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PubMed2025

Identification of BoRR gene family in cauliflower: roles in curd development and salt tolerance.

BACKGROUND: Cauliflower, as an important vegetable crop, the research on its curd formation mechanism and stress-responsive gene networks is of great significance for improving its quality, yield and abiotic stress tolerance. The response regulator (RR) gene family plays a crucial role in the regulation of various life processes of many organisms. In this research, a comprehensive analysis of the BoRR gene family in cauliflower was carried out. RESULTS: A Total of 57 BoRR genes were identified in cauliflower and classified into seven subtypes (type A/B-I/B-II/B-IV/C/B-PRR/Clock PRR) based on sequence homology. Chromosomal mapping showed even distribution across genomes, while physicochemical analysis revealed diverse protein properties (134-915 amino acids, pI 4.51-9.19) with predominant nuclear localization. Structural analyses found all BoRR proteins contain REC-type domains, with subtype-specific features: type A has REC_typeA_ARR, type B harbors REC_typeB_ARR domains, and Clock PRR shows circadian-related psREC_RR domains. Exon numbers range from 2 to 10, with type A BoRR genes having shorter CDS lengths. Collinearity analysis identified 28 pairs of gene duplicates (26 inter-chromosomal). Comparative analysis showed 133 collinear pairs with Brassica napus, 96 with Brassica. rapa, and only 1 with monocots specie (rice and maize). Promoter analysis identified hormone-responsive motifs (ABRE, TGACG), development-related elements (ARE), and stress-responsive sequences (e.g., MBS for drought tolerance) in the promoters of BoRR genes. GO enrichment linked BoRR genes to phosphorelay signaling, cytokinin/ethylene response, and developmental processes like meristem maintenance. Expression profiling during curd development showed type A genes (BoRR23/27/34/38/45) up-regulated in vegetative-reproductive transition, BoRR3/6/12/32/54 in curd enlargement, and several genes like BoRR49 in flower bud differentiation. Salt stress (1.5% NaCl) induced transient expression in 8 of 9 selected BoRR genes at day 1 after treatment. qRT-PCR validated their roles in developmental regulation and salt tolerance. CONCLUSION: This study provides valuable insights into the BoRR gene family in cauliflower, laying a foundation for further understanding its genetic mechanisms and potentially guiding efforts to enhance curd quality and salt tolerance in cauliflower.

Salt Tolerance↗
PubMed2025

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by pathogenic variants in the SLC16A2 gene. Although most reported variants are found in protein-coding regions or adjacent junctions, structural variations (SVs) within non-coding regions have not been previously reported. METHODS: We investigated two male siblings with severe neurodevelopmental disorders and spasticity, who had remained undiagnosed for over a decade and were negative from exome sequencing, utilizing long-read HiFi genome sequencing. We conducted a comprehensive analysis including short-tandem repeats (STRs) and SVs to identify the genetic cause in this familial case. RESULTS: While coding variant and STR analyses yielded negative results, SV analysis revealed a novel hemizygous deletion in intron 1 of the SLC16A2 gene (chrX:74,460,691 - 74,463,566; 2,876 bp), inherited from their carrier mother and shared by the siblings. Determination of the breakpoints indicates that the deletion probably resulted from Alu/Alu-mediated rearrangements between homologous AluY pairs. The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process, as well as a regulatory element including an eQTL (rs1263181) that is implicated in the tissue-specific regulation of SLC16A2 expression, notably in skeletal muscle and thyroid tissues. CONCLUSIONS: This report, to our knowledge, is the first to describe a non-coding deletion associated with AHDS, demonstrating the potential utility of long-read sequencing for undiagnosed patients. Although interpreting variants in non-coding regions remains challenging, our study highlights this region as a high priority for future investigation and functional studies.

Humans↗
PubMed2007

IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells.

IL-4 has distinct effects on the differentiation and functional properties of CD8+ T cells. In vivo studies have shown that it is critical for the development of protective memory responses against tumors and infections by Leishmania and Plasmodium parasites. The intracellular signaling events mediated by IL-4/IL-4 receptor (IL-4R) interactions on CD4+ T cells have been studied extensively; however, the nature of IL-4-induced signaling on CD8+ T cells has not been characterized. Using naïve, activated, as well as differentiated CD8+ T cells, we show that IL-4 has a strong in vivo and in vitro antiapoptotic effect on activated and resting CD8+ T cells. We demonstrate that IL-4 induces the phosphorylation of the IL-4R, which is followed by the activation of at least two distinct intracellular signaling cascades: the Jak1/STAT6 and the insulin receptor substrate/PI-3K/protein kinase B pathways. We also found that IL-4 induces the Jak3-mediated phosphorylation and nuclear migration of STAT1, STAT3, and STAT5 in naïve, activated, as well as differentiated, IFN-gamma-producing CD8+ T cells. The induction of this broad signaling activity in CD8+ T cells coincides with a transcriptional activity of suppressors of cytokine signaling genes, which are decreased significantly in comparison with CD4+ T cells. To our knowledge, this report constitutes the first comprehensive analysis of the signaling events that shape CD8+ T cell responses to IL-4.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2002

Comprehensive and definitive structural identities of Pneumocystis carinii sterols.

