Spontaneous cell polarization: Feedback control of Cdc42 GTPase breaks cellular symmetry.

Spontaneous polarization without spatial cues, or symmetry breaking, is a fundamental problem of spatial organization in biological systems. This question has been extensively studied using yeast models, which revealed the central role of the small GTPase switch Cdc42. Active Cdc42-GTP forms a coherent patch at the cell cortex, thought to result from amplification of a small initial stochastic inhomogeneity through positive feedback mechanisms, which induces cell polarization. Here, I review and discuss the mechanisms of Cdc42 activity self-amplification and dynamic turnover. A robust Cdc42 patch is formed through the combined effects of Cdc42 activity promoting its own activation and active Cdc42-GTP displaying reduced membrane detachment and lateral diffusion compared to inactive Cdc42-GDP. I argue the role of the actin cytoskeleton in symmetry breaking is not primarily to transport Cdc42 to the active site. Finally, negative feedback and competition mechanisms serve to control the number of polarization sites.

STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and meta-analysis.

AIM: The prediction of return of spontaneous circulation (ROSC) during resuscitation of patients suffering of cardiac arrest (CA) is particularly challenging. Regional cerebral oxygen saturation (rSO2) monitoring through near-infrared spectrometry is feasible during CA and could provide guidance during resuscitation. METHODS: We conducted a systematic review and meta-analysis on the value of rSO2 in predicting ROSC both after in-hospital (IH) or out-of-hospital (OH) CA. Our search included MEDLINE (PubMed) and EMBASE, from inception until April 4th, 2015. We included studies reporting values of rSO2 at the beginning of and/or during resuscitation, according to the achievement of ROSC. RESULTS: A total of nine studies with 315 patients (119 achieving ROSC, 37.7%) were included in the meta-analysis. The majority of those patients had an OHCA (n=225, 71.5%; IHCA: n=90, 28.5%). There was a significant association between higher values of rSO2 and ROSC, both in the overall calculation (standardized mean difference, SMD -1.03; 95%CI -1.39,-0.67; p<0.001), and in the subgroups analyses (rSO2 at the beginning of resuscitation: SMD -0.79; 95%CI -1.29,-0.30; p=0.002; averaged rSO2 value during resuscitation: SMD -1.28; 95%CI -1.74,-0.83; p<0.001). CONCLUSIONS: Higher initial and average regional cerebral oxygen saturation values are both associated with greater chances of achieving ROSC in patients suffering of CA. A note of caution should be made in interpreting these results due to the small number of patients and the heterogeneity in study design: larger studies are needed to clinically validate cut-offs for guiding cardiopulmonary resuscitation.

Spontaneous perforation of gallbladder with intrahepatic biloma formation: sonographic signs and correlation with computed tomography

Spontaneous perforation of gallbladder is a severe and infrequent complication of acute cholecystitis that requires early and accurate diagnosis. Concomitant development of intrahepatic collections is rarely observed in such cases. The present report emphasizes the relevance of imaging studies in this setting, describing the typical sonographic and tomographic findings for the diagnosis of such condition.

Spontaneous rupture of ovarian cystadenocarcinoma: pre- and post-rupture computed tomography evaluation

AbstractEpithelial ovarian tumors are the most common malignant ovarian neoplasms and, in most cases, eventual rupture of such tumors is associated with a surgical procedure. The authors report the case of a 54-year-old woman who presented with spontaneous rupture of ovarian cystadenocarcinoma documented by computed tomography, both before and after the event. In such cases, a post-rupture staging tends to be less favorable, compromising the prognosis.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Investigating the spontaneous formation of SDS micelle in aqueous solution using a coarse-grained force field

A 1µs Molecular Dynamic simulation was performed with a realistic model system of Sodium Dodecyl Sulfate (SDS) micelles in aqueous solution, comprising of 360 DS-, 360 Na+ and 90000 water particles. After 300 ns three different micellar shapes and sizes 41, 68 and 95 monomers, were observed. The process led to stabilization in the total number of SDS clusters and an increase in the micellar radius to 2.23 nm, in agreement with experimental results. An important conclusion, is be aware that simulations employed in one aggregate, should be considered as a constraint. Size and shape distribution must be analyzed.

Physicochemical properties of lecithin-based nanoemulsions obtained by spontaneous emulsification or high-pressure homogenization

Nanoemulsions composed of a medium-chain triglyceride oil core stabilized by rapeseed or sunflower lecithins were prepared by spontaneous emulsification and high-pressure homogenization. These nanoemulsions are compared with formulations stabilized by egg lecithin. Nanoemulsions obtained by high-pressure homogenization display larger droplet size (230 to 440 nm) compared with those obtained by spontaneous emulsification (190 to 310 nm). The zeta potentials of the emulsions were negative and below -25 mV. Zeta potential inversion occurred between pH 3.0 and 4.0. The results demonstrate the feasibility of preparing lipid emulsions comprising rapeseed or sunflower lecithins by spontaneous emulsification and high-pressure homogenization.

AVOIDING FIRST-YEAR UNIVERSITY CHEMISTRY TEXTBOOKS’ MISREPRESENTATIONS IN THE TEACHING OF SPONTANEOUS REACTIONS

This paper summarizes the misrepresentations related to Gibbs energy in general chemistry textbooks. These misrepresentations arise from a problem in the terminology textbooks use. Thus, after reviewing the proper definition of each of the terms analyzed, we present two problems to exemplify the correct treatment of the quantities involved, which may help in the discussion and clarification of the misleading conventions and assumptions reported in this study.

Spontaneous rupture of renal angiomyolipoma during pregnancy

Renal angiomyolipoma is a benign tumor, composed of adipocytes, smooth muscle cells and blood vessels. The association with pregnancy is rare and related with an increased risk of complications, including rupture with massive retroperitoneal hemorrhage. The follow-up is controversial because of the lack of known cases, but the priorities are: timely diagnosis in urgent cases and a conservative treatment when possible. The mode of delivery is not consensual and should be individualized to each case. We report a case of a pregnant woman with 18 weeks of gestation admitted in the emergency room with an acute right low back pain with no other symptoms. The diagnosis of rupture of renal angiomyolipoma was established by ultrasound and, due to hemodinamically stability, conservative treatment with imaging and clinical monitoring was chosen. At 35 weeks of gestation, it was performed elective cesarean section without complications for both mother and fetus.

Do induced twin pregnancies influence the obstetric and neonatal results of multiple births born before 32 weeks? Comparison to spontaneous gestation

PURPOSE: To compare obstetric outcomes of induced preterm twin births (under 32 weeks gestation) with those spontaneously conceived. METHODS: Prospective study of twin pregnancies (25 induced and 157 spontaneously conceived) developed over a period of 16 years in a tertiary obstetric center. Demographic factors, obstetric complications, gestational age at delivery, mode of delivery, birth weight and immediate newborn outcome were compared. RESULTS: The analysis of obstetrical complications concerning urinary or other infections, hypertensive disorders of pregnancy, gestational diabetes, fetal malformations, intrauterine fetal death, intrauterine growth restriction and intrauterine discordant growth reveal no significant statistical differences between the two groups. First trimester bleeding was higher in the induced group (24 versus 8.3%, p=0.029). The cesarean delivery rate was 52.2% in spontaneous gestations and 64% in induced gestations. Gestational age at delivery, birth weight, Apgar scores at first and fifth minutes, admissions to Neonatal Intensive Care Unit and puerperal complications show no statistically significant differences between the two groups. These results were independent of chorionicity and induction method. CONCLUSION: The mode of conception did not influence obstetric and neonatal outcomes. Although induced pregnancies have higher risk of first trimester bleeding, significant differences were not observed regarding other obstetric and puerperal complications and neonatal results.

Spontaneous poisoning by larvae of Perreyia flavipes (Pergidae) in sheep

From a flock of 175 Texel sheep 25 animals died after consumption of a sawfly larvae subsequently identified as Perreyia flavipes. The disease occurred in June-July 2006 on a farm located in the county of Encruzilhada do Sul, Rio Grande do Sul, Brazil. Although there were 11 cattle in the same paddock, none of them was affected. High numbers of compact masses containing up to 150 larvae were scattered in the paddock where the animals were grazing. Most affected sheep showed severe apathy during 24-36 h before death, but weakness, muscular tremors and depression were also observed. Necropsy was performed on six sheep and the main macroscopic lesions were hemorrhages in the subcutaneous tissues, endocardium, gallbladder wall, and abomasal mucosa. In all animals was found hydrothorax, hydropericardium, ascites, and mild jaundice. Edema in the abomasal folds, mesentery, perirenal tissues, and gallbladder wall were also seen. The livers were yellowish with disseminated pinpoint hemorrhages in the parenchyma and had an enhanced lobular pattern. Perreyia flavipes larval body fragments and heads were found in the forestomach contents of the six sheep. Feces were scant, dry and formed balls coated by mucus and streaks of blood. Similar contents were also present at the end of the cecum. Prominent microscopic lesions included severe and diffuse periacinar or massive necrosis of hepatocytes associated with multifocal random hemorrhages. Diffuse necrosis of lymphoid follicles in lymph nodes and Peyer's patches, lymphoid depletion and necrosis in germinative centers of the spleen, and diffuse vacuolization in the renal tubular epithelia were also seen.