Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia.

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional ß-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.

An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS).

Neurovegetative and autonomic symptoms are common presentations of various diseases, ranging from psychosomatic to severe organic disorders. A 23-year-old man presented with a history of recurrent presyncope, dizziness, and tachycardia. Repeated diagnostic work-up in various clinical settings could not identify any definite cause for approximately eight years. However, the incidental detection of postprandial and exercise-induced hypoglycemia was suggestive of an insulin-related disorder. A 72 h plasma glucose fasting test revealed endogenous hyperinsulinism. Upon imaging studies, no tumor mass potentially indicating insulinoma could be detected. 68Ga-DOTA-Exendin-4 PET/CT showed diffuse tracer enrichment throughout the whole pancreas. A subtotal pancreatectomy was performed, and the diagnosis of diffuse, adult-onset nesidioblastosis was established histopathologically. This corresponds to the clinical findings of a functional ß-cell disorder, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). After nine months, the symptoms recurred, making complete pancreatectomy necessary. Postoperative laboratory evaluation exhibited no residual endogenous C-peptide production. This case illustrates the diagnostic challenges in patients presenting with unspecific, neurovegetative and autonomic symptoms with a severe and rare underlying cause.

Improving the relevance of paleontology to climate change policy.

Paleontology has provided invaluable basic knowledge on the history of life on Earth. The discipline can also provide substantial knowledge to societal challenges such as climate change. The long-term perspective of climate change impacts on natural systems is both a unique selling point and a major obstacle to becoming more pertinent for policy-relevant bodies like the Intergovernmental Panel on Climate Change (IPCC). Repeated experiments on the impacts of climate change without anthropogenic disturbance facilitate the extraction of climate triggers in biodiversity changes. At the same time, the long timescales over which paleontological changes are usually assessed are beyond the scope of policymakers. Based on first-hand experience with the IPCC and a quantitative analysis of its cited literature, we argue that the differences in temporal scope are less of an issue than inappropriate framing and reporting of most paleontological publications. Accepting that some obstacles will remain, paleontology can quickly improve its relevance by targeting climate change impacts more directly and focusing on effect sizes and relevance for projections, particularly on higher-end climate change scenarios.

Climate change disrupts core habitats of marine species.

Driven by climate change, marine biodiversity is undergoing a phase of rapid change that has proven to be even faster than changes observed in terrestrial ecosystems. Understanding how these changes in species composition will affect future marine life is crucial for conservation management, especially due to increasing demands for marine natural resources. Here, we analyse predictions of a multiparameter habitat suitability model covering the global projected ranges of >33,500 marine species from climate model projections under three CO2 emission scenarios (RCP2.6, RCP4.5, RCP8.5) up to the year 2100. Our results show that the core habitat area will decline for many species, resulting in a net loss of 50% of the core habitat area for almost half of all marine species in 2100 under the high-emission scenario RCP8.5. As an additional consequence of the continuing distributional reorganization of marine life, gaps around the equator will appear for 8% (RCP2.6), 24% (RCP4.5), and 88% (RCP8.5) of marine species with cross-equatorial ranges. For many more species, continuous distributional ranges will be disrupted, thus reducing effective population size. In addition, high invasion rates in higher latitudes and polar regions will lead to substantial changes in the ecosystem and food web structure, particularly regarding the introduction of new predators. Overall, our study highlights that the degree of spatial and structural reorganization of marine life with ensued consequences for ecosystem functionality and conservation efforts will critically depend on the realized greenhouse gas emission pathway.

Ancient Reef Traits, a database of trait information for reef-building organisms over the Phanerozoic.

Trait-based approaches are increasingly relevant to understand ecological and evolutionary patterns. A comprehensive trait database for extant reef corals is already available and widely used to reveal vulnerabilities to environmental disturbances including climate change. However, the lack of similar trait compilations for extinct reef builders prevents the derivation of generalities from the fossil record and to address similar questions. Here we present the Ancient Reef Traits Database (ARTD), which aims to compile trait information of various reef-building organisms in one single repository. ARTD contains specimen-level data from both published and unpublished resources. In this first version, we release 15 traits for 505 genera and 1129 species, comprising a dataset of 17,841 trait values of Triassic to mid-Holocene scleractinian corals, the dominant reef-builders in the modern ocean. Other trait data, including for other reef-building organisms, are currently being collated.

