Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by 相似文献   

DNA dynamics and endogeneous fields

In this paper we investigate the influence of endogeneous AC fields, generated by a living cell itself, on DNA dynamics. Both quantum nonlinear vibron-phonon interaction model and a model of a highly localized excitation are used. The transition of a broad solitonic excitation into a highly localized one affected by AC fields is calculated using Kubo's formalism for linear response of the system.     

The use of scientometric parameters for the evaluation of scientific contributions

This paper deals with the application of scientometric parameters in the evaluation of scientists, either as individuals or in small formal groups. The parameters are divided into two groups: parameters of scientific productivity and citation parameters. The scientific productivity was further subdivided into three types of parameters: (i) total productivity, (ii) partial productivity, and (iii) productivity in scientific fields and subfields. These citation parameters were considered: (i) impact factors of journals, (ii) impact factors of scientific fields and subfields, (iii) citations of individual papers, (iv) citations of individual authors, (v) expected citation rates and relative citation rates, and (vi) self-citations, independent citations and negative citations. Particular attention was payed to the time-dependence of the scientometric parameters. If available, numeric values of the world parameters were given and compared with the data about the scientific output of Croatian scientists.     

Dermatoglyphic analysis in bipolar affective disorder and schizophrenia--"continuum of psychosis" hypothesis corroborated?

Dermatoglyphic features are thought to be indicators of events in the early embryonal stages. They might also be associated with the developmental disorders of the central nervous system (CNS) including schizophrenia. Dermatoglyphic features of 92 male patients with bipolar affective disorder (BPAD) (unipolar depression and schizoaffective psychosis were excluded from the study) were compared with those of 195 males with schizophrenia (SCH) and both with those of 200 male controls (control group-CG). DSM-III-R criteria were used for the diagnostic evaluation. Quantitative analysis showed only one statistically significant difference between BPAD and SCH patients groups, regarding the c-d ridge count of the left hand. The canonical discriminant analysis did not permit correct classification (only 59.23% of cases were correctly classified) between BPAD and SCH. Numerous quantitative dermatoglyphic features of both BPAD and SCH differed significantly from those of the control subjects. Finger ridge counts as well as palmar ridge counts were markedly lower in BPAD and SCH as compared to the controls. These findings are not in contradiction with the hypothesis claiming that psychoses are a set of diverse expressions (due also to noninherited factors) of a single underlying entity.     

Qualitative dermatoglyphic traits in ovarian cancer patients: a case-control study

The authors investigated the correlation between the occurrence of certain qualitative dermatoglyphic traits and the susceptibility to ovarian cancer, using the case-control design. A sample of 168 diseased cases, treated at the University Department of Gynecologic Oncology in Zagreb, Croatia between 1996-1997 was compared to 200 healthy females, investigated at the Institute for Anthropological Research in Zagreb. The results showed significant differences between ovarian cancer cases and healthy controls regarding the frequency of arches on the fingers of both hands (10-11% vs. 4-5%, respectively, p < 0.05), and of characteristic patterns on the palms of right hand (33% vs. 54% in 3rd interdigital space (IS), p < 0.001; 39% vs. 47% in 4th IS, p < 0.05) and of the left hand (42% vs. 58% in 4th IS, p < 0.001; 24% vs. 34% in hypothenar, p < 0.01). Although probably neither very sensitive nor specific, these findings could still be used in addition to other diagnostic procedures, as a rough screening method in early detecting of ovarian cancer.     

High frequencies and grade expressions of Carabelli's trait in a sample of the Croatian population

Although it is generally accepted that Europeans exhibit the highest frequencies of Carabelli's trait (70-90%), these values represent the expression of all possible morphological grades. When only a well-defined trait expression is considered (grades 5th, 6th and 7th), the frequency is much lower, not more than 19.2% for the 5th grade, and significantly less for the 6th and 7th grades. Our observations based on the study of the Croatian (Central European) populations show the highest frequencies for grade of the trait (exceeding 23%). Comparative data for European or European derived populations demonstrate significant variation in grade expression. While the previously published data suggest that the highest grade of the trait expression does not exceed 10%, our figures show the highest yet known frequency of a well-defined trait.     

