Patterning and dynamics of membrane adhesion under hydraulic stress

Hydraulic fracturing plays a major role in cavity formation during embryonic development, when pressurized fluid opens microlumens at cell-cell contacts, which evolve to form a single large lumen. However, the fundamental physical mechanisms behind these processes remain masked by the complexity and specificity of biological systems. Here, we show that adhered lipid vesicles subjected to osmotic stress form hydraulic microlumens similar to those in cells. Combining vesicle experiments with theoretical modelling and numerical simulations, we provide a physical framework for the hydraulic reconfiguration of cell-cell adhesions. We map the conditions for microlumen formation from a pristine adhesion, the emerging dynamical patterns and their subsequent maturation. We demonstrate control of the fracturing process depending on the applied pressure gradients and the type and density of membrane bonds. Our experiments further reveal an unexpected, passive transition of microlumens to closed buds that suggests a physical route to adhesion remodeling by endocytosis

Effect of 20 mg Fluorogestone Acetate (FGA) Sponges on Reproductive Parameters of Dairy Ovine Breeds in Southern Italy

Background: Intravaginal devices containing progestins are widely used for oestrus synchronization in sheep. Progestins give economic benefits to farmers but may have some limitations and the efficacy strictly depends on farm management. There are different devices, with different molecules (progesterone, medroxyprogesterone acetate, fluorogestone acetate), different dosages and long (12-14 days) and short-term (5-7 days) protocols. Experimental studies often include a limited number of animals and are held at different latitudes and with different system of management. To our knowledge, there are few reports in the literature on field application of the recently licensed 20 mg fluorogestone acetate (FGA) sponges in large ewe flocks, excluding the registration trials. Materials, Methods & Results: This study was designed to evaluate oestrous synchronization in 2 different breeds. A total of 1100 Lacaune (L) and 618 Sarda (S) were assigned to 8 groups, comparing multiparous (M) and nulliparous (N) and those synchronized in November (n) and May (m). The animals were assigned to 8 groups: LMm (n. 556), LNm (n. 180), SMm (n. 70), SNm (n. 32), LMn (n. 242), LNn (n. 222), SMn (n. 440) e SNn (n. 76). The intravaginal sponge was inserted for 14 days. At sponge withdrawal, eCG (400 IU, IM) was injected, and rams were joined into flocks 30 h later with a male/female ratio of 1:8. Transrectal ultrasonography was performed for pregnancy diagnosis after 30 days. Fertility parameters such as oestrus (OR), pregnancy (PR), lambing rates (LR) and prolificacy were calculated. Fisher exact test was used to compare parameters of each group with the corresponding and significance was set at P < 0.01. The use of intravaginal sponges in this study was easily performed in all animals. In nulliparous groups, digital insertion of the sponge, instead of the applicator, was preferred to avoid discomfort. Sponge loss was observed in 2% of treated ewes. At the removal of the sponge, mild vaginal contamination was observed in 90% of the ewes. Ultrasound finding of embryo resorption, pseudopregnancy and pyometra were found in rates under 2%. The loss of pregnancy ranged from 0 to 3.6% without significant differences among groups. The SMn group showed the best performances (0.91 OR, 0.88 PR, 0.85 LR), significantly higher than the other groups. Prolificacy was maximum in the LMn (1.68) and minimum in the SNm group (1.06), without significant differences among groups. Discussion: The 14-day regimen based on 20 mg FGA-releasing intravaginal devices is an easy and satisfactory synchronization regimen to improve the productivity and the fertility of sheep farm, and this can be managed and optimized in different breeding conditions. In this study, Sarda breed shows a good adaption to the environment with adult ewes giving the best results in reproductive season. However young Sarda ewes were less productive especially in non-breading season. Lacaune showed good reproductive potential, young and adult ewes responded to progestins in reproductive and non-reproductive season. It was confirmed that the reproductive performance is affected by season, age, and breed. This study encourages the breeding of indigenous breeds by implementing the management with modern technologies. The imported highly productive breeds, if well managed, can give a production less influenced by seasonal variables and age. Keywords: ewe, sheep, Lacaune, Sarda, oestrus synchronization, progestins, intravaginal device, indigenous breeds