Pneumocystis causes a type of pneumonia in immunodeficient mammals, such as AIDS patients. Mammals cannot alkylate the C-24 position of the sterol side chain, nor can they desaturate C-22. Thus, the reactions leading to these sterol modifications are particularly attractive targets for the development of drugs against fungal and protozoan pathogens that make them. In the present study, the definitive structures of 43 sterol molecular species in rat-derived Pneumocystis carinii were elucidated by nuclear magnetic resonance spectroscopy. Ergosterol, Delta(5,7) sterols, trienes, and tetraenes were not among them. Most (32 of the 43) were 24-alkylsterols, products of S-adenosyl-L-methionine:C-24 sterol methyl transferase (SAM:SMT) enzyme activity. Their abundance is consistent with the suggestion that SAM:SMT is highly active in this organism and that the enzyme is an excellent anti-Pneumocystis drug target. In contrast, the comprehensive analysis strongly suggest that P. carinii does not form Delta(22) sterols, thus C-22 desaturation does not appear to be a drug target in this pathogen. The lanosterol derivatives, 24-methylenelanost-8-en-3 beta-ol and (Z)-24-ethylidenelanost-8-en-3 beta-ol (pneumocysterol), previously identified in human-derived Pneumocystis jiroveci, were also detected among the sterols of the rat-derived P. carinii organisms.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids.

Farnesoid X receptor knockout (Fxr(-/-)) mice cannot upregulate the bile salt export pump in bile acid loading or cholestatic conditions. To investigate whether Fxr(-/-) mice differ in bile acid detoxification compared with wild-type mice, we performed a comprehensive analysis of bile acids extracted from liver, bile, serum, and urine of naive and common bile duct-ligated wild-type and Fxr(-/-) mice using electrospray and gas chromatography mass spectrometry. In addition, hepatic and renal gene expression levels of Cyp2b10 and Cyp3a11, and protein expression levels of putative renal bile acid-transporting proteins, were investigated. We found significantly enhanced hepatic bile acid hydroxylation in Fxr(-/-) mice, in particular hydroxylations of cholic acid in the 1beta, 2beta, 4beta, 6alpha, 6beta, 22, or 23 position and a significantly enhanced excretion of these metabolites in urine. The gene expression level of Cyp3a11 was increased in the liver of Fxr(-/-) mice, whereas the protein expression levels of multidrug resistance-related protein 4 (Mrp4) were increased in kidneys of both genotypes during common bile duct ligation. In conclusion, Fxr(-/-) mice detoxify accumulating bile acids in the liver by enhanced hydroxylation reactions probably catalyzed by Cyp3a11. The metabolites formed were excreted into urine, most likely with the participation of Mrp4.

Animals↗
PubMed2002

A second gene for peroxisomal HMG-CoA reductase? A genomic reassessment.

HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonate, the rate-limiting step of eukaryotic isoprenoid biosynthesis, and is the main target of cholesterol-lowering drugs. The classical form of the enzyme is a transmembrane-protein anchored to the endoplasmic reticulum. However, during the last years several lines of evidence pointed to the existence of a second isoform of HMGCR localized in peroxisomes, where mevalonate is converted further to farnesyl diphosphate. This finding is relevant for our understanding of the complex regulation and compartmentalization of the cholesterogenic pathway. Here we review experimental evidence suggesting that the peroxisomal activity might be due to a second HMGCR gene in mammals. We then present a comprehensive analysis of completely sequenced eukaryotic genomes, as well as the human and mouse genome drafts. Our results provide evidence for a large number of independent duplications of HMGCR in all eukaryotic kingdoms, but not for a second gene in mammals. We conclude that the peroxisomal HMGCR activity in mammals is due to alternative targeting of the ER enzyme to peroxisomes by an as yet uncharacterized mechanism.