Emergence patterns of locally novel plant communities driven by past climate change and modern anthropogenic impacts.

Anthropogenic disturbance and climate change can result in dramatic increases in the emergence of new, ecologically novel, communities of organisms. We used a standardised framework to detect local novel communities in 2135 pollen time series over the last 25,000 years. Eight thousand years of post-glacial warming coincided with a threefold increase in local novel community emergence relative to glacial estimates. Novel communities emerged predominantly at high latitudes and were linked to global and local temperature change across multi-millennial time intervals. In contrast, emergence of locally novel communities in the last 200 years, although already on par with glacial retreat estimates, occurred at midlatitudes and near high human population densities. Anthropogenic warming does not appear to be strongly associated with modern local novel communities, but may drive widespread emergence in the future, with legacy effects for millennia after warming abates.

Fast-growing species shape the evolution of reef corals.

Ecological interactions are ubiquitous on tropical coral reefs, where sessile organisms coexist in limited space. Within these high-diversity systems, reef-building scleractinian corals form an intricate interaction network. The role of biotic interactions among reef corals is well established on ecological timescales. However, its potential effect on macroevolutionary patterns remains unclear. By analysing the rich fossil record of Scleractinia, we show that reef coral biodiversity experienced marked evolutionary rate shifts in the last 3 million years, possibly driven by biotic interactions. Our models suggest that there was an overwhelming effect of staghorn corals (family Acroporidae) on the fossil diversity trajectories of other coral groups. Staghorn corals showed an unparalleled spike in diversification during the Pleistocene. But surprisingly, their expansion was linked with increases in both extinction and speciation rates in other coral families, driving a nine-fold increase in lineage turnover. These results reveal a double-edged effect of diversity dependency on reef evolution. Given their fast growth, staghorn corals may have increased extinction rates via competitive interactions, while promoting speciation through their role as ecosystem engineers. This suggests that recent widespread human-mediated reductions in staghorn coral cover, may be disrupting the key macroevolutionary processes that established modern coral reef ecosystems.

Deep-time climate legacies affect origination rates of marine genera.

Biodiversity dynamics are shaped by a complex interplay between current conditions and historic legacy. The interaction of short- and long-term climate change may mask the true relationship of evolutionary responses to climate change if not specifically accounted for. These paleoclimate interactions have been demonstrated for extinction risk and biodiversity change, but their importance for origination dynamics remains untested. Here, we show that origination probability in marine fossil genera is strongly affected by paleoclimate interactions. Overall, origination probability increases by 27.8% [95% CI (27.4%, 28.3%)] when a short-term cooling adds to a long-term cooling trend. This large effect is consistent through time and all studied groups. The mechanisms of the detected effect might be manifold but are likely connected to increased allopatric speciation with eustatic sea level drop caused by sustained global cooling. We tested this potential mechanism through which paleoclimate interactions can act on origination rates by additionally examining a proxy for habitat fragmentation. This proxy, continental fragmentation, has a similar effect on origination rates as paleoclimate interactions, supporting the importance of allopatric speciation through habitat fragmentation in the deep-time fossil record. The identified complex nature of paleoclimate interactions might explain contradictory conclusions on the relationship between temperature and origination in the previous literature. Our results highlight the need to account for complex interactions in evolutionary studies both between and among biotic and abiotic factors.

Increase in marine provinciality over the last 250 million years governed more by climate change than plate tectonics.

Amidst long-term fluctuations of the abiotic environment, the degree to which life organizes into distinct biogeographic provinces (provinciality) can reveal the fundamental drivers of global biodiversity. Our understanding of present-day biogeography implies that changes in the distribution of continents across climatic zones have predictable effects on habitat distribution, dispersal barriers and the evolution of provinciality. To assess marine provinciality through the Phanerozoic, here we (a) simulate provinces based on palaeogeographic reconstructions and global climate models and (b) contrast them with empirically derived provinces that we define using network analysis of fossil occurrences. Simulated and empirical patterns match reasonably well and consistently suggest a greater than 15% increase in provinciality since the Mesozoic era. Although both factors played a role, the simulations imply that the effect of the latitudinal temperature gradient has been twice as important in determining marine provinciality as continental configuration.

Out of the extratropics: the evolution of the latitudinal diversity gradient of Cenozoic marine plankton.

