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Estimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in biodiversity hotspots with Mediterranean and tropical climates. The large genus Erica is a prime example, as a large proportion of its 851 species, all shrubs or small trees, are endemic to the Cape Floristic Region (CFR) of South Africa. Almost two hundred are known to be threatened and a further hundred are ‘Data Deficient’. We need to target conservation efforts and research to fill the most problematic knowledge gaps. This can be especially challenging in large genera, such as Erica, with numerous threatened species that are closely related. One approach involves combining knowledge of phylogenetic diversity with that of IUCN threat status to identify the most Evolutionarily Distinct and Globally Endangered (EDGE) species. We present an expanded and improved phylogenetic hypothesis for Erica (representing 65% of described species diversity) and combine this with available threat and distribution data to identify species and geographic areas that could be targeted for conservation effort to maximise preservation of phylogenetic diversity (PD). The resulting 39 EDGE taxa include 35 from the CFR. A further 32 high PD, data deficient taxa are mostly from outside the CFR, reflecting the low proportion of assessed taxa outside South Africa. The most taxon-rich areas are found in the south-western CFR. They are not the most phylogenetically diverse, but do include the most threatened PD. These results can be cross-referenced to existing living and seed-banked ex situ collections and used to target new and updated threat assessments and conservation action.

Species identification is fundamental to all aspects of biology and conservation. The process can be challenging, particularly in groups including many closely related or similar species. The problem is confounded by the absence of an up-to-date taxonomic revision, but even with such a resource all but professional botanists may struggle to recognise key species, presenting a substantial barrier to vital work such as surveys, threat assessments, and seed collection for ex situ conservation. Genus Erica: An Identification Aid is a tool to help both amateurs and professionals identify (using a limited number of accessible characteristics) and find information about the 851 species and many subspecific taxa of the genus Erica. We present an updated version 4.00, with new features including integrating distribution data from GBIF and iNaturalist, links to taxonomic resources through World Flora Online, and a probability function for identifications, that is freely available for PCs. It remains a work in progress: We discuss routes forward for collaboratively improving this resource.

Glucose plays a key role in shaping pancreatic [beta] cell function. Thus, deciphering the mechanisms by which this nutrient stimulates [beta] cells holds therapeutic promise for combating [beta] cell failure in type 2 diabetes (T2D). [beta] cells respond to hyperglycemia in part by rewiring their mRNA metabolism, yet the mechanisms governing these changes remain poorly understood. Here, we identify a requirement for the RNA-binding protein PCBP2 in maintaining [beta] cell function basally and during sustained hyperglycemic challenge. PCBP2 was induced in primary mouse islets incubated with elevated glucose and was required to adapt insulin secretion. Transcriptomic analysis of primary Pcbp2-deficient [beta] cells revealed impacts on basal and glucose-regulated mRNAs encoding core components of the insulin secretory pathway. Accordingly, Pcbp2-deficient [beta] cells exhibited defects in calcium flux, insulin granule ultrastructure and exocytosis, and the amplification pathway of insulin secretion. Further, PCBP2 was induced by glucose in primary human islets, was downregulated in islets from T2D donors, and impacted genes commonly altered in islets from donors with T2D and linked to single-nucleotide polymorphisms associated with T2D. Thus, these findings establish a paradigm for PCBP2 in governing basal and glucose-adaptive gene programs critical for shaping the functional state of [beta] cells., Introduction Glucose uptake and metabolism are the most physiologically important driver of insulin release from pancreatic islet [beta] cells, a highly specialized class of endocrine cells that secrete this hormone [...]