Il microcarcinoma papillare della tiroide. Implicazioni cliniche e strategia terapeutica

Gli Autori riportano la propria esperienza sulle implicazioni cli - niche e le strategie terapeutiche del microcarcinoma papillare della tiroide, valutando 412 pazienti sottoposti ad intervento chirurgico per patologia tiroidea. Essi sottolineano l’attuale problematica della diagnosi “incidentale” postoperatoria, la relativa strategia terapeutica adiuvante, il frequente riscontro di una patologia tiroidea benigna associata, fattori che giustificano, oltre le note motivazioni oncologi - che, la scelta della tiroidectomia totale di principio

The cosmic web of dwarf galaxies in a warm versus cold dark matter universe: mock galaxies in CDM and WDM simulations

Using cosmological simulations, we show that the cosmic web of dwarf galaxies in a warm dark matter (WDM) universe, wherein low mass halo formation is heavily suppressed, is nearly indistinguishable to that of a cold dark matter (CDM) universe whose low mass halos are not seen because galaxy formation is suppressed below some threshold mass. Low mass warm dark matter halos are suppressed nearly equally in all environments. For example, WDM voids in the galaxy distribution are neither larger nor emptier than CDM voids, once normalized to the same total galaxy number density and assuming galaxy luminosity scales with halo mass. It is thus a challenge to find hints about the dark matter particle in the cosmic web of galaxies. However, if the scatter between dwarf galaxy luminosity and halo properties is large, low mass CDM halos would sometimes host bright galaxies thereby populating voids that would be empty in WDM. Future surveys that will capture the small scale clustering in the local volume could thus help determine whether the CDM problem of the over-abundance of small halos with respect to the number density of observed dwarf galaxies has a cosmological solution or an astrophysical solution

Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients

The immune system seems to play a fundamental role in breast cancer responsiveness to chemotherapy. We investigated two peripheral indicators of immunity/inflammation, i.e. neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in order to reveal a possible relationship with pathological complete response (pCR) in patients with early or locally advanced breast cancer treated with neoadjuvant chemotherapy (NACT). We retrospectively analyzed 373 consecutive patients affected by breast cancer and candidates to NACT. The complete blood cell count before starting NACT was evaluated to calculate NLR and PLR. ROC curve analysis determined threshold values of 2.42 and 104.47 as best cut-off values for NLR and PLR, respectively. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ 2 or Fisher's exact test as appropriate. Univariate and multivariate analyses were performed using a logistic regression model. NLR and PLR were not significantly associated with pCR if analyzed separately. However, when combining NLR and PLR, patients with a NLRlow/PLRlow profile achieved a significantly higher rate of pCR compared to those with NLRhigh and/or PLRhigh (OR 2.29, 95% CI 1.22-4.27, p 0.009). Importantly, the predictive value of NLRlow/PLRlow was independent from common prognostic factors such as grading, Ki67, and molecular subtypes. The combination of NLR and PLR may reflect patients' immunogenic phenotype. Low levels of both NLR and PLR may thus indicate a status of immune system activation that may predict pCR in breast cancer patients treated with NACT

Probing deformed commutators with macroscopic harmonic oscillators

A minimal observable length is a common feature of theories that aim to merge quantum physics and gravity. Quantum mechanically, this concept is associated to a nonzero minimal uncertainty in position measurements, which is encoded in deformed commutation relations. In spite of increasing theoretical interest, the subject suffers from the complete lack of dedicated experiments and bounds to the deformation parameters are roughly extrapolated from indirect measurements. As recently proposed, low-energy mechanical oscillators could allow to reveal the effect of a modified commutator. Here we analyze the free evolution of high quality factor micro- and nano-oscillators, spanning a wide range of masses around the Planck mass $m_{\mathrm{P}}$ (${\approx 22\,\mu\mathrm{g}}$), and compare it with a model of deformed dynamics. Previous limits to the parameters quantifying the commutator deformation are substantially lowered.Comment: 11 pages, 3 figures, reference adde

Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial

Background: A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs). Patients & methods: Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks). Results: Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5). Conclusion: Capecitabine and gemcitabine is highly active in TETs