Pectin methyl esterases and rhamnogalacturonan hydrolases: weapons for successful Monilinia laxa infection in stone fruit?

The secretion of cell wall‐degrading enzymes is one of the mechanisms used by necrotrophic fungi to colonize host tissues. However, information about virulence factors of Monilinia spp., the causal agents of brown rot in stone fruit, is scarce. Plant cell walls have three main components that are broken down by fungal enzymes: cellulose, hemicellulose and pectin. In order to identify Monilinia laxa candidate proteins involved in pectin hydrolysis, two in vitro approaches were conducted: (i) phenotypic and ecophysiological characterization of growth of the pathogen at different pHs, in glucose‐ and pectin‐containing solid media for 7 days' incubation; and (ii) expression analysis of genes encoding M. laxa pectin methyl esterases (MlPMEs) and rhamnogalacturonan hydrolases (MlRG‐HYDs) after incubation for 0.5, 2, 6, 24 and 48 h in glucose‐ and pectin‐containing liquid media. Phenotypic tests showed the role of carbon source on M. laxa growth rate and aggressiveness, and indicated that pectinases were greatly affected by pH. Gene expression analyses uncovered differences among members of each family of pectinases and between the two families, defining sets of genes expressed at earlier (0.5–6 h) and later (48 h) phases. Notably, the up‐ or down‐regulation of these target genes was carbon source‐dependent. Finally, an in vivo study confirmed the synergistic and complementary role that these genes play in the M. laxa–stone fruit pathosystem. Based on these results, it is hypothesized that MlPME2, MlRG‐HYD1 and MlRG‐HYD2 may be potential virulence factors of M. laxa in the process from infection to colonization.info:eu-repo/semantics/acceptedVersio

Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing

Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forceswith their velocity. Implementing this idea in amechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters

The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling

Histone variants within the H2A family show high divergences in their C-terminal regions. In this work, we have studied how these divergences and in particular, how a part of the H2A COOH-terminus, the docking domain, is implicated in both structural and functional properties of the nucleosome. Using biochemical methods in combination with Atomic Force Microscopy and Electron Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within the nucleosome. Deletion of this domain or replacement with the incomplete docking domain from the variant H2A.Bbd results in significant structural alterations in the nucleosome, including an increase in overall accessibility to nucleases, un-wrapping of ∼10 bp of DNA from each end of the nucleosome and associated changes in the entry/exit angle of DNA ends. These structural alterations are associated with a reduced ability of the chromatin remodeler RSC to both remodel and mobilize the nucleosomes. Linker histone H1 binding is also abrogated in nucleosomes containing the incomplete docking domain of H2A.Bbd. Our data illustrate the unique role of the H2A-docking domain in coordinating the structural-functional aspects of the nucleosome properties. Moreover, our data suggest that incorporation of a ‘defective’ docking domain may be a primary structural role of H2A.Bbd in chromatin

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

The repulsive lattice gas, the independent-set polynomial, and the Lov\'asz local lemma

We elucidate the close connection between the repulsive lattice gas in equilibrium statistical mechanics and the Lovasz local lemma in probabilistic combinatorics. We show that the conclusion of the Lovasz local lemma holds for dependency graph G and probabilities {p_x} if and only if the independent-set polynomial for G is nonvanishing in the polydisc of radii {p_x}. Furthermore, we show that the usual proof of the Lovasz local lemma -- which provides a sufficient condition for this to occur -- corresponds to a simple inductive argument for the nonvanishing of the independent-set polynomial in a polydisc, which was discovered implicitly by Shearer and explicitly by Dobrushin. We also present some refinements and extensions of both arguments, including a generalization of the Lovasz local lemma that allows for "soft" dependencies. In addition, we prove some general properties of the partition function of a repulsive lattice gas, most of which are consequences of the alternating-sign property for the Mayer coefficients. We conclude with a brief discussion of the repulsive lattice gas on countably infinite graphs.Comment: LaTex2e, 97 pages. Version 2 makes slight changes to improve clarity. To be published in J. Stat. Phy

Formative Research on Perceptions of Biobanking: What Community Members Think

Preparing healthy community members with timely communications prior to engaging them in a request to donate biospecimens promises to improve the experience of biobanking participation. To this end, a qualitative study was conducted to assess community member knowledge, attitudes, beliefs, and informational needs about cancer-related biospecimen collection in a large metropolitan area in southwest Florida. The study utilized purposive sampling techniques to recruit a total of 95 participants to participate in 12 focus groups, segmented by race/ethnicity and language preference (mixed race, African American only, and Spanish speaking) and age (18–29, 30–54, and 55 and older). Focus group interviews were analyzed using content analysis to identify emergent themes. Overall, participants in the 30 years and older groups were favorable toward participating in biobanking if their concerns were addressed, such as confidentiality and consent issues, in contrast to participants aged 18–29 who were more skeptical. For all participants, the desire to participate in research that seeks new cancer treatments outweighed mistrust. Moreover, many cited the potential scientific benefit for future generations as a primary motivator. Finally, in some groups a therapeutic misconception was expressed, where participants expressed a willingness to forego confidentiality of their health status in exchange for therapeutic benefit. This study contributes to the literature on community perceptions of the benefits and barriers of biobanking and adds to the development of meaningful education communication priming tools to advance understandings about biobanking

Whole systems approaches to obesity and other complex public health challenges: a systematic review

Background: Increasing awareness of the complexity of public health problems, including obesity, has led to growing interest in whole systems approaches (WSAs), defined as those that consider the multifactorial drivers of overweight and obesity, involve transformative co-ordinated action across a broad range of disciplines and stakeholders, operate across all levels of governance and throughout the life course. This paper reports a systematic review of WSAs targeting obesity and other complex public health and societal issues, such as healthy lifestyles for prevention of non-communicable disease. Methods: Seven electronic databases were searched from 1995 to 2018. Studies were included if there had been an effort to implement a WSA. Study selection was conducted by one reviewer with a random 20% double checked. Data extraction and validity assessment were undertaken by one reviewer and checked by a second reviewer. Narrative synthesis was undertaken. Results: 65 articles were included; 33 about obesity. Most examined multicomponent community approaches, and there was substantial clinical and methodological heterogeneity. Nevertheless, a range of positive health outcomes were reported, with some evidence of whole systems thinking. Positive effects were seen on health behaviours, body mass index (BMI), parental and community awareness, community capacity building, nutrition and physical activity environments, underage drinking behaviour and health, safety and wellbeing of community members, self-efficacy, smoking and tobacco-related disease outcomes. Features of successful approaches reported in process evaluations included: full engagement of relevant partners and community; time to build relationships, trust and capacity; good governance; embedding within a broader policy context; local evaluation; finance. Conclusions: Systems approaches to tackle obesity can have some benefit, but evidence of how to operationalise a WSA to address public health problems is still in its infancy. Future research should: (a) develop an agreed definition of a WSA in relation to obesity, (b) look across multiple sectors to ensure consistency of language and definition, (c) include detailed descriptions of the approaches, and (d) include process and economic evaluations