Heterozygosity for the IVS-I-5 (G-->C) mutation with a G-->A change at codon 18 (Val-->Met; Hb Baden) in cis and a T-->G mutation at codon 126 (Val-->Gly; Hb Dhonburi) in trans resulting in a thalassemia intermedia.

We have analyzed the hemoglobins of a young German patient with beta-thalassemia intermedia and of his immediate family and included in these studies an evaluation of possible nucleotide changes in the beta-globin genes through sequencing of amplified DNA. One chromosome of the propositus and one of his father's carried the GTG-->GGG mutation at codon 126 leading to the synthesis of Hb Dhonburi or alpha 2 beta (2)126(H4)Val-->Gly; this variant is slightly unstable and is associated with mild thalassemic features. His second chromosome and one of his mother's had the common IVS-I-5 (G-->C) mutation that leads to a rather severe beta(+)-thalassemia and the GTG-->ATG mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. This newly discovered beta-chain variant, named Hb Baden, was present for only 2-3% in both the patient and his mother. This low amount results from a decreased splicing of RNA at the donor splice-site of the first intron that is nearly completely deactivated by the IVS-I-5 (G-->C) thalassemic mutation. The chromosome with the codon 18 (GTG-->ATG) and the IVS-I-5 (G-->C) mutations has thus far been found only in this German family; analysis of 51 chromosomes from patients with the IVS-I-5 (G-->C) mutation living in different countries failed to detect the codon 18 (GTG-->ATG) change.     

Localization of a novel integrin of the beta 1 subfamily in human tissues.

We have previously described a novel integrin composed of a beta 1-chain non-covalently linked to an alpha-chain which is biochemically different from those known so far (i.e., alpha 1-alpha 7 and alpha v). This molecule has been identified with a monoclonal antibody (MAb) termed 10.1.2 raised against long-term cultured human thymic epithelial cells (TEC). In this study we analyzed the immunohistochemical distribution of this new integrin in a variety of human tissues. MAb 10.1.2 stains several types of endothelial and epithelial cells. Among the endothelia, a strong reaction was detected in the HEV of lymphoid organs including thymus, lymph node, tonsil, and mucosa-associated lymphoid tissue. Epithelial localizations of note were those in the basal layer of the epidermis and of other stratified squamous epithelia, where the lateral and apical but not the deep surfaces of most cells were stained. A variety of water-electrolyte transporting cells in sweat glands, salivary glands, and kidney were also stained at their deep surface. The latter findings suggest that this molecule may subserve other functions in addition to those related to cell adhesion.     

The antimycin-A-insensitive respiratory pathway of Candida parapsilosis: evidence for a second quinone involved specifically in its functioning

The involvement of a quinone in the antimycin A-insensitive electron transfer from NADH-dehydrogenase to cytochrome c via the alternative respiratory chain of Candida parapsilosis, by-passing complex II, has been studied. After a partial extraction of quinones, the residual respiration was fully antimycin-A-sensitive, but reincorporation of the organic extract partially restored an antimycin A-insensitive respiration. Analysis of quinone content by HPLC, after purification by thin-layer chromatography, evidenced another quinone species in a very low amount. Myxothiazol and stigmatellin were shown to inhibit the alternative pathway but at a higher concentration than required to inhibit the classical pathway. Cytochrome spectra analysis showed that, in the presence of high myxothiazol concentrations, cytochromes c and aa3 were not reduced, while they were in the presence of antimycin A. It is suggested that the secondary pathway of C. parapsilosis involved a specific quinone pool which can be displaced from its binding site by high concentrations of myxothiazol or analogous compounds.     

Microcarrier culture of bowes melanoma cells in serum-free medium with Human plasma fraction IV-4+ V

Bowes melanoma cells were cultivated successfully in a serum-free medium which was constructed by the concept of maximum retention of proteins from fractionated human plasma having growth stimulatory activities. The cells could be cultivated in the serum-free medium without any adaptation period. The major serum-free component of the medium was the fraction IV-4 + V of the Cohn fractionation process of human plasma. Approximately six times increase of tissue-type plasminogen activator (t-PA) activity as compared with that in serum-free medium even though the cell growth was much slower. In addition, the growth stimulatory activities of thrombin and fibronectin were investigated during the cultivation of Bowes melanoma cells in this serum-free medium. These proteins contributed significantly to the enhanced growth of cells by reducing doubling time to 25 and 35 h as compared with 55 h in the serum-free medium without them. Especially, fibronectin supported cells to propagate near to the maximum cell density achieved in the medium with 10% FBS.     

Diurnal changes in psychophysiological variables of school girls: comparison with regard to age and teacher's appreciation of learning.

