Metastatic colonization potential of primary tumour cells in mice.

A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo

Correlation of collagenase secretion with metastatic-colonization potential in naturally occurring murine mammary tumours.

We report evidence for the secretion of a true mammalian collagenase active against Type 1 collagen, by naturally-occurring mammary tumours of the mouse and show that tumours capable of heavily colonizing the lungs secrete significantly more of this enzyme than those with low pulmonary-colonization potential, or non-neoplastic proliferating (e.g. lactating) mammary tissue. Plasminogen activator is secreted in greater quantity by tumours than by normal tissues, but there is no significant difference in the amount produced by tumours with high or low pulmonary-colonization potential. These findings correlate well with our earlier morphological observations of marked connective tissue destruction in the vicinity of invading tumours and metastatic deposits, and indicate that protease release is implicated in the mechanism of tumour spread

Speculations on the application of foliar 13C discrimination to reveal groundwater dependency of vegetation and provide estimates of root depth and rates of groundwater use

© Author(s) 2018. Groundwater-dependent vegetation is globally distributed, having important ecological, social, and economic value. Along with the groundwater resources upon which it depends, this vegetation is under increasing threat through excessive rates of groundwater extraction. In this study we examined one shallow-rooted and two deep-rooted tree species at multiple sites along a naturally occurring gradient in depth-to-groundwater. We measured (i) stable isotope ratios of leaves (δ 13C), xylem, and groundwater (δ 2H and δ 18O); and (ii) leaf-vein density. We established that foliar discrimination of 13C (Δ13C) is a reliable indicator of groundwater use by vegetation and can also be used to estimate rooting depth. Through comparison with a continental-scale assessment of foliar Δ13C, we also estimated the upper limits to annual rates of groundwater use. We conclude that maximum rooting depth for both deep-rooted species ranged between 9.4 and 11.2 m and that annual rates of groundwater use ranged from ca. 1400 to 1700 mm for Eucalyptus camaldulensis and from 600 to 900 mm for Corymbia opaca. Several predictions about hydraulic and leaf traits arising from the conclusion that these two species made extensive use of groundwater were supported by additional independent studies of these species in central Australia

Disk wakes in nonlinear stratification

Nonlinearity of density stratification modulates buoyancy effects. We report results from a body-inclusive large eddy simulation (LES) of a wake in nonlinear stratification, specifically for a circular disk at diameter-based Reynolds number ($Re$) of $5000$. Five density profiles are considered; the benchmark has linear stratification and the other four have hyperbolic tangent profiles to model a pycnocline. The disk moves inside the central core of the pycnocline in two of those four cases and, in the other two cases with {a} shifted density profile, the disk moves partially/completely outside the pycnocline. The maximum buoyancy frequency ($N_{max}$) for all the profiles is the same. The first part of the study investigates the centered cases. Nonuniform stratification results in increasing wake turbulence relative to the benchmark owing to reduced suppression of turbulence production as well as the wave trapping in the pycnocline. Steady lee waves are also quantified to understand limitations of linear theory. The second part pays attention to the effect of a relative shift between the pycnocline and the disk. The wake defect velocity decays faster in the cases with a shift. The effect of disk location on the Kelvin wake waves (a family of steady waves within the pycnocline) and its modal form is obtained and explained by solving the Taylor-Goldstein equation. The family of unsteady internal gravity waves that are generated by the wake is also studied and the effect of disk shift is quantified.Comment: 23 pages, 15 plots, submitted to Journal of Fluid Mechanic

Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success

Mammalian spermatozoa undergo a strong selection process along the female tract to guarantee fertilization by good quality cells, but risks of fertilization with DNA-damaged spermatozoa have been reported. In contrast, most external fertilizers such as fish seem to have weaker selection procedures. This fact, together with their high prolificacy and external embryo development, indicates that fish could be useful for the study of the effects of sperm DNA damage on embryo development. We cryopreserved sperm from rainbow trout using egg yolk and low-density lipoprotein as additives to promote different rates of DNA damage. DNA fragmentation and oxidization were analyzed using comet assay with and without digestion with restriction enzymes, and fertilization trials were performed. Some embryo batches were treated with 3-aminobenzamide (3AB) to inhibit DNA repair by the poly (ADP-ribose) polymerase, which is an enzyme of the base excision repair pathway. Results showed that all the spermatozoa cryopreserved with egg yolk carried more than 10% fragmented DNA, maintaining fertilization rates of 61.1+/-2.3 but a high rate of abortions, especially during gastrulation, and only 14.5+/-4.4 hatching success. Furthermore, after 3AB treatment, hatching dropped to 3.2+/-2.2, showing that at least 10% DNA fragmentation was repaired. We conclude that trout sperm maintains its ability to fertilize in spite of having DNA damage, but that embryo survival is affected. Damage is partially repaired by the oocyte during the first cleavage. Important advantages of using rainbow trout for the study of processes related to DNA damage and repair during development have been reported. Reproduction (2010) 139 989-997Junta de Castilla y Leon (Spain) [LE007A06]; University of Leoninfo:eu-repo/semantics/publishedVersio

HIF1α is required for NK cell metabolic adaptation during virus infection

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF1α-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response