Endemic goitre and plasmatic levels of vitamins A and E in the school-children on the island of Krk, Croatia

A total of 1975 school-children on the island of Krk aged 7-19 years of life were included in this study. The purpose was to establish the goitre status and plasmatic level of vitamins A and E in the examined children with the enlarged thyroid gland. The goitre prevalence was 29.8%. The average plasmatic values of vitamins A and E in the children with enlarged thyroids were statistically significantly lower from the reference values. Mentioned goitre prevalence at the level of moderate and heavier endemic goitre speaks on behalf of alimentary iodine deficiency. But the goiter examinations suggested the idoine deficiency not to be the only etiological factor of goitre on the island of Krk. Lower average plasmatic values of vitamins A and E in the examined with the enlarged thyroids referred to this fact to a certain degree.     

Poly(ADP-ribose) polymerase-1: association with nuclear lamins in rodent liver cells

The distribution of poly(ADP-ribose) polymerase-1 (PARP-1) over different nuclear compartments was studied by nuclear fractionation procedures and Western analysis revealing a prominent role of the nuclear matrix. This structure is operationally defined by the solubility properties of the A- and B-type lamins under defined experimental conditions. We consistently observed that most of the nuclear matrix-associated PARP-1 partitioned, in an active form, with the insoluble, lamin-enriched protein fractions that were prepared by a variety of established biochemical procedures. These PARP-1-protein interactions resisted salt extraction, disulfide reduction, RNase and DNase digestion. An inherent ability of PARP-1 to reassemble with the lamins became evident after a cycle of solubilization/dialysis using either urea or Triton X-100 and disulfide reduction, indicating that these interactions were dominated by hydrophobic forces. Together with in vivo crosslinking and co-immunoprecipitation experiments our results show that the lamins are prominent PARP-1-binding partners which could contribute to the functional sequestration of the enzyme on the nuclear matrix.     

Circadian components in energy and tension and their relation to physiological activation and performance

The purpose of the study was to examine validity of R. Thayer's activation model regarding 24h variations of two subjective dimensions of activation (Energy and Tension), and their 24 h relations with indices of physiological activation and performance efficiency. The participants of the study (n = 28 females) spent 26 h under controlled laboratory conditions. Self-ratings of subjective activation and measurements of oral temperature, electrodermal activity, and performance on a visual vigilance task were done every 4 h. Twenty-four-hour variations were examined by means of repeated measures analyses of variance and by group mean cosinor analyses before and after controlling for the data trends. Self-ratings on both dimensions of subjective activation showed significant 24 h variation. Energy showed both nonrhythmic and endogenously determined circadian variation, while 24h variation of tension was dominantly nonrhythmic and most probably determined by exogenous factors. Significant 24 h covariation was found between energy and body temperature. A negative correlation between 24 h variation of energy and tension was also found. Considering low and intermediate levels of subjective activation established over the 24 h in this study, the association of the two dimensions of subjective activation did not prove to be consistent with the assumptions of Thayer's model.     

Positive regulation of ERK activation and MKP-1 expression by peroxovanadium complex bpV (phen)

Lower micromolar concentrations of peroxovanadium compound potassium bisperoxo(1,10-phenanthroline)oxovanadate (V) [bpV (phen)] stimulate RINm5F cell metabolic activity. 1 and 3 mol/L bpV (phen) induces strong and sustained activation of extracellular signal-regulated kinase (ERK). However, it seems that bpV (phen) does not effect c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In addition, bpV (phen) induces mitogen-activated protein kinase phosphatase-1 (MKP-1) expression. We found that ERK activation could be completely abolished if RINm5F cells were incubated with both bpV (phen) and PD 98059, a specific inhibitor of upstream ERK kinase MEK1. On the other hand, this combined treatment up-regulated activation of stress kinases, JNK and p38 MAPK, significantly suppressed MKP-1 expression and induced cell death. Thus, our results suggest that the mechanism underlying bpV (phen) survival-enhancing effect could be associated with induced ERK activation and MKP-1 expression.