Quasi-Stationary Distributions for Models of Heterogeneous Catalysis

We construct the quasi-stationary (QS) distribution for two models of heterogeneous catalysis having two absorbing states: the ZGB model for the oxidation of CO, and a version with noninstantaneous reactions. Using a mean-field-like approximation, we study the quasi-stationary surface coverages, moment ratios and the lifetime of the QS state. We also derive an improved, consistent one-site mean-field theory for the ZGB model.Comment: 18 pages, 13 figure

Small GTPases and formins in mammalian oocyte maturation: cytoskeletal organizers

The maturation process of mammalian oocytes accompanies an extensive rearrangement of the cytoskeleton and associated proteins. As this process requires a delicate interplay between the cytoskeleton and its regulators, it is often targeted by various external and internal adversaries that affect the congression and/or segregation of chromosomes. Asymmetric cell division in oocytes also requires specific regulators of the cytoskeleton, including formin-2 and small GTPases. Recent literature providing clues regarding how actin filaments and microtubules interact during spindle migration in mouse oocytes are highlighted in this review

Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.

Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer

Cranial biomechanics in basal urodeles: the Siberian salamander (Salamandrella keyserlingii) and its evolutionary and developmental implications

Developmental changes in salamander skulls, before and after metamorphosis, afect the feeding capabilities of these animals. How changes in cranial morphology and tissue properties afect the function of the skull are key to decipher the early evolutionary history of the crown-group of salamanders. Here, 3D cranial biomechanics of the adult Salamandrella keyserlingii were analyzed under diferent tissue properties and ossifcation sequences of the cranial skeleton. This helped unravel that: (a) Mechanical properties of tissues (as bone, cartilage or connective tissue) imply a consensus between the stifness required to perform a function versus the fxation (and displacement) required with the surrounding skeletal elements. (b) Changes on the ossifcation pattern, producing fontanelles as a result of bone loss or failure to ossify, represent a trend toward simplifcation potentially helping to distribute stress through the skull, but may also imply a major destabilization of the skull. (c) Bone loss may be originated due to biomechanical optimization and potential reduction of developmental costs. (d) Hynobiids are excellent models for biomechanical reconstruction of extinct early urodeles

A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats

Accepted ManuscriptChronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.CPN was funded by CIHR Vanier Graduate Scholarship (338319); APVS was funded by Fundação para a Ciência e Tecnologia (SFRH/BPD/52078/2013); ERH was funded by CIHR Postdoctoral Fellowship (MFE-123712); SA was funded by a Queen Elizabeth II Graduate Scholarship in Science and Technology; ÉCD was funded by the Canadian Institute of Health Research (MOP-25953)info:eu-repo/semantics/publishedVersio

New highlights on stroma–epithelial interactions in breast cancer

Although the stroma in which carcinomas arise has been previously regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of tumor cells, it is now generally acknowledged that stromal changes are required for the establishment of cancer. In the present article, we discuss three recent publications that highlight the complex role the stroma has during the development of cancer and the potential for targeting the stroma by therapeutic approaches

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis

Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion:Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal

AbstractOver the last 15years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: “how does an ischemic stroke evolve?” Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi-automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model applied to ischemic stroke, we have insights into relevant microscopic dynamic models simulating the evolution of brain ischemia in the hope to further promising and challenging 4D imaging-based dynamic models. By depicting the major pitfalls and the advanced aspects of the different reviewed methods, we present an overall critique of their performances and concluded our discussion by suggesting some recommendations for future research work focusing on one or more of the three addressed problems

SIP metagenomics identifies uncultivated Methylophilaceae as dimethylsulphide degrading bacteria in soil and lake sediment.

Dimethylsulphide (DMS) has an important role in the global sulphur cycle and atmospheric chemistry. Microorganisms using DMS as sole carbon, sulphur or energy source, contribute to the cycling of DMS in a wide variety of ecosystems. The diversity of microbial populations degrading DMS in terrestrial environments is poorly understood. Based on cultivation studies, a wide range of bacteria isolated from terrestrial ecosystems were shown to be able to degrade DMS, yet it remains unknown whether any of these have important roles in situ. In this study, we identified bacteria using DMS as a carbon and energy source in terrestrial environments, an agricultural soil and a lake sediment, by DNA stable isotope probing (SIP). Microbial communities involved in DMS degradation were analysed by denaturing gradient gel electrophoresis, high-throughput sequencing of SIP gradient fractions and metagenomic sequencing of phi29-amplified community DNA. Labelling patterns of time course SIP experiments identified members of the Methylophilaceae family, not previously implicated in DMS degradation, as dominant DMS-degrading populations in soil and lake sediment. Thiobacillus spp. were also detected in (13)C-DNA from SIP incubations. Metagenomic sequencing also suggested involvement of Methylophilaceae in DMS degradation and further indicated shifts in the functional profile of the DMS-assimilating communities in line with methylotrophy and oxidation of inorganic sulphur compounds. Overall, these data suggest that unlike in the marine environment where gammaproteobacterial populations were identified by SIP as DMS degraders, betaproteobacterial Methylophilaceae may have a key role in DMS cycling in terrestrial environments.HS was supported by a UK Natural Environment Research Council Advanced Fellowship NE/E013333/1), ÖE by a postgraduate scholarship from the University of Warwick and an Early Career Fellowship from the Institute of Advanced Study, University of Warwick, UK, respectively. Lawrence Davies is acknowledged for help with QIIME