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Tumor-infiltrating immune cells (TIICs) have become an important source of markers for predicting the clinical outcomes of cancer patients. However, measurements of cellular heterogeneity vary due to the frequently updated reference genomes and gene annotations. In this study, we systematically collected and evaluated the infiltration pattern of 65 immune cells. We constructed the Immune Cell Pair (ICP) score based on the cell pair algorithm in 3,715 samples and across 12 independent cancer types, among which, the ICP score from six cancer types was further validated in 2,228 GEO samples. An extensive tumorigenic and immunogenomic analysis was subsequently conducted. As a result, the ICP score showed a robust reliability and efficacy in predicting the survival of patients with gliomas, in pan-cancer samples, and six independent cancer types. Notably, the ICP score was correlated with the genomic alteration features in gliomas. Moreover, the ICP score exhibited a remarkable association with multiple immunomodulators that could potentially mediate immune escape. Finally, the ICP score predicted immunotherapeutic responses with a high sensitivity, allowing a useful tool for predicting the overall survival and guiding immunotherapy for cancer patients.

Engineered nanomaterials (ENMs) are increasingly used in consumer products due to their unique physicochemical properties, but the specific hazards they pose to the structural and functional integrity of endothelial barriers remain elusive. When assessing the effects of ENMs on vascular barrier function, endothelial cell monolayers are commonly used as in vitro models. Monolayer models, however, do not offer a granular understanding of how the structure–function relationships between endothelial cells and tissues are disrupted due to ENM exposure. To address this issue, we developed a micropatterned endothelial cell pair model to quantitatively evaluate the effects of 10 ENMs (8 metal/metal oxides and 2 organic ENMs) on multiple cellular parameters and determine how these parameters correlate to changes in vascular barrier function. This minimalistic approach showed concerted changes in endothelial cell morphology, intercellular junction formation, and cytoskeletal organization due to ENM exposure, which were then quantified and compared to unexposed pairs using a “similarity scoring” method. Using the cell pair model, this study revealed dose-dependent changes in actin organization and adherens junction formation following exposure to representative ENMs (Ag, TiO2 and cellulose nanocrystals), which exhibited trends that correlate with changes in tissue permeability measured using an endothelial monolayer assay. Together, these results demonstrate that we can quantitatively evaluate changes in endothelial architecture emergent from nucleo-cytoskeletal network remodeling using micropatterned cell pairs. The endothelial pair model therefore presents potential applicability as a standardized assay for systematically screening ENMs and other test agents for their cellular-level structural effects on vascular barriers.

Pairs of corresponding cytotoxic drug sensitive and resistant cell lines are powerful tools to develop treatment strategies. Developing cytotoxic drug resistant cell lines is a well-established method in cancer research. In more than fifty years of sulfur mustard (SM) resistant research such a cell pair has never been produced. Hereinafter we describe the first successful approach to develop a SM resistant keratinocyte cell line. Starting with the SM sensitive keratinocyte cell line HaCaT we used a strategy of continuous exposure with gradually increased concentrations. Cells were cultured in total for more than 40 months starting with an initial concentration of 0.07 μM SM twice a week up to a final concentration of 7.2 μM SM. The achieved cell line HaCaT/SM had an LC50 resistance increase of 4.7-fold and an LC90 increase of 8.2-fold. Hereinafter we demonstrate the production of the first sulfur mustard (SM) resistant cell line. The new achieved cell line called HaCaT/SM is able to tolerate a continuous exposure of an SM concentration, which is associated with an inhibitory effect of 93% within the original HaCaT cells, which were used as starting point.

Microbial desalination cells (MDCs) are being developed as a low-energy desalination technology. Most MDCs in the previous studies contained one cell pair (CP, a pair of cation and anion exchange membranes) and very few had multiple CPs (

Mathematical modeling of the electric activity of pairs of true (central) and latent (peripheral) sinoatrial pacemaker cells coupled through gap junctions revealed that attenuation of coupling conductance increases the beat phase shift; below a critical conductance there is no synchronization. The phase difference also depends on the type of interacting cells, being maximal for a “central”-“peripheral” cell pair.

Early after depolarizations (EADs) induce triggered activity in Purkinje (P) fibers that can initiate ventricular (V) arrhythmias. However, it is unclear whether PV interactions suppress or induce EAD formation at the discrete Purkinje-ventricular junctions (PVJs). Using a PV cell pair approach based on the Tan and Joyner coupling circuit, we determined the extent to which EADs initiated in P myocytes were suppressed by coupling to V cells. Our results suggest that PV interactions tend to suppress EAD formation at the PVJ except under pathological conditions (e.g., infarction) in which the V mass is severely reduced.

