Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery

Background. Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. Methods. Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow–derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γ_c^null mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. Results. MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. Discussion. These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.     

WRITING AMISH CULTURE INTO GENES: BIOLOGICAL REDUCTIONISM IN A STUDY OF MANIC DEPRESSION

Critical realism is used to explore the problem of reductionism in a classic (the Amish Study) andwidely-cited study of manic depression. Along withrelated ideas drawn from the works of R.C.Lewontin, Arthur Kleinman, and Byron Good, it isshown that natural and social scientists deployatomistic and holistic reductionism; this, in turn,leads to the construction of artificially closedsystems' through the control of variables orexogenous forces. The psychiatric genetic studies ofthe Amish were predicated on the assumption thatAmish society is homogeneous and unchanging and,therefore, closed. We conclude by arguing thatinteractions between behaviors and genes, where theyexist, take place only within open systems, characterizedby multiple mechanisms – social andbiological – that together co-determineany event. To move forward, it is argued, behavior and generesearch requires recognition and resolution of thephilosophical conundrums that accompany reductionism.     

Magnitude and variations of groundwater seepage along a Florida marine shoreline

Direct groundwater inputs are receiving increasingattention as a potential source of nutrients and otherdissolved constituents to the coastal ocean. Seepageinto St. George Sound, Florida was measuredextensively from 1992 to 1994 using seepage meters. Spatial and temporal variations were documented alonga 7-km stretch of coastline and up to 1 km from shore. Measurements were made at 3 transects perpendicular toshore and 1 transect parallel to shore. The generalresults indicated that seepage decreased with distancefrom shore (2 of 3 transects), and substantialtemporal and spatial variability was observed inseepage flow from nearshore sediments. In addition,trends in mean monthly integrated seepage rates weresimilar to precipitation patterns measured at a nearbycoastal weather station. Based on these measurements, weestimate that the magnitude of groundwater seepage intothe study area is substantial, representing from 0.23 to4.4 m3 sec-1of flow through the sediments, approximately equivalentto a first magnitude spring. Although it is unknown howrepresentative this region is with respect to globalgroundwater discharge, it demonstrates thatgroundwater flow can be as important as riverine andspring discharge in some cases. Our subsurfacedischarge rates suggest groundwater is an importanthydrologic source term for this region and may beimportant to the coastal biogeochemistry as well.     

Sex Determination and Sex Ratios in Crocodylus palustris

Incubation temperature determines sex in the mugger crocodile,Crocodylus palustris. Exclusively females are produced at constanttemperatures of 28.0°C through 31°C. At 32.5°C,only males are produced. Both sexes are produced in varyingproportions at 31.5, 32.0, and 33.0°C. Embryo survival isnot affected within this range, but developmental rate and totalincubation time are strongly temperature dependent. In naturalnests laid in breeding enclosures, cool incubation temperaturesproduced only females whereas males were produced only in warmnests. Clutch sex ratios were female or male biased. Yearlysex ratios (=percent male) varied from 0.05 to 0.58; overallsex ratio during six nesting seasons was 0.24 (1 male: 3 females).Sex ratio and incubation time vary with nest location and temperaturein a manner consistent with the constant temperature results.Incubation time decreases with increasing incubation temperature,and is an accurate predictor of sex ratio in the field and laboratory. To date, temperature-dependent sex determination (TSD) has beenreported in five species of Crocodylus and in three speciesof Alligatorinae; but the TSD patterns in these groups differ.The TSD pattern of C. palustris is similar to that of C. porosus.Nesting in C. palustris is synchronized with the seasonal availabilityof thermal regimes suitable for incubation. Resultant sex ratiosare a consequence of when and where eggs are laid. Early nestsare located in warm, sunny sites; in contrast, late season nestsare located in the shade. An egg transplant experiment demonstratedthat sex ratios could be altered by simple manipulations ofnest temperatures in the field. The adaptive significance ofTSD in crocodilians may relate to the influence of incubationtemperature on various hatchling attributes, particularly growth.     

A Cell Wall-degrading {alpha}-1,3-arabinofuranosidase Produced by the Potato Dry Rot Pathogen Fusarium caeruleum (Lib.) Sacc.

Fusarium caeruleum produced an arabanase which showed maximalactivity at pH 3·5 and which liberated arabinose andits oligomers from -l,3-arabinofuranan and isolated potato tuberparenchyma cell walls. This enzyme was most active in dry rotlesions produced in susceptible potato tubers by a fast-growingisolate of F. caeruleum. This arabanase is not of primary importancein causing tissue maceration, protoplast death or electrolyteloss but it may play a secondary role in these processes.     

Some Biochemical Effects of Glyphosate on Plant Meristems

Glyphosate promoted the activity of phenylalanine ammonia lyase(PAL) in both single node rhizome buds of Agropyron repens androot tips of wheat seedlings, in the latter case correlatinginversely with decline in respiratory activity. Differentialrates of ¹⁴C-amino acid incorporation suggest that glyphosatedepleted the phenylalanine protein precursor pool with resultantinhibition of protein synthesis, as evidenced by a rapid declinein the level of ‘soluble’ protein. Promotion ofPAL is assumed to occur by derepression through decline in end-productlevels. Activities of shikimate: NADP oxidoreductase (SORase),chorismate mutase, and polyphenol oxidase (PPO) were also elevated,but to lesser extents than for PAL.     

Growth Response to Hormones by a New Rat Ovary Cell Line

SEVERAL endocrine cell lines established in recent years show a functional response to hormones in vitro¹ but, except for one mammary cell line², none of them exhibits the normal hormone requirement for growth in vivo. We have now isolated a rat ovarian cell line whose growth in vitro is markedly stimulated by bovine luteinizing hormone (LH-NIH-B7), a pituitary gonadotrophin and by dexamethasone, a synthetic glucocorticoid. This cell line provides the first permanent in vitro system for studying the growth stimulation of gonadal cells by hormones.     

Powdery mildew of tobacco (Erysiphe cichoracearum DC.)

In water culture experiments, tobacco plants of Hicks variety were supplied with factorial combinations of high and low concentrations of nitrogen, phosphorus and potassium. Incidence of powdery mildew and growth and chemical composition of infected and healthy plants were compared.
There was more disease when all elements were supplied at the higher of two concentrations, but the increase in infection was less than the increase in growth. Plants grown in media containing a low ratio of potassium to nitrogen produced the least susceptible leaves; their disease indices were up to 30 times less than those of plants that received the full nutrient treatment. Potassium-deficient leaves had thinner cell walls, larger water content, smaller sugar and potassium contents, and greater amino nitrogen and magnesium contents, compared with those of plants grown in any of the other media. The possible relation between these characteristics and susceptibility to Erysiphe cichoracearum DC. are discussed.