Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program

Tissue and vessel wall stiffening alters endothelial cell properties and contributes to vascular dysfunction. However, whether extracellular matrix (ECM) stiffness impacts vascular development is not known. Here we show that matrix stiffness controls lymphatic vascular morphogenesis. Atomic force microscopy measurements in mouse embryos reveal that venous lymphatic endothelial cell (LEC) progenitors experience a decrease in substrate stiffness upon migration out of the cardinal vein, which induces a GATA2-dependent transcriptional program required to form the first lymphatic vessels. Transcriptome analysis shows that LECs grown on a soft matrix exhibit increased GATA2 expression and a GATA2-dependent upregulation of genes involved in cell migration and lymphangiogenesis, including VEGFR3. Analyses of mouse models demonstrate a cell-autonomous function of GATA2 in regulating LEC responsiveness to VEGF-C and in controlling LEC migration and sprouting in vivo. Our study thus uncovers a mechanism by which ECM stiffness dictates the migratory behavior of LECs during early lymphatic development.Peer reviewe

Reggeon exchange from gauge/gravity duality

We perform the analysis of quark-antiquark Reggeon exchange in meson-meson scattering, in the framework of the gauge/gravity correspondence in a confining background. On the gauge theory side, Reggeon exchange is described as quark-antiquark exchange in the t channel between fast projectiles. The corresponding amplitude is represented in terms of Wilson loops running along the trajectories of the constituent quarks and antiquarks. The paths of the exchanged fermions are integrated over, while the "spectator" fermions are dealt with in an eikonal approximation. On the gravity side, we follow a previously proposed approach, and we evaluate the Wilson-loop expectation value by making use of gauge/gravity duality for a generic confining gauge theory. The amplitude is obtained in a saddle-point approximation through the determination near the confining horizon of a Euclidean "minimal surface with floating boundaries", i.e., by fixing the trajectories of the exchanged quark and antiquark by means of a minimisation procedure, which involves both area and length terms. After discussing, as a warm-up exercise, a simpler problem on a plane involving a soap film with floating boundaries, we solve the variational problem relevant to Reggeon exchange, in which the basic geometry is that of a helicoid. A compact expression for the Reggeon-exchange amplitude, including the effects of a small fermion mass, is then obtained through analytic continuation from Euclidean to Minkowski space-time. We find in particular a linear Regge trajectory, corresponding to a Regge-pole singularity supplemented by a logarithmic cut induced by the non-zero quark mass. The analytic continuation leads also to companion contributions, corresponding to the convolution of the same Reggeon-exchange amplitude with multiple elastic rescattering interactions between the colliding mesons.Comment: 60+1 pages, 14 figure

Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis

<p>Abstract</p> <p>Background</p> <p>Timely identification of pathogens is crucial to minimize mortality in patients with severe infections. Detection of bacterial and fungal pathogens in blood by nucleic acid amplification promises to yield results faster than blood cultures (BC). We analyzed the clinical impact of a commercially available multiplex PCR system in patients with suspected sepsis.</p> <p>Methods</p> <p>Blood samples from patients with presumed sepsis were cultured with the Bactec 9240™ system (Becton Dickinson, Heidelberg, Germany) and aliquots subjected to analysis with the LightCycler^®SeptiFast^®(SF) Test (Roche Diagnostics, Mannheim, Germany) at a tertiary care centre. For samples with PCR-detected pathogens, the actual impact on clinical management was determined by chart review. Furthermore a comparison between the time to a positive blood culture result and the SF result, based on a fictive assumption that it was done either on a once or twice daily basis, was made.</p> <p>Results</p> <p>Of 101 blood samples from 77 patients, 63 (62%) yielded concordant negative results, 14 (13%) concordant positive and 9 (9%) were BC positive only. In 14 (13%) samples pathogens were detected by SF only, resulting in adjustment of antibiotic therapy in 5 patients (7,7% of patients). In 3 samples a treatment adjustment would have been made earlier resulting in a total of 8 adjustments in all 101 samples (8%).</p> <p>Conclusion</p> <p>The addition of multiplex PCR to conventional blood cultures had a relevant impact on clinical management for a subset of patients with presumed sepsis.</p

Quality evaluation of olive oil by statistical analysis of multicomponent stable isotope dilution assay data of aroma active compounds

An instrumental method for the evaluation of olive oil quality was developed. Twenty-one relevant aroma active compounds were quantified in 95 olive oil samples of different quality by headspace solid phase microextraction (HS-SPME) and dynamic headspace coupled to GC-MS. On the basis of these stable isotope dilution assay results, statistical evaluation by partial least-squares discriminant analysis (PLS-DA) was performed. Important variables were the odor activity values of ethyl isobutanoate, ethyl 2-methylbutanoate, 3-methylbutanol, butyric acid, E,E-2,4-decadienal, hexanoic acid, guaiacol, 2-phenylethanol, and the sum of the odor activity values of Z-3-hexenal, E-2-hexenal, Z-3-hexenyl acetate, and Z-3-hexenol. Classification performed with these variables predicted 88% of the olive oils? quality correctly. Additionally, the aroma compounds, which are characteristic for some off-flavors, were dissolved in refined plant oil. Sensory evaluation of these models demonstrated that the off-flavors rancid, fusty, and vinegary could be successfully simulated by a limited number of odorants

