Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases

Complex hierarchical structure governs emergent properties in biopolymeric materials; yet, the material processing involved remains poorly understood. Here, we investigated the multi-scale structure and composition of the mussel byssus cuticle before, during and after formation to gain insight into the processing of this hard, yet extensible metal cross-linked protein composite. Our findings reveal that the granular substructure crucial to the cuticle’s function as a wear-resistant coating of an extensible polymer fiber is pre-organized in condensed liquid phase secretory vesicles. These are phase-separated into DOPA-rich proto-granules enveloped in a sulfur-rich proto-matrix which fuses during secretion, forming the sub-structure of the cuticle. Metal ions are added subsequently in a site-specific way, with iron contained in the sulfur-rich matrix and vanadium coordinated by DOPA-catechol in the granule. We posit that this hierarchical structure self-organizes via phase separation of specific amphiphilic proteins within secretory vesicles, resulting in a meso-scale structuring that governs cuticle function

Genetic diversity of common toads (Bufo bufo) along the Norwegian coast : disjunct distribution of locally dominant haplotypes

Little is known about the phylogeographic history of amphibian populations along the western Fennoscandinavian coast. In the present study, we focus on the common toad (Bufo bufo) and document the spatial distribution of mitochondrial DNA (cytb) haplotypes at 20 localities along its coastal Norwegian range. Two common haplotypes (out of eight haplotypes in total) were represented by 142 out of the 154 (92%) investigated individuals. However, they were shared at only three localities and clustered at two separate geographic regions each. The most common haplotype (55% of individuals) has previously been found to be abundant across central and eastern Europe, whereas the second most common haplotype (37% of individuals) has so far only been recorded in Sweden. The disjunct distribution of genetic lineages is in line with an assumption that the Norwegian coastline was postglacially colonised both from the south as well as across mountain passes from the east. Our data support previous studies on the phylogeography of Fennoscandinavia that revealed that post-glacial recolonisation patterns led to a pronounced spatial structure of local populations

Differential response at the seafloor during Palaeocene and Eocene ocean warming events at Walvis Ridge, Atlantic Ocean (ODP Site 1262)

The Latest Danian Event (LDE, c. 62.1 Ma) is an early Palaeogene hyperthermal or transient (<200 ka) ocean warming event. We present the first deep-sea benthic foraminiferal faunal record to study deep-sea biotic changes together with new benthic (Nuttallides truempyi) stable isotope data from Walvis Ridge Site 1262 (Atlantic Ocean) to evaluate whether the LDE was controlled by similar processes as the minor early Eocene hyperthermals. The spacing of the double negative δ13C and δ18O excursion and the slope of the δ18O–δ13C regression are comparable, strongly suggesting a similar orbital control and pacing of eccentricity maxima as well as a rather homogeneous carbon pool. However, in contrast to early Eocene hyperthermals, the LDE exhibits a remarkable stability of the benthic foraminiferal fauna. This lack of benthic response could be related to the absence of threshold-related circulation changes or better pre-adaptation to elevated deep-sea temperatures, as the LDE was superimposed on a cooling trend, in contrast to early Eocene warming

Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology.

Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease.First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future

«Smarter Medicine»: 5 Interventionen, die in der ambulanten allgemeinen inneren Medizin vermieden werden sollten

Seit 2012 befasst sich die Schweizerische Gesellschaft für Allgemeine Innere Medizin mit der Problematik der Überdiagnostik und Überversorgung in der Medizin. Nun hat sie beschlossen, eine Liste mit fünf Untersuchungen auf dem Gebiet der ambulanten allgemeinen inneren Medizin zusammenzustellen, die ohne oder mit nur geringem Nutzen bei zahlreichen Patienten durchgeführt werden, gleichzeitig jedoch unerwünschte Nebenwirkungen haben können und zum Anstieg der Gesundheitskosten beitragen

Conseil-santé dans la médecine de premier recours, partie 2

Les maladies non transmissibles (MNT, en anglais «non-communicable diseases») ont gagné du terrain dans le monde entier. Les approches de conseil fourni au cabinet médical ont déjà été présentées dans un premier article. Le présent article se consacre aux conditions permettant à ces approches de déployer leur efficacité au niveau de la population. Ceci est illustré sur la base des programmes suisses actuels «Vivre sans tabac», PAPRICA et «Coaching Santé» ainsi que de l’exemple historique «Ça débouche sur quoi?»

Intuitionistc probability and the Bayesian objection to dogmatism

Given a few assumptions, the probability of a conjunction is raised, and the probability of its negation is lowered, by conditionalising upon one of the conjuncts. This simple result appears to bring Bayesian confirmation theory into tension with the prominent dogmatist view of perceptual justification – a tension often portrayed as a kind of ‘Bayesian objection’ to dogmatism. In a recent paper, David Jehle and Brian Weatherson observe that, while this crucial result holds within classical probability theory, it fails within intuitionistic probability theory. They conclude that the dogmatist who is willing to take intuitionistic logic seriously can make a convincing reply to the Bayesian objection. In this paper, I argue that this conclusion is premature – the Bayesian objection can survive the transition from classical to intuitionistic probability, albeit in a slightly altered form. I shall conclude with some general thoughts about what the Bayesian objection to dogmatism does and doesn’t show