Disease relevance of PAF1

• The 19q13 amplicon in pancreatic cancer cells contains a novel pancreatic differentiation 2 (PD2) gene (accession number AJ401156), which was identified by differential screening analysis [1].
• An overall measurement of the "amount" of pyloric hypertrophy was introduced: pyloric volume (PV), which was equated to 1/4 pi x PD2 x PL [2].
• We found that PD2 reduction (i.e., PD2s < 1.2) precedes lethal arrhythmias by hours, but is not reduced in high-risk controls (p < 0.001; sensitivity, 91%; specificity, 85%) [3].
• To this end, QT and RR intervals were extracted from twenty four patients with acute myocardial infarction (AMI) and 13 controls, and a measure of local dimensional complexity (pointwise correlation dimension, PD2) was calculated [4].

High impact information on PAF1

• In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression [5].
• Formation of a trimeric complex with hPAF stimulates H2B monoubiquitination activity in vitro [5].
• Accordingly, UbcH6, RNF20/40, and the hPAF complex are recruited to transcriptionally active genes in vivo [5].
• Ctk1 loss does not appear to have a substantial effect on histone H2B monoubiquitination levels or COMPASS and Paf1 complex phosphorylation [6].
• PD2 is a modular protein composed of RNA recognition motif, DEAD-boxes, an aspartic/serine (DS)-domain, a regulator of the chromosome condensation domain and myc-type helix-loop-helix domains [1].

Biological context of PAF1

• The PD2 sequence is highly conserved from Drosophila to humans with up to 98% identity between rodent and human, suggesting the functional importance of PD2/hPaf1 to maintain cellular homeostasis [1].
• We evaluated tubular ultrastructural changes using electron microscopy and estimated spectrophotometrically activity or concentrations of succinate dehydrogenase (SDH), cytochromes a and c, which are components of mitochondrial respiratory chain, on postnatal days 2 and 9 (PD2 and PD9) [7].
• The PD2 gene sequence was amplified by PCR and two introns were shown to interrupt the coding region [8].
• This may arise because the PD2 is sensitive to the net degrees of freedom of the heartbeat generator, which, under the influence of the nerves and the coronary circulation, can be shifted so the resulting dynamics cause the initiation of lethal arrhythmogenesis [9].
• METHOD: A measure of local dimensional complexity (pointwise correlation dimension, PD2), as well as spectral analysis measures (LF, low-frequency range; HF, high-frequency range) were calculated for the heart rate time series of 10 elderly inpatients with MDD (70+/-7 years) before and after ECT [10].

Anatomical context of PAF1

• In addition, we have demonstrated that the overexpression of PD2 in the NIH 3T3 cells result in enhanced growth rates in vitro and tumor formation in vivo [1].
• Between PDI and PD2 the decline in EDV was higher than that for Ki (caudate 44% and putamen 46% for EDV vs. 21% and 34%, respectively, for Ki) [11].
• A small fraction of the ingested radioactivity was recovered in urine (4 +/- 1%) and excreted in flatus (< or = 1%) and in feces as volatile fatty acids (VFAs) (< 1%) and bacteria (3-4%); the remaining radioactivity in stools, 33 +/- 3% (PD1) and 32 +/- 4% (PD2), was assumed to be intact PD [12].
• Enalapril disrupted inner mitochondrial membranes of developing cortical and medullary tubular cells on PD2 and PD9 [7].
• The intracellular calcium-blocking agent TMB8 also induced a reduction of the contractile responses to PD1 and PD2 consistent with the well established role of intracellular calcium in smooth muscle constriction [13].

Associations of PAF1 with chemical compounds

• Inoculation with DC1 (but not PD2) also accelerated mineralisation of pyrene, where the half-life decreased from 155 days to 18 days in the sand soil, and from 216 days to 33 days in organic soil [14].
• However, the half-life of phenanthrene decreased from 86 days in non-inoculated sand soil and 80 days in the non-inoculated organic soil to 3.6 days in the sand and 3.1 days in organic soil when inoculated with PD2, and to 6.6 days in the sand and 8.7 days in the organic soil when inoculated with DC1 [14].
• Baseline values and acid tolerance curves were similar in CAPD patients on regular Dianeal (lactate 35 mEq/l) and Dianeal PD2 (lactate 40 mEq/l) [15].
• The dose response curve of nifedipine yielded a significantly greater PD2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (PD2 value [5.82+/-0.34] versus the above groups [range 3.10+/-0.09-3.52+/-0.14] (P <0.01)) [16].
• Inoculation of soil with bacteria (a Gram-negative rod [PD2] and a 4-membered consortium [DC1]) accelerated mineralisation of phenanthrene and pyrene (but not naphthalene) added individually to a pristine sand and a pristine organic soil [14].

Analytical, diagnostic and therapeutic context of PAF1

• The dimensionality of chaotic strange attractors was estimated from the EEG at each of 14 scalp electrodes, using the point correlation dimension PD2 algorithm [17].
• Thus PD2 of heartbeat intervals may provide an important diagnostic test and early warning sign of VF [3].
• Northern blotting and RT-PCR analyses indicate that PD2 is expressed predominantly in petals, pistils of open flowers and leaves of the almond tree [8].
• Based on sequence analysis, we have defined three classes of S-like RNase genes, with the PD2 RNase gene representing a distinct class [8].
• Compared to that seen in the control group, in the Z-score maps of the scalp distribution of the PD2, a marked asymmetry was seen and the absolute PD2 values showed a low-dimensional area in the parietal region, ipsilateral to the stroke [18].

References