Downregulation of p57kip2 promotes cell invasion via LIMK/cofilin pathway in human nasopharyngeal carcinoma cells

The members of Rho family are well known for their regulation of actin cytoskeleton to control cell migration. The Cip/kip members of cyclin‐dependent (CDK) inhibitors have shown to implicate in cell migration and cytoskeletal dynamics. p57^kip2, a CDK inhibitor, is frequently down‐regulated in several malignancy tumors. However, its biological roles in human nasopharyngeal carcinoma (NPC) cells remained to be investigated. Here, we found p57^kip2 has nuclear and cytoplasm distributions and depletion of endogenous p57^kip2 did not change the cell‐cycle progression. Inhibition of cell proliferation by mitomycin C promoted FBS‐mediated cell migration and accompanied with the downregulation of ΔNp63α and p57^kip2, but did not change the level of p27^kip1, another CDK inhibitor. By using siRNA transfection and cell migration/invasion assays, we found that knockdown of p57^kip2, but not ΔNp63α, involved in promotion of NPC cell migration and invasion via decrease of phospho‐cofilin (p‐cofilin). Treatment with Y‐27632, a specific ROCK inhibitor, we found that dysregulation of ROCK/cofilin pathway decreased p‐cofilin expression and induced cell migration. This change of p‐cofilin induced actin remodeling and pronounced increase of membrane protrusions. Further, silence of p57^kip2 not only decreased the interaction between p57^kip2 and LIMK‐1 assayed by immunoprecipitation but also reduced the level of phospho‐LIMK1/2. Therefore, this study indicated that dysregulation of p57^kip2 promoted cell migration and invasion through modulation of LIMK/cofilin signaling and suggested this induction of inappropriate cell motility might contribute to promoting tumor cell for metastasis. J. Cell. Biochem. 112: 3459–3468, 2011. © 2011 Wiley Periodicals, Inc.     

Female competition and its evolutionary consequences in mammals

Following Darwin's original insights regarding sexual selection, studies of intrasexual competition have mainly focused on male competition for mates; by contrast, female reproductive competition has received less attention. Here, we review evidence that female mammals compete for both resources and mates in order to secure reproductive benefits. We describe how females compete for resources such as food, nest sites, and protection by means of dominance relationships, territoriality and inter‐group aggression, and by inhibiting the reproduction of other females. We also describe evidence that female mammals compete for mates and consider the ultimate causes of such behaviour, including competition for access to resources provided by mates, sperm limitation and prevention of future resource competition. Our review reveals female competition to be a potentially widespread and significant evolutionary selection pressure among mammals, particularly competition for resources among social species for which most evidence is currently available. We report that female competition is associated with many diverse adaptations, from overtly aggressive behaviour, weaponry, and conspicuous sexual signals to subtle and often complex social behaviour involving olfactory signalling, alliance formation, altruism and spite, and even cases where individuals appear to inhibit their own reproduction. Overall, despite some obvious parallels with male phenotypic traits favoured under sexual selection, it appears that fundamental differences in the reproductive strategies of the sexes (ultimately related to parental investment) commonly lead to contrasting competitive goals and adaptations. Because female adaptations for intrasexual competition are often less conspicuous than those of males, they are generally more challenging to study. In particular, since females often employ competitive strategies that directly influence not only the number but also the quality (survival and reproductive success) of their own offspring, as well as the relative reproductive success of others, a multigenerational view ideally is required to quantify the full extent of variation in female fitness resulting from intrasexual competition. Nonetheless, current evidence indicates that the reproductive success of female mammals can also be highly variable over shorter time scales, with significant reproductive skew related to competitive ability. Whether we choose to describe the outcome of female reproductive competition (competition for mates, for mates controlling resources, or for resources per se) as sexual selection depends on how sexual selection is defined. Considering sexual selection strictly as resulting from differential mating or fertilisation success, the role of female competition for the sperm of preferred (or competitively successful) males appears particularly worthy of more detailed investigation. Broader definitions of sexual selection have recently been proposed to encompass the impact on reproduction of competition for resources other than mates. Although the merits of such definitions are a matter of ongoing debate, our review highlights that understanding the evolutionary causes and consequences of female reproductive competition indeed requires a broader perspective than has traditionally been assumed. We conclude that future research in this field offers much exciting potential to address new and fundamentally important questions relating to social and mating‐system evolution.     

