Factor F3 Research Articles

Kohonen neural network and factor analysis based approach to geochemical data pattern recognition

Kohonen neural network (KNN) and factor analysis are applied to regional geochemical pattern recognition for a Pb–Zn–Mo–Ag mining area around Sheduolong in Qinghai Province, China. Prior to factor analysis, the geochemical data are classified by KNN. The results demonstrate that the 4-factor model accounted for 67% of the variation in the data. Factor F1, a Pb–Zn–Mo factor and Factor F4, an Au–Ag factor, correlates with monzonitic granite intrusions and particularly with Pb–Zn–Mo–Ag mineralization within those rocks. Factor F2, an As–Co factor, correlates with metamorphic rocks of paleoproterozoic Baishahe formation. Factor F3, a Bi–Cu factor, correlates with granodiorite intrusions. The factor score maps suggest a revised location of faults and their mineralization significance in coarse geological map. The approach not only effectively interprets the geological significance of the factors, but also reduces the area of exploration targets.

Structure of aminopeptidase N from Escherichia coli suggests a compartmentalized, gated active site

Aminopeptidase N from Escherichia coli is a major metalloprotease that participates in the controlled hydrolysis of peptides in the proteolytic pathway. Determination of the 870-aa structure reveals that it has four domains similar to the tricorn-interacting factor F3. The thermolysin-like active site is enclosed within a large cavity with a volume of 2,200 A(3), which is inaccessible to substrates except for a small opening of approximately 8-10 A. The substrate-based inhibitor bestatin binds to the protein with minimal changes, suggesting that this is the active form of the enzyme. The previously described structure of F3 had three distinct conformations that were described as "closed," "intermediate," and "open." The structure of aminopeptidase N from E. coli, however, is substantially more closed than any of these. Taken together, the results suggest that these proteases, which are involved in intracellular peptide degradation, prevent inadvertent hydrolysis of inappropriate substrates by enclosing the active site within a large cavity. There is also some evidence that the open form of the enzyme, which admits substrates, remains inactive until it adopts the closed form.

Structure of the Whole Cytosolic Region of ATP-Dependent Protease FtsH

An ATP-dependent protease, FtsH, digests misassembled membrane proteins in order to maintain membrane integrity and digests short-lived soluble proteins in order to control their cellular regulation. This enzyme has an N-terminal transmembrane segment and a C-terminal cytosolic region consisting of an AAA+ ATPase domain and a protease domain. Here we present two crystal structures: the protease domain and the whole cytosolic region. The cytosolic region fully retains an ATP-dependent protease activity and adopts a three-fold-symmetric hexameric structure. The protease domains displayed a six-fold symmetry, while the AAA+ domains, each containing ADP, alternate two orientations relative to the protease domain, making "open" and "closed" interdomain contacts. Apparently, ATPase is active only in the closed form, and protease operates in the open form. The protease catalytic sites are accessible only through a tunnel following from the AAA+ domain of the adjacent subunit, raising a possibility of translocation of polypeptide substrate to the protease sites through this tunnel.

Crystal Structures of the Tricorn Interacting Factor F3 from Thermoplasma acidophilum, a Zinc Aminopeptidase in Three Different Conformations

The tricorn interacting factor F3 is an 89 kDa zinc aminopeptidase from the archaeon Thermoplasma acidophilum. Together with the tricorn interacting factors F1 and F2, F3 degrades the tricorn protease products and thus completes the proteasomal degradation pathway by generating free amino acids. Here, we present the crystal structures of F3 in three different conformations at 2.3 A resolution. The zinc aminopeptidase is composed of four domains: an N-terminal saddle-like beta-structure domain; a thermolysin-like catalytic domain; a small barrel-like beta-structure domain; and an alpha-helical C-terminal domain, the latter forming a deep cavity at the active site. Three crystal forms provide snapshots of the molecular dynamics of F3 where the C-terminal domain can adapt to form an open, an intermediate and a nearly closed cavity, respectively. With the conserved Zn(2+)-binding motifs HEXXH and NEXFA as well as the N-terminal substrate-anchoring glutamate residues, F3 together with the leukotriene A4 hydrolase, represents a novel gluzincin subfamily of aminoproteases. We discuss the functional implications of these structures with respect to the underlying catalytic mechanism, substrate recognition and processing, and possible component interactions.