Societal Impact Statement Human‐caused habitat destruction and transformation is resulting in a cascade of impacts to biological diversity, of which arguably the most fundamental is species extinctions. The Global Conservation Consortia (GCC) are a means to pool efforts and expertise across national boundaries and between disciplines in the attempt to prevent such losses in focal plant groups. GCC Erica coordinates an international response to extinction threats in one such group, the heaths, or heathers, of which hundreds of species are found only in South Africa's spectacularly diverse Cape Floristic Region. Summary Effectively combating the biodiversity crisis requires coordinated conservation efforts. Botanic Gardens Conservation International (BGCI) and numerous partners have established Global Conservation Consortia (GCC) to collaboratively develop and implement comprehensive conservation strategies for priority threatened plant groups. Through these networks, institutions with specialised collections and staff can leverage ongoing work to optimise impact for threatened plant species. The genus Erica poses a challenge similar in scale to that of the largest other GCC group, Rhododendron, but almost 700 of the around 800 known species of Erica are concentrated in a single biodiversity hotspot, the Cape Floristic Region (CFR) of South Africa. Many species are known to be threatened, suffering the immediate impacts of habitat destruction, invasive species, changes in natural fire regimes and climate change. Efforts to counter these threats face general challenges: disproportionate burden of in situ conservation falling on a minority of the community, limited knowledge of species‐rich groups, shortfalls in assessing and monitoring threat, lack of resources for in situ and limitations of knowledge for ex situ conservation efforts and in communicating the value of biological diversity to a public who may never encounter it in the wild. GCC Erica brings together the world's Erica experts, conservationists and the botanical community, including botanic gardens, seed banks and organisations in Africa, Madagascar, Europe, the United States, Australia and beyond. We are collaboratively pooling our unique sets of skills and resources to address these challenges in working groups for conservation prioritisation, conservation in situ, horticulture, seed banking, systematic research and outreach.

Interrogating the ecological and geographic factors that influence population divergence dynamics can reveal why some groups of organisms diversify more prolifically than others. One such group is the heathers (Erica, Ericaceae), the largest plant genus in the Cape Floristic Region. We study Erica abietina, a highly variable species complex with four subspecies differing in geographic range, habitat and pollination syndrome. We test for population differentiation, hybridisation, introgression and pollinator‐driven divergence using genotyping‐by‐sequencing on samples across the entire distribution. We find five variably distinct genetic groups, with one subspecies comprising two independent lineages that are geographically isolated and occur on different soil types. Phylogenetic analysis suggests two independent shifts between bird and insect pollination, with accompanying genetic divergence. However, for one pair of populations with different pollinators, we uncover several individuals of hybrid origin at a site of sympatry. These results suggest that floral differentiation driven by divergent selection acts in concert with geographic isolation to maintain reproductive isolation and promote speciation. Our investigations reveal a highly dynamic system whose diversity has been shaped by a variety of interacting forces. We suggest that such a system could be a model for much of the diversification of the Cape flora. [ABSTRACT FROM AUTHOR]

We previously reported a depletion of murine regenerating islet-derived protein 2 (REG2) in pancreatic islets of glutathione peroxidase-1 (Gpx1) overexpressing (OE) mice. The present study was to explore if and how the REG2 depletion contributed to an augmented glucose stimulated insulin secretion (GSIS) in OE islets. After we verified a consistent depletion (90%, p

BACKGROUND Multiple islet autoantibodies (AAbs) predict the development of type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in only approximately 15% of individuals who are positive for single AAbs (generally against glutamic acid decarboxylase [GADA]); hence, the single GADA+ state may represent an early stage of T1D.METHODS Here, we functionally, histologically, and molecularly phenotyped human islets from nondiabetic GADA+ and T1D donors.RESULTS Similar to the few remaining β cells in the T1D islets, GADA+ donor islets demonstrated a preserved insulin secretory response. By contrast, α cell glucagon secretion was dysregulated in both GADA+ and T1D islets, with impaired glucose suppression of glucagon secretion. Single-cell RNA-Seq of GADA+ α cells revealed distinct abnormalities in glycolysis and oxidative phosphorylation pathways and a marked downregulation of cAMP-dependent protein kinase inhibitor β (PKIB), providing a molecular basis for the loss of glucose suppression and the increased effect of 3-isobutyl-1-methylxanthine (IBMX) observed in GADA+ donor islets.CONCLUSION We found that α cell dysfunction was present during the early stages of islet autoimmunity at a time when β cell mass was still normal, raising important questions about the role of early α cell dysfunction in the progression of T1D.FUNDING This work was supported by grants from the NIH (3UC4DK112217-01S1, U01DK123594-02, UC4DK112217, UC4DK112232, U01DK123716, and P30 DK019525) and the Vanderbilt Diabetes Research and Training Center (DK20593).

Estimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in biodiversity hotspots with Mediterranean and tropical climates. The large genus Erica is a prime example, as a large proportion of its 851 species, all shrubs or small trees, are endemic to the Cape Floristic Region (CFR) of South Africa. Almost two hundred are known to be threatened and a further hundred are 'Data Deficient'. We need to target conservation efforts and research to fill the most problematic knowledge gaps. This can be especially challenging in large genera, such as Erica, with numerous threatened species that are closely related. One approach involves combining knowledge of phylogenetic diversity with that of IUCN threat status to identify the most Evolutionarily Distinct and Globally Endangered (EDGE) species. We present an expanded and improved phylogenetic hypothesis for Erica (representing 65% of described species diversity) and combine this with available threat and distribution data to identify species and geographic areas that could be targeted for conservation effort to maximise preservation of phylogenetic diversity (PD). The resulting 39 EDGE taxa include 35 from the CFR. A further 32 high PD , data deficient taxa are mostly from outside the CFR , reflecting the low proportion of assessed taxa outside South Africa. The most taxon-rich areas are found in the south-western CFR. They are not the most phylogenetically diverse, but do include the most threatened PD. These results can be cross-referenced to existing living and seed-banked ex situ collections and used to target new and updated threat assessments and conservation action. [ABSTRACT FROM AUTHOR]

Abstract Understanding how and why rates of evolutionary diversification vary is a key issue in evolutionary biology, ecology, and biogeography. Evolutionary rates are the net result of interacting processes summarized under concepts such as adaptive radiation and evolutionary stasis. Here, we review the central concepts in the evolutionary diversification literature and synthesize these into a simple, general framework for studying rates of diversification and quantifying their underlying dynamics, which can be applied across clades and regions, and across spatial and temporal scales. Our framework describes the diversification rate (d) as a function of the abiotic environment (a), the biotic environment (b), and clade‐specific phenotypes or traits (c); thus, d ~ a,b,c. We refer to the four components (a–d) and their interactions collectively as the “Evolutionary Arena.” We outline analytical approaches to this framework and present a case study on conifers, for which we parameterize the general model. We also discuss three conceptual examples: the Lupinus radiation in the Andes in the context of emerging ecological opportunity and fluctuating connectivity due to climatic oscillations; oceanic island radiations in the context of island formation and erosion; and biotically driven radiations of the Mediterranean orchid genus Ophrys. The results of the conifer case study are consistent with the long‐standing scenario that low competition and high rates of niche evolution promote diversification. The conceptual examples illustrate how using the synthetic Evolutionary Arena framework helps to identify and structure future directions for research on evolutionary radiations. In this way, the Evolutionary Arena framework promotes a more general understanding of variation in evolutionary rates by making quantitative results comparable between case studies, thereby allowing new syntheses of evolutionary and ecological processes to emerge.

Abstract Background The coincidence of long distance dispersal (LDD) and biome shift is assumed to be the result of a multifaceted interplay between geographical distance and ecological suitability of source and sink areas. Here, we test the influence of these factors on the dispersal history of the flowering plant genus Erica (Ericaceae) across the Afrotemperate. We quantify similarity of Erica climate niches per biogeographic area using direct observations of species, and test various colonisation scenarios while estimating ancestral areas for the Erica clade using parametric biogeographic model testing. Results We infer that the overall dispersal history of Erica across the Afrotemperate is the result of infrequent colonisation limited by geographic proximity and niche similarity. However, the Drakensberg Mountains represent a colonisation sink, rather than acting as a “stepping stone” between more distant and ecologically dissimilar Cape and Tropical African regions. Strikingly, the most dramatic examples of species radiations in Erica were the result of single unique dispersals over longer distances between ecologically dissimilar areas, contradicting the rule of phylogenetic biome conservatism. Conclusions These results highlight the roles of geographical and ecological distance in limiting LDD, but also the importance of rare biome shifts, in which a unique dispersal event fuels evolutionary radiation.

