Polymerizing the fibre between bacteria and host cells: the biogenesis of functional amyloid fibres

Amyloid fibres are proteinaceous aggregates associated with several human diseases, including Alzheimer's, Huntington's and Creutzfeldt Jakob's. Disease-associated amyloid formation is the result of proteins that misfold and aggregate into β sheet-rich fibre polymers. Cellular toxicity is readily associated with amyloidogenesis, although the molecular mechanism of toxicity remains unknown. Recently, a new class of ‘functional’ amyloid fibres was discovered that demonstrates that amyloids can be utilized as a productive part of cellular biology. These functional amyloids will provide unique insights into how amyloid formation can be controlled and made less cytotoxic. Bacteria produce some of the best-characterized functional amyloids, including a surface amyloid fibre called curli. Assembled by enteric bacteria, curli fibres mediate attachment to surfaces and host tissues. Some bacterial amyloids, like harpins and microcinE492, have exploited amyloid toxicity in a directed and functional manner. Here, we review and discuss the functional amyloids assembled by bacteria. Special emphasis will be paid to the biology of functional amyloid synthesis and the connections between bacterial physiology and pathology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75549/1/j.1462-5822.2008.01148.x.pd

Amortised Inference in Neural Networks for Small-Scale Probabilistic Meta-Learning

The global inducing point variational approximation for BNNs is based on using a set of inducing inputs to construct a series of conditional distributions that accurately approximate the conditionals of the true posterior distribution. Our key insight is that these inducing inputs can be replaced by the actual data, such that the variational distribution consists of a set of approximate likelihoods for each datapoint. This structure lends itself to amortised inference, in which the parameters of each approximate likelihood are obtained by passing each datapoint through a meta-model known as the inference network. By training this inference network across related datasets, we can meta-learn Bayesian inference over task-specific BNNs

Differentially private partitioned variational inference

Learning a privacy-preserving model from sensitive data which are distributed across multiple devices is an increasingly important problem. The problem is often formulated in the federated learning context, with the aim of learning a single global model while keeping the data distributed. Moreover, Bayesian learning is a popular approach for modelling, since it naturally supports reliable uncertainty estimates. However, Bayesian learning is generally intractable even with centralised non-private data and so approximation techniques such as variational inference are a necessity. Variational inference has recently been extended to the non-private federated learning setting via the partitioned variational inference algorithm. For privacy protection, the current gold standard is called differential privacy. Differential privacy guarantees privacy in a strong, mathematically clearly defined sense. In this paper, we present differentially private partitioned variational inference, the first general framework for learning a variational approximation to a Bayesian posterior distribution in the federated learning setting while minimising the number of communication rounds and providing differential privacy guarantees for data subjects. We propose three alternative implementations in the general framework, one based on perturbing local optimisation runs done by individual parties, and two based on perturbing updates to the global model (one using a version of federated averaging, the second one adding virtual parties to the protocol), and compare their properties both theoretically and empirically.Comment: Published in TMLR 04/2023: https://openreview.net/forum?id=55Bcghgic

Floral Color Properties of Serpentine Seep Assemblages Depend on Community Size and Species Richness

Functional traits, particularly those that impact fitness, can shape the ecological and evolutionary relationships among coexisting species of the same trophic level. Thus, examining these traits and properties of their distributions (underdispersion, overdispersion) within communities can provide insights into key ecological interactions (e.g., competition, facilitation) involved in community assembly. For instance, the distribution of floral colors in a community may reflect pollinator-mediated interactions between sympatric plant species, and the phylogenetic distribution of color can inform how evolutionary contingencies can continue to shape extant community assemblages. Additionally, the abundance and species richness of the local habitat may influence the type or strength of ecological interactions among co-occurring species. To evaluate the impact of community size and species richness on mechanisms shaping the distribution of ecologically relevant traits, we examined how floral color (defined by pollinator color vision models) is distributed within co-flowering assemblages. We modeled floral reflectance spectra of 55 co-flowering species using honeybee (Apis mellifera) and syrphid fly (Eristalis tenax) visual systems to assess the distributions of flower color across 14 serpentine seep communities in California. We found that phylogenetic relatedness had little impact on the observed color assemblages. However, smaller seep communities with lower species richness were more overdispersed for flower color than larger, more species-rich communities. Results support that competitive exclusion could be a dominant process shaping the species richness of flower color in smaller-sized communities with lower species richness, but this is less detectable or overwhelmed by other processes at larger, more speciose communities