Animals↗
PubMed1983

Hepatic ganglioside abnormalities in a patient with familial erythrophagocytic lymphohistiocytosis.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disease of unknown pathogenesis. Because of evidence of increased circulating and hepatic lipids in FEL, we performed a comprehensive analysis of the hepatic lipids of a patient with this disease. In contrast to normal qualitative characteristics and to normal or only mildly elevated concentrations of total lipids, neutral lipids, phospholipids, and neutral glycosphingolipids, this study reports a significant elevation of acidic glycosphingolipids, gangliosides (387 versus 147 nmole lipid-bound sialic acid/g wet weight, patient versus control). This quantitative abnormality was unusual in that it included disproportionately increased concentrations of most of the minor hepatic ganglioside species rather than either a marked increase in one single or a generalized nonspecific increase in all gangliosides, which is characteristic of known disorders exhibiting hepatic ganglioside storage. Activities of the hepatic lysosomal glycosylhydrolases which are important in ganglioside metabolism were therefore assessed by using artificial substrates. Of the enzymes tested, beta-galactosidase activity alone was remarkable, being moderately reduced (33% of that of the normal liver); no biochemical explanation for the reduction was found. The findings suggest FEL may be associated with a unique quantitative and qualitative abnormality in hepatic gangliosides, the cause of which remains to be elucidated.

Child, Preschool↗
PubMed1984

A comparison of three methods for scoring figure drawings.

Figure drawings obtained from 758 white male medical students were scored using three different methods. Method I involved 16 different physical size measurements; Method II involved six separate sophistication of body concept ratings; and Method III involved 42 separate aspects of the drawings weighted in direct proportion to their relative frequency of occurrence in the sample studied (conventionality scoring). Separate factor analyses of the scores derived from each method revealed that Methods I and II each reflect only a single underlying factor, and that these factors are uncorrelated in the population studied. Method III yielded eight meaningful factors, each of which may be construed as an independent area of conventionality/deviancy. An overall conventionality/deviancy score was also derived. It is believed that these three methods of scoring capture most of the variance inherent in existing figure drawing scoring systems, but that use of all three is necessary for a comprehensive analysis.

Factor Analysis, Statistical↗
PubMed1985

Distinguishing child diagnostic types with early memories.

The present study attempts to correct design weaknesses in earlier studies which assessed the use of early memories (EMs) in identifying psychopathology in children. A new EM scoring system, the CEMSS, was developed to provide an objective, comprehensive analysis of the reported EMs. Subjects were 64 boys, SES IV and V, 8 through 12 years old from four diagnostic groups--Delinquent, Hyperactive, Somatic Complaints, and Schizoid. Overall, the CEMSS provided an effective means to distinguish the diagnostic groups, p less than or equal to .01. The results suggest that content variables best distinguished the type of presenting psychopathology, whereas an earlier study found that structural EM variables most reliably identified the degree of psychopathology.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

The existential function of close relationships: introducing death into the science of love.

Originally, terror management theory proposed two psychological mechanisms in dealing with the terror of death awareness-cultural worldview validation and self-esteem enhancement. In this article, we would like to promote the idea of close relationships as an additional death-anxiety buffering mechanism and review a growing body of empirical data that support this contention. Based on a comprehensive analysis of the sociocultural and personal functions of close relationships, we formulate two basic hypotheses that have received empirical support in a series of experimental studies. First, death reminders heighten the motivation to form and maintain close relationships. Second, the maintenance of close relationships provides a symbolic shield against the terror of death, whereas the breaking of close relationships results in an upsurge of death awareness. In addition, we present empirical evidence supporting the possibility that close relationships function as a related yet separate mechanism from the self-esteem and cultural worldview defenses.

Adaptation, Psychological↗
PubMed1999

Comparative analyses of mechanistic differences among antiestrogens.

Antiestrogens such as tamoxifen are one of the most effective methods of treating estrogen receptor (ERalpha) positive breast cancers; however, the effectiveness of this therapy is limited by the almost universal development of resistance to the drug. If antiestrogens are recognized differently by the cell as it has been suggested, then in disease conditions where tamoxifen fails to function effectively, a mechanistically different antiestrogen might yield successful results. Although many antiestrogens have been developed, a direct comparison of their mechanisms of action is lacking, thus limiting their utility. Therefore, to determine if there are mechanistic differences among available antiestrogens, we have carried out a comprehensive analysis of the molecular mechanisms of action of 4-hydroxy-tamoxifen (40HT), idoxifene, raloxifene, GW7604, and ICI 182,780. Using a novel set of peptides that recognize different surfaces on ERalpha, we have found that following binding to ERalpha, each ligand induces a distinct ERalpha-ligand conformation. Furthermore, transcriptional assays indicate that each ERalpha-ligand complex is recognized distinctly by the transcription machinery, and consequently, antiestrogens vary in their ability to inhibit estradiol- and 40HT-mediated activities. Relative binding assays have shown that the affinity of these ligands for ERalpha is not always representative of their inhibitory activity. Using this assay, we have also shown that the pharmacology of each antiestrogen is influenced differently by hormone binding proteins. Furthermore, GW7604, like ICI 182,780, but unlike the other antiestrogens evaluated, decreases the stability of the receptor. Overall, our results indicate that there are clear mechanistic distinctions among each of the antiestrogens studied. However, GW7604 and ICI 182,780 differ more significantly from tamoxifen than idoxifene and raloxifene. These data, which reveal differences among antiestrogens, should assist in the selection of compounds for the clinical regulation of ERalpha function.