Échelle neurocomportementale révisée : étude de la validité concourante

Cognitive and behavioral impairment are a major source of disability in daily living of patients with traumatic brain injury (TBI). The Neurobehavioral Rating Scale-Revised (NRS-R) is a short, easy-to administer interview tool developed to improve assessment by clinicians. Data are available on its criterion validity and reliability, but the concurrent validity of the French NRS-R was not yet documented. Objective. – To assess the concurrent validity of the NRS-R with current psychometric tests. Method. – One hundred and four patients with TBI enrolled in a community adjustment program underwent concurrent examination with the NRS-R, cognitive tests assessing memory, attention, and executive functions, and scales of anxiety (STAI) and depressive mood (CES-D). Intercorrelations were undertaken between these variables and the five factors of the NRS-R: F1, intentional behavior; F2, lowered emotional state; F3, survival-oriented behaviour/hightened emotional state; F4, arousal state; and F5, language. Patients were 82 men and 22 women, the mean age was 28.5 years, and 70% had severe TBI (Glasgow coma score [GCS] below 8 on admission). They were assessed 52 months on average after their injury. Results. – Factor F1 was correlated with results on the GCS ( P < 0.05), the Tower of London test (TL, P < 0.01), the Trail Making Test (TMT, P < 0.01), divided attention (DA) and inhibition (IN) subscales of the Zimmermann and Fimm’s Attention battery (TEA) ( P < 0.01) and reverse digit span (DS, P < 0.05). Factor F2 was positively related to age at injury, time since injury (TSI) ( P < 0.05) and CESD and STAI scores ( P < 0.001). Factor F3 was related to DA ( P < 0.01) TL scores and TSI ( P < 0.05). Factor F4 was related to TL, TMT, DA, flexibility, DS ( P < 0.05), TSI, duration of post-traumatic amnesia, CES-D score ( P < 0.05) and STAI scores ( P < 0.01). Factor F5 was related to GCS, DA ( P < 0.05), and reaction time on the subscales IN and Go/nogo (GO) of the TEA battery ( P < 0.01). The NRS-R total score was related to CESD, STAI scores, TMT score, DA ( P < 0.01) and TL score, IN and GO scores and TSI ( P < 0.05). Discussion. – As McCauley et al found with the English version of the NRS-R, significant relationships were found between NRS-R factor scores, cognitive tests and emotional scales. Relationships were also found between factor scores and indicators of injury severity and time since injury. These data suggest fair concurrent validity of the NRS-R.

The aerosol at Barrow, Alaska: long-term trends and source locations

Aerosol data consisting of condensation nuclei (CN) counts, black carbon (BC) mass, aerosol light scattering (SC), and aerosol optical depth (AOD) measured at Barrow, Alaska from 1977 to 1994 have been analyzed by three-way positive matrix factorization (PMF3) by pooling all of the different data into one large three-way array. The PMF3 analysis identified four factors that indicate four different combinations of aerosol sources active throughout the year in Alaska. Two of the factors (F1, F2) represent Arctic haze. The first Arctic haze have factor F1 is dominant in January–February while the second factor F2 is dominant in March–April. They appear to be material that is generally ascribed to long-range transported anthropogenic particles. A lower ratio of condensation nuclei to scattering coefficient loadings is obtained for F2 indicating larger particles. Factor F3 is related to condensation nuclei. It has an annual cycle with two maxima, March and July–August indicating some involvement of marine biogenic sources. The fourth factor F4 represents the contribution to the stratospheric aerosol from the eruptions of El Chichon and Mt. Pinatubo. No significant long-term trend for F1 was detected while F2 shows a negative trend over the period from 1982 to 1994 but not over the whole measurement period. A positive trend of F3 over the whole period has been observed. This trend may be related to increased biogenic sulfur production caused by reductions in the sea-ice cover in the Arctic and/or an air temperature increase in the vicinity of Barrow. Potential source contribution function (PSCF) analysis showed that in winter and spring during 1989 to 1993 regions in Eurasia and North America are the sources of particles measured at barrow. In contrast to this, large areas in the North Pacific Ocean and the Arctic Ocean was contributed to observed high concentrations of CN in the summer season. Three-way positive matrix factorization was an effective method to extract time-series information contained in the measured quantities. PSCF was useful for the identification possible source areas and the potential pathways for the Barrow aerosol. The effects of long-distance transport, photochemical aerosol production, emissions from biogenic activities in the ocean, volcanic eruptions on the aerosol measurements made at Barrow were extracted using this combined methodology.

Unifying theory of errors for the analytical methods of concentration-dependent distribution, immunoassay and substoichiometric and subsuperequivalence isotope dilution

The statistical uncertainty of results for the concentration-dependent distribution of analyte A, which enters a bimolecular heterogeneous reaction with reagent B after which individual analytical responses SA and SAB are measured, has been expressed as the product of three factors, f1, f2, and f3; and these have been tabulated and assessed in numerical form. The first factor f1 depends on the ratio of variable amounts of analyte A to a constant added amount (e.g., the tracer). Ideally, f1= 1 at large variable amounts, and at low amounts f1=∞; the optimum practical ratio of analyte to additive lies in the interval 1:1 to 4:1. The second factor f2 depends firstly on the yield of analyte binding; ideally, f2= 1 for quantitative yields of the reaction with substoichiometric (subequivalent) amounts of reagent B; however, even at lower yields, the uncertainty of analysis does not increase seriously (f2 < 2). The third factor f3 depends on the mode of measurement of the analytical responses SA and SAB. The ideal ratio of signals (e.g., radioactivity or absorbance) used for quantifying free and bound analyte is I=SA/SAB= 1, for which f3= 1. Under optimum performance, the statistical uncertainty for concentration-dependent distribution, radioimmunoassay, and subsuperequivalence isotope dilution analysis methods appears to be of the same order as the errors of analytical response measurements. Simplicity of evaluation of error propagation is demonstrated.

Convective growth of parametrically unstable modes in inhomogeneous media

By a suitable definition of an amplification coefficient, a convenient analytic criterion for convective instability of damped parametrically coupled unstable modes in an inhomogeneous medium is obtained. The net growth factor F3 on propagation through the resonant interaction region is found to be given by F3 = exp[(πγ20/κ′v1v2)F(√ν1ν2/γ0)], where the reduction factor F(x) = (2/π)[acos(x) − x√1−x2]. This can readily be seen to reduce to the usual inhomogeneous gain formula when damping is negligible and F=1, and to manifest the homogeneous convective threshold, γ20 ≳ ν1ν2. This result should find useful application in laser fusion plasmas, where damping and spatial inhomogeneity are frequently suppression mechanisms of comparable importance for laser-driven parametric instabilities.

Atypical distribution of asymmetric acetylcholinesterase in mutant PC12 pheochromocytoma cells lacking a cell surface heparan sulfate proteoglycan.

We studied the distribution of the molecular forms of acetylcholinesterase (AChE) in a stable variant (F3) of the rat pheochromocytoma cell line, PC12, that lacks a heparan sulfate proteoglycan on the cell surface. After treatment with nerve growth factor F3 cells synthesize less 4S enzyme, and more 10S and 16S enzyme than normal PC12 cells. This distribution is similar to that seen in normal cells after incubation with beta-D-xylosides, molecules that interfere with proteoglycan assembly. Using collagenase treatment and membrane-permeable and -impermeable inhibitors of AChE, we determined the cellular location of the AChE forms. Although in normal cells greater than 90% of the 16S AChE is on the cell surface, approximately 60% is present in an internal pool in the variant. Following irreversible inhibition of all forms of AChE in the variant, the newly synthesized 16S AChE appears in the internal pool after a 1-h lag, but is not detected on the cell surface until after 2.5 h. Our results thus show that 16S AChE is assembled internally within neuronal cells and that alterations in the synthesis and distribution of proteoglycans affect the total amount and cellular localization of the 16S AChE form.

Ribosomal binding of bacteriophage RNA with different components of initiation factor F3

Experiments in bacterial cell-free extracts show that the initiation factor F3 can be fractionated into multiple components on a DEAE-cellulose column. Two purified components independently directed the binding of the bacteriophage R17 RNA to ribosomes at the coat-protein initiation site as measured by the synthesis of the first dipeptide or by the protection of the messenger against nucleolytic attack. Two other fractions yielded progressively increased amounts of binding at the ‘A’' protein initiation site relative to the unfractionated initiation factors.

Studies on the interaction between ribosomes and 14 CH 3 -F 3 initation factor.

Initiation factor F3 has been purified fromEscherichia coli and labelledin vitro by reductive alkylation. The14CH3−F3 so obtained had a specific activity of about 1 000 cpm/μg and was shown to have retained its biological activity. Labelled F3 binds to 30S ribosomal subunits ofEscherichia coli andBacillus stearothermophilus, but does not bind to either 70S ribosomes or 50S ribosomal subunits. The stoichiometry of the binding indicates that one molecule of14CH3−F3 is bound to each 30S ribosomal subunit. Several antibiotics, known to interact with 30S subunits, inhibit the binding. Functional studies indicate that F3 is released from 30S ribosomes as a result of the formation of the “70S initiation complex”.

Ribosomal binding of labelled initiation factor F3.

The following two articles clarify the involvement of initiation factor F3 in the translation of messenger RNA. First, Sabol and Ochoa tell how they used 35S-labelled F3 to prove that 70S ribosomes, released at polypeptide chain termination, are dissociated when F3 binds to the 30S ribosomal subunit.

Messenger discriminating species of initiation factor F3.

Species of the polypeptide chain initiation factor F3 with high selectivity toward either MS2 or T4 phage messenger RNAs have been isolated from normal E. coli cells.

Role of Initiation Factor F3

Role of Initiation Factor F3

Effect of a Purified Initiation Factor F3 (B) on the Selection of Ribosomal Binding Sites on Phage MS2 RNA

STUDIES with T4 mRNA showed that initiation factor F2 (C) promotes the attachment of ribosomes to mRNA1. On the 30S ribosomal subunit this effect is independent of the function of F2 in the binding of formylmethionyl tRNA2, whereas formation of a 70S-mRNA complex depends on the binding of fMet-tRNA3. Template competition experiments4 showed that, with F2 (C), the ribosome seems to have the same affinity for synthetic polynucleotides as for natural mRNA. Addition of initiation factor F3 (B), however, leads to preferential binding of ribosomes to the natural mRNA. This suggests4 that while factor F2 (C) binds the ribosome to any site on the mRNA, the function of factor F3 (B) is to recognize some specific signal in natural mRNA corresponding, perhaps, to the beginning of a cistron. Fractionation of initiation factor F3 (B) into several species differing in their specificity for different mRNA templates5 gave further support to the hypothesis that this protein can select binding sites. An excellent system to demonstrate this effect of F3 (B) would be the binding of ribosomes to RNA from E. coli RNA bacteriophages, since Steitz6 has analysed and determined the nucleotide sequence of the three binding sites corresponding to the three cistrons of R17 mRNA. Experiments were thus undertaken to study the effect of a purified fraction of F3 (B) on the binding of ribosomes to the different sites of such a phage RNA.

Control of single ribosome formation by an initiation factor for protein synthesis.

30 and 50S ribosomal subunits, released from polysomes upon polypeptide chain termination, possess a high affinity for each other and readily form single ribosomes. Highly purified initiation factor F3(B), acting stoichiometrically, prevents the formation of single ribosomes without promoting their dissociation. These findings are interpreted in terms of a ribosome cycle in which a limiting amount of factor F3(B) controls the number of ribosomes active in protein synthesis, in response to metabolic changes in the cell, by regulating the flow of ribosomal subunits into polysomes or into a sidetrack pool of synthetically inactive single ribosomes. The reported apparent ribosome dissociation activity of F3(B) is explained.

Activity of initiation factor F3 in dissociating Escherichia coli ribosomes.

Pure initiation factor F3 dissociates 70S ribosomes into 30S and 50S subunits in a way which suggests that in vivo interaction with runoff ribosomes is responsible for their dissociation into subunits.

Purification and properties of initiation factor F3.

Homogeneous preparations of initiation factor F3 have both RNA binding and ribosome dissociation activities. But although DF activity could entirely account for the role of F3 in the ribosome cycle this factor has an additional function in formation of the initiation complex that may be related to its RNA binding properties.

The isolation of a basic coupling factor from preparations of factor F3.

The isolation of a basic coupling factor from preparations of factor F3.

あさがほ屬ノ遺傳學的研究

A genetic analysis showed the fact that the representation of fasciation in the Japanese morning glory, at least in my specimens, is determined by three recessive factors, f1, f2 and f3. There occur about 20%-25% of crossing over between f1 and f2, and these two factors link closely with p, pear leaf factor. The frequency of crossing over between f1 and p is ca. 2.5%. The strong accompanyment of the fasciated stem and pear leaf is due to the linkage. In the hybrid progeny, there appeared some false normals. Under these conditions the segregating mode of fasciation in the hybrid progeny was very complicated. The factor f3 links with v, variegation factor, in a moderate intensity.