Response to geometrical visual illusions in non-human animals: a meta-analysis.

Visual illusions have been studied in many non-human species, spanning a wide range of biological and methodological variables. While early reviews have proved useful in providing an overview of the field, they have not been accompanied by quantitative analysis to systematically evaluate the contribution of biological and methodological moderators on the proportion of illusory choice. In the current meta-analytical study, we confirm that geometrical visual illusion perception is a general phenomenon among non-human animals. Additionally, we found that studies testing birds report stronger illusion perception compared to other classes, as do those on animals with lateral-positioned eyes compared to animals with forward-facing eyes. In terms of methodological choices, we found a positive correlation between the number of trials during training or testing and the effect sizes, while studies with larger samples report smaller effect sizes. Despite studies that trained animals with artificial stimuli showing larger effect sizes compared with those using spontaneous testing with naturalistic stimuli, like food, we found more recent studies prefer spontaneous choice over training. We discuss the challenges and bottlenecks in this area of study, which, if addressed, could lead to more successful advances in the future.

Coherent Control and Spectroscopy of a Semiconductor Quantum Dot Wigner Molecule.

Semiconductor quantum dots containing more than one electron have found wide application in qubits, where they enable readout and enhance polarizability. However, coherent control in such dots has typically been restricted to only the lowest two levels, and such control in the strongly interacting regime has not been realized. Here we report quantum control of eight different transitions in a silicon-based quantum dot. We use qubit readout to perform spectroscopy, revealing a dense set of energy levels with characteristic spacing far smaller than the single-particle energy. By comparing with full configuration interaction calculations, we argue that the dense set of levels arises from Wigner-molecule physics.

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro.

Chronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of a therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 h at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells. The antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

Interface effects on acceptor qubits in silicon and germanium.

Dopant-based quantum computing implementations often require the dopants to be situated close to an interface to facilitate qubit manipulation with local gates. Interfaces not only modify the energies of the bound states but also affect their symmetry. Making use of the successful effective mass theory we study the energy spectra of acceptors in Si or Ge taking into account the quantum confinement, the dielectric mismatch and the central cell effects. The presence of an interface puts constraints to the allowed symmetries and leads to the splitting of the ground state in two Kramers doublets (Mol et al 2015 Appl. Phys. Lett. 106 203110). Inversion symmetry breaking also implies parity mixing which affects the allowed optical transitions. Consequences for acceptor qubits are discussed.

Conceptual DFT, machine learning and molecular docking as tools for predicting LD50 toxicity of organothiophosphates.

CONTEXT: Several descriptors from conceptual density functional theory (cDFT) and the quantum theory of atoms in molecules (QTAIM) were utilized in Random Forest (RF), LASSO, Ridge, Elastic Net (EN), and Support Vector Machines (SVM) methods to predict the toxicity (LD50) of sixty-two organothiophosphate compounds. The A-RF-G1 and A-RF-G2 models were obtained using the RF method, yielding statistically significant parameters with good performance, as indicated by R2 values for the training set (R2Train) and R2 values for the test set (R2Test), around 0.90. METHODS: The molecular structure of all organothiophosphates was optimized via the range-separated hybrid functional ωB97XD with the 6-311 + + G** basis set. Seven hundred and eighty-seven descriptors have been processed using a variety of machine learning algorithms: RF LASSO, Ridge, EN and SVM to generate a predictive model. The properties were obtained with Multiwfn, AIMALL and VMD programs. Docking simulations were performed by using AutoDock 4.2 and LigPlot + programs. All the calculations in this work are carried out in Gaussian 16 program package.

A single hole spin with enhanced coherence in natural silicon.

Semiconductor spin qubits based on spin-orbit states are responsive to electric field excitations, allowing for practical, fast and potentially scalable qubit control. Spin electric susceptibility, however, renders these qubits generally vulnerable to electrical noise, which limits their coherence time. Here we report on a spin-orbit qubit consisting of a single hole electrostatically confined in a natural silicon metal-oxide-semiconductor device. By varying the magnetic field orientation, we reveal the existence of operation sweet spots where the impact of charge noise is minimized while preserving an efficient electric-dipole spin control. We correspondingly observe an extension of the Hahn-echo coherence time up to 88 µs, exceeding by an order of magnitude existing values reported for hole spin qubits, and approaching the state-of-the-art for electron spin qubits with synthetic spin-orbit coupling in isotopically purified silicon. Our finding enhances the prospects of silicon-based hole spin qubits for scalable quantum information processing.

Biofunctionalization on alkylated silicon substrate surfaces via "click" chemistry.

Biofunctionalization of silicon substrates is important to the development of silicon-based biosensors and devices. Compared to conventional organosiloxane films on silicon oxide intermediate layers, organic monolayers directly bound to the nonoxidized silicon substrates via Si-C bonds enhance the sensitivity of detection and the stability against hydrolytic cleavage. Such monolayers presenting a high density of terminal alkynyl groups for bioconjugation via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC, a "click" reaction) were reported. However, yields of the CuAAC reactions on these monolayer platforms were low. Also, the nonspecific adsorption of proteins on the resultant surfaces remained a major obstacle for many potential biological applications. Herein, we report a new type of "clickable" monolayers grown by selective, photoactivated surface hydrosilylation of α,ω-alkenynes, where the alkynyl terminal is protected with a trimethylgermanyl (TMG) group, on hydrogen-terminated silicon substrates. The TMG groups on the film are readily removed in aqueous solutions in the presence of Cu(I). Significantly, the degermanylation and the subsequent CuAAC reaction with various azides could be combined into a single step in good yields. Thus, oligo(ethylene glycol) (OEG) with an azido tag was attached to the TMG-alkyne surfaces, leading to OEG-terminated surfaces that reduced the nonspecific adsorption of protein (fibrinogen) by >98%. The CuAAC reaction could be performed in microarray format to generate arrays of mannose and biotin with varied densities on the protein-resistant OEG background. We also demonstrated that the monolayer platform could be functionalized with mannose for highly specific capturing of living targets (Escherichia coli expressing fimbriae) onto the silicon substrates.

Enhancing the dipolar coupling of a S-T0 qubit with a transverse sweet spot.

A fundamental challenge for quantum dot spin qubits is to extend the strength and range of qubit interactions while suppressing their coupling to the environment, since both effects have electrical origins. Key tools include the ability to take advantage of physical resources in different regimes, and to access optimal working points, sweet spots, where dephasing is minimized. Here, we explore an important resource for singlet-triplet qubits: a transverse sweet spot (TSS) that enables transitions between qubit states, a strong dipolar coupling, and leading-order protection from electrical fluctuations. Of particular interest is the possibility of transitioning between the TSS and symmetric operating points while remaining continuously protected. This arrangement is ideal for coupling qubits to a microwave cavity, because it combines tunability of the coupling with noise insensitivity. We perform simulations with [Formula: see text]-type electrical noise, demonstrating that two-qubit gates mediated by a resonator can achieve fidelities >99% under realistic conditions.

Virtual-photon-mediated spin-qubit-transmon coupling.

Spin qubits and superconducting qubits are among the promising candidates for realizing a solid state quantum computer. For the implementation of a hybrid architecture which can profit from the advantages of either approach, a coherent link is necessary that integrates and controllably couples both qubit types on the same chip over a distance that is several orders of magnitude longer than the physical size of the spin qubit. We realize such a link with a frequency-tunable high impedance SQUID array resonator. The spin qubit is a resonant exchange qubit hosted in a GaAs triple quantum dot. It can be operated at zero magnetic field, allowing it to coexist with superconducting qubits on the same chip. We spectroscopically observe coherent interaction between the resonant exchange qubit and a transmon qubit in both resonant and dispersive regimes, where the interaction is mediated either by real or virtual resonator photons.

Copper-Catalyzed Click Reaction on/in Live Cells.

We demonstrated that copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction could be performed inside live mammalian cells without using a chelating azide. Under optimized conditions, the reaction was performed in human ovary cancer cell line OVCAR5 in which newly synthesized proteins were metabolically modified with homopropargylglycine (HPG). This model system allowed us to estimate the efficiency of the reaction on the cell membranes and in the cytosol using mass spectrometry. We found that the reaction was greatly promoted by a tris(triazolylmethyl)amine CuI ligand tethering a cell-penetrating peptide. Uptake of the ligand, copper, and a biotin-tagged azide in the cells was determined to be 69 ± 2, 163 ± 3 and 1.3 ± 0.1 µM, respectively. After 10 minutes of reaction, the product yields on the membrane and cytosolic proteins were higher than 18% and 0.8%, respectively, while 75% cells remained viable. By reducing the biothiols in the system by scraping or treatment with N-ethylmalemide, the reaction yield on the cytosolic proteins was greatly improved to ~9% and ~14%, respectively, while the yield on the membrane proteins remained unchanged. The results indicate that out of many possibilities, deactivation of the current copper catalysts by biothiols is the major reason for the low yield of CuAAC reaction in the cytosol. Overall, we have improved the efficiency for CuAAC reaction on live cells by 3-fold. Despite the low yielding inside live cells, the products that strongly bind to the intracellular targets can be detected by mass spectrometry. Hence, the in situ CuAAC reaction can be potentially used for screening of cell-specific enzyme inhibitors or biomarkers containing 1,4-substituted 1,2,3-triazoles.

Cancer, retrodifferentiation, and the myth of Faust.

The close relationship at the molecular level between cellular differentiation and neoplasia has been evidenced by the discovery in adult individuals of fetospecific antigens and fetal type isozymes associated with many spontaneous and experimentally induced malignant tumors. One question in relation with this finding is whether cancerous tumors develop from the differentiation of a tissue reserve of stem cells or by a process of retrodifferentiation, i.e., the nucleocytoplasmic stepwise reversion of cells toward stationary states with simplified structure and less information content. The question is not merely academic; elucidation of the nature of the target cells from which neoplastic growth emerges has obviously physiopathological and therapeutic implications. This contribution is an analysis of the nature and the mechanism of cellular retrodifferentiation and a discussion of its possible role in regeneration and metaplasia, as well as in neoplastic development. Throughout living systems, retrodifferentiation appears as a common adaptive process for the maintenance of cell integrity against deleterious agents of varied etiology (physical, chemical,and viral). While preserving the entire information encoded on its genome, cells undergoing retrodifferentiation lose morphological and functional complexity by virtue of a process of self-deletion of cytoplasmic structures and the transition to a more juvenile pattern of gene expression. This results in a progressive uniformization of originally distinct cell phenotypes and to a decrease of responsiveness to regulatory signals operational in adult cells. Retrodifferentiation is normally counterbalanced by a process of reontogeny that tends to restore the terminal phenotypes from where the reversion started. This explains why retrodifferentiation remains invariably associated to cell regeneration and tissue repair. There is an ever growing evidence that neoplastic transformation in vivo and in vitro is frequently preceded and/or accompanied by biochemical, morphological, and behavioral transitions characteristic of a cell undergoing retrodifferentiation. Contrary to what occurs in regenerating tissues, the "unbalanced" character of tumor-associated retrodifferentiation seems to be a property linked to cancer. The question arises why a unique mechanism of cell rejuvenation is in physiological conditions (regeneration), followed by a process of reontogeny, while in neoplasia the process remains incomplete or does not occur and leads to the emergence of a population of persistently dividing cells. It is to be hoped that a careful study of retrodifferentiation in physiological and tumoral models will help to distinguish that which in neoplastic development can be relevant to an adaptive cell behavior from that which might eventually be the result of specific or constitutive alterations.

Uptake of radiolabeled alpha-fetoprotein by mouse mammary carcinomas and its usefulness in tumor scintigraphy.

The ability to internalize alpha-fetoprotein (AFP) and serum albumin, which is characteristic of embryonic and fetal elements undergoing differentiation, may reappear in some cultured neoplastic cells (i.e., the MCF-7 human breast cancer cell line). The in vivo uptake of AFP by spontaneous carcinomas of the CH3/Bi mouse was investigated. Nineteen mice were given i.v. injections of approximately 10 muCi of mouse 125I-AFP (0.6 to 4 micrograms of AFP according to the specific ratio of the preparation used). Four to 7 days later, the animals were sacrificed. The radioactivity concentration in the tumor was the highest among all solid tissues examined. Tumor:liver radioactivity ratios were clearly positive [3.6 +/- 0.3 (S.E.)] in 27 of 31 specimens studied. Microscopy examination of autoradiograms from various tissue sections confirmed the selective accumulation of radioactive AFP in the tumors. In order to assess the specificity of AFP uptake by mammary tumors, 4 mice were given simultaneous injections of 125I-AFP and 131I-ovalbumin, respectively. Compared to AFP, the retention of ovalbumin was very low in all tissues studied, including the tumor. The possibility of tumor localization of radiolabeled AFP by external photoscanning was also explored. Two mice were given injections of 131I-AFP, one mouse received 131I-serum albumin, and one was given 131I-ovalbumin. Images were obtained 6 days after with a standard gamma-camera linked to a computer with data display. About 50% of the total radioactivity retained was concentrated in the tumor areas of mice given injections of iodinated AFP, while it was only 15% in the mouse that received 131I-serum albumin. No tumor image could be detected in the mouse given ovalbumin. These results show that the ability to internalize AFP, common to many tissues during ontogenesis, may also be shared by neoplastic cells which develop later in life. They also prove the preferential uptake of AFP by the tumors compared to normal tissues and the usefulness of AFP as a radiotracer for mammary carcinomas. The latter represents a novel approach to tumor detection.

Trypsin inhibitor from cow colostrum. Isolation, electrophoretic characterization and immunologic properties.

Trypsin inhibitor from cow colostrum has been purified by affinity chromatography of colostral proteins on insolubilized trypsin. The method described compares favourably, in both simplicity and yield, with previous methods developed for the isolation of this inhibitor. Gel electrophoresis followed by characterization of antitrypsin activity allows the demonstration of four molecular forms of bovine colostral trypsin inhibitor in both crude colostral whey and purified preparations of the inhibitor. Immunoelectrophoresis of each of these materials with antisera specific for this inhibitor reveals a single precipitation line of broad anodic mobility. By immunodiffusion tests, the precipitation lines in preparations of purified inhibitor and colostral whey appear immunologically identical. In contrast, absence of crossed reactivity was observed between bovine colostral trypsin inhibitor and trypsin inhibitors of bovine serum. This strongly suggests the high specificity of this inhibitor as a colostral and milk constituent.

Carrier-protein-mediated enhancement of fatty-acid binding and internalization in human T-lymphocytes.

Albumin and alpha-fetoprotein (AFP) are members of a multigene family which also includes vitamin-D-binding protein. Previous work in our laboratory has provided experimental support for the suggestion that the entry of unsaturated fatty acids into growing, normal and neoplastic cells may be regulated by AFP. In the actual study we have examined the role of human serum albumin (HSA) as a carrier protein, when compared to AFP, on the uptake (binding and internalization) of fatty acids by resting and PHA-activated human lymphocytes. Radioiodinated human HSA and tritiated oleic and arachidonic acids were used under different experimental conditions to follow the binding of the protein and fatty acids (FA) to cells. Time-course uptake at 4 degrees C of HSA and of oleic and arachidonic acids bound to HSA (FA/HSA molar ratio = 1) by either resting or activated T-lymphocytes exhibited a steady state of binding. The amount of FA bound was much greater than the corresponding amount of HSA, suggesting that T-lymphocytes bear distinct binding sites for albumin and fatty acids. A saturable process of FA binding was observed at constant unbound FA concentration in the incubation medium when the HSA-to-FA molar ratio was fixed at 1 and the concentrations of both HSA and FA were increased simultaneously. This saturable component of binding reflects an intrinsic regulatory effect of HSA, probably operating throughout the interaction of the protein with specific cell receptors. At varying unbound FA concentrations, binding curves showed two distinct components: a non-linear portion which could indicate the presence of a saturable process operating at low concentrations of unbound, free FA, followed by a second part which increased linearly with the concentration of unbound FA. The amount of FA bound at 4 degrees C and bound and internalized at 37 degrees C by both types of cell was considerably higher in the presence than in the absence of carrier proteins. On the contrary, carrier proteins were without effect on the distribution pattern of internalized oleic or arachidonic acid. Taken together, these observations suggest that: (i) the binding and entry of FA into cells is enhanced by the two carrier-proteins at low concentrations of free, unbound fatty acids in the vicinity of the cell surface, and (ii) fatty-acid uptake seems regulated by a dual-receptor mechanism involving HSA and/or AFP receptors as well as plasma-membrane FA-binding proteins.

Membrane proteins from lymphoblastoid cells showing cross-affinity for alpha-fetoprotein and albumin. Isolation and characterization.

AFP or SA immobilized on nitrocellulose membranes (AFP-NC or SA-NC) were used as affinity matrices to purify cell membrane proteins with affinity for AFP (AFP-BP) and for SA (SA-BP) from membrane-enriched extracts of Raji cells (a B-lymphoma cell line), as well as for normal resting and activated peripheral blood lymphocytes (PBMC). SDS-PAGE and ligand blotting assays showed that AFP-BP and SA-BP isolated from Raji cells are probably identical molecules. They consisted of two sets of polypeptides of 31 kDa and 18 kDa. The glycoprotein nature of isolated 31 kDa and 18 kDa peptides was suggested by positive staining with Schiff's reagent, and amino-acid analysis revealed similar amino-acid composition for the two glycoproteins. In human PHA-activated PBMC, only the 18 kDa polypeptide was identified and isolated as AFP-BP or SA-BP. As in Raji cells, this 18 kDa polypeptide, isolated by affinity for AFP or for SA, appeared to be the same molecule. Contrary to Raji cells and activated PBMC, no proteins with an affinity for AFP or for SA were identified or isolated in resting PBMC. These observations strongly suggest that the isolated 31 kDa and 18 kDa glycoproteins are probably AFP receptors previously demonstrated in several neoplastic and normal cells undergoing growth and/or differentiation; indeed, they were identical to albumin-binding proteins described by others.

