Consequences of cell-to-cell P-glycoprotein transfer on acquired multidrug resistance in breast cancer: a cell population dynamics model

Cancer is a proliferation disease affecting a genetically unstable cell population, in which molecular alterations can be somatically inherited by genetic, epigenetic or extragenetic transmission processes, leading to a cooperation of neoplastic cells within tumoral tissue. The efflux protein P-glycoprotein (P gp) is overexpressed in many cancer cells and has known capacity to confer multidrug resistance to cytotoxic therapies. Recently, cell-to-cell P-gp transfers have been shown. Herein, we combine experimental evidence and a mathematical model to examine the consequences of an intercellular P-gp trafficking in the extragenetic transfer of multidrug resistance from resistant to sensitive cell subpopulations. We report cell-to-cell transfers of functional P-gp in co-cultures of a P-gp overexpressing human breast cancer MCF-7 cell variant, selected for its resistance towards doxorubicin, with the parental sensitive cell line. We found that P-gp as well as efflux activity distribution are progressively reorganized over time in co-cultures analyzed by flow cytometry. A mathematical model based on a Boltzmann type integro-partial differential equation structured by a continuum variable corresponding to P-gp activity describes the cell populations in co-culture. The mathematical model elucidates the population elements in the experimental data, specifically, the initial proportions, the proliferative growth rates, and the transfer rates of P-gp in the sensitive and resistant subpopulations. We confirmed cell-to-cell transfer of functional P-gp. The transfer process depends on the gradient of P-gp expression in the donor-recipient cell interactions, as they evolve over time. Extragenetically acquired drug resistance is an additional aptitude of neoplastic cells which has implications in the diagnostic value of P-gp expression and in the design of chemotherapy regimensComment: 13 pages, 8 figures, 1 tabl

Helping behaviour during cooperative learning and learning gains

Is helping behaviour (i.e., solicited help and peer tutoring) during cooperative learning (CL) related to subsequent learning gains? And can teachers influence pupils’ helping behaviour? One hundred one 5th grade pupils from multiethnic schools, 10-12 years old, participated in the study. Forty two pupils (31 immigrant) worked in an experimental condition, characterized by the stimulation of solicited high quality help and 59 (24 immigrant) worked in a control condition. It was found that learning gains were predicted positively by pupils’ unsolicited helping behaviour (i.e., peer tutoring) and negatively by solicited help. Furthermore, teachers were able to affect pupils’ low quality solicited help only. Lastly, immigrant pupils used less helping behaviour than local pupils, irrespective of CL setting

The Gaseous Extent of Galaxies and the Origin of \lya Absorption Systems. III. Hubble Space Telescope Imaging of \lya-Absorbing Galaxies at z < 1

We present initial results of a program to obtain and analyze HST WFPC2 images of galaxies identified in an imaging and spectroscopic survey of faint galaxies in fields of HST spectroscopic target QSOs. We measure properties of 87 galaxies, of which 33 are associated with corresponding \lya absorption systems and 24 do not produce corresponding \lya absorption lines to within sensitive upper limits. Considering only galaxy and absorber pairs that are likely to be physically associated and excluding galaxy and absorber pairs within 3000 \kms of the background QSOs leaves 26 galaxy and absorber pairs and seven galaxies that do not produce corresponding \lya absorption lines to within sensitive upper limits. Redshifts of the galaxy and absorber pairs range from 0.0750 to 0.8912 with a median of 0.3718, and impact parameter separations of the galaxy and absorber pairs range from 12.4 to $157.4 h^{-1}$ kpc with a median of $62.4 h^{-1}$ kpc. The primary result of the analysis is that the amount of gas encountered along the line of sight depends on the galaxy impact parameter and B-band luminosity but does not depend strongly on the galaxy average surface brightness, disk-to-bulge ratio, or redshift. This result confirms and improves upon the anti-correlation between \lya absorption equivalent width and galaxy impact parameter found previously by Lanzetta et al. (1995). There is no evidence that galaxy interactions play an important role in distributing tenuous gas around galaxies in most cases. Galaxies might account for all \lya absorption systems with $W > 0.3$ \AA, but this depends on the unknown luminosity function and gaseous cross sections of low-luminosity galaxies as well as on the uncertainties of the observed number density of \lya absorption systems.Comment: Minor changes. Figure 1 stays intact and is available at ftp://ftp.ess.sunysb.edu/pub/lanzetta/wfpc

Respiration and Heart Rate at the Surface between Dives in Northern Elephant Seals

