ESTIMATION OF POTENTIAL RISK OF ACL RUPTURE IN FEMALE SOCCER PLAYERS AND EFFECTIVENESS OF A PREVENTION TRAINING PROGRAM

The purpose of this study was to make an estimation of the potential risk of ACL rupture in female soccer players by means of video based analysis and controlled by biome-chanical testing as well as to relate to effects by carrying out an 8 week specific training program. Results show that video based screening seems to be suitable in order to achieve a good estimation of the risk for ACL injuries without large expenditure. The per-formed ACL prevention training program shows a slight reduction of the potential risk of ACL rupture

Mountain gorillas maintain strong affiliative biases for maternal siblings despite high male reproductive skew and extensive exposure to paternal kin

Evolutionary theories predict that sibling relationships will reflect a complex balance of cooperative and competitive dynamics. In most mammals, dispersal and death patterns mean that sibling relationships occur in a relatively narrow window during development and/or only with same-sex individuals. Besides humans, one notable exception is mountain gorillas, in which non-sex-biased dispersal, relatively stable group composition, and the long reproductive tenures of alpha males mean that animals routinely reside with both maternally and paternally related siblings, of the same and opposite sex, throughout their lives. Using nearly 40,000 hr of behavioral data collected over 14 years on 699 sibling and 1235 non-sibling pairs of wild mountain gorillas, we demonstrate that individuals have strong affiliative preferences for full and maternal siblings over paternal siblings or unrelated animals, consistent with an inability to discriminate paternal kin. Intriguingly, however, aggression data imply the opposite. Aggression rates were statistically indistinguishable among all types of dyads except one: in mixed-sex dyads, non-siblings engaged in substantially more aggression than siblings of any type. This pattern suggests mountain gorillas may be capable of distinguishing paternal kin but nonetheless choose not to affiliate with them over non-kin. We observe a preference for maternal kin in a species with a high reproductive skew (i.e. high relatedness certainty), even though low reproductive skew (i.e. low relatedness certainty) is believed to underlie such biases in other non-human primates. Our results call into question reasons for strong maternal kin biases when paternal kin are identifiable, familiar, and similarly likely to be long-term groupmates, and they may also suggest behavioral mismatches at play during a transitional period in mountain gorilla society

Nanoparticle tethered antioxidant response element as a biosensor for oxygen induced toxicity in retinal endothelial cells

Purpose: A novel system, based on biosensor DNA tethered to a nanoparticle, was developed for the treatment of retinopathy of prematurity. Methods: The construction of a five-layered nanoparticle was visualized with gel electrophoresis. Transcriptionally active PCR products (TAP) containing the biosensor sequence, were bioconjugated to the surface of magnetic nanoparticles yielding biosensor tethered magnetic nanoparticles (MNP). The biosensor was based on an enhanced green fluorescent protein (EGFP) reporter gene driven by an enhanced antioxidant response element ( ARE). Image analysis and flow cytometry were used to characterize MNP delivery and biosensor activity. Results: The MNP penetrated dividing and migrating cells more often than quiescent endothelial cells in a wound-healing in vitro assay. Prussian blue staining demonstrated that more cells have nanoparticle cores than are transfected. When compared to naked TAP alone, MNP transfected more cells in a dose dependent manner. Both the biosensor alone and MNP induce gene expression in the presence of hyperoxia, greater than 1.5 fold over normoxic controls. These data also show that the MNP had a signal to noise ratio of 0.5 greater than the plasmid form of the biosensor as demonstrated by flow cytometry. Conclusions: This approach has the potential to allow the endothelial cells of the retinal vasculature to prevent or treat themselves after hyperoxic insult, rather than systemic treatment to protect or treat only the retina

Construction, gene delivery, and expression of DNA tethered nanoparticles

PURPOSE: Layered nanoparticles have the potential to deliver any number of substances to cells both in vitro and in vivo. The purpose of this study was to develop and test a relatively simple alternative to custom synthesized nanoparticles for use in multiple biological systems, with special focus on the eye. METHODS: The biotin-labeled transcriptionally active PCR products (TAP) were conjugated to gold, semiconductor nanocrystals, and magnetic nanoparticles (MNP) coated with streptavidin. The process of nanoparticle construction was monitored with gel electrophoresis. Fluorescence microscopy followed by image analysis was used to examine gene expression levels from DNA alone and tethered MNP in human hepatoma derived Huh-7 cells. Adult retinal endothelial cells from both dog (ADREC) and human (HREC) sources were transfected with nanoparticles and reporter gene expression evaluated with confocal and fluorescent microscopy. Transmission electron microscopy was used to quantify the concentration of nanoparticles in a stock solution. Nanoparticles were evaluated for transfection efficiency, determined by fluorescence microscopy cell counts. Cells treated with MNP were evaluated for increased reactive oxygen species (ROS) and necrosis with flow cytometry. RESULTS: Both 5' and 3' biotin-labeled TAP bound equally to MNP and there were no differences in functionality between the two tethering orientations. Free DNA was easily removed by the use of magnetic columns. These particles were also able to deliver genes to a human hepatoma cell line, Huh-7, but transfection efficiency was greater than TAP. The semiconductor nanocrystals and MNP had the highest transfection efficiencies. The MNP did not induce ROS formation or necrosis after 48 h of incubation. CONCLUSIONS: Once transfected, the MNP had reporter gene expression levels equivalent to TAP. The nanoparticles, however, had better transfection efficiencies than TAP. The magnetic nanoparticles were the most easily purified of all the nanoparticles tested. This strategy for bioconjugating TAP to nanoparticles is valuable because nanoparticle composition can be changed and the system optimized quickly. Since endothelial cells take up MNP, this strategy could be used to target neovascularization as occurs in proliferative retinopathies. Multiple cell types were used to test this technology and in each the nanoparticles were capable of transfection. In adult endothelial cells the MNP appeared innocuous, even at the highest doses tested with respect to ROS and necrosis. This technology has the potential to be used as more than just a vector for gene transfer, because each layer has the potential to perform its own unique function and then degrade to expose the next functional layer

CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

Particulate ligands including cholesterol crystals and amyloid fibrils induce NLRP3-dependent production of interleukin-1β (IL-1β) in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands including oxidized-LDL, amyloid-β and amylin peptides accumulate in these diseases. Here we identify a CD36-mediated endocytic pathway that coordinates the intracellular conversion of these soluble ligands to crystals or fibrils, resulting in lysosomal disruption and NLRP3-inflammasome activation. Consequently, macrophages lacking CD36 failed to elicit IL-1β production in response to these ligands and targeting CD36 in atherosclerotic mice reduced serum IL-1β and plaque cholesterol crystal accumulation. Collectively, these findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation

Factors associated with shunt dynamic in patients with cryptogenic stroke and patent foramen ovale: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>As previously reported there is evidence for a reduction in right to left shunt (RLS) in stroke patients with patent foramen ovale (PFO). This occurs predominantly in patients with cryptogenic stroke (CS). We therefore analysed factors associated with a shunt reduction on follow-up in stroke patients suffering of CS.</p> <p>Methods</p> <p>On index event PFO and RLS were proven by transesophageal echocardiography and contrast-enhanced transcranial Doppler-sonography (ce-TCD). Silent PE was proved by ventilation perfusion scintigraphy (V/Q) within the stroke work-up on index event; all scans were re-evaluated in a blinded manner by two experts. The RLS was re-assessed on follow-up by ce-TCD. A reduction in shunt volume was defined as a difference of ≥20 microembolic signals (MES) or the lack of evidence of RLS on follow-up. For subsequent analyses patients with CS were considered; parameters such as deep vein thrombosis (DVT) and silent pulmonary embolism (PE) were analysed.</p> <p>Results</p> <p>In 39 PFO patients suffering of a CS the RLS was re-assessed on follow-up. In all patients (n = 39) with CS a V/Q was performed; the median age was 40 years, 24 (61.5%) patients were female. In 27 patients a reduction in RLS was evident. Silent PE was evident in 18/39 patients (46.2%). Factors such as atrial septum aneurysm, DVT or even silent PE were not associated with RLS dynamics. A greater time delay from index event to follow-up assessment was associated with a decrease in shunt volume (median 12 vs. 6 months, <it>p </it>= 0.013).</p> <p>Conclusions</p> <p>In patients with CS a reduction in RLS is not associated with the presence of a venous embolic event such as DVT or silent PE. A greater time delay between the initial and the follow-up investigation increases the likelihood for the detection of a reduction in RLS.</p

Europeanisation should meet international constructivism: the Nordic Plus group and the internalisation of political conditionality by France and the United Kingdom

This article is a plausibility probe for the significance of international constructivist ‘mediating factors’ to explain variation in Europeanisation outcomes. It applies a most similar systems design (or Mill's method of difference) to show that the UK has internalised political conditionality to a larger extent than France at least partially because it has been the object of stronger socialisation pressures within the ‘Nordic Plus’ group. The article contributes to the literature on Europeanisation and development cooperation in two important ways. First, it enlarges its scope of analysis, both geographically (beyond new European Union member states) and thematically (beyond simple measures of aid quality and/or quantity). Second, it emphasises the importance of international (versus domestic) mediating factors. The empirical analysis focusses on three cases of aid sanctions in response to human rights abuses and democratic setbacks: Zimbabwe 2002, Madagascar 2009 and Mozambique 2009

Measurement of the Depth of Maximum of Extensive Air Showers above 10^18 eV

We describe the measurement of the depth of maximum, Xmax, of the longitudinal development of air showers induced by cosmic rays. Almost four thousand events above 10^18 eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106 +35/-21) g/cm^2/decade below 10^(18.24 +/- 0.05) eV and (24 +/- 3) g/cm^2/decade above this energy. The measured shower-to-shower fluctuations decrease from about 55 to 26 g/cm^2. The interpretation of these results in terms of the cosmic ray mass composition is briefly discussed.Comment: Accepted for publication by PR

PTPN11 mutations are not responsible for the Cardiofaciocutaneous (CFC) syndrome

Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomalies/mental retardation syndrome characterized by congenital heart defects, characteristic facial appearance, short stature, ectodermal abnormalities and mental retardation. It was described in 1986, and to date is of unknown genetic etiology. All reported cases are sporadic, born to non-consanguineous parents and have apparently normal chromosomes. Noonan and Costello syndromes remain its main differential diagnosis. the recent finding of PTPN11 missense mutations in 45-50% of the Noonan patients studied with penetrance of almost 100% and the fact that in animals mutations of this gene cause defects of semilunar valvulogenesis, made PTPN11 mutation screening in CFC patients a matter of interest. We sequenced the entire coding region of the PTPN11 gene in ten well-characterised CFC patients and found no base changes. We also studied PTPN11 cDNA in our patients and demonstrated that there are no interstitial deletions either. the genetic cause of CFC syndrome remains unknown, and PTPN11 can be reasonably excluded as a candidate gene for the CFC syndrome, which we regard as molecular evidence that CFC and Noonan syndromes are distinct genetic entities.Univ Sacred Heart, Ist Genet Med, I-00168 Rome, ItalyUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Med Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Dermatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Med Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Dermatol, São Paulo, BrazilWeb of Scienc