Condensed tannin,an antibiotic chemical from Gossypium hirsutum

Antibiotic activity against Heliothis virescens was found in flower buds of Gossypium hirsutum, experimental stock Texas 254. Relatively low antibiotic activity was found in hexane extract, high activity in methanolic extract and residue, and no activity in acetone and water extracts. A condensed tannin having a molecular weight of 4850 was isolated from methanolic extract by column chromatography on Sephadex G-25. It was the major antibiotic component, 3.4% of the dried flower bud. The condensed tannin at 0.2% in the diet retarded larval growth by 84%.     

The Surface Exclusion System of RP1: Investigation of the Roles of trbJ and trbK in the Surface Exclusion, Transfer, and Slow-Growth Phenotypes

The contiguous trbJ and trbK genes of RP1 were cloned individually to study their effects. Surface exclusion was conferred only by trbK and only when gene dosage was high or when trbJ was also present in cis or in trans. This suggests that in the low-copy-number RP1, surface exclusion is due to a two-gene interaction in which trbK is the dominant partner. Among surface exclusion genes, trbJ is novel in yielding a periplasmic product that is also essential for conjugal transfer. This cellular location and the disturbed membrane function that accompanies TrbJ-processing probably accounts for the retarded growth caused by trbJ⁺ clones in Pseudomonas aeruginosa strain PAO.     

Cloning of rat brain succinyl-CoA:3-oxoacid CoA-transferase cDNA. Regulation of the mRNA in different rat tissues and during brain development.

3-Oxoacid CoA-transferase, which catalyses the first committed step in the oxidation of ketone bodies, is uniquely regulated in developing rat brain. Changes in 3-oxoacid CoA-transferase activity in rat brain during the postnatal period are due to changes in the relative rate of synthesis of the enzyme. To study the regulation of this enzyme, we identified, with a specific polyclonal rabbit anti-(rat 3-oxoacid CoA-transferase), two positive cDNA clones (approx. 800 bp) in a lambda gtll expression library, constructed from poly(A)+ RNA from brains of 12-day-old rats. One of these clones (lambda CoA3) was subcloned into M13mp18 and subjected to further characterization. Labelled single-stranded probes prepared by primer extension of the M13mp18 recombinant hybridized to a 3.6 kb mRNA. Rat brain mRNA enriched by polysome immunoadsorption for a single protein of size 60 kDa which corresponds to the precursor form of 3-oxoacid CoA-transferase was also found to be similarly enriched for the hybridizable 3.6 kb mRNA complementary to lambda CoA3. Affinity-selected antibody to the lambda CoA3 fusion protein inhibited 3-oxoacid CoA-transferase activity present in rat brain mitochondrial extracts. The 3.6 kb mRNA for 3-oxoacid CoA-transferase was present in relative abundance in rat kidney and heart, to a lesser extent in suckling brain and mammary gland and negligible in the liver. The specific mRNA was also found to be 3-fold more abundant in the brain from 12-day-old rats as compared with 18-day-old foetuses and adult rats, corresponding to the enzyme activity and relative rate of synthesis profile during development. These data suggest that 3-oxoacid CoA-transferase enzyme activity is regulated at a pretranslational level.     

Design,synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment

A series of 4′-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ_1–42 aggregation (60.0% and 78.2%, respectively) and Cu²⁺-induced Aβ_1–42 aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.     

Trabecular architecture and joint loading of the proximal humerus in extant hominoids,Ateles, and Australopithecus africanus

Objectives

Several studies have investigated potential functional signals in the trabecular structure of the primate proximal humerus but with varied success. Here, we apply for the first time a “whole‐epiphyses” approach to analysing trabecular bone in the humeral head with the aim of providing a more holistic interpretation of trabecular variation in relation to habitual locomotor or manipulative behaviors in several extant primates and Australopithecus africanus.

Materials and methods

We use a “whole‐epiphysis” methodology in comparison to the traditional volume of interest (VOI) approach to investigate variation in trabecular structure and joint loading in the proximal humerus of extant hominoids, Ateles and A. africanus (StW 328).

Results

There are important differences in the quantification of trabecular parameters using a “whole‐epiphysis” versus a VOI‐based approach. Variation in trabecular structure across knuckle‐walking African apes, suspensory taxa, and modern humans was generally consistent with predictions of load magnitude and inferred joint posture during habitual behaviors. Higher relative trabecular bone volume and more isotropic trabeculae in StW 328 suggest A. africanus may have still used its forelimbs for arboreal locomotion.

Discussion

A whole‐epiphysis approach to analysing trabecular structure of the proximal humerus can help distinguish functional signals of joint loading across extant primates and can provide novel insight into habitual behaviors of fossil hominins.