497 research outputs found
Emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension
Right ventricular (RV) function is the primary prognostic factor for both morbidity and mortality in pulmonary hypertension (PH). RV hypertrophy is initially an adaptive physiological response to increased overload; however, with persistent and/or progressive afterload increase, this response frequently transitions to more pathological maladaptive remodeling. The mechanisms and disease processes underlying this transition are mostly unknown. Angiogenesis has recently emerged as a major modifier of RV adaptation in the setting of pressure overload. A novel paradigm has emerged that suggests that angiogenesis and angiogenic signaling are required for RV adaptation to afterload increases and that impaired and/or insufficient angiogenesis is a major driver of RV decompensation. Here, we summarize our current understanding of the concepts of maladaptive and adaptive RV remodeling, discuss the current literature on angiogenesis in the adapted and failing RV, and identify potential therapeutic approaches targeting angiogenesis in RV failure
Pim-1 : a new biomarker in pulmonary arterial hypertension
Provirus integration site for Moloney murine leukemia virus (Pim-1) is an oncoprotein overexpressed in lungs from pulmonary arterial hypertension (PAH) patients and involved in cell proliferation via the activation of the NFAT/STAT3 signaling pathway. We hypothesized that Pim-1 plasma levels would predict the presence of PAH and correlate with disease severity. Pim-1 plasma levels were measured at the time of catheterization in 49 PAH patients, including nonvasoreactive (n = 19) and vasoreactive idiopathic PAH (n = 5), and PAH related to connective tissue disease (n = 16) and congenital heart disease (n = 9). Fifty controls were also recruited. The capacity of Pim-1 to discriminate PAH from controls and its association with disease severity were assessed. Pim-1 plasma levels were higher in PAH than in controls (9.6 ± 4.0 vs. 7.2 ± 2.4 ng/mL, P < 0.01). Pim-1 appropriately discriminated proliferative PAH from controls (AUC = 0.78 to 0.94 using ROC curves). Among PAH patients, Pim-1 correlated with traditional markers of PAH severity. The 1-year survival was 97% and 47% for PAH patients with baseline Pim-1 levels lower and higher than 11.1 ng/mL, respectively (HR 11.4 (3.3â39.7); P <0.01). After adjustment for hemodynamic and biochemical variables, Pim-1 levels remained an independent predictor of mortality (P < 0.01). Pim-1 is a promising new biomarker in PAH
Chromosomal control of pig populations in France: 2002-2006 survey
The chromosomal control of pig populations has been widely developed in France over the last ten years. By December 31st, 2006, 13 765 individuals had been karyotyped in our laboratory, 62% of these since 2002. Ninety percent were young purebred boars controlled before service in artificial insemination centres, and 3% were hypoprolific boars. So far, 102 constitutional structural chromosomal rearrangements (67 since 2002) have been described. Fifty-six were reciprocal translocations and 8 peri- or paracentric inversions. For the first time since the beginning of the programme and after more than 11 000 pigs had been karyotyped, one Robertsonian translocation was identified in 2005 and two others in 2006. The estimated prevalence of balanced structural chromosomal rearrangements in a sample of more than 7700 young boars controlled before service was 0.47%. Twenty-one of the 67 rearrangements described since 2002 were identified in hypoprolific boars. All were reciprocal translocations. Twelve mosaics (XX/XY in 11 individuals, XY/XXY in one individual) were also diagnosed. Two corresponded to hypoprolific boars, and three to intersexed animals. The results presented in this communication would justify an intensification of the chromosomal control of French and, on a broader scale, European and North-American pig populations
Quixo Is Solved
Quixo is a two-player game played on a 55 grid where the players try
to align five identical symbols. Specifics of the game require the usage of
novel techniques. Using a combination of value iteration and backward
induction, we propose the first complete analysis of the game. We describe
memory-efficient data structures and algorithmic optimizations that make the
game solvable within reasonable time and space constraints. Our main conclusion
is that Quixo is a Draw game. The paper also contains the analysis of smaller
boards and presents some interesting states extracted from our computations.Comment: 19 page
Reply to comment by Yanni Gunnell and Marc Calvet on "Origin of the highly elevated Pyrenean peneplain"
4 p.International audienceGunnell and Calvet [2006] (hereinafter referred to asGC) challenge the recent model that we proposed for theorigin of the highly elevated Pyrenean peneplain by contest-ing our morphometric analysis of this chain and the relationwe made between the morphological evolution and thepiedmont sedimentation. Their reasoning is as follows: (1)According to Calvet [1996] (on which their comment islargely based) the high-elevation, low-relief surfaces in theEastern Pyrenees are remnants of a peneplain that devel-oped before the Pliocene from applanation near to sea level,and which was later uplifted by 2000 m during the Plio-Quaternary (in other words, GC belong to the ââapplanationââschool, whereas we woul d belong to the ââaltiplanationââschool); (2) high-elevation, low-relief surfaces do not existin the Central Pyrenees; (3) therefore the relationships wemade between the morphology of the Central Pyrenees andthe pattern of the detrital sedimentation in the adjacent Ebroforeland basin is meaningless; (4) contrary to the initialinterpretation of Calvet [1996], GC recognize that crustalthickening did not develop since the Pliocene in the EasternPyrenees, so they appeal to another geodynamical processsuch as extension or lithosphere delamination to explain thesupposed uplift
Silencing mutated ÎČ-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R
Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating ÎČ-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/ÎČ-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target.
