RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis

Tumor suppression that is mediated by oncogene-induced senescence (OIS) is considered to function as a safeguard during development of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that regulate OIS in PDAC are poorly understood. Here, we have determined that nuclear RelA reinforces OIS to inhibit carcinogenesis in the Kras mouse model of PDAC. Inactivation of RelA accelerated pancreatic lesion formation in Kras mice by abrogating the senescence-associated secretory phenotype (SASP) gene transcription signature. Using genetic and pharmacological tools, we determined that RelA activation promotes OIS via elevation of the SASP factor CXCL1 (also known as KC), which activates CXCR2, during pancreatic carcinogenesis. In Kras mice, pancreas-specific inactivation of CXCR2 prevented OIS and was correlated with increased tumor proliferation and decreased survival. Moreover, reductions in CXCR2 levels were associated with advanced neoplastic lesions in tissue from human pancreatic specimens. Genetically disabling OIS in Kras mice caused RelA to promote tumor proliferation, suggesting a dual role for RelA signaling in pancreatic carcinogenesis. Taken together, our data suggest a pivotal role for RelA in regulating OIS in preneoplastic lesions and implicate the RelA/CXCL1/CXCR2 axis as an essential mechanism of tumor surveillance in PDAC

Banded mongooses avoid inbreeding when mating with members of the same natal group

Inbreeding and inbreeding avoidance are key factors in the evolution of animal societies, influencing dispersal and reproductive strategies which can affect relatedness structure and helping behaviours. In cooperative breeding systems, individuals typically avoid inbreeding through reproductive restraint and/or dispersing to breed outside their natal group. However, where groups contain multiple potential mates of varying relatedness, strategies of kin recognition and mate choice may be favoured. Here, we investigate male mate choice and female control of paternity in the banded mongoose (Mungos mungo), a cooperatively-breeding mammal where both sexes are often philopatric and mating between relatives is known to occur. We find evidence suggestive of inbreeding depression in banded mongooses, indicative of a benefit to avoiding breeding with relatives. Successfully breeding pairs were less related than expected under random mating, which appeared to be driven by both male choice and female control of paternity. Male banded mongooses actively guard females to gain access to mating opportunities, and this guarding behaviour is preferentially directed towards less closely related females. Guard-female relatedness did not affect the guard’s probability of gaining reproductive success. However, where mate-guards are unsuccessful they lose paternity to males that are less related to the females than themselves. Together our results suggest that both sexes of banded mongoose use kin discrimination to avoid inbreeding. Although this strategy appears to be rare among cooperative breeders, it may be more prominent in species where relatedness to potential mates is variable, and/or where opportunities for dispersal and mating outside of the group are limited

The effect of parathyroidectomy and thyroidectomy upon the subsequent levels of calcium and phosphorus in the blood of swine

Although considerable -work has been conducted on thyroid and parathyroid function in several species of animals, thus far, such studies in swine are obscure. The results of early studies on the effects of thyroidectomy in other species were badly clouded because of the simultaneous removal of the parathyroids. It is now accepted that the two organs are anatomically and physiologically separate structures. In most mammals the thyroid gland consists of two lobes—one on each side of the trachea close to its junction with the larynx. The Lobes are usually connected by an isthmus crossing the ventral surface of the trachea. The pig is an exception in that the thyroid gland is a mono lobed structure located on the ventral surface of the trachea just above the thoracic aperture. The parathyroids, present in amphibians, reptiles, birds and mammals, are believed to have essentially the same function. There are usually two pairs of parathyroids. Marked variations the position of the glands are seen in the different species, and, indeed, the position varies somewhat in animals of the same species. Location of these pyriform bodies is commonly on the posterior s\irface of the lateral lobes of the thyroid. Again, the pig proves to be an exception by having only two parathyroid glands—one in each anterior tip of the thymus gland (Schlotthauer and Higgins, 1934;Littledike, 1965). Optimal activity in animals is expected to occur when there is a proper balance of secretory activity of all the endocrine glands. Both The thyroid and parathyroid glands play an important part in this balance.Thyroid effects on metabolism, growth, and sexual maturity are well known; parathyroid regulation of calcium and phosphorus metabolism in many species is also well documented. Extirpation of these glands produces a well-established syndrome of clinical symptoms; however, most of this knowledge is based on data compiled from research on dogs, cats,and rats. Relatively little attention has been devoted to the effects of the hormones of these glands on calcium and phosphorus metabolism in the pig. The present investigation was conducted to determine the specific effects of parathyroidectomy and thyroidectomy on levels of calcium and phosphorus in the blood. The pig was chosen as the experimental animal because it is the only mammal that has an anatomically separated parathyroid and thyroid gland

Trace level detection of analytes using artificial olfactometry

The present invention provides a device for detecting the presence of an analyte, wherein said analyte is a microorganism marker gas. The device comprises a sample chamber having a fluid inlet port for the influx of the microorganism marker gas; a fluid concentrator in flow communication with the sample chamber, wherein the fluid concentrator has an absorbent material capable of absorbing the microorganism marker gas and thereafter releasing a concentrated microorganism marker gas; and an array of sensors in fluid communication with the concentrated microorganism marker gas. The sensor array detects and identifies the marker gas upon its release from fluid concentrate