Characteristics, distribution and morphogenesis of subtidal microbial systems in Shark Bay, Australia

The distribution, nature and extent of microbial deposits in Hamelin Pool, Shark Bay have been investigated and mapped with emphasis on the occurrence, external morphologies, internal fabrics, constructional mechanisms, microbial communities, growth rates and sediment associations in the intertidal and previously little researched subtidal zone. Detailed georeferenced substrate mapping revealed extensive subtidal microbial deposits occupying approximately 300 km2 of the total Holocene 1400 km2 area of Hamelin Pool. The Microbial Pavement covers 227 km2 of the subtidal substrate that together with columnar structures reveals a subtidal microbial habitat which occupies an area 10 times larger than the area of the intertidal deposits. Microbial carbonate is composed of aragonite (80–98%) that reveals high positive values of δ13C (+4.46 to +5.88) and δ18O (+3.06 to +3.88) as a characteristic of the highly evaporative environment with extensive microbial activity. Oldest dated heads are 1915 and 1680 14C years BP, and the overall system was deposited in two stages; the first between 2000 and 1200 and the last from 900 years BP to the present. Slow growth rates vary from less than 0.1 mm/year to 0.5 mm/year. Different internal fabrics were constructed according to their position in relation to the littoral zone by distinct microbial communities, and lateral fabric relations have been established.Evidence of shallowing upward fabric sequences of microbial origin reflects relative falling sea levels during the late Holocene and is likely useful in ancient environmental interpretation. A sequence of events and mechanisms are described emphasizing differences between the stromatolitic, thrombolitic and cryptomicrobial deposits in Shark Bay. The new substrate map and depositional history for this distinctive and peculiar microbial habitat establish the significance of subtidal structures and emphasize the geoscientific importance of Hamelin Pool, especially with respect to early life studies and ancient analogues for understanding microbial activity, deposit characteristics, fenestral fabrics and distribution

Heterogeneous Development of b-Cell Populations in Diabetes-Resistant and-Susceptible Mice

Progressive dysfunction and failure of insulin-releasing β-cells are a hallmark of type 2 diabetes (T2D). To study mechanisms of β-cell loss in T2D, we performed islet single-cell RNA sequencing of two obese mouse strains differing in their diabetes susceptibility. With mice on a control diet, we identified six β-cell clusters with similar abundance in both strains. However, after feeding of a diabetogenic diet for 2 days, β-cell cluster composition markedly differed between strains. Islets of diabetes-resistant mice developed into a protective β-cell cluster (Beta4), whereas those of diabetes-prone mice progressed toward stress-related clusters with a strikingly different expression pattern. Interestingly, the protective cluster showed indications of reduced β-cell identity, such as downregulation of GLUT2, GLP1R, and MafA, and in vitro knockdown of GLUT2 in β-cells-mimicking its phenotype-decreased stress response and apoptosis. This might explain enhanced β-cell survival of diabetes-resistant islets. In contrast, β-cells of diabetes-prone mice responded with expression changes indicating metabolic pressure and endoplasmic reticulum stress, presumably leading to later β-cell loss. In conclusion, failure of diabetes-prone mice to adapt gene expression toward a more dedifferentiated state in response to rising blood glucose levels leads to β-cell failure and diabetes development

Targeting Neuroinflammation to Treat Alzheimer’s Disease

Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets