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PubMed1983

Immunological correlates between multiple isolated subunits of Androctonus australis and Limulus polyphemus hemocyanins: an evolutionary approach.

Immunological cross-reactivities between isolated subunits of the scorpion Androctonus australis (Aa) and of the horseshoe crab Limulus polyphemus (Lp) hemocyanins were studied using subunit-specific antibodies prepared through immunoadsorption to pure immobilized subunits. Rocket immunoelectrophoreses of the various subunits of both hemocyanins were carried out at constant antigen concentration against the various subunit-specific antibody preparations. Then the data were analyzed through factorial correspondence analysis and compared to the respective intramolecular locations of the subunits in both hemocyanins. The results show that the dimeric subunits located in the central part of each (4 X 6)meric structure (Aa whole molecule and Lp half molecule) were strongly preserved. In addition, the (8 X 6)mer-forming subunit of Lp hemocyanin (LpIV) and the subunit occupying the same intramolecular position in Aa hemocyanin (Aa5A) were also strongly preserved. Besides the strong antigenic relatedness, less pronounced crossed immunoprecipitations or no precipitation at all were observed between subunits with homologous positions suggesting a minor structural and/or functional roles for these subunits. All the antigen-antibody combinations leading to an absence of immunoprecipitation were screened for the presence of soluble immunocomplexes by radioimmunological tests. In all cases, soluble immunocomplexes were observed. These results suggest the following evolution scenario. First, the central dimeric subunits, responsible of the dodecamer aggregation (Aa3C and 5B and LpV and VI) were already differentiated when Merostomata diverged from Arachnida. Second, the differentiation of the (8 X 6)mer-forming subunit occurred in the Merostomata ramification in a preserved subunit already possessing a functional advantage. Third, the differentiation of subunits Aa3A and Aa3B recently occurred in the scorpion ramification.

Animals↗
PubMed1998

Surgical indications and timing of repair of traumatic ruptures of the thoracic aorta.

BACKGROUND: The outcome of patients with acute traumatic rupture of the thoracic aorta after motor vehicle accidents is strongly conditioned by injuries to other districts. The timing of repair is controversial when the patients arrive alive to the hospital. METHODS: A series of 42 patients with acute traumatic rupture of the thoracic aorta observed between January 1980 and June 1996 was divided into two groups: group I underwent immediate repair (21 patients) and in group II operation was performed after intensive medical treatment and management of the associated lesions and monitoring of the aortic tear. RESULTS: The mortality in group I patients was 19% and the morbidity was more significant than in group II where no deaths were reported and complications were minor. CONCLUSIONS: Patients with acute traumatic rupture of the thoracic aorta may have a better fighting chance if aortic operation is postponed to the most favorable moment after undergoing life-sustaining measures and management of the major associated lesions. Needless to say, evolution should be closely monitored by computed tomographic scans and magnetic resonance imaging.

Accidents, Traffic↗
PubMed2000

Cyclophosphamide and other new agents for the treatment of severe aplastic anemia.

Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed.

Anemia, Aplastic↗
PubMed1970

Comparative studies of bile salts. 5 alpha-Chimaerol, a new bile alcohol from the white sucker Catostomus commersoni Lacépède.

1. G.l.c. examination of bile alcohols prepared from the sucker Catostomus commersoni Lacépède (family Catostomidae) showed that although 5alpha-cyprinol (5alpha-cholestane-3alpha,7alpha,12alpha,26,27-pentol) was a minor constituent, the principal bile alcohol was an undescribed substance, probably present in the bile as the C-26 sulphate ester, whose i.r., n.m.r. and mass spectra agreed with the structure 5alpha-cholestane-3alpha,7alpha,12alpha,24,26-pentol. 2. M(D) studies suggest that this 5alpha-chimaerol is the 24(+), 25S enantiomer and that 5beta-chimaerol (chimaerol) from Chimaera monstrosa bile also has the 24(+), 25S configuration. These findings imply that bile alcohol biosynthesis in suckers and chimaeras includes stereospecific oxidation of cholesterol at C-26. 3. C. commersoni bile acids (present in minor amounts) probably consist largely of 3alpha,7alpha,12alpha-trihydroxy-5alpha-cholan-24-oic acid (allocholic acid). 4. 5alpha-Chimaerol sulphate and 5alpha-cyprinol sulphate are probably biochemically equivalent as bile salts, and can be considered as arising by parallel evolution.

Animals↗
PubMed1995

Infantile autosomal dominant distal myopathy.

INTRODUCTION: Distal myopathies are currently regarded as a non-homogeneous group of disorders including different autosomal dominant, recessive and sporadic forms. MATERIAL AND METHODS: The cases of a mother and her son and daughter are described and compared to previously reported cases from 4 families. Despite minor differences, the clinical picture is remarkably homogeneous, both within the same family and among different families. CONCLUSION: A distinct clinical form can be identified including: a) autosomal dominant inheritance; b) onset in infancy or childhood with peroneal muscles weakness; c) not disabling evolution in spite of possible late involvement of muscles others than tibio-peroneal; d) usually normal serum CK and other muscle enzymes; e) EMG evidence of primary myogenic damage; f) morphological findings of non-specific myopathy. Because of the benign evolution and the absence of true dystrophic changes in most biopsies we suggest the term infantile autosomal dominant distal myopathy should be preferred to infantile autosomal dominant distal muscular dystrophy.

Adolescent↗
PubMed1978

Intracellular serine protease of Bacillus subtilis: sequence homology with extracellular subtilisins.

Intracellular serine protease was isolated from stationary-grown Bacillus subtilis A-50 cells and purified to homogeneity. The molecular weight of the enzyme is 31,000 +/- 1,000, with an isoelectric point of 4.3. Its amino acid composition is characteristically enriched in glutamic acid content, differing from that of extra-cellular subtilisins. The enzyme is completely inhibited with phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Intracellular protease possesses negligible activity towards bovine serum albumin and hemoglobin, but has 5- to 20-fold higher specific activity against p-nitroanilides of benzyloxycarbonyl tripeptides than subtilisin BPN'. Esterolytic activity of the enzyme is also higher than that of subtilisin BPN'. The enzyme is sequence homologous with secretory subtilisins throughout 50 determined NH2-terminal residues, indicating the presence of duplicated structural genes for serine proteases in the B. subtilis genome. The occurrence of two homologous genes in the cell might accelerate the evolution of serine protease not only by the loosening of selective constrainst, but also by creation of sequence variants by means of intragenic recombination. Three molecular forms of intracellular protease were found, two of them with NH2-terminal glutamic acid and one minor form, three residues longer, with asparagine as NH2 terminus. These data indicate the possible presence of an enzyme precursor proteolytically modified during cell growth.

Amino Acid Sequence↗
PubMedDate not supplied

[Adenolymphoma and microadenolymphoma. Histomorphogenetic considerations].

Histomorphogenetic considerations. Seventy three consecutive cases of parotid adenolymphoma were studied. Clinical data (age, sex, site, diagnostic hypothesis, type of surgery), macroscopy (examination of all nodules associated with adenolymphoma and related topography), microscopy (morphological analysis by means of conventional stainings, histochemistry, immunohistochemistry, semiquantitative and morphometric evaluations), with special regard to the lymphoid stroma, were correlated in order to investigate histo-morphogenetic aspects. In 44 cases, lymph nodes were detected (156:83 intraparotid and 73 periparotid). In 18 cases the adenolymphoma resulted multifocal. In 14 of them multifocality was due to the presence of only microscopic (clinically unsuspected) additional adenomas in intraparotid lymph nodes (20 microadenolymphomas). A further microadenolymphoma with 6 associated lymph nodes was occasional finding in a case of sialadenitis. Inclusions of salivary epithelium were observed in 46 intraparotid lymph nodes, were metaplastic (different types of metaplasia) in 23 of them, and were associated with 16 microadenolymphomas. Inclusions and microadenomas were both absent in periparotid lymph nodes. This study strongly supports the intralymphonodal histogenesis of the adenolymphoma and emphasizes the role of the ductal metaplastic changes of the salivary inclusions in the development of the adenomatous proliferation. A model of morphogenetic evolution (with related diagnostic problems) from intralymphonodal inclusions to microadenolymphoma and successively to clinical tumour (macroadenolymphoma) is proposed on the basis of the sequential rearrangement of the various morphological and morphofunctional observations. With special reference to the characteristics of the lymphoid stroma, a minor role of specific immunological mechanisms in the etiopathogenesis of the adenolymphoma is suggested.

Adenolymphoma↗
PubMed1995

[Clinical usefulness of transesophageal echocardiography in heart surgery complications].

The role of monoplane transesophageal echocardiography (TEE) in rapid decision making process was investigated in 115 critically ill patients (pts) with early postoperative complications after cardio-thoracic surgery (hypotension, central venous pressure and/or wedge pressure elevation, electrocardiographic S-T segment elevation). Systolic and diastolic function of left ventricle, left ventricular wall motion abnormalities, right ventricular function, valves or prosthetic valves function, left ventricular outflow tract and morphologic changes were evaluated. Echocardiographic diagnoses were classified as: useful, incomplete, not diagnostic, misleading, unexpected. Echocardiographic diagnoses were confirmed by surgical or pathologic findings in all patients operated or dead. All but one patients, who needed surgical therapy, were operated on the basis of echo-diagnosis alone. Therapeutic changes induced by echo-diagnosis were evaluated and classified as major and minor. Diagnosis was fast (7 +/- 2 m) and sure (no complication). TEE was useful in 91% of cases (105/115 pts), incomplete in 2.3% (3/115 pts), not diagnostic in 2.3% (3/115 pts) and misleading in 3.4% of cases (4/115 pts). TEE findings made major therapeutic changes necessary in 66.9% (77/115 pts); there was a shift from medical to surgical therapy in 28% (41/115 pts); in 14.7% (17/115 pts) minor changes in drug therapy were made. TEE was also useful in quick and safe placement of devices (Swan-Ganz catheter, intra aortic balloon pump, endocardial pace maker, ventricular assist device) and in guiding urgent pericardiocentesis. The effects of medical therapy and evolution of ventricular dysfunction were well monitored by TEE. In our experience TEE was a very useful tool for management of early complications after cardio-thoracic surgery.

Cardiac Surgical Procedures↗
PubMed1995

Structural and function modification of DNA by mitomycin C. Mechanism of the DNA sequence specificity of mitomycins.

Mitomycin C (MC) is a clinically used antitumor agent, which upon reductive activation activates and cross-links DNA. The covalent products of alkylation and cross-linking by the unnatural synthetic enantiomer of MC (ent-MC) were isolated as drug-deoxyguanosine monoadducts and drug-deoxyguanosine bisadducts and were fully characterized structurally. Specificity of alkylation and cross-linking of guanines in the CpG.CpG sequence was observed by ent-MC, similarly to that observed previously by MC. These findings define the mechanism of recognition of the CpG.CpG sequence of DNA by the mitomycins in the minor groove. In contrast, the natural MC metabolite, 2,7-diaminomitosene (2,7-DAM) which lacks the aziridine alkylator function is shown to recognize and alkylate guanines only the GpG.CpC sequence in the major groove, by a different mechanism. Thoughts on the molecular evolution of the basic mitomycin structure as a very efficient lethal DNA cross-linker are discussed.

Antibiotics, Antineoplastic↗
PubMed1998

Regional cerebral blood flow in juvenile systemic lupus erythematosus: a prospective SPECT study. Single photon emission computed tomography.

OBJECTIVE: Using single photon emission computed tomography (SPECT) we evaluated the presence and evolution of changes in brain perfusion in juvenile systemic lupus erythematosus (JSLE). METHODS: SPECT was performed in 14 patients with active JSLE divided in 2 groups: the first included 7 patients without central nervous system (CNS) involvement and the second 7 patients with minor neuropsychiatric symptoms (headache, reactive depression, cognitive impairment, mood swing). SPECT findings were compared to seroimmunological and magnetic resonance imaging (MRI) data. After 6 month followup, a second SPECT scan was performed in 12 of 14 patients. RESULTS: At baseline, SPECT showed perfusion defects in 2 patients without neuropsychiatric symptoms and in 5 patients with CNS involvement. In one of the 7 patients with altered SPECT, MRI showed focal hyperintensities. MRI alterations were observed in another patient who had a normal SPECT scan. Cortical atrophy was present in 5 of 14 patients. Correlation between neuropsychiatric manifestations and SPECT findings was not clearly evident because the major part of JSLE patients with CNS involvement and with SPECT alterations had multiple symptoms, but showed focal hypoperfusion on SPECT imaging. No significant association was found between seroimmunological data and SPECT findings. At followup, improvement of perfusion alterations was observed in 6 of 7 patients with altered SPECT and, in 3 of them, findings might be attributed to changes in steroid treatment. CONCLUSION: Perfusion abnormalities in SLE may represent reversible lesions or subclinical CNS involvement. Moreover, SPECT imaging appears to be useful in detecting and monitoring CNS involvement in SLE.

Adolescent↗
PubMed1989

[Evolution of antibodies and ABH plasmatic transferases in transplants with ABH difference between the recipient and donor].

Another important aspect of these transplants is the possibility of assessing the variations in the activity of serum ABH transferases in receptors of organs with ABH typing different from theirs. The antigenicity of these enzymes has been proven, antitransferase antibodies being found in BMT with minor mismatch, A-group receptors of O-group bone-marrow, and in SOT with major mismatch, O-group receptors of B-group liver. The study of the properties of such antibodies is of great interest in the course of GVHD or HVGD, in either form of transplant, as well as in the knowledge of the biochemical and immunologic characteristics of these ABH enzymes.

ABO Blood-Group System↗
PubMed1999

Theileria parva ribosomal internal transcribed spacer sequences exhibit extensive polymorphism and mosaic evolution: application to the characterization of parasites from cattle and buffalo.

We sequenced the rRNA genes and internal transcribed spacers (ITS) of several Theileria parva isolates in an attempt to distinguish between the causative agents of East coast fever and Corridor disease. The small subunit (SSU) and large subunit (LSU) rRNA genes from a cloned T. p. lawrencei parasite were sequenced; the former was identical to that of T. p. parva Muguga, and there were minor heterogeneities in the latter. The 5.8S gene sequences of 11 T. parva isolates were identical, but major differences were found in the ITS. Six characterization oligonucleotides were designed to hybridize within the variable ITS1 region; 93.5% of T. p. parva isolates examined were detected by probe TPP1 and 81.8% of T. p. lawrencei isolates were detected by TPL2 and/or TPL3a. There was no absolute distinction between T. p. parva and T. p. lawrencei and the former hybridized with fewer of the probes than did the latter. It therefore seems that a relatively homogenous subpopulation of T. parva has been selected in cattle from a more diverse gene pool in buffalo. The ITSs of both T. p. parva and T. p. lawrencei contained different combinations of identifiable sequence segments, resulting in a mosaic of segments in any one isolate, suggesting that the two populations undergo genetic recombination and that their gene pools are not completely separate.

Animals↗
PubMed1989

Interplanetary dust particles collected in the stratosphere: observations of atmospheric heating and constraints on their interrelationships and sources.

The majority of the interplanetary dust particles (IDPs) collected in the stratosphere belong to one of three major classes, the first two dominated by the anhydrous minerals olivine and pyroxene, and the third by hydrous layer-lattice silicates. Infrared spectroscopy and transmission electron microscopy studies show that the different IDP classes represent different types of dust that exist as individual particles in interplanetary space. The majority of the collected IDPs smaller than 30 micrometers in diameter in the layer-lattice silicate and pyroxene classes appear not to have been heated to temperatures above 600 degrees C during atmospheric entry. The relatively low maximum temperatures experienced by these IDPs during atmospheric entry imply that they arrive at the top of the atmosphere with low geocentric encounter velocities. This limits the possible encounter trajectories for these particles to relatively circular, prograde orbits. As a result, it is unlikely that these IDPs are from Earth-crossing comets or asteroids. Asteroids, and comets having low inclinations and perihelia outside 1.2 AU, appear to be the best candidates for the parent bodies of the pyroxene and layer-lattice silicate particles. Chemical and mineralogical information suggests that the pyroxene-rich IDPs are from comets and the layer-lattice silicate-rich IDPs are from asteroids. The collected IDPs dominated by olivine appear to include a larger fraction of particles heating above 600 degrees C, suggesting that these particles were captured from more eccentric orbits. This, and the observation of the infrared spectral features of olivine in several comets suggest these particles have a cometary origin. Since much of the collected dust has apparently been captured from nearly circular, prograde orbits and since there are no appropriate parent bodies presently in such orbits, these results provide an experimental confirmation that the Poynting-Robertson effect exists as a nongravitational force important in the orbital evolution of dust in the Solar System.

Atmosphere↗
PubMed1997

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis.

GB virus C/hepatitis G virus is a newly described virus. Classification of GB virus C/hepatitis G virus into genotypes has not been established. We analyzed nucleotide sequences within the 5' untranslated region of GB virus C/hepatitis G virus isolates and segregated these isolates into genotypes. Twenty serum samples with GB virus C/hepatitis G virus RNA from Australia, Cameroon, the Congo, Japan, Mongolia, and Bangladesh were studied. Reverse transcription and polymerase chain reaction were used to obtain GB virus C/hepatitis G virus RNA. After nucleotide sequences from the 5' untranslated region were determined, 68 nucleotide sequences, including 48 previously reported sequences, were analyzed by molecular evolutionary methods. The phylogenetic tree of the 5' untranslated region showed that all strains could be divided into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3). Bootstrap analysis indicated that the strains could be divided into three major genotypes but could not be further subdivided. Moreover, frequency histograms of pairwise distances between nucleotide sequences demonstrated only one peak. These result indicated that GB virus C/hepatitis G virus can be classified into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3), and should not be divided into minor subtypes.

Base Sequence↗
PubMed2004

Two mitochondrial lineages in Korean freshwater Corbicula (Corbiculidae: bivalvia).

The Korean freshwater Corbicula was surveyed genetically by sequencing 614-bp homologous fragment of mitochondrial cytochrome oxidase I subunit. Among a total of 127 individuals collected from 12 Korean freshwater localities we found only two COI haplotypes and these differed by a total of 9 base substitutions. Although the sequence divergence between the two haplotypes is moderate (p = 1.47%), placing the two mitotypic sequences in the context of Asian mtDNA phylogeny reveals that Korean freshwater Corbicula is comprised of two independent freshwater mitochondrial lineages. These results are in serious disagreement with the long-standing conclusions of earlier conchology-based taxonomic work on Korean Corbicula in which a number of species names (a minimum of 10 nominal species) have been used. This indicates that morphological characteristics alone are poor criteria for species-level identification in this group. In addition, our COI dataset shows that there is an extremely low level of genetic variation in Korean freshwater populations, suggesting that these populations have passed through a severe population bottleneck that greatly reduced their genetic variability. Our data also provide new information on the biogeographic distribution of Korean freshwater Corbicula. When haplotypic frequencies were compared, it was evident that the two Korean freshwater mitochondrial lineages have achieved very different distribution ranges: the predominant lineage (FWKR1) is widely distributed in Korean freshwater systems, whereas the minor lineage (FWKR2) is restricted to a relatively narrow range.

Animals↗
PubMed1996

Little evidence for clonal evolution of malignant haematopoietic cells following relapse after autologous bone marrow transplantation.

By screening for immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in bone marrow samples aspirated at different time points during the course of disease from 43 patients with acute leukaemia we have analysed the extent of clonal evolution after autologous bone marrow transplantation (ABMT) and addressed the issue of whether the Southern Blot method has the power to reveal clonal proliferations representing minimal residual disease (MRD) in the autologous bone marrow grafts. Our results show that no clonal proliferations were detectable in any of the 43 bone marrow grafts analysed, even after we analysed DNA preparations in 5 cases from cells highly enriched for cells of the original malignant immunophenotype. Moreover, as judged by the Ig- and TCR gene configurations in 11 patients, relapse arose from the original clone even though minor clonal variations did occur in about half of the relapsing patients. We conclude that while the Southern Blot method can detect gene receptor rearrangements in the majority of patients with acute leukaemias and high-grade non-Hodgkins lymphomas, it is not useful for predicting relapse after ABMT. On the other hand, it is possible-by employing it-to evaluate whether or not relapse after ABMT arises from the original malignant clone and to what extent clonal evolution has taken place.

Acute Disease↗
PubMed1997

[The influence of clinical presentation and metabolic control of insulin dependent diabetes in the evolution of residual insulin secretion. A prospective study at five years].

BACKGROUND: To study the influence of clinical, metabolic and immunological parameters during the first years of the evolution of insulin-dependent diabetes mellitus (IDDM) on the long-term residual insulin secretion (IS). PATIENTS AND METHODS: 186 IDDM subjects diagnosed from 1986 to 1993 were included; 135 subjects have completed a two year follow-up, and 57 have completed a five year follow-up. The influence of individual characteristics at diagnosis (age, sex, clinical presentation, islet-cell antibodies) and during the first two years of follow-up (IS, metabolic control) on IS at five years was evaluated by multiple linear regression. Differences between groups were evaluated by non-parametric tests. RESULTS: 18 patients had a significant insulin secretion at five years (post-glucagon C-peptide > or = 0.15 nmol/l). They showed minor significant differences in sex (77.7 vs 48.7% of males, p = 0.03), duration of symptoms (12.9 vs 7.2 weeks, p = 0.01), ketoacidosis at diagnosis (23.3 vs 46.1%, p = 0.07) and ICA positivity at diagnosis (41.1 vs 69.4%, p = 0.05). They also had a better metabolic control (8.8 vs 10.8% of HbA1, p < 0.001) with lss insulin (0.48 vs 0.71 Ul/kg, p < 0.001) during the first two years of evolution. Initial IS was similar, but differences became significant at 6 months. In the multivariate analysis, only metabolic control during the second year of evolution (p = 0.008), ketoacidosis at diagnosis (p = 0.026) and sex (p = 0.026) had an independent influence on IS at five years. A more intensified therapeutic approach introduced in 1990 induced a better metabolic control and higher IS during the first years of follow-up. CONCLUSION: The absence of ketoacidosis at diagnosis and a good metabolic control during the first two years can have a positive influence in the long-term preservation of IS in IDDM patients.

Adult↗
PubMed2006

Metabolic analysis of adaptive evolution for in silico-designed lactate-producing strains.

Experimental evolution is now frequently applied to many biological systems to achieve desired objectives. To obtain optimized performance for metabolite production, a successful strategy has been recently developed that couples metabolic engineering techniques with laboratory evolution of microorganisms. Previously, we reported the growth characteristics of three lactate-producing, adaptively evolved Escherichia coli mutant strains designed by the OptKnock computational algorithm. Here, we describe the use of (13)C-labeled experiments and mass distribution measurements to study the evolutionary effects on the fluxome of these differently designed strains. Metabolic flux ratios and intracellular flux distributions as well as physiological data were used to elucidate metabolic responses over the course of adaptive evolution and metabolic differences among strains. The study of 3 unevolved and 12 evolved engineered strains as well as a wild-type strain suggests that evolution resulted in remarkable improvements in both substrate utilization rate and the proportion of glycolytic flux to total glucose utilization flux. Among three strain designs, the most significant increases in the fraction of glucose catabolized through glycolysis (>50%) and the glycolytic fluxes (>twofold) were observed in phosphotransacetylase and phosphofructokinase 1 (PFK1) double deletion (pta- pfkA) strains, which were likely attributed to the dramatic evolutionary increase in gene expression and catalytic activity of the minor PFK encoded by pfkB. These fluxomic studies also revealed the important role of acetate synthetic pathway in anaerobic lactate production. Moreover, flux analysis suggested that independent of genetic background, optimal relative flux distributions in cells could be achieved faster than physiological parameters such as nutrient utilization rate.

Acetate-CoA Ligase↗