Blood Proteins↗
PubMed1993

The rat proenkephalin germ line promoter contains multiple binding sites for spermatogenic cell nuclear proteins.

Rat and mouse spermatogenic cells contain a family of 1700-nucleotide (nt) proenkephalin mRNAs that are generated from an alternate, germ cell-specific promoter. This promoter is located approximately 350 base pairs (bp) downstream of the promoter used in somatic cells, within the first intron for the somatic transcript. In a previous study, rat proenkephalin-chloramphenicol acetyltransferase fusion genes containing both promoters were shown to be transcribed selectively from the germ cell promoter and in the correct developmental pattern in spermatogenic cells of transgenic mice. In the present study it was found that spermatogenic cell-specific transgene expression was maintained after deletion of the upstream somatic promoter. This result establishes that the rat proenkephalin germ-line promoter is capable of functioning independently of transcriptional elements associated with the somatic promoter and localizes the requisite spermatogenic cell cis-elements to a 500-bp region encompassing the germ cell initiation sequences. A comprehensive analysis of binding sites for rat spermatogenic cell nuclear factors within this 500-bp region was performed using gel-shift and DNAse I footprinting techniques. Eight distinct binding regions were identified, each of which formed one or more cell-specific complexes with nuclear proteins from rat spermatogenic cells. These results suggest that multiple cis-acting elements may cooperate in the cell-specific and developmental regulation of rat proenkephalin gene transcription during spermatogenesis.

Animals↗
PubMed2006

Surviving glioblastoma for more than 5 years: the patient's perspective.

The authors performed a comprehensive analysis of the functional outcome of 10 patients who had survived 5 years from a diagnosis of glioblastoma. Neurologic deficits were mild in most patients, but neuropsychological testing demonstrated cognitive deficits in all patients. Depression and anxiety were common. Although most patients thought that their social functioning and work ability were impaired, little reduction in overall quality of life was perceived.

Activities of Daily Living↗
PubMed1980

Structural conflicts in the neighborhood health center program: the national and local perspectives.

The paper reports the findings of a study of the neighborhood health center (NHC) program which was initiated by the Office of Economic Opportunity (OEO) in 1965. The study focuses on the structure of the NHC system (funding agency, operating agency, and community board), analyzes the goals of the different sets of actors, and argues that the conflicts which evolved within the system were the natural outcome of the divergence in the goals of the different actors. Based on a series of 88 in-depth interviews with key health officials in OEO as well as project officers in NHCs throughout the country, the study suggests a framework for a more comprehensive analysis of the outcome of the NHC program and notes the implications of these findings for some current health legislation.

Community Health Centers↗
PubMed2006

Defective receptor expression and dendritic cell differentiation of monocytes in glioblastomas.

OBJECTIVE: Better characterization of the changes that occur in the circulating monocytes of patients with glioblastoma has become more important recently as monocyte-derived dendritic cells are used as adjuvants in the development of glioma vaccines. This study seeks to develop understanding of the phenotypic changes that occur in circulating monocytes of patients with intracranial cancer and to assess the ability of these cells to differentiate into mature dendritic cells. METHODS: Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1, TNFRII, and GMCSFR were compared between three cohorts: patients with intracranial glioblastoma (n = 15), patients with intracranial metastases (n = 9), and a group of healthy controls (n = 10). Monocytes were then tested for their ability to differentiate into mature dentritic cells based on morphology, CD83 expression and high levels of co-stimulatory molecules. RESULTS: Comprehensive analysis of monocyte receptor expression demonstrated significantly reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma but not in patients with intracranial metastases compared with a group of healthy controls. GMCSFR expression was significantly reduced in both patients with glioblastoma and intracranial metastases. Additionally, the monocytes of patients with glioblastoma showed a reduced capacity to differentiate into mature dendritic cells as identified by CD83 expression, receptor expression, and morphology. CONCLUSION: Peripheral monocytes are phenotypically altered in the setting of glioblastoma and display a reduced functional capacity to differentiate into mature dendritic cells.

