A Role for auxin during actinorhizal symbioses formation?

The symbiotic interaction between the soil bacteria Frankia and actinorhizal plants leads to the formation of nitrogen-fixing nodules resembling modified lateral roots. Little is known about the signals exchanged between the two partners during the establishment of these endosymbioses. However, a role for plant hormones has been suggested.Recently, we studied the role of auxin influx activity during actinorhizal symbioses. An inhibitor of auxin influx was shown to perturb nodule formation. Moreover we identified a functional auxin influx carrier that is produced specifically in Frankia-infected cells. These results together with previous data showing auxin production by Frankia lead us to propose a model of auxin action during the symbiotic infection process.Key words: lateral roots, nitrogen fixation, Frankia, AUX1, actinorhizal symbioses, phenylacetic acid, auxin influxActinorhizal symbioses result from the interaction between the soil actinomycete Frankia and plants belonging to eight angiosperm families collectively called actinorhizal plants.¹ This symbiotic interaction leads to the formation of a new organ on the root system, the actinorhizal nodule, where the bacteria are hosted and fix nitrogen.² Unlike legume nodules, actinorhizal nodules are structurally and developmentally related to lateral roots.³ Little is known about the signals exchanged between the two partners during the establishment of the symbiosis.² Diffusible signals are emitted by Frankia at early stages of the interaction resulting in root hair deformation.² The chemical nature of these signals remains unknown, however, detailed studies revealed that they are different from rhizobial Nod factors.⁴ Phytohormones are chemicals that control many developmental processes⁵ and have been linked to many plant-microbe interactions. Recently, we studied the role of auxin influx in actinorhizal nodule formation in the tropical tree Casuarina glauca.⁶     

Role of Mg2+ in Chromomycin A3 – DNA Interaction: A Molecular Modeling Study

Chromomycin A₃ (CHR) is an antitumor antibiotic that inhibits macromolecular biosynthesis by reversibly binding to double stranded DNA via the minor groove, with GC-base specificity. At and above physiological pH when CHR is anionic, interaction of CHR with DNA requires the presence of divalent metal ions like Mg²⁺. However, at acidic pHthe molecule is neutral and it binds DNA even in absence of Mg²⁺. Molecular dynamics simulation studies at 300K of neutral CHR and 1:1 CHR:Mg²⁺ complexes formed at pH 5.2 and 8.0 show that hydrophobicity of CHR:Mg²⁺ complex formed with the neutral drug is greater than that of the two other species. Interactions of CHR with DNA in presence and absence of Mg²⁺ have been studied by simulated annealing to understand the role of Mg²⁺ in the DNA binding potential of CHR. This shows that the antibiotic has the structural potential to bind to DNA even in the absence of metal ion. Evaluation of the direct interaction energy between the ligand and DNA does not explain the observed GC-base specificity of the antibiotic. When energy contributions from structural alteration of the interacting ligand and DNA as a sequel to complex formation are taken into account, atrue picture of the theoretical binding propensity emerges. This implies that DNA and/or the ligand undergo significant structural alterations during the process of association, particularly in presence of Mg²⁺. Accessible surface area calculations give idea about the entropy contribution to the binding free energy which is found to be different depending upon the presence and absence of Mg²⁺.     

A Potential Role for Creatine in Drug Abuse?

Supplemental creatine has been promoted for its positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Creatine is found in high protein foods, such as fish or meat, and is also produced endogenously from the biosynthesis of arginine, glycine, and methionine. Changes in brain creatine levels, as measured using magnetic resonance spectroscopy, are seen in individuals exposed to drugs of abuse and depressed individuals. These changes in brain creatine indicate that energy metabolism differs in these populations relative to healthy individuals. Recent work shows that creatine supplementation has the ability to function in a manner similar to antidepressant drugs and can offset negative consequences of stress. These observations are important in relation to addictive behaviors as addiction is influenced by psychological factors such as psychosocial stress and depression. The significance of altered brain levels of creatine in drug-exposed individuals and the role of creatine supplementation in models of drug abuse have yet to be explored and represent gaps in the current understanding of brain energetics and addiction.     

