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Alzheimer's disease (AD) is linked to the abnormal accumulation of amyloid ? peptide (A?) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (Silybum marianum), has been shown to significantly inhibit A? aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B's clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin's mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its antiaggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolution, that is, TEM, ThT fluorescence, CD, and NMR spectroscopy, we profile the interactions of the trehalose conjugate with both A? monomers and oligomers and evidence that silybin may shield the "toxic" surfaces formed by the N-terminal and central hydrophobic regions of A?. Finally, comparative analysis with silybin A, a less active diastereoisomer of silybin B, revealed how even subtle differences in chemical structure may entail different effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin's therapeutic potential.

Type 2 diabetes (T2D) is characterized by a gradual decline in pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycaemia, chronic hyperglycaemia itself is also detrimental for beta-cell function, probably by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycaemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing. Current strategies aim to improve glycaemic control, either by promoting endogenous insulin secretion, such as sulfonylureas, or by mechanisms that may impact the beta cell indirectly, for example, providing beta-cell rest through insulin treatment. Although overall long-term success is limited with currently available interventions, in this review we argue that strategies that induce beta-cell rest have considerable potential to preserve long-term beta-cell function. This is based on laboratory-based studies involving human islets as well as clinical studies employing intensive insulin therapy, thiazolidinediones, bariatric surgery, short-acting glucagon-like peptide (GLP)-1 receptor agonists and a promising new class of diabetes drugs, sodium-glucose-linked transporter (SGLT)-2 inhibitors. Nevertheless, a lack of long-term clinical studies that focus on beta-cell function for the newer glucose-lowering agents, as well as commonly used combination therapies, preclude a straightforward conclusion; this gap in our knowledge should be a focus of future studies.

Prospective data are limited on human papillomavirus (HPV) acquisition and clearance among circumcised men from resource-limited geographical regions, particularly Africa. The goal of this study was to estimate incidence and clearance of type-specific genital HPV infection in men. Penile exfoliated cell specimens were collected from the glans/coronal sulcus and shaft of 1,037 circumcised Kenyan men at baseline and 6-, 12- and 18-month follow-up visits between 2003–2007. Specimens were tested with GP5+/6+ PCR to detect 44 HPV types. The median age of participants at baseline was 21 years (range 18–28). The 12- and 18-month incidence rates (IRs) for any HPV were 34.9/100 person-years (95% confidence interval [CI]: 31.2–39.0) and 36.4/100 person-years (95% CI: 32.9–40.2), respectively. The 18-month cumulative risk for high-risk HPV was 30% compared to 16% for low-risk HPV. Cumulative risk was not associated with age or anatomical site. The estimated probability of any HPV infection clearing by 12 months was 0.92. Time until HPV clearance was not associated with age, anatomical site, or whether HPV infection type was high-risk or low-risk. HPV IRs among circumcised men in this study were comparable to other circumcised populations.

The Apicomplexa are an important group of obligate intracellular parasites that include the causative agents of human diseases like malaria and toxoplasmosis. They evolved from free-living, phototrophic ancestors, and how this transition to parasitism occurred remains an outstanding question. One potential clue lies in coral reefs, where environmental DNA surveys have uncovered several lineages of uncharacterized, basally-branching apicomplexans. Reef-building corals form a well-studied symbiotic relationship with the photosynthetic dinoflagellate Symbiodinium, but identification of other key microbial symbionts of corals has proven elusive. Here, we used community surveys, genomics, and microscopy to identify an apicomplexan lineage, which we name 'corallicola', that was found in high prevalence (>80%) across all major groups of corals. In-situ fluorescence and electron microscopy confirmed that corallicola lives intracellularly within the tissues of the coral gastric cavity, and possesses clear apicomplexan ultrastructural features. We sequenced the plastid genome, which lacked all genes for photosystem proteins, indicating that corallicola harbours a non-photosynthetic plastid (an apicoplast). However, the corallicola plastid differed from all other known apicoplasts because it retains all four genes involved in chlorophyll biosynthesis. Hence, corallicola shares characteristics with both its parasitic and free-living relatives, implicating it as an evolutionary intermediate, and suggesting that a unique ancestral biochemistry likely operated during the transition from phototrophy to parasitism.