Glucagon, a hormone released from pancreatic α cells, plays a key role in maintaining euglycemia. New insights into the signaling pathways that control glucagon secretion may stimulate the development of novel therapeutic agents. In this study, we investigated the potential regulation of α cell function by G proteins of the Gq family. The use of a chemogenetic strategy allowed us to selectively activate Gq signaling in mouse α cells in vitro and in vivo. Acute stimulation of α cell Gq signaling led to elevated plasma glucagon levels, accompanied by increased insulin release and improved glucose tolerance. Moreover, chronic activation of this pathway greatly improved glucose tolerance in obese mice. We also identified an endogenous Gq-coupled receptor (vasopressin 1b receptor; V1bR) that was enriched in mouse and human α cells. Agonist-induced activation of the V1bR strongly stimulated glucagon release in a Gq-dependent fashion. In vivo studies indicated that V1bR-mediated glucagon release played a key role in the counterregulatory hyperglucagonemia under hypoglycemic and glucopenic conditions. These data indicate that α cell Gq signaling represents an important regulator of glucagon secretion, resulting in multiple beneficial metabolic effects. Thus, drugs that target α cell–enriched Gq-coupled receptors may prove useful to restore euglycemia in various pathophysiological conditions.

Iron-sulfur (Fe-S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR-210-ISCU1/2 axis cause Fe-S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR-210 and repression of the miR-210 targets ISCU1/2 down-regulated Fe-S levels. In mouse and human vascular and endothelial tissue affected by PH, miR-210 was elevated accompanied by decreased ISCU1/2 and Fe-S integrity. In mice, miR-210 repressed ISCU1/2 and promoted PH. Mice deficient in miR-210, via genetic/pharmacologic means or via an endothelial-specific manner, displayed increased ISCU1/2 and were resistant to Fe-S-dependent pathophenotypes and PH. Similar to hypoxia or miR-210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise-induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR-210-ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe-S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings.

Apocynaceae (the dogbane and milkweed family) is one of the ten largest flowering plant families, with approximately 5,350 species and diverse morphology and ecology, ranging from large trees and lianas that are emblematic of tropical rainforests, to herbs in temperate grasslands, to succulents in dry, open landscapes, and to vines in a wide variety of habitats. Despite a specialized and conservative basic floral architecture, Apocynaceae are hyperdiverse in flower size, corolla shape, and especially derived floral morphological features. These are mainly associated with the development of corolline and/or staminal coronas and a spectrum of integration of floral structures culminating with the formation of a gynostegium and pollinaria—specialized pollen dispersal units. To date, no detailed analysis has been conducted to estimate the origin and diversification of this lineage in space and time. Here, we use the most comprehensive time-calibrated phylogeny of Apocynaceae, which includes approximately 20% of the species covering all major lineages, and information on species number and distributions obtained from the most up-to-date monograph of the family to investigate the biogeographical history of the lineage and its diversification dynamics. South America, Africa, and Southeast Asia (potentially including Oceania), were recovered as the most likely ancestral area of extant Apocynaceae diversity; this tropical climatic belt in the equatorial region retained the oldest extant lineages and these three tropical regions likely represent museums of the family. Africa was confirmed as the cradle of pollinia-bearing lineages and the main source of Apocynaceae intercontinental dispersals. We detected 12 shifts toward accelerated species diversification, of which 11 were in the APSA clade (apocynoids, Periplocoideae, Secamonoideae, and Asclepiadoideae), eight of these in the pollinia-bearing lineages and six within Asclepiadoideae. Wind-dispersed comose seeds, climbing growth form, and pollinia appeared sequentially within the APSA clade and probably work synergistically in the occupation of drier and cooler habitats. Overall, we hypothesize that temporal patterns in diversification of Apocynaceae was mainly shaped by a sequence of morphological innovations that conferred higher capacity to disperse and establish in seasonal, unstable, and open habitats, which have expanded since the Eocene-Oligocene climate transition.