Role of hippocalcin in mediating Aβ toxicity

Alzheimer's disease (AD) is the most common cause of dementia, and amyloid-β (Aβ) plaques and tau-containing tangles are its histopathological hallmark lesions. These do not occur at random; rather, the neurodegenerative process is stereotyped in that it is initiated in the entorhinal cortex and hippocampal formation. Interestingly, it is the latter brain area where the calcium-sensing enzyme hippocalcin is highly expressed. Because calcium deregulation is a well-established pathomechanism in AD, we aimed to address the putative role of hippocalcin in human AD brain and transgenic mouse models. We found that hippocalcin levels are increased in human AD brain and in Aβ plaque-forming APP23 transgenic mice compared to controls. To determine the role of hippocalcin in Aβ toxicity, we treated primary cultures derived from hippocalcin knockout (HC KO) mice with Aβ and found them to be more susceptible to Aβ toxicity than controls. Likewise, treatment with either thapsigargin or ionomycin, both known to deregulate intracellular calcium levels, caused an increased toxicity in hippocampal neurons from HC KO mice compared to wild-type. We found further that mitochondrial complex I activity increased from 3 to 6months in hippocampal mitochondria from wild-type and HC KO mice, but that the latter exhibited a significantly stronger aging phenotype than wild-type. Aβ treatment induced significant toxicity on hippocampal mitochondria from HC KO mice already at 3months of age, while wild-type mitochondria were spared. Our data suggest that hippocalcin has a neuroprotective role in AD, presenting it as a putative biomarker.     

Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

The organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact.     

Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility

Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.     

A Role for the αvβ3 Integrin in the Transmigration of Monocytes

The β2 integrins and intercellular adhesion molecule-1 (ICAM-1) are important for monocyte migration through inflammatory endothelium. Here we demonstrate that the integrin αvβ3 is also a key player in this process. In an in vitro transendothelial migration assay, monocytes lacking β3 integrins revealed weak migratory ability, whereas monocytes expressing β3 integrins engaged in stronger migration. This migration could be partially blocked by antibodies against the integrin chains αL, β2, αv, or IAP, a protein functionally associated with αvβ3 integrin. Transfection of β3 integrin chain cDNA into monocytes lacking β3 integrins resulted in expression of the αvβ3 integrin and conferred on these cells an enhanced ability to transmigrate through cell monolayers expressing ICAM-1. These monocytes also engaged in αLβ2-dependent locomotion on recombinant ICAM-1 which was enhanced by αvβ3 integrin occupancy. Antibodies against IAP were able to revert this αvβ3 integrin-dependent cell locomotion to control levels. Finally, adhesion assays revealed that occupancy of αvβ3 integrin could decrease monocyte binding to ICAM-1.In conclusion, we show that αvβ3 integrin modulates αLβ2 integrin-dependent monocyte adhesion to and migration on ICAM-1. This could represent a novel mechanism to promote monocyte motility on vascular ICAM-1 and initiate subsequent transendothelial migration.     

Interhemispheric Differences in Indices of α Activity Spectral Power Electroencephalogram during Bicycle Ergometry

An EEG study during bicycle ergometry in the prone position with the load growing stepwise to submaximal heart rate was carried out in 30 volunteers in order to investigate the spectrum parameters and interhemispheric differences in α activity on the encephalogram. Comparative analysis of EEG data showed a statistically significant increase in α power indices in both hemispheres at the final stage of aerobic exercise and in the course of recovery period with the highest power values recorded in the left hemisphere. Analysis of interhemispheric differences demonstrated right-hemisphere activation during the entire period of the research.     

Male aggression during mating: evidence for sexual coercion in a female dominant primate?

In this article we document male sexual coercion of a Lemur catta female on St. Catherines Island (SCI), USA. Data presented in this paper were collected on one free-ranging L. catta group during October-November 2002 using all-occurrences sampling for agonism and reproductive behavior. We observed a male forcefully attempting to mate with a year-old estrous female. Despite the fact that we observed this female to present to the male during her estrus, throughout the episode the male employed the use of force, and achieved penile intromission on at least one occasion while the female struggled and resisted. We interpret his behavior as sexual coercion. As measured by sexual presents, the female appeared to more strongly prefer two other males as mates, yet each of these males gained fewer mounts and less cumulative time spent in mounts than the coercive male. The coercive male was one of two group males with the lowest observed mating success, suggesting that coercion might be a strategy used by males who are not highly sexually preferred. Females undergo early sexual maturation at this site owing to provisioning, and can therefore enter estrus before fully attaining dominance over males. As such, these data suggest that one consequence of provisioning a wild L. catta population (or of maintaining L. catta in captivity) may be that young females can be the targets of sexual coercion if they reach sexual maturity before fully achieving social dominance over males. In conclusion, male sexual coercion can occur in L. catta despite the female dominance characteristic of this species, and can constrain the mating behavior of females.     

A Role for NF-κB Activity in Skin Hyperplasia and the Development of Keratoacanthomata in Mice

Background

Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin.

Methods

A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice) with increased NF-κB activity.

Results

The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata.

Conclusion

Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.