Similar to patient tumor specimen the H295 cell line derived from an ACC harbors a natural activating ÎČ-catenin mutation. We herein assess the in vitro and in vivo effect of ÎČ-catenin inactivation using a doxycyclin (dox) inducible shRNA plasmid in H295R adrenocortical cancer cells line (clone named shÎČ).
Following dox treatment a profound reduction in ÎČ-catenin expression was detectable in shÎČ clones in comparison to control clones (Ctr). Accordingly, we observed a decrease in Wnt/ÎČcatenin-dependent luciferase reporter activity as well as a decreased expression of AXIN2 representing an endogenous ÎČ-catenin target gene. Concomitantly, ÎČ-catenin silencing resulted in a decreased cell proliferation, cell cycle alterations with cell accumulation in the G1 phase and increased apoptosis in vitro. In vivo, on established tumor xenografts in athymic nude mice, 9 days of ÎČ-catenin silencing resulted in a significant reduction of CTNNB1 and AXIN2 expression. Moreover, continous ÎČ-catenin silencing, starting 3 days after tumor cell inoculation, was associated with a complete absence of tumor growth in the shÎČ group while tumors were present in all animals of the control group.
In summary, these experiments provide evidences that Wnt/ÎČ-catenin pathway inhibition in ACC is a promising therapeutic target
BET Signaling:A Novel Therapeutic Target for Pulmonary Hypertension? Reply
Therapeutic cell differentiatio
Reliability of molecular host-identification methods for ticks: an experimental in vitro study with Ixodes ricinus
Background:
Reliable information on host use by arthropod vectors is required to study pathogen transmission
ecology and to predict disease risk. Direct observation of host use is often difficult or impossible and indirect
methods are therefore necessary. However, the reliability of currently available methods to identify the last host of
blood-feeding arthropods has not been evaluated, and may be particularly problematic for ticks because host
blood has been digested at capture. Biases in host detection may lead to erroneous conclusions on both vector
ecology and pathogen circulation.
Methods:
Here, we experimentally tested for biases in host detection using the generalist three-host tick
Ixodes
ricinus
as a model system. We fed ticks using an artificial feeding system and amplified blood meal traces post-moult
(i.e., in the succeeding unfed life stage) via both a quantitative real-time polymerase chain reaction assay and a
reverse line blotting method. We then experimentally tested for three types of biases in host detection: 1) time
post-moult, 2) tick life stage and 3) host type (non-nucleated mammal blood versus nucleated avian blood), and
compared these biases between the two molecular methods.
Results:
Our results show that all three factors can influence host detection in ticks but not necessarily in the
expected way. Although host detection rates decreased with time post-moult, mammal blood tended to be more
readily detected than bird blood. Tick life stage was also an important factor; detection was higher in nymphs than
in adults and, in some cases, remnants from both larval and nymphal blood meals could be detected in the adult
stage. These biases were similar for the two detection techniques.
Conclusions:
We show that different factors associated with questing ticks may influence our ability to correctly
infer previous host use and that these factors may bias inferences from field-based studies. As these biases may
be common to other vector-borne disease systems, their implications for our understanding of vector ecology
and disease transmission require more explicit consideration
Integrated dataset of anatomical, morphological, and architectural traits for plant species in Madagascar
In this work, we present a dataset, which provides information on the structural diversity of some endemic tropical species in Madagascar. The data were from CIRAD xylotheque (since 1937), and were also collected during various fieldworks (since 1964). The field notes and photographs were provided by French botanists; particularly by Francis Hallé. The dataset covers 250 plant species with anatomical, morphological, and architectural traits indexed from digitized wood slides and fieldwork documents. The digitized wood slides were constituted by the transverse, tangential, and radial sections with three optical magnifications. The main specific anatomical traits can be found within the digitized area. Information on morphological and architectural traits were indexed from digitized field drawings including notes and photographs). (Résumé d'auteur
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