BACKGROUND. Multiple islet autoantibodies (AAbs) predict the development of type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in only approximately 15% of individuals who are positive for single AAbs (generally against glutamic acid decarboxylase [GADA]); hence, the single [GADA.sup.+] state may represent an early stage of T1D. METHODS. Here, we functionally, histologically, and molecularly phenotyped human islets from nondiabetic [GADA.sup.+] and T1D donors. RESULTS. Similar to the few remaining [beta] cells in the T1D islets, [GADA.sup.+] donor islets demonstrated a preserved insulin secretory response. By contrast, [alpha] cell glucagon secretion was dysregulated in both [GADA.sup.+] and T1D islets, with impaired glucose suppression of glucagon secretion. Single-cell RNA-Seq of [GADA.sup.+] [alpha] cells revealed distinct abnormalities in glycolysis and oxidative phosphorylation pathways and a marked downregulation of cAMP-dependent protein kinase inhibitor p (PKIB), providing a molecular basis for the loss of glucose suppression and the increased effect of 3-isobutyl-1-methylxanthine (IBMX) observed in [GADA.sup.+] donor islets. CONCLUSION. We found that [alpha] cell dysfunction was present during the early stages of islet autoimmunity at a time when p cell mass was still normal, raising important questions about the role of early [alpha] cell dysfunction in the progression of T1D. FUNDING. This work was supported by grants from the NIH (3UC4DK112217-01S1, U01DK123594-02, UC4DK112217, UC4DK112232, U01DK123716, and P30 DK019525) and the Vanderbilt Diabetes Research and Training Center (DK20593)., Introduction Longitudinal studies have shown that individuals who are at high genetic risk for or have a family history of type 1 diabetes (T1D), who later develop diabetes, progress through [...]

Species identification is fundamental to all aspects of biology and conservation. The process can be challenging, particularly in groups including many closely related or similar species. The problem is confounded by the absence of an up-to-date taxonomic revision, but even with such a resource all but professional botanists may struggle to recognise key species, presenting a substantial barrier to vital work such as surveys, threat assessments, and seed collection for ex situ conservation. Genus Erica: An Identification Aid is a tool to help both amateurs and professionals identify (using a limited number of accessible characteristics) and find information about the 851 species and many subspecific taxa of the genus Erica. We present an updated version 4.00, with new features including integrating distribution data from GBIF and iNaturalist, links to taxonomic resources through World Flora Online, and a probability function for identifications, that is freely available for PCs. It remains a work in progress: We discuss routes forward for collaboratively improving this resource. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic β cell failure plays a central role in the development of type 2 diabetes (T2D). While the transcription factors shaping the β cell gene expression program have received much attention, the post-transcriptional controls that are activated in β cells during stress are largely unknown. We recently identified JUND as a pro-oxidant transcription factor that is post-transcriptionally upregulated in β cells during metabolic stress. Here we seek to uncover the mechanisms underlying this maladaptive response to metabolic stress. Methods: RNA-protein and protein-protein interactions were measured using RNA immunoprecipitation and co-immunoprecipitation, respectively, in Min6 cells and mouse islets. Phos-tag analyses were used to assess hnRNPK phosphorylation in primary mouse and human islets and Min6 cells. Translating ribosome affinity purification (TRAP) followed by RT-qPCR was used to identify changes in the ribosome occupancy of mRNAs in Min6 cells. Gene depletion studies used lentiviral delivery of CRISPR-Cas9 to Min6 cells. Apoptosis was measured in primary islets using a cell-permeable dye with a fluorescence readout of activated cleaved caspase-3 and-7. Results: A de novo motif analysis was performed on a subset of genes previously found to be regulated at the level of ribosome binding during PDX1-deficiency, which identified a poly-cytosine (polyC) motif in the 3′UTR of the transcript encoding JUND. The polyC-binding protein hnRNPK bound to the mRNA encoding JUND, leading us to hypothesize that hnRNPK regulates JUND expression during glucolipotoxicity. Indeed, loss of hnRNPK blocked the post-transcriptional upregulation of JUND during metabolic stress. hnRNPK was phosphorylated in mouse and human islets during glucolipotoxicity and in islets of diabetic db/db mice. The MEK/ERK signaling pathway was both necessary and sufficient for the phosphorylation of hnRNPK, upregulation of JUND levels, and induction of pro-oxidant and pro-inflammatory genes. Further, we identified the RNA helicase DDX3X as a new binding partner for hnRNPK that is required for efficient translation of JUND mRNA. Loss of hnRNPK reduced DDX3X binding to translation machