Computer simulation of the phase diagram for a fluid confined in a fractal and disordered porous material

We present a grand canonical Monte Carlo simulation study of the phase diagram of a Lennard-Jones fluid adsorbed in a fractal and highly porous aerogel. The gel environment is generated from an off-lattice diffusion limited cluster-cluster aggregation process. Simulations have been performed with the multicanonical ensemble sampling technique. The biased sampling function has been obtained by histogram reweighting calculations. Comparing the confined and the bulk system liquid-vapor coexistence curves we observe a decrease of both the critical temperature and density in qualitative agreement with experiments and other Monte Carlo studies on Lennard-Jones fluids confined in random matrices of spheres. At variance with these numerical studies we do not observe upon confinement a peak on the liquid side of the coexistence curve associated with a liquid-liquid phase coexistence. In our case only a shouldering of the coexistence curve appears upon confinement. This shoulder can be associated with high density fluctuations in the liquid phase. The coexisting vapor and liquid phases in our system show a high degree of spatial disorder and inhomogeneity.Comment: 8 pages, 8 figures, to be published in Phys. Rev.

Liquid-liquid coexistence in the phase diagram of a fluid confined in fractal porous materials

Multicanonical ensemble sampling simulations have been performed to calculate the phase diagram of a Lennard-Jones fluid embedded in a fractal random matrix generated through diffusion limited cluster aggregation. The study of the system at increasing size and constant porosity shows that the results are independent from the matrix realization but not from the size effects. A gas-liquid transition shifted with respect to bulk is found. On growing the size of the system on the high density side of the gas-liquid coexistence curve it appears a second coexistence region between two liquid phases. These two phases are characterized by a different behaviour of the local density inside the interconnected porous structure at the same temperature and chemical potential.Comment: 5 pages, 4 figures. To be published in Europhys. Letter

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Severidade da mancha foliar de diplodia (Stenocarpella macrospora) e sua relação com a incidência do patógeno e a germinação, em grãos de híbridos comerciais e experimentais de milho (Zea mays L.).

O fungo Stenocarpella macrospora (Sin. Diplodia macrospora) é um dos patógenos associados ao complexo de podridões de colmo e espiga e, em híbridos suscetíveis, pode causar também grandes lesões foliares. O objetivo deste trabalho foi avaliar a severidade do fungo via mancha foliar (Stenocarpella macrospora) e a sua relação com a incidência do patógeno em grãos de milho, bem como avaliar o efeito dessa incidência sobre a germinação de grãos de diferentes híbridos de milho. Para tanto, foram instalados experimentos com híbridos comerciais e experimentais em dois anos consecutivos (2002/2003 e 2003/2004), no campo experimental da Dow AgroSciences, no município de Uberaba (MG)

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

Cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exerts antineoplastic effects on various types of human cancer. We recently showed that treatment with 15d-PGJ2 induces apoptosis accompanied by downregulation of the oncogenic signal transducer and activator of transcription 3 (Stat3) signalling in human oral squamous cell carcinoma (SCC) cells. The current study examines the effects of 15d-PGJ2 on the epidermal growth factor receptor (EGFR) and Janus Kinase (JAK)-mediated signalling pathways. Inhibition of Stat3 by 15d-PGJ2 was abolished by exogenous stimulation with transforming growth factor alpha (TGF-α), but not interleukin 6 (IL-6), supporting a selective effect of 15d-PGJ2 on IL-6-mediated signalling. Importantly, 15d-PGJ2 selectively abrogated constitutive and IL-6-mediated JAK phosphorylation without affecting EGFR-activated levels. Moreover, the inhibitory effect of 15d-PGJ2 on JAK signalling required the reactive α,β-unsaturated carbon within the cyclopentenone ring. Targeting of JAK signalling using a specific JAK inhibitor also abolished Stat3 phosphorylation and resulted in apoptosis in oral SCC cells. Our findings provide the first evidence for 15d-PGJ2–mediated downregulation of constitutive and IL-6-induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR-independent Stat3 activation by 15d-PGJ2 represent a promising approach for induction of apoptosis in oral SCC cells

Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition

OPN/CD44v6 overexpression in laryngeal dysplasia and correlation with clinical outcome

Laryngeal dysplasia is a common clinical concern. Despite major advancements, a significant number of patients with this condition progress to invasive squamous cell carcinoma. Osteopontin (OPN) is a secreted glycoprotein, whose expression is markedly elevated in several types of cancers. We explored OPN as a candidate biomarker for laryngeal dysplasia. To this aim, we examined OPN expression in 82 cases of dysplasia and in hyperplastic and normal tissue samples. OPN expression was elevated in all severe dysplasia samples, but not hyperplastic samples, with respect to matched normal mucosa. OPN expression levels correlated positively with degree of dysplasia (P=0.0094) and negatively with disease-free survival (P<0.0001). OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. CD44v6 expression correlated negatively with disease-free survival, as well (P=0.0007). Taken as a whole, our finding identify OPN and CD44v6 as predictive markers of recurrence or aggressiveness in laryngeal intraepithelial neoplasia, and overall, point out an important signalling complex in the evolution of laryngeal dysplasia

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Background Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Methods Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Results Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. Conclusion For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further

A new RASS galaxy cluster catalogue with low contamination extending to z similar to 1 in the DES overlap region

We present the MARD-Y3 catalogue of between 1086 and 2171 galaxy clusters (52 per cent and 65 per cent new) produced using multicomponent matched filter (MCMF) follow-up in 5000 deg2 of DES-Y3 optical data of the ∼20 000 overlapping ROSAT All-Sky Survey source catalogue (2RXS) X-ray sources. Optical counterparts are identified as peaks in galaxy richness as a function of redshift along the line of sight towards each 2RXS source within a search region informed by an X-ray prior. All peaks are assigned a probability fcont of being a random superposition. The clusters lie at 0.02 <z< 1.1 with more than 100 clusters at z > 0.5. Residual contamination is 2.6 per cent and 9.6 per cent for the cuts adopted here. For each cluster we present the optical centre, redshift, rest frame X-ray luminosity, M500 mass, coincidence with NWAY infrared sources, and estimators of dynamical state. About 2 per cent of MARD-Y3 clusters have multiple possible counterparts, the photo-z’s are high quality with σ z/(1 + z) = 0.0046, and ∼1 per cent of clusters exhibit evidence of X-ray luminosity boosting from emission by cluster active galactic nuclei. Comparison with other catalogues (MCXC, RM, SPT-SZ, Planck) is performed to test consistency of richness, luminosity, and mass estimates. We measure the MARD-Y3 X-ray luminosity function and compare it to the expectation from a fiducial cosmology and externally calibrated luminosity- and richness–mass relations. Agreement is good, providing evidence that MARD-Y3 has low contamination and can be understood as a simple two step selection – X-ray and then optical – of an underlying cluster population described by the halo mass function