In Hydra vulgaris at the level of dissociated single cells endodermal cells adhere to each other more readily than to ectodermal cells at the initial adhesion. The time required for adhesion to occur between two adjacent cells is shorter for both endodermal and ectodermal homotypic cell adhesions once the initial adhesion of the first pair of cells has been established. It is confirmed that contact of an aggregated pair with additional homotypic cells facilitates the occurrence of homotypic adhesions; heterotypic adhesions are discouraged. This suggests that adhesion of homotypic cells contributes to an increased readiness for subsequent homotypic cells to adhere.

The idea that the junctional conductance might be modulated was verified in the 1970’s (1, 2). It is known since Engelmann (3) that "the death of a cardiac cell does not result in the death of the apposing cells" ("der Tod schreitet nicht von Zelle auf Zelle for"). This important conclusion was based on the observation that the injury potential induced by lesion of cardiac muscle soon vanishes (healing-over) — a phenomenon that was not related to the depolarization of the surface cell membrane because a new lesion applied near the previous one re-established the injury potential (8).

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the transfer of action potentials from cell to cell and to assess the electrical properties of cardiac gap junctions. An attempt was made to correlate the impulse transfer with the conductance of the gap junction membrane and the number of operational gap junction channels.

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the resistance of the nexal membrane, rn. Each cell of a cell pair was connected to a voltage-clamp circuit to obtain simultaneous whole-cell, tight-seal recordings. With this technique, rn was determined under experimental conditions aimed at primarily modifying [Ca2+]i. Moderate changes in [Ca2+]i (produced by trains of depolarizing voltage-clamp pulses activating the slow inward current, or alterations in [Ca2+]o from 0.5 to 10 mM), resulted in no change in rn for normally coupled cell pairs (rn = 5 M omega), but small and reversible changes in slightly uncoupled preparations (rn greater than or equal to 50 M omega). Large increases in rn developed with substantial elevations in [Ca2+]i (secondary to [Na+]o-withdrawal, exposure to strophanthidin in conjunction with isi, or Ca2+-dialysis). Increases in rn brought about via elevation in [Ca2+]i always were accompanied by cell shortening consistent with a sustained contracture. The current-voltage relationship of the nexal membrane was ohmic regardless of whether rn was low (control) or elevated (after increasing [Ca2+]i).

In the preceding paper (H. Keshishian and D. Bentley, 1983a, Dev. Biol. 96, 89–102) the events leading to the morphogenesis of nerve 5B1 in the grasshopper embryonic metathoracic leg were presented. Here the role of later differentiating peripheral neurons in establishing the other major nerves of the leg is examined. In addition to the (tibial 1) (Ti1) pioneer neuron cell pairs that establish nerve 5B1 in the tibia, femur, and coxa-trochanter, six later differentiating cells and/or cell pairs were identified and examined with respect to their role in peripheral nerve ontogeny. Nerve path pioneering was observed in two cell pairs of the distal tarsus (Ta1 and Ta2), by neurons of the posterior proximal tibia (Ti2), the posterior midfemur (neurons F3 and F4), and by an additional cell pair in the anterior coxal-trochanteral region of the limb bud (cell pair, CT2). In addition, efferent projections onto limb bud epithelia played an important role in establishing nerve branches. In two nerves the axonal trajectory from the periphery to the CNS is established by afferent and efferent pathfinding axons meeting halfway and overgrowing each other's established projections. For each nerve branch examined it was found that axons projected initially to the cell bodies of previously arising neurons along the trajectory. The location along the limb bud ectoderm where neurons arise, and hence their ultimate cell body positions, played an important role in organizing the fasciculation of follower axons and establishing branch points.

1. 1. The Q 10 temperature coefficients of several electrophysiological parameters of Retzius cells were examined by microelectrode recording in segmental ganglia from the horse leech, Haemopis marmorata (Say), at temperatures between 5 and 25°C. 2. 2. The action potential characteristics of Retzius cells have temperature coefficients which are suggestive of processes mediated by chemical reactions: duration, 3.1; rate of rise, 3.8; rate of decline, 2.3; and amplitude of the after-potential, 2.5. 3. 3. The membrane and electrotonic characteristics have coefficients which are suggestive of physical or diffusional processes: membrane resistance varies with temperature ( Q 10 , 1.55) while the attenuation factor ( Q 10 , 1.25) and resistance of the electrotonic junction ( Q 10 , 1.05) vary inversely with temperature. 4. 4. An analysis of the impulses in either Retzius cell and of the electrotonic depolarization of the homologous neuron indicates that the cell pair is functionally asymmetric and their loci of impulse initiation are more distant from their neurosomata than their electrotonic junction.

