Group selection and kin selection: two concepts but one process.

In a recent paper, Traulsen and Nowak use a multilevel selection model to show that cooperation can be favored by group selection in finite populations [Traulsen A, Nowak M (2006) Proc Natl Acad Sci USA 103:10952-10955]. The authors challenge the view that kin selection may be an appropriate interpretation of their results and state that group selection is a distinctive process "that permeates evolutionary processes from the emergence of the first cells to eusociality and the economics of nations." In this paper, we start by addressing Traulsen and Nowak's challenge and demonstrate that all their results can be obtained by an application of kin selection theory. We then extend Traulsen and Nowak's model to life history conditions that have been previously studied. This allows us to highlight the differences and similarities between Traulsen and Nowak's model and typical kin selection models and also to broaden the scope of their results. Our retrospective analyses of Traulsen and Nowak's model illustrate that it is possible to convert group selection models to kin selection models without disturbing the mathematics describing the net effect of selection on cooperation.

Foxm1 expression in prostate epithelial cells is essential for prostate carcinogenesis.

The treatment of advanced prostate cancer (PCa) remains a challenge. Identification of new molecular mechanisms that regulate PCa initiation and progression would provide targets for the development of new cancer treatments. The Foxm1 transcription factor is highly up-regulated in tumor cells, inflammatory cells, and cells of tumor microenvironment. However, its functions in different cell populations of PCa lesions are unknown. To determine the role of Foxm1 in tumor cells during PCa development, we generated two novel transgenic mouse models, one exhibiting Foxm1 gain-of-function and one exhibiting Foxm1 loss-of-function under control of the prostate epithelial-specific Probasin promoter. In the transgenic adenocarcinoma mouse prostate (TRAMP) model of PCa that uses SV40 large T antigen to induce PCa, loss of Foxm1 decreased tumor growth and metastasis. Decreased prostate tumorigenesis was associated with a decrease in tumor cell proliferation and the down-regulation of genes critical for cell proliferation and tumor metastasis, including Cdc25b, Cyclin B1, Plk-1, Lox, and Versican. In addition, tumor-associated angiogenesis was decreased, coinciding with reduced Vegf-A expression. The mRNA and protein levels of 11β-Hsd2, an enzyme playing an important role in tumor cell proliferation, were down-regulated in Foxm1-deficient PCa tumors in vivo and in Foxm1-depleted TRAMP C2 cells in vitro. Foxm1 bound to, and increased transcriptional activity of, the mouse 11β-Hsd2 promoter through the -892/-879 region, indicating that 11β-Hsd2 was a direct transcriptional target of Foxm1. Without TRAMP, overexpression of Foxm1 either alone or in combination with inhibition of a p19(ARF) tumor suppressor caused a robust epithelial hyperplasia, but was insufficient to induce progression from hyperplasia to PCa. Foxm1 expression in prostate epithelial cells is critical for prostate carcinogenesis, suggesting that inhibition of Foxm1 is a promising therapeutic approach for prostate cancer chemotherapy.

The dmf1/mid1 gene is essential for correct positioning of the division septum in fission yeast.

Little is known about the mechanisms that establish the position of the division plane in eukaryotic cells. Wild-type fission yeast cells divide by forming a septum in the middle of the cell at the end of mitosis. Dmf1 mutants complete mitosis and initiate septum formation, but the septa that form are positioned at random locations and angles in the cell, rather than in the middle. We have cloned the dmf1 gene as a suppressor of the cdc7-24 mutant. The dmf1 mutant is allelic with mid1. The gene encodes a novel protein containing a putative nuclear localization signal, and a carboxy-terminal PH domain. In wild-type cells, Dmf1p is nuclear during interphase, and relocates to form a medial ring at the cell cortex coincident with the onset of mitosis. This relocalization occurs before formation of the actin ring and is associated with increased phosphorylation of Dmf1p. The Dmf1p ring can be formed in the absence of an actin ring, but depends on some of the genes required for actin ring formation. When the septum is completed and the cells separate, Dmf1p staining is once again nuclear. These data implicate Dmf1p as an important element in assuring correct placement of the division septum in Schizosaccharomyces pombe cells.

Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression.

Wound healing proceeds by the concerted action of a variety of signals that have been well identified. However, the mechanisms integrating them and coordinating their effects are poorly known. Herein, we reveal how PPARbeta/delta (PPAR: peroxisome proliferator-activated receptor) follows a balanced pattern of expression controlled by a crosstalk between inflammatory cytokines and TGF-beta1. Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/remodeling events. This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1 activity and DNA binding that results in an inhibition of the AP-1-driven induction of the PPARbeta/delta promoter. As expected from these observations, wound biopsies from Smad3-null mice showed sustained PPARbeta expression as compared to those of their wild-type littermates. Together, these findings suggest a mechanism for setting the necessary balance between inflammatory signals, which trigger PPARbeta/delta expression, and TGF-beta1/Smad3 that governs the timely decrease of this expression as wound healing proceeds to completion.

BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration.

Muscle stem cells and their progeny play a fundamental role in the regeneration of adult skeletal muscle. We have previously shown that activation of the canonical Wnt/beta-catenin signaling pathway in adult myogenic progenitors is required for their transition from rapidly dividing transient amplifying cells to more differentiated progenitors. Whereas Wnt signaling in Drosophila is dependent on the presence of the co-regulator Legless, previous studies of the mammalian ortholog of Legless, BCL9 (and its homolog, BCL9-2), have not revealed an essential role of these proteins in Wnt signaling in specific tissues during development. Using Cre-lox technology to delete BCL9 and BCL9-2 in the myogenic lineage in vivo and RNAi technology to knockdown the protein levels in vitro, we show that BCL9 is required for activation of the Wnt/beta-catenin cascade in adult mammalian myogenic progenitors. We observed that the nuclear localization of beta-catenin and downstream TCF/LEF-mediated transcription, which are normally observed in myogenic progenitors upon addition of exogenous Wnt and during muscle regeneration, were abrogated when BCL9/9-2 levels were reduced. Furthermore, reductions of BCL9/9-2 inhibited the promotion of myogenic differentiation by Wnt and the normal regenerative response of skeletal muscle. These results suggest a critical role of BCL9/9-2 in the Wnt-mediated regulation of adult, as opposed to embryonic, myogenic progenitors.

Insecticidal, repellent, antimicrobial activity and phytotoxicity of essential oils: With special reference to limonene and its suitability for control of insect pests : Review

Selostus: Monoterpeenit kasvinsuojelussa: erityisesti limoneenin vaikutus eri eliöryhmiin

Essential residues in the H-NS binding site of Hha, a co-regulator of horizontally acquired genes in Enterobacteria

Proteins of the Hha/YmoA family co-regulate with H-NS the expression of horizontally acquired genes in Enterobacteria. Systematic mutations of conserved acidic residues in Hha have allowed the identification of D48 as an essential residue for H-NS binding and the involvement of E25. Mutations of these residues resulted in deregulation of sensitive genes in vivo. D48 is only partially solvent accessible, yet it defines the functional binding interface between Hha and H-NS confirming that Hha has to undergo a conformational change to bind H-NS. Exposed acidic residues, such as E25, may electrostatically facilitate and direct the approach of Hha to the positively charged region of H-NS enabling the formation of the final complex when D48 becomes accessible by a conformational change of Hha.

Assessing inter-rater reliability when the raters are fixed: two concepts and two estimates.

Intraclass correlation (ICC) is an established tool to assess inter-rater reliability. In a seminal paper published in 1979, Shrout and Fleiss considered three statistical models for inter-rater reliability data with a balanced design. In their first two models, an infinite population of raters was considered, whereas in their third model, the raters in the sample were considered to be the whole population of raters. In the present paper, we show that the two distinct estimates of ICC developed for the first two models can both be applied to the third model and we discuss their different interpretations in this context.

Interactions between respiration and systemic hemodynamics. Part I: basic concepts.

The topic of cardiorespiratory interactions is of extreme importance to the practicing intensivist. It also has a reputation for being intellectually challenging, due in part to the enormous volume of relevant, at times contradictory literature. Another source of difficulty is the need to simultaneously consider the interrelated functioning of several organ systems (not necessarily limited to the heart and lung), in other words, to adopt a systemic (as opposed to analytic) point of view. We believe that the proper understanding of a few simple physiological concepts is of great help in organizing knowledge in this field. The first part of this review will be devoted to demonstrating this point. The second part, to be published in a coming issue of Intensive Care Medicine, will apply these concepts to clinical situations. We hope that this text will be of some use, especially to intensivists in training, to demystify a field that many find intimidating.

Study of inner ear and lateral line hair cell regeneration

Death of sensory hair cells in the inner ear results in two global health problems that millions of people around the world suffer: hearing loss and balance disorders. Hair cells convert sound vibrations and head movements into electrical signals that are conveyed to the brain, and as a result of aging, exposure to noise, modern drugs or genetic predisposition, hair cells die. In mammals, the great majority of hair cells are produced during embryogenesis, and hair cells that are lost after birth are not replaceable. However, in the last decades, researches have shown some model organisms that retain the ability to regenerate hair cells damaged after embryogenesis, such as Zebrafish and chicken, providing clues as to the cellular and molecular mechanisms that may block hair cell regeneration in mammals. This discovery initiated a search for methods to stimulate regeneration or replacement of hair cells in mammals, a search that, if fruitful, will revolutionize the treatment of hearing loss and balance disorders. One aim of my project is to study the role of retinoic acid in adult Zebrafish and in mice, which is a metabolite of vitamin A known as an essential molecule to activate hair cell regeneration after cells damaged in Zebrafish embryo. We want to study important genes involved in retinoic acid pathway, such as Aldh1a3 and RARs genes, to check what their role is in the inner ear of adult Zebrafish and compare result obtained in the inner ear of mice. On the other hand, Zebrafish lateral line contains neuromast, which are formed by the same structure than the inner ear: hair cells surrounded by supporting cells and neurons. The lateral line is a structure below the skin's surface that makes easier to damage hair cells to study their regeneration. For that reason, another aim of my project is to study how Sox2 and Atoh1, essential genes during the inner ear development, change their expression during hair cell regeneration in the lateral line. In my project, the most important concepts related to Zebrafish world are explained in order to understand why we have studied this animal and these essential genes. Then, techniques that we used are explained, with their protocol attached in the annexes. Finally, results of my project are shown, but many of them were not expected and they would be needed to follow studying.

Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.

New concepts in the pathophysiology of infective endocarditis.

Endocarditis pathogens colonize valves with pre-existing sterile vegetations or valves with minimal endothelial lesions. Inflamed endothelia produce cytokines, integrins, and tissue factor, which in turn attract fibronectin, monocytes, and platelets. Bacteria attaching to such structures further activate the cascade, becoming embedded and protected from host defenses. Staphylococcus aureus also actively invade the endothelium, causing apoptosis and endothelial damage. Knowledge of this interplay identifies host factors as potential therapeutic targets. Blocking infection by modulating host factors might be opportune because host factors are conserved. In contrast, interfering with bacterial virulence factors might be more complicated because they vary among different bacteria.