All underwater activities of diving mammals are constrained by the need for surface gas exchange. Our aim was to measure respiratory rate (fb) and heart rate (fh) at the surface between dives in free-ranging northern elephant seals Mirounga angustirostris. We recorded fb and fh acoustically in six translocated juveniles, 1.8-2. 4 years old, and three migrating adult males from the rookery at Ano Nuevo, California, USA. To each seal, we attached a diving instrument to record the diving pattern, a satellite tag to track movements and location, a digital audio tape recorder or acoustic datalogger with an external hydrophone to record the sounds of respiration and fh at the surface, and a VHF transmitter to facilitate recovery. During surface intervals averaging 2.2+/−0.4 min, adult males breathed a mean of 32.7+/−5.4 times at a rate of 15. 3+/−1.8 breaths min(−)(1) (means +/− s.d., N=57). Mean fh at the surface was 84+/−3 beats min(−)(1). The fb of juveniles was 26 % faster than that of adult males, averaging 19.2+/−2.2 breaths min(−)(1) for a mean total of 41.2+/−5.0 breaths during surface intervals lasting 2.6+/−0.31 min. Mean fh at the surface was 106+/−3 beats min(−)(1). fb and fh did not change significantly over the course of surface intervals. Surface fb and fh were not clearly associated with levels of exertion, such as rapid horizontal transit or apparent foraging, or with measures of immediately previous or subsequent diving performance, such as diving duration, diving depth or swimming speed. Together, surface respiration rate and the duration of the preceding dive were significant predictors of surface interval duration. This implies that elephant seals minimize surface time spent loading oxygen depending on rates of oxygen uptake and previous depletion of stores

A search for molecules in damped Lyman-alpha absorbers occulting millimetre-loud quasars

We have used the SEST 15-metre and Onsala 20-metre telescopes to perform deep (r.m.s. >~ 30 mJy) integrations of various molecular rotational transitions towards damped Lyman-alpha absorption systems (DLAs) known to occult millimetre-loud quasars. We have observed 6 new systems and improved the existing limits for 11 transitions. These limits may be approaching the sensitivities required to detect new systems and we present a small number of candidate systems which we believe warrant further observation.Comment: 7 pages, 1 PS figure, 4 tables. Accepted by A&

Computer-supported collaborative inquiry learning and classroom scripts

This study examined the influence of classroom-script structure (high vs. low) during computer-supported collaborative inquiry learning on help-seeking processes and learning gains in 54 student pairs in secondary science education. Screen- and audio-capturing videos were analysed according to a model of the help-seeking process. Results show that the structure of the classroom script substantially affects patterns of student help seeking and learning gain in the classroom. Overall, students in the high-structured classroom-script condition sought less help but learnt more than those in the low-structured classroom-script condition

A catalogue of damped Lyman alpha absorption systems and radio flux densities of the background quasars

We present a catalogue of the 322 damped Lyman alpha absorbers taken from the literature. All damped Lyman alpha absorbers are included, with no selection on redshift or quasar magnitude. Of these, 123 are candidates and await confirmation using high resolution spectroscopy. For all 322 objects we catalogue the radio properties of the background quasars, where known. Around 60 quasars have radio flux densities above 0.1 Jy and approximately half of these have optical magnitudes brighter than V = 18. This compilation should prove useful in several areas of extragalactic/cosmological research.Comment: 26 Pages, 12 PS tables, 1 embedded table. Accepted by PASA. Continuously updated online catalogue available at http://www.phys.unsw.edu.au/~sjc/dl

Osmoregulation of the Australian freshwater crocodile, Crocodylus johnstoni, in fresh and saline waters

An unusual saltwater population of the "freshwater" crocodilian, Crocodylus johnstoni, was studied in the estuary of the Limmen Bight River in Australia's Northern Territory and compared with populations in permanently freshwater habitats. Crocodiles in the river were found across a large salinity gradient, from fresh water to a salinity of 24 mg.ml-1, more than twice the body fluid concentration. Plasma osmolarity, concentrations of plasma Na+, Cl-, and K+, and exchangeable Na+ pools were all remarkably constant across the salinity spectrum and were not substantially higher or more variable than those in crocodiles from permanently freshwater habitats. Body fluid volumes did not vary; condition factor and hydration status of crocodiles were not correlated with salinity and were not different from those of crocodiles from permanently fresh water. C. johnstoni clearly has considerable powers of osmoregulation in waters of low to medium salinity. Whether this osmoregulatory competence, extends to continuously hyperosmotic environments is not known, but distributional data suggest that C. johnstoni in hyperosmotic conditions may require periodic access to hypoosmotic water. The study demonstrates a physiological capacity for colonisation of at least some estuarine waters by this normally stenohaline freshwater crocodilian