Neoadjuvant chemoradiation compared to neoadjuvant radiation alone and surgery alone for Stage II and III soft tissue sarcoma of the extremities

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA).</p> <p>Methods</p> <p>We conducted a retrospective chart review of 112 cases.</p> <p>Results</p> <p>Treatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR.</p> <p>Conclusions</p> <p>NCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.</p

Tree of Sex: A database of sexual systems

The vast majority of eukaryotic organisms reproduce sexually, yet the nature of the sexual system and the mechanism of sex determination often vary remarkably, even among closely related species. Some species of animals and plants change sex across their lifespan, some contain hermaphrodites as well as males and females, some determine sex with highly differentiated chromosomes, while others determine sex according to their environment. Testing evolutionary hypotheses regarding the causes and consequences of this diversity requires interspecific data placed in a phylogenetic context. Such comparative studies have been hampered by the lack of accessible data listing sexual systems and sex determination mechanisms across the eukaryotic tree of life. Here, we describe a database developed to facilitate access to sexual system and sex chromosome information, with data on sexual systems from 11,038 plant, 705 fish, 173 amphibian, 593 non-avian reptilian, 195 avian, 479 mammalian, and 11,556 invertebrate species

The architecture of Abell 1386 and its relationship to the Sloan Great Wall

We present new radial velocities from AAOmega on the Anglo-Australian Telescope for 307 galaxies (b_J < 19.5) in the region of the rich cluster Abell 1386. Consistent with other studies of galaxy clusters that constitute sub-units of superstructures, we find that the velocity distribution of A1386 is very broad (21,000--42,000 kms^-1, or z=0.08--0.14) and complex. The mean redshift of the cluster that Abell designated as number 1386 is found to be ~0.104. However, we find that it consists of various superpositions of line-of-sight components. We investigate the reality of each component by testing for substructure and searching for giant elliptical galaxies in each and show that A1386 is made up of at least four significant clusters or groups along the line of sight whose global parameters we detail. Peculiar velocities of brightest galaxies for each of the groups are computed and found to be different from previous works, largely due to the complexity of the sky area and the depth of analysis performed in the present work. We also analyse A1386 in the context of its parent superclusters: Leo A, and especially the Sloan Great Wall. Although the new clusters may be moving toward mass concentrations in the Sloan Great Wall or beyond, many are most likely not yet physically bound to it.Comment: 21 pages, 9 figures, includes the full appendix table. Accepted for publication in MNRA

Multilocus Sex Determination Revealed in Two Populations of Gynodioecious Wild Strawberry, Fragaria vesca subsp bracteata

Gynodioecy, the coexistence of females and hermaphrodites, occurs in 20% of angiosperm families and often enables transitions between hermaphroditism and dioecy. Clarifying mechanisms of sex determination in gynodioecious species can thus illuminate sexual system evolution. Genetic determination of gynodioecy, however, can be complex and is not fully characterized in any wild species. We used targeted sequence capture to genetically map a novel nuclear contributor to male sterility in a self-pollinated hermaphrodite of Fragaria vesca subsp. bracteata from the southern portion of its range. To understand its interaction with another identified locus and possibly additional loci, we performed crosses within and between two populations separated by 2000 km, phenotyped the progeny and sequenced candidate markers at both sex-determining loci. The newly mapped locus contains a high density of pentatricopeptide repeat genes, a class commonly involved in restoration of fertility caused by cytoplasmic male sterility. Examination of all crosses revealed three unlinked epistatically interacting loci that determine sexual phenotype and vary in frequency between populations. Fragaria vesca subsp. bracteata represents the first wild gynodioecious species with genomic evidence of both cytoplasmic and nuclear genes in sex determination. We propose a model for the interactions between these loci and new hypotheses for the evolution of sex determining chromosomes in the subdioecious and dioecious Fragaria.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Genetics Society of America. The published article can be found at: http://www.g3journal.org/ Supporting data available online at: http://g3journal.org/content/5/12/2759/suppl/DC1Keywords: sex determination, dioecy, gynodioecy, Fragaria, male sterilityKeywords: sex determination, dioecy, gynodioecy, Fragaria, male sterilit