Adult↗
PubMed2003

Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain.

The insect brain is traditionally subdivided into the trito-, deuto- and protocerebrum. However, both the neuromeric status and the course of the borders between these regions are unclear. The Drosophila embryonic brain develops from the procephalic neurogenic region of the ectoderm, which gives rise to a bilaterally symmetrical array of about 100 neuronal precursor cells, called neuroblasts. Based on a detailed description of the spatiotemporal development of the entire population of embryonic brain neuroblasts, we carried out a comprehensive analysis of the expression of segment polarity genes (engrailed, wingless, hedgehog, gooseberry distal, mirror) and DV patterning genes (muscle segment homeobox, intermediate neuroblast defective, ventral nervous system defective) in the procephalic neuroectoderm and the neuroblast layer (until stage 11, when all neuroblasts are formed). The data provide new insight into the segmental organization of the procephalic neuroectodem and evolving brain. The expression patterns allow the drawing of clear demarcations between trito-, deuto- and protocerebrum at the level of identified neuroblasts. Furthermore, we provide evidence indicating that the protocerebrum (most anterior part of the brain) is composed of two neuromeres that belong to the ocular and labral segment, respectively. These protocerebral neuromeres are much more derived compared with the trito- and deutocerebrum. The labral neuromere is confined to the posterior segmental compartment. Finally, similarities in the expression of DV patterning genes between the Drosophila and vertebrate brains are discussed.

Animals↗
PubMed2000

Regulation of mouse lens fiber cell development and differentiation by the Maf gene.

Maf is a basic domain/leucine zipper domain protein originally identified as a proto-oncogene whose consensus target site in vitro, the T-MARE, is an extended version of an AP-1 site normally recognized by Fos and Jun. Maf and the closely related family members Neural retina leucine zipper (Nrl), L-Maf, and Krml1/MafB have been implicated in a wide variety of developmental and physiologic roles; however, mutations in vivo have been described only for Krml1/MafB, in which a loss-of-function causes abnormalities in hindbrain development due to failure to activate the Hoxa3 and Hoxb3 genes. We have used gene targeting to replace Maf coding sequences with those of lacZ, and have carried out a comprehensive analysis of embryonic expression and the homozygous mutant phenotype in the eye. Maf is expressed in the lens vesicle after invagination, and becomes highly upregulated in the equatorial zone, the site at which self-renewing anterior epithelial cells withdraw from the cell cycle and terminally differentiate into posterior fiber cells. Posterior lens cells in Maf(lacZ) mutant mice exhibit failure of elongation at embryonic day 11.5, do not express (&agr;)A- and all of the (beta)-crystallin genes, and display inappropriately high levels of DNA synthesis. This phenotype partially overlaps with those reported for gene targeting of Prox1 and Sox1; however, expression of these genes is grossly normal, as is expression of Eya1, Eya2, Pax6, and Sox2. Recombinant Maf protein binds to T-MARE sites in the (alpha)A-, (beta)B2-, and (beta)A4-crystallin promoters but fails to bind to a point mutation in the (alpha)A-crystallin promoter that has been shown previously to be required for promoter function. Our results indicate that Maf directly activates many if not all of the (beta)-crystallin genes, and suggest a model for coordinating cell cycle withdrawal with terminal differentiation.

Animals↗
PubMed2000

Tissue-specific regulation of cyclin E transcription during Drosophila melanogaster embryogenesis.

Cyclin E is an essential regulator of S phase entry. We have previously shown that transcriptional regulation of the gene that encodes Drosophila cyclin E, DmcycE, plays an important role in the control of the G(1) to S phase transition during development. We report here the first comprehensive analysis of the transcriptional regulation of a G(1 )phase cell cycle regulatory gene during embryogenesis. Analysis of deficiencies, a genomic transformant and reporter gene constructs revealed that DmcycE transcription is controlled by a large and complex cis-regulatory region containing tissue- and stage-specific components. Separate regulatory elements for transcription in epidermal cells during cell cycles 14-16, central nervous system cells and peripheral nervous system cells were found. An additional cis-regulatory element drives transcription in thoracic epidermal cells that undergo a 17th cell cycle when other epidermal cells have arrested in G(1 )phase prior to terminal differentiation. The complexity of DmcycE transcriptional regulation argues against a model in which DmcycE transcription is regulated simply and solely by G(1) to S phase transcription regulators such as RB, E2F and DP. Rather, our study demonstrates that tissue-specific transcriptional regulatory mechanisms are important components of the control of cyclin E transcription and thus of cell proliferation in metazoans.

Animals↗