Ninety-five nonresident girls of a private school volunteered for the study with the teachers' help as well as parental consent. Ages were approximately 8, 9, and 10 years. They were synchronized with diurnal activity from 0730 to 2100 h and nocturnal rest. Fatigue, drowsiness, and attention were self-rated using visual analogue scales; oral temperature was self-measured and a letter cancellation test was performed. Each of these variables was measured at school at 0900, 1100, 1400, and 1600 h on Mondays, Thursdays, Fridays, and Saturdays for two consecutive weeks in 1987 (March 30-April 11) and again in 1989 (March 13-25) when the youngest group had become 10 years old. According to conventional teacher evaluation of learning (learning performance) within each group, three subgroups were formed: top third, middle third, and bottom third. Time series (more than 50,000 data) were analyzed according to several statistical methods, but mainly chronograms with ANOVA. Similar diurnal changes in oral temperature were validated for each group and subgroups. The occurrence of a diurnal change in self-rated variables (fatigue and drowsiness) and score in letter cancellation was age related: no detection in the 8-year-old group (and subgroups) and validation (p less than 0.002) in 9- and 10-year-old groups (and respective subgroups). A good learning performance was associated with a reduced drowsiness in school girls of 9 and 10 years. Age-related, time-of-day differences in drowsiness (when detected) as well as learning performance effect were not associated with observed duration of sleep. Validated changes in self-rated fatigue were close to that of drowsiness. At 0900 h, girls of 9 and 10 years were more tired when belonging to the bottom third than top third subgroup. Whatever the time of day, self-rated attention was greater in the top than in the bottom third for these girls. Differences related to learning performance were validated in each grade. However, best scores were recorded for the bottom third in the 8-year-old group, while best scores were provided by top third subgroups in 10-year-old girls. It seems that in girls around 8 years of age, critical changes can be detected with regard to the (ontogenic?) occurrence of time-of-day differences in a set of psychophysiologic variables as well as influential effects of learning performance on the same variables. Reported finding are compatible with the hypothesis of circadian oscillators working at the level of the cortex of the human brain.     

Première biozonation du Pléistocène Européen,principal résultat biostratigraphique de l'étude des Rhinocerotidae (Mammalia,Perissodactyla) du Miocène terminal au Pléistocène supérieur d'Europe Occidentale

For the Uppermost Miocene the already known zones MN 9 to MN 13 are used without any change; they prove to be particularly useful for the study of fossil rhinocerotids. The Plio-Villafranchian age corresponds to the zones 14 to 19, the definition of the first five being completed and the last being new. Middle to Upper Pleistocene age deals with the zones 20 to 26, all being new and defined following the same principles.     

Gut microbiome in gastrointestinal cancer: a friend or foe?

The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.     

植物光信号途径重要新调控因子TZP的研究进展

TZP(TANDEM ZINC-FINGER/PLUS3)是近年来鉴定到的一个光信号转导途径新组分,在光介导的植物生长发育过程中发挥重要调控作用。TZP不仅负调控蓝光信号途径,参与光敏色素B(phyB)介导的开花调控过程,还参与调控phyA在体内的蛋白质磷酸化。对TZP生化活性和作用机制的深入研究,不仅有助于进一步完善光信号调控网络,也可为设计和培育具有耐密理想株型及高光效作物新品种提供理论依据。该文系统总结了TZP在植物光信号途径中发挥的重要调控作用,并提出未来TZP功能研究的重要问题。     

Development and Validation of a DNA Methylation-related Classifier of Circulating Tumour Cells to Predict Prognosis and to provide a therapeutic strategy in Lung Adenocarcinoma

Background: A significant factor influencing the prognosis of lung adenocarcinoma (LUAD) is tumor metastasis. Studies have shown that abnormal DNA methylation in circulating tumor cells (CTCs) is associated with tumour metastasis. Based on the genes expressed in CTCs that play an important role in DNA methylation, we hope to build a risk model to predict prognosis and provide a therapeutic strategy in LUAD.Methods: The CTC sequencing data for LUAD were obtained from {"type":"entrez-geo","attrs":{"text":"GSE74639","term_id":"74639"}}GSE74639, which contains 10 CTC samples and 6 primary tumour samples. To carefully assess the clinical value, functional status, involvement of the tumor microenvironment (TME) based on the risk model, and genetic variants based on based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), a reliable risk model was successfully built.Results: Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model. Both the training and validation cohorts'' stability and accuracy of the risk model were evaluated. Each patient in the TCGA-LUAD cohort received a risk score, and based on the median score, they were divided into high- and low-risk groups. The tumors in the high-risk group in this study were classified as "cold" and immunosuppressed, which may be linked to a poor prognosis. The tumors in the low-risk group, however, were deemed "hot" and had immune hyperfunction linked to a positive prognosis. Additionally, patients in the low-risk group showed greater sensitivity to immunotherapy than those in the high-risk group.Conclusions: Based on DMGs of CTCs from LUAD, we successfully developed a predictive risk model and discovered differences in biological function, TME, genetic variation, and clinical outcomes between those at high and low risk group.