Fatty acids bound to alpha-fetoprotein and albumin during rat development.

The time-course levels and composition of the fatty acids bound to rat alpha-fetoprotein (AFP) and albumin from several sources, were determined throughout development, and related to the intake of lipids from milk and the compositional changes in brain and liver fatty acids. The major fatty acids bound to AFP were acids bound to AFP were polyunsaturated and mainly docosahexaenoic acid (22:6(n-3], either from fetal serum (23.1%) or whole fetuses (21.6%), whereas palmitic (34.1%) and oleic (29.9%) acids were the main acids bound to albumin from the same sources. Amniotic fluid AFP contained less fatty acids (0.8 mol/mol protein) than that of fetal serum (1.4 mol/mol protein), and especially noticeable was a reduced amount of 22:6 (9.6%). Both AFP-concanavalin A microforms showed identical fatty acid composition. Levels of 22:6 bound to AFP decreased quickly after birth until a minimum at 8-10 days, increasing moderately thereafter. This minimum is coincident in time with a maximal accumulation of this fatty acid by brain and a loss of 22:6 by liver. Except for colostrum, levels of 22:6 in milk lipids were low and fairly constant, but always greater than those of its precursor, linolenic acid (18:3 (n-3]. These results support a specialized role of AFP in the plasma transport and tissue delivery of polyunsaturated fatty acids, and mainly docosahexaenoic acid.

Fatty acid metabolism in human lymphocytes. II. Activation of fatty acid desaturase-elongase systems during blastic transformation.

The fatty acid desaturation-elongation ability of human T-lymphocytes during blastic transformation was determined both by gas-liquid chromatography and incubation with radiolabeled precursors. Human peripheral blood mononuclear cells (PBMC) were activated with phytohemagglutinin (PHA) and cultured in media supplemented with different fatty acids (18:0, 18:1(n - 9), 18:2(n - 6), 18:3(n - 3) and 20:4(n - 6)) at a final concentration of 30 microM. All the fatty acids added were elongated by activated PBMC and the maximal activity was observed on 20:4(n - 6) (a 25% of conversion to 22:4(n - 6)). Supplementation with stearic acid increased the proportion of oleic (from 21.4% to 23.7%) and eicosaenoic (from 3.1% to 5.7%) acids in cellular lipids, indicating the existence of a delta 9-desaturase activity. Supplementation with linoleic and linoleic acids increased slightly the cell content in their more unsaturated derivatives. Direct measurement of desaturase activities was performed by incubating quiescent and activated PBMC with [1-14C]stearic, [1-14C]linoleic and [1-14C]linolenic acids. Quiescent cells exhibited a very low delta 9-desaturase and no sign of delta 6-desaturase activity. A moderate and progressive activation of delta 9-, delta 6- and delta 5-desaturases was observed during blastic transformation of human PBMC. Up to 8% of 18:0 was converted to monoenes, 4% and 1.5% of 18:2(n - 6) was converted to trienes and tetraenes, respectively, and 14.5% of 18:3(n - 3) was converted to pentaenes. The maximal relative activities were found after 48 h of PHA-stimulation for delta 9-desaturase (around 90 pmol of 18:0 converted per 10(6) cells in the last 24 h) and at 72 h for delta 6- and delta 5-desaturases (around 75 and 140 pmol of 18:2 and 18:3, respectively, converted per 10(7) cells in the last 24 h). Although these activities are not enough to explain all the changes in fatty acid composition of human PBMC during blastic transformation, they may contribute to a more controlled cell phospholipid composition.

Fatty acid metabolism in human lymphocytes. I. Time-course changes in fatty acid composition and membrane fluidity during blastic transformation of peripheral blood lymphocytes.

