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We report the effects of quercetin, a flavonoid present in human diet, on early stage beta-amyloid (Aβ) aggregation – a seminal event in Alzheimer’s disease. Molecular level changes in Aβ arrangements are monitored by time-resolved emission spectral (TRES) measurements of the fluorescence of Aβ’s single tyrosine intrinsic fluorophore (Tyr). The results suggest that quercetin binds beta-amyloid oligomers at early stages of their aggregation, which leads to the formation of modified oligomers and hinders the creation of beta-sheet structures, potentially preventing the onset of Alzheimer’s disease.

Sizzled (Szl) is both a secreted frizzled related protein (sFRP) and a naturally occurring inhibitor of the zinc metalloproteinase bone morphogenetic protein-1 (BMP-1), a key regulator of extracellular matrix assembly and growth factor activation. Here we present a new crystal structure for Szl which differs from that previously reported by a large scale (90°) hinge rotation between its cysteine-rich and netrin-like domains. We also present results of a molecular docking analysis showing interactions likely to be involved in the inhibition of BMP-1 activity by Szl. When compared with known structures of BMP-1 in complex with small molecule inhibitors, this reveals features that may be helpful in the design of new inhibitors to prevent the excessive accumulation of extracellular matrix that is the hallmark of fibrotic diseases.

Plankton ecologists ultimately focus on forecasting, both applied and environmental outcomes. We review how appreciating planktonic ciliates has become central to these predictions. We explore the 350-year-old canon on planktonic ciliates and examine its steady progression, which has been punctuated by conceptual insights and technological breakthroughs. By reflecting on this process, we offer suggestions as to where future leaps are needed, with an emphasis on predicting outcomes of global warming. We conclude that in terms of climate change research: (i) climatic hotspots (e.g. polar oceans) require attention; (ii) simply adding ciliate measurements to zooplankton/phytoplankton-based sampling programs is inappropriate; (iii) elucidating the rare biosphere's functional ecology requires culture-independent genetic methods; (iv) evaluating genetic adaptation (microevolution) and population composition shifts is required; (v) contrasting marine and freshwaters needs attention; (vi) mixotrophy needs attention; (vii) laboratory and field studies must couple automated measurements and molecular assessment of functional gene expression; (viii) ciliate trophic diversity requires appreciation; and (ix) marrying gene expression and function, coupled with climate change scenarios is needed. In short, continued academic efforts and financial support are essential to achieve the above; these will lead to understanding how ciliates will respond to climate change, providing tools for forecasting.

The Ehlers–Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders. Vascular EDS (vEDS) is caused by pathogenic variants in COL3A1, most frequently glycine substitutions. We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance. Clinical and molecular data for seven families with three different Glu>Lys substitutions in COL3A1 were analyzed. These Glu>Lys variants were reclassified from variants of unknown significance to either pathogenic or likely pathogenic in accordance with American College of Medical Genetics and Genomics guidelines. All individuals with these atypical variants exhibited skin hyperextensibility as seen in individuals with classical EDS and classical-like EDS and evidence of tissue fragility as seen in individuals with vEDS. The clinical data demonstrate the overlap between the different EDS subtypes and underline the importance of next-generation sequencing gene panel analysis. The three different Glu>Lys variants point toward a new variant type in COL3A1 causative of vEDS, which has consistent clinical features. This is important knowledge for COL3A1 variant interpretation. Further follow-up data are required to establish the severity of tissue fragility complications compared with patients with other recognized molecular causes of vEDS.

The procollagen C-propeptides of the fibrillar collagens play key roles in the intracellular assembly of procollagen molecules from their constituent polypeptides chains, and in the extracellular assembly of collagen molecules into fibrils. Here we review recent advances in understanding the molecular mechanisms controlling C-propeptide trimerization which have revealed the importance of inter-chain disulphide bonding and a small number of charged amino acids in the stability and specificity of different types of chain association. We also show how the crystal structure of the complex between the C-propeptide trimer of procollagen III and the active fragment of procollagen C-proteinase enhancer-1 leads to a detailed model for accelerating release of the C-propeptides from procollagen by bone morphogenetic protein-1 and related proteinases. We then discuss the effects of disease-related missense mutations in the C-propeptides in relation to the sites of these mutations in the three-dimensional structure. While in general there is a good correlation between disease severity and structure-based predictions, there are notable exceptions, suggesting new interactions involving the C-propeptides yet to be characterized. Mutations affecting proteolytic release of the C-propeptides from procollagen are discussed in detail. Finally, the roles of recently discovered interaction partners for the C-propeptides are considered during fibril assembly and cross-linking.

Hip pathology is common amongst athletes and the general population. The mechanics of cycling have the potential to exacerbate symptomatic hip pathology and progress articular pathology in patients with morphologic risk factors such as femoroacetabular impingement. A professional fit of the bicycle to the individual which aims to optimize hip joint function can allow patients with hip pathology to exercise in comfort when alternative high impact exercise such as running may not be possible. Conversely improper fit of the bicycle can lead to hip symptoms in otherwise healthy individuals who present with risk factors for hip pain. Accordingly a bike fit can form part of the overall management strategy in a cyclist with hip symptoms. The purpose of this clinical commentary is to discuss hip pathomechanics with respect to cycling, bicycle fitting methodology and the options available to a physical therapist to optimize hip mechanics during the pedaling action.

M13 bacteriophage is a key instrument in phage display applications, as well as a possible antibacterial therapeutic agent due to its highly restrictive bacterial pathogenesis, and other applications. The traditional phage purification process is usually achieved by gradient ultracentrifugation or a combination of precipitation, centrifugation and microfiltration. These approaches easily lead to long process times, high operational costs, phage aggregation and consequent product loss (approximately 60%). This work is thus focused on an alternative potential large-scale process to achieve high yield and purity while minimizing the operational costs. Electrostatic-based separation processes are also common biomolecules purification techniques. Although anion exchange chromatography has been used before to purify several viral particles, this technique has been poorly reported for the purification of M13 phage. In a recent work, our group has demonstrated the use of a predominant anion exchange process, where a polymeric ionic liquid (PIL) was used as an alternative separation matrix for M13 bacteriophage. In this work, a variety of system parameters was studied, including chemical structure of the cation and the anion, the crosslinker nature and its concentration, either in batch adsorption/elution or chromatographic operation mode. The PIL-based chromatographic operation mode revealed to be a suitable separation process for M13 from directly filtered E. coli supernatant, reaching over 70% M13 recovery and 4.6 purification factor in a single step. To our knowledge, this is the first time that PILs have been reported as separation agents for bioproducts from complex mixtures.

M13 is a filamentous, non-lytic bacteriophage that infects Escherichia coli via the F pilus. Currently, phage M13 is widely used in phage display technology and bio-nanotechnology, and is considered a possible antibacterial therapeutic agent, among other applications. Conventional phage purification involves 5-7 operational steps, with high operational costs and significant product loss (approximately 60%). In this work, we propose a scalable purification process for M13 bacteriophage using a novel stationary phase based on a polymeric ionic liquid (PIL) with a positively charged backbone structure. Poly (1-vinyl-3-ethyl imidazolium bis(trifluoromethylsulfonyl) imide) - poly(VEIM-TFSI) predominantly acted as an anion exchanger under binding-elution mode. This revealed to be a rapid and simple method for the recovery of phage M13 with an overall separation yield of over 70% after a single downstream step. To the best of our knowledge, PILs have never been used as separation matrices for biological products and the results obtained, together with the large number of cations and anions available to prepare PILs, illustrate well the large potential of the proposed methodology.