An experimental investigation is presented of the electrodialysis of acetate or butyrate with chloride, in a continuous-flow unit with a membrane area of 50 cm.2 separating a test cell pair. The effects on the transport of the individual anions are established of several independent variables, including membrane type, organic specie, mole fraction of organic in the feed, and current density. Polarization is evident at a current density of 8 ma./cm.2 A semi-empirical equation is developed and, utilizing the experimental data, the equation yields the cell constant and the ratio of the diffusivity of each anion to the film thickness. The equation, relating the purification factor (ratio of feed and effluent concentrations) and the key independent variables, may be utilized to correlate and extend a rather limited number of data points for other chemical systems in other continuous-flow units. For both membranes, both organic species, and over a wide range of feed mole fractions and current densities, the mole fraction of an anion transported across the membrane can be related to the feed mole fraction by a simple power relation, indicating a convenient way of expressing membrane selectivity. On presente les resultats d'nne etude experimentale de l'electrodialyse d'un acetate ou butyrate avec un chlorure dans un dispositif a debit continu dans lequel une surface de membrane de 50 cm3 separe deux piles d'essai. On a determine les effets qu'exercent sur le transport d'anions individuels plusieurs variables independantes telles que le genre de membrane, la nature du produit organique et sa fraction moleculaire dans l'alimentation, et la densite du courant. La polarisation apparait nettement lorsque la densite du courant est 8 ma./cm2. On a mis au point une equation semi-empirique et, en utilisant les resultats experimentaux, cette equation fournit des precisions sur la constante des piles et le rapport de diffusivite entre chaque anion et l'epaisseur de la pellicule. On peut utiliser l'equation, qui etablit une correlation entre le facteur de purification (rapport entre l'alimentation et les concentrations de l'effluent) et les principales variables independantes, pour etablir des correlations et fournir un nombre plutot limite de points de repere dans le cas d'autres systemes chimiques dans des dispositifs a debit continu. Pour les deux membranes et genres de produit organique et dans le cas d'une gamme considerable de fractions moleculaires d'alimentation et de densites de courant, on peut etablir une correlation entre la fraction moleculaire d'une anion transporte par la membrane et la fraction moleculaire d'alimentation. grâce a une simple relation d'energie qui indique un moyen convenable d'exprimer la selectivite des membranes.

Hoffman, Heiner (New York University, New York, N.Y.), and Michael E. Frank . Time-lapse photomicrography of lashing, flexing, and snapping movements in Escherichia coli and Corynebacterium microcultures. J. Bacteriol. 90: 789–795. 1965.—A series of four consecutive photomicrographs of snapping by an Escherichia coli cell pair indicates that this maneuver consists initially of lashing movements of one cell unattached to the underlying surface and consequent flexion of the second cell, which is strongly attached to the underlying surface at its distal end. This is followed by a final unidirectional movement of the unattached cell which carries the attached cell with it. Lashing movements were also observed in microcultures of fusobacteria and a Corynebacterium , and photomicrographs were obtained of the latter. The observations cannot be interpreted to support the conventional hypothesis that snapping is a response to partial rupture of the capsule during cell division. A new hypothesis is suggested which is based upon motile intracellular granules that have been observed to break out of E. coli , corynebacteria, and fusobacteria cells, typically from the cell ends. Photomicrographs of the minute granules were obtained for both E. coli and the Corynebacterium .

MANY types of cells have membrane junctions so organized as to allow the passage of molecules from the interior of one cell to another with little loss to the outside1–6. At least in some cases, a large part if not all of the surface membrane seems to be capable of this organization, for if the junction is broken and the cell pair rejoined at some other place, the system can become fully communicating within seconds or minutes7,8. Evidently the membranes must undergo profound structural changes in such a way that previously impermeable surface regions become highly permeable. This implies a close spatial matching of the joining regions on the two membranes. The question arises whether such matching can be effected between membranes that differ from each other. To find something out about this problem, we have paired cultured cells from different organs and species, measuring the communication between cells electrically.

Hoffman and Frank1 have recently described what they call “snapping movements” during division of Escherichia coli. The evidence presented consists of “a time-lapse series of four photomicrographs … inadvertently obtained from a microculture of E. coli during the snapping of a cell pair”. The whole snapping sequence appears to have taken about one minute seventeen seconds, and is described as follows: “The sister cell on the right side of the photomicrograph (Fig. 2) exhibits a blurring interpreted as owing to a vibrating motion of the cell with its proximal end acting as a moving pivot. The proximal end of the second cell is slightly blurred from movement as well, indicating cell flexion with the midpoint of the cells as the pivot. The right-hand cell at one point during these movements seems to have paused in the long axis of its sister for an appreciable time, since its photographic image in this position is more fully developed than in any other. Fig. 3, photographed at one minute nine seconds from zero-time, indicates continued back and forth motion which was followed by a sudden large hinge movement of the cell in a counterclockwise direction, and a consequent decrease in the obtuseness of the angle formed with its sister … ”.