Many ecological and evolutionary hypotheses have been proposed to explain the latitudinal diversity gradient, i.e. the increase in species richness from the poles to the tropics. Among the evolutionary hypotheses, the 'out of the tropics' (OTT) hypothesis has received considerable attention. The OTT posits that the tropics are both a cradle and source of biodiversity for extratropical regions. To test the generality of the OTT hypothesis, we explored the spatial biodiversity dynamics of unicellular marine plankton over the Cenozoic era (the last 66 Myr). We find large-scale climatic changes during the Cenozoic shaped the diversification and dispersal of marine plankton. Origination was generally more likely in the extratropics and net dispersal was towards the tropics rather than in the opposite direction, especially during the warmer climates of the early Cenozoic. Although migration proportions varied among major plankton groups and climate phases, we provide evidence that the extratropics were a source of tropical microplankton biodiversity over the last 66 Myr.

Extinction risk controlled by interaction of long-term and short-term climate change.

Assessing extinction risk from climate drivers is a major goal of conservation science. Few studies, however, include a long-term perspective of climate change. Without explicit integration, such long-term temperature trends and their interactions with short-term climate change may be so dominant that they blur or even reverse the apparent direct relationship between climate change and extinction. Here we evaluate how observed genus-level extinctions of arthropods, bivalves, cnidarians, echinoderms, foraminifera, gastropods, mammals and reptiles in the geological past can be predicted from the interaction of long-term temperature trends with short-term climate change. We compare synergistic palaeoclimate interaction (a short-term change on top of a long-term trend in the same direction) to antagonistic palaeoclimate interaction such as long-term cooling followed by short-term warming. Synergistic palaeoclimate interaction increases extinction risk by up to 40%. The memory of palaeoclimate interaction including the climate history experienced by ancestral lineages can be up to 60 Myr long. The effect size of palaeoclimate interaction is similar to other key factors such as geographic range, abundance or clade membership. Insights arising from this previously unknown driver of extinction risk might attenuate recent predictions of climate-change-induced biodiversity loss.

Victims of ancient hyperthermal events herald the fates of marine clades and traits under global warming.

Organismic groups vary non-randomly in their vulnerability to extinction. However, it is unclear whether the same groups are consistently vulnerable, regardless of the dominant extinction drivers, or whether certain drivers have their own distinctive and predictable victims. Given the challenges presented by anthropogenic global warming, we focus on changes in extinction selectivity trends during ancient hyperthermal events: geologically rapid episodes of global warming. Focusing on the fossil record of the last 300 million years, we identify clades and traits of marine ectotherms that were more prone to extinction under the onset of six hyperthermal events than during other times. Hyperthermals enhanced the vulnerability of marine fauna that host photosymbionts, particularly zooxanthellate corals, the reef environments they provide, and genera with actively burrowing or swimming adult life-stages. The extinction risk of larger sized fauna also increased relative to non-hyperthermal times, while genera with a poorly buffered internal physiology did not become more vulnerable on average during hyperthermals. Hyperthermal-vulnerable clades include rhynchonelliform brachiopods and bony fish, whereas resistant clades include cartilaginous fish, and ostreid and venerid bivalves. These extinction responses in the geological past mirror modern responses of these groups to warming, including range-shift magnitudes, population losses, and experimental performance under climate-related stressors. Accordingly, extinction mechanisms distinctive to rapid global warming may be indicated, including sensitivity to warming-induced seawater deoxygenation. In anticipation of modern warming-driven marine extinctions, the trends illustrated in the fossil record offer an expedient preview.

Increased extinction in the emergence of novel ecological communities.

Environmental change is transforming ecological assemblages into new configurations, resulting in novel communities. We developed a robust methodology to detect novel communities, examine patterns of emergence, and quantify probabilities of local demographic turnover in transitions to and from novel communities. Using a global dataset of Cenozoic marine plankton communities, we found that the probability of local extinction, origination, and emigration during transitions to a novel community increased two to four times that of background community changes. Although rare, novel communities were five times more likely than chance to shift into another novel state. For marine plankton communities at a 100,000-year time grain, novel communities were sensitive to further extinctions and substantial community change.

A possible link between coral reef success, crustose coralline algae and the evolution of herbivory.