The time-course changes in fatty acid composition of human T-lymphocytes during blastic transformation were analysed, as well as the variations in membrane fluidity determined by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), using a fluorescence-activated cell sorter. The more important changes observed, in activated relative to quiescent cells, started after 24 h and consisted in an increase in the proportion of oleic (18:1(n - 9)), docosapentaenoic (22:5(n - 3)) and docosahexaenoic (22:6(n - 3)) acids and a decrease in that of linoleic (18:2(n - 6)) and arachidonic (20:4(n - 6)) acids. This represented a relative increase of 26% for 18:1, 56% for 22:5 and 84% for 22:6 in peripheral blood mononuclear cells (PBMC) and 35%, 182% and 94%, respectively, in purified T-lymphocytes, both activated for 72 h. The decrease in n - 6 fatty acids was of 42% for 18:2 and 14% for 20:4 in PBMC and 30% and 19%, respectively, for 72 h. The decrease in n - 6 fatty acids was of 42% for 18:2 and 14% for 20:4 in PBMC and 30% and phosphatidylethanolamine) rather than neutral lipids. The 18:1/18:0 ratio increased greatly in major cell phospholipids. The proportion of 20:4, 22:5 and 22:6 in phosphatidylinositol was not significantly altered after 72 h of activation. The molar ratio cholesterol/phospholipids was reduced in 72-h-activated lymphocytes (0.29) compared to quiescent cells (0.5). On the other hand, the stimulation of human T-lymphocytes caused a significant decrease in the order parameter (S) of DPH, according to the observed changes in lipid composition. After 72 h in culture, the S value for quiescent and stimulated T-lymphocytes was 0.530 and 0.326, respectively. In conclusion, the blastic transformation of human T-lymphocytes is associated with changes in lipid composition which modify the physical properties of their membranes. These modifications could modulate, in turn, the activity of membrane proteins implicated in the process of blastic transformation.

Activation of an alpha-fetoprotein/receptor pathway in human normal and malignant peripheral blood mononuclear cells.

Alpha-fetoprotein (AFP) is mainly synthesized by the fetal liver and the yolk sac with minor contributions of several non-hepatic fetal tissues, variable according to the species considered. Most fetal cells, whatever their origin, possess the ability to bind and to endocytose the protein. This property, which is considered to be lost in differentiated cells of the adult, may be resumed in tumoral cells and is due to the expression of specific AFP receptors at the cell surface. Cytochemical and immunological approaches, combined with in situ hybridization, were used to investigate the specific uptake and synthesis of human AFP in several classes of peripheral blood mononuclear cells (PBMC) and in several malignant cell lines of hematopoietic origin. With the exception of quiescent T lymphocytes, all cells investigated specifically bound AFP. Both normal and malignant blood mononuclear cells expressed mRNA transcripts of AFP which were translated into the protein during a well established period of cellular growth. These results suggest that an AFP/receptor autocrine system might operate in normal and malignant blood mononuclear cells. Its physiological role is discussed in relation to recent work from our laboratory--providing experimental evidence that AFP, throughout its interaction with specific cell receptors, regulates and facilitates the entry of fatty acids into living cells undergoing growth and differentiation.

Increased cytotoxicity of polyunsaturated fatty acids on human tumoral B and T-cell lines compared with normal lymphocytes.

Epidemiological and experimental data suggest that fatty acids may modulate the growth of tumor cells. We have analyzed the effect of different types of fatty acids, bound to serum proteins in physiological conditions, on the lipid composition and growth of human neoplastic B and T-cell lines and compared their effect on normal lymphocyte proliferation. Fatty acids with 0 to 2 unsaturations (stearic, oleic, and linoleic), at concentrations up to 50 or 100 microM did not significantly affect the proliferation of leukemic cells. However, long-chain polyunsaturated fatty acids (PUFA), and mainly docosahexaenoic (22:6, n-3), were cytotoxic at concentrations greater than or equal to 20 microM after 48-72 h in culture. Simultaneous supplementation with vitamin E restored normal cell growth. The amount of end-products of lipid peroxidation in cells correlated with the observed toxicity but the amount of superoxides did not. Fatty acid supplementations increased cell triacylglycerol content but did not affect the degree of unsaturation of phospholipids, cholesterol/phospholipids molar ratio, or membrane fluidity. Glutathione-S-transferase activity was low in Raji and CEM cells, moderate in lymphocytes and high in Ramos cells and did not increase with supplementations. The proliferation of normal lymphocytes, which produced lower amounts of end-products of lipid perodixation, was not inhibited, but in some cases stimulated, by PUFA (with the exception of 30 microM 22:6). The extension of these results to situations in vivo could lead to use of PUFA for delaying leukemia progression or in adjuvant chemotherapy.