Paternity of Subordinates Raises Cooperative Effort in Cichlids

Background In cooperative breeders, subordinates generally help a dominant breeding pair to raise offspring. Parentage studies have shown that in several species subordinates can participate in reproduction. This suggests an important role of direct fitness benefits for cooperation, particularly where groups contain unrelated subordinates. In this situation parentage should influence levels of cooperation. Here we combine parentage analyses and detailed behavioural observations in the field to study whether in the highly social cichlid Neolamprologus pulcher subordinates participate in reproduction and if so, whether and how this affects their cooperative care, controlling for the effect of kinship. Methodology/Principal Findings We show that: (i) male subordinates gained paternity in 27.8% of all clutches and (ii) if they participated in reproduction, they sired on average 11.8% of young. Subordinate males sharing in reproduction showed more defence against experimentally presented egg predators compared to subordinates not participating in reproduction, and they tended to stay closer to the breeding shelter. No effects of relatedness between subordinates and dominants (to mid-parent, dominant female or dominant male) were detected on parentage and on helping behaviour. Conclusions/Significance This is the first evidence in a cooperatively breeding fish species that the helping effort of male subordinates may depend on obtained paternity, which stresses the need to consider direct fitness benefits in evolutionary studies of helping behaviour

Technikgenese: Einflußfaktoren der Technisierung jenseits traditioneller Technikfolgenforschung

Ausgehend davon, daß das Verhältnis von Technikgeneseforschung zu Technikfolgenforschung komplementär sein muß, werden in dem Beitrag die strukturellen, institutionellen und organisatorischen, die kognitiven wie perzeptiven Voraussetzungen dafür untersucht, welche Technikfolgen wie systematisch und rational in frühen Phasen der Technikentstehung wahrgenommen, berücksichtigt und technisch umgesetzt werden und welche nicht, um in der sozialwissenschaftlichen Rekonstruktion der Bedingungen technischer Innovationen die gesellschaftlichen und organisatorischen Einflußparameter, die Selektionsprozesse bei der Neueinführung von Techniken prägen, manifest werden zu lassen. Ziele und Grundlagen der sozialwissenschaftlichen Technikgeneseforschung werden dargestellt. Indem Technikgenese in organisationskulturellen Kontexten analysiert wird, wird ein neuer Forschungsansatz konzipiert, der im Kern beansprucht, das Selektions- und Entscheidungsverhalten von Organisationen mit Hilfe von Erklärungskategorien zu erfassen. Der zentrale Beitrag des organisationskulturellen Forschungsansatzes der Technikgenese liegt in der Möglichkeit, diejenigen Faktoren herauszukristallisieren, die eine Organisation dazu befähigen, innovative Impulse selbst zu generieren oder entsprechende Stimuli aus ihrer Umwelt aufzunehmen und umzusetzen. Abschließend wird das weitere Vorgehen sozialwissenschaftlicher Forschung zur Technikgenese skizziert. (ICA

Phenolic compounds of Galega Vulgar and Cobrançosa olive oils along early ripening stages

In this study, the lipophilic and hydrophilic phenol composition of virgin olive oils (VOO) obtained from olives from two of the most important Portuguese cultivars (‘Galega Vulgar’ and ‘Cobrançosa’), harvested at different ripening stages and under two irrigation schemes (rain fed and irrigated), was evaluated. Phenolic alcohols (hydroxytyrosol and tyrosol), phenolic acids and derivatives and flavonoids (luteolin and apigenin), as well as tocopherols were quantified. Lipophilic (>300 mg kg 1) and hydrophilic phenols (>600 mg kg 1) were present in high contents in both VOO, for early ripening stages. Gamma-tocopherol content is higher in ‘Galega Vulgar’ VOO. Total phenols showed a decrease between ripening index 2.5 and 3.5. The dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), also known as oleacein, was the major phenolic compound identified in both oils. The concentration of free hydroxytyrosol and tyrosol in both VOO is very low while their esterified derivatives, like 3,4-DHPEA-EDA and p- HPEA-EDA, are much more abundantinfo:eu-repo/semantics/publishedVersio

Helper Response to Experimentally Manipulated Predation Risk in the Cooperatively Breeding Cichlid Neolamprologus pulcher

Background We manipulated predation risk in a field experiment with the cooperatively breeding cichlid Neolamprologus pulcher by releasing no predator, a medium- or a large-sized fish predator inside underwater cages enclosing two to three natural groups. We assessed whether helpers changed their helping behaviour, and whether within-group conflict changed, depending on these treatments, testing three hypotheses: ‘pay-to-stay’ PS, ‘risk avoidance’ RA, or (future) reproductive benefits RB. We also assessed whether helper food intake was reduced under risk, because this might reduce investments in other behaviours to save energy. Methodology/Principal Findings Medium and large helpers fed less under predation risk. Despite this effect helpers invested more in territory defence, but not territory maintenance, under the risk of predation (supporting PS). Experimentally covering only the breeding shelter with sand induced more helper digging under predation risk compared to the control treatment (supporting PS). Aggression towards the introduced predator did not differ between the two predator treatments and increased with group member size and group size (supporting PS and RA). Large helpers increased their help ratio (helping effort/breeder aggression received, ‘punishment’ by the dominant pair in the group) in the predation treatments compared to the control treatment, suggesting they were more willing to PS. Medium helpers did not show such effects. Large helpers also showed a higher submission ratio (submission/ breeder aggression received) in all treatments, compared to the medium helpers (supporting PS). Conclusions/Significance We conclude that predation risk reduces helper food intake, but despite this effect, helpers were more willing to support the breeders, supporting PS. Effects of breeder punishment suggests that PS might be more important for large compared to the medium helpers. Evidence for RA was also detected. Finally, the results were inconsistent with RB