Crustose coralline red algae (CCA) play a key role in the consolidation of many modern tropical coral reefs. It is unclear, however, if their function as reef consolidators was equally pronounced in the geological past. Using a comprehensive database on ancient reefs, we show a strong correlation between the presence of CCA and the formation of true coral reefs throughout the last 150 Ma. We investigated if repeated breakdowns in the potential capacity of CCA to spur reef development were associated with sea level, ocean temperature, CO2 concentration, CCA species diversity, and/or the evolution of major herbivore groups. Model results show that the correlation between the occurrence of CCA and the development of true coral reefs increased with CCA diversity and cooler ocean temperatures while the diversification of herbivores had a transient negative effect. The evolution of novel herbivore groups compromised the interaction between CCA and true reef growth at least three times in the investigated time interval. These crises have been overcome by morphological adaptations of CCA.

Drivers of beta diversity in modern and ancient reef-associated soft-bottom environments.

Beta diversity, the compositional variation among communities, is often associated with environmental gradients. Other drivers of beta diversity include stochastic processes, priority effects, predation, or competitive exclusion. Temporal turnover may also explain differences in faunal composition between fossil assemblages. To assess the drivers of beta diversity in reef-associated soft-bottom environments, we investigate community patterns in a Middle to Late Triassic reef basin assemblage from the Cassian Formation in the Dolomites, Northern Italy, and compare results with a Recent reef basin assemblage from the Northern Bay of Safaga, Red Sea, Egypt. We evaluate beta diversity with regard to age, water depth, and spatial distance, and compare the results with a null model to evaluate the stochasticity of these differences. Using pairwise proportional dissimilarity, we find very high beta diversity for the Cassian Formation (0.91 ± 0.02) and slightly lower beta diversity for the Bay of Safaga (0.89 ± 0.04). Null models show that stochasticity only plays a minor role in determining faunal differences. Spatial distance is also irrelevant. Contrary to expectations, there is no tendency of beta diversity to decrease with water depth. Although water depth has frequently been found to be a key factor in determining beta diversity, we find that it is not the major driver in these reef-associated soft-bottom environments. We postulate that priority effects and the biotic structuring of the sediment may be key determinants of beta diversity.

Past and future decline of tropical pelagic biodiversity.

A major research question concerning global pelagic biodiversity remains unanswered: when did the apparent tropical biodiversity depression (i.e., bimodality of latitudinal diversity gradient [LDG]) begin? The bimodal LDG may be a consequence of recent ocean warming or of deep-time evolutionary speciation and extinction processes. Using rich fossil datasets of planktonic foraminifers, we show here that a unimodal (or only weakly bimodal) diversity gradient, with a plateau in the tropics, occurred during the last ice age and has since then developed into a bimodal gradient through species distribution shifts driven by postglacial ocean warming. The bimodal LDG likely emerged before the Anthropocene and industrialization, and perhaps ∼15,000 y ago, indicating a strong environmental control of tropical diversity even before the start of anthropogenic warming. However, our model projections suggest that future anthropogenic warming further diminishes tropical pelagic diversity to a level not seen in millions of years.

Marine Biodiversity and Geographic Distributions Are Independent on Large Scales.

Fundamental ecological and evolutionary theories, such as community saturation and diversity-dependent diversification, assume that biotic competition restricts resource use, and thus limits realized niche breadth and geographic range size [1-3]. This principle is called competitive exclusion. The corollary (ecological release) posits that, after competitors disappear from a region, species that were previously excluded will invade. Hundreds of field experiments have demonstrated ecological release in living populations. However, few of these studies were conducted in marine environments, and almost no work extended beyond 10 years and 1,000 km2 [4, 5]. In limited investigation of marine taxa at larger spatiotemporal scales, macroecologists and paleobiologists have observed little evidence of competitive exclusion [6-9]. Here, we quantified spatial trends in the rich and densely sampled fossil history of brachiopods and bivalves, while accounting for inconsistent sampling coverage through time using a new method of spatial standardization. The number of potential competitors in a region did not explain the geographic distribution of constituent species or genera. Furthermore, although ecological release predicts species to expand after extinction events, survivors of intervals with net species loss expanded as rarely as species in other intervals. Regression model estimates indicated different spatial responses of brachiopods and bivalves, and of habitat specialists and generalists, but no effect from changes in number of potential competitors. Biotic competition may control the distribution of populations, but, on larger spatiotemporal scales, non-competitive factors may have driven biogeographic patterns of brachiopods and bivalves.