were determined. One TCS ( SCO5403/5404)-deleted mutant with phenotype change was obtained. Here, we report the characterization of this novel TCS, designated as RapA1/A2 ( regulation of both actinorhodin and a type I polyketide), using genetic and proteomic approaches. Although growth and morphological analyses showed no difference between the knockout mutant and wild-type strain M145, a visible decrease of the production of actinorhodin (Act) was observed in rapA1/A2 mutant. The decrease can be restored by introducing rapA1/A2 genes on an integrative vector. A 2D-gel based proteomic analysis showed that knockout of rapA1/A2 resulted in reduced expression of a putative 3-oxoacyl-[acyl-carrier protein] reductase that is part of a biosynthetic cluster for a cryptic type I polyketide. Further reverse-transcriptase-polymerase chain reaction (RT-PCR) analyses confirmed that expression levels of several biosynthetic genes and the respective pathway-specific regulatory genes actII-ORF4 and kasO for these two clusters were all down-regulated in the rapA1/A2 mutant, compared to M145. Taken together, the results demonstrated that RapA1/A2 may serve as a positive regulator for biosynthesis of both Act and the uncharacterized polyketide in S. coelicolor, and the effects exerted by RapA1/A2 were dependent on the pathway-specific regulatory genes. [ABSTRACT FROM AUTHOR]

Xanthomonas oryzae pv . oryzae causes bacterial leaf blight, one of the most widespread and destructive bacterial diseases in rice. In order to understand the gene of zinc uptake regulator ( zur) involved in virulence of the pathogen in rice, we generated a mutant OSZRM by homologous suicide plasmid integration. The mutant failed to grow in NYGB medium supplemented with Zn2+ or Fe3+ at a concentration of 500 μM or 6 mM, whereas the wild-type strain grew well at the same conditions. The zur mutant was hypersensitive to hydrogen peroxide and exhibited reduction catalase activity and the production of extracellular polysaccharide (EPS). Interestingly, the mutant showed a reduction in virulence on rice but still kept triggering hypersensitive response (HR) in tobacco. When the mutant was complemented with the zur gene, the response was recovered to wild-type. These results suggested that zur gene is a functional member of the Zur regulator family that controls zinc and iron homeostasis, oxidative stress, and EPS production, which is necessary for virulence in X. oryzae pv. oryzae. [ABSTRACT FROM AUTHOR]

Biotin is an important nutritional supplement but is difficult to manufacture effectively. Here we present a trial of biotin production using the food yeast Candida utilis. In this system, we cloned the C. utilis biotin synthase (BIO2) gene, the gene of the rate-limiting enzyme for biotin biosynthesis, and assembled it under the control of a strong promoter. A series of plasmids were constructed to direct the integration of the BIO2 gene, either high-copy integration with 18S rDNA fragment or low-copy integration with URA3 or HIS3 fragment. The BIO2 gene can be successfully integrated into the C. utilis chromosome and can drive biotin production using these plasmids. The biotin yield in this system can reach 100-fold above the endogenous level in a small-scale culture. Although the biotin production is not stable if the selection pressure is removed, this system has the potential to produce biotin-rich feed or food additives directly without the requirement of further purification. [ABSTRACT FROM AUTHOR]

An ORF located immediately downstream of glnR gene was cloned from Amycolatopsis mediterranei U32 and was named lh3. Sequence analysis revealed that lh3 encodes a putative acetyltransferase, which shows high amino acid sequence similarities to the mycothiol synthase (MshD) from other actinomycetes. For functional analysis, mutation in lh3 gene was generated by gene replacement with an apramycin resistance gene through homologous recombination. Compared with the wild type strain, the resulting mutant was more sensitive to H2O2, apramycin and erythromycin by two- to three-fold. These results suggest that the lh3 gene plays an important role in the course of detoxification in A. mediterranei U32. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the sensitivity, specificity, and spatial distribution of the product of p28 gene (p28GANK protein) in human hepatocellular carcinoma (HCC) and nonhepatocellular carcinomas in relation to immunostaining with Cytokeratin 18 (CK18), α-fetoprotein (AFP), and Hepatocyte paraffin 1 (HepPar1). Method. In this retrospective study, formalin-fixed paraffin-embedded tissues from 24 HCCs, five intrahepatic cholangiocarcinomas (ICC), five combined hepatocellular cholangiocarcinomas (C-HCC-CC) and mine metastatic hepatic carcinomas (MHC) were immunostained for p28GANK as well as CK18, AFP and HepPar1. Only cases with more intensified staining in carcinoma contrast to the adjacent liver tissues were accepted as positive. Result. In HCC, p28GANK was expressed restrictively in hepatocytes of both para-lesion and carcinoma liver tissues, while absent in the bile duct epithelial cells, Kupffer cells, and other interstitial cells. The positive staining of p28GANK was noted in 16 (66.7%) specimens of HCC and three (60.0%) specimens of C-HCC-CC, and no specific lesion staining was found in all tested specimens of ICC and MHC. Sensitivity and specificity for hepatocyte-originated carcinoma were, respectively, 65.5% and 100% for p28GANK, 79.3% and 85.2% for CK18, 20.7% and 100% for AFP, 79.3% and 92.0% for HepPar1. Conclusion. The hepatocytic staining for p28GANK is clearly useful in differentiating hepatocyte-originated carcinoma from non-HCC. p28GANK may be used as an ancillary marker for the diagnosis of HCC. [ABSTRACT FROM AUTHOR]

This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogenous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value < 0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome Iq that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Cloning of genes in expression libraries, such as the yeast two-hybrid system (Y2H), is based on the assumption that the loss of target genes is minimal, or at worst, managable. However, the expression of genes or gene fragments that are capable of interacting with E. coli or yeast gene products in these systems has been shown to be growth inhibitory, and therefore these clones are underrepresented (or completely lost) in the amplified library. Results: Analysis of candidate genes as Y2H fusion constructs has shown that, while stable in E. coli and yeast for genetic studies, they are rapidly lost in growth conditions for genomic libraries. This includes the rapid loss of a fragment of the E. coli cell division gene ftsZ which encodes the binding site for ZipA and FtsA. Expression of this clone causes slower growth in E. coli. This clone is also rapidly lost in yeast, when expressed from a GAL1 promoter, relative to a vector control, but is stable when the promoter is repressed. We have demonstrated in this report that the construction of libraries for the E. coli and B. subtilis genomes without passaging through E. coli is practical, but the number of transformants is less than for libraries cloned using E. coli as a host. Analysis of several clones in the libraries that are strongly growth inhibitory in E. coli include genes for many essential cellular processes, such as transcription, translation, cell division, and transport. Conclusion: Expression of Y2H clones capable of interacting with E. coli and yeast targets are rapidly lost, causing a loss of complexity. The strategy for preparing Y2H libraries described here allows the retention of genes that are toxic when inappropriately expressed in E. coli, or yeast, including many genes that represent potential antibacterial targets. While these methods are generally applicable to the generation of Y2H libraries from any source, including mammalian and plant genomes, the potential of functional clones interacting with host proteins to inhibit growth would make this approach most relevant for the study of prokaryotic genomes. [ABSTRACT FROM AUTHOR]

The article describes the results of a molecular epidemiological study of HIV-1-infected injection drug users in Taiwan from January 2004 to April 2005. All HIV-1-positive specimens collected contained detectable sequences, including 105 from the C2-V3 region of env and 87 from the protease and reverse transcriptase genes of pol. The results provide information relevant to the development of antiretroviral therapy and vaccine in Taiwan and may aid public health workers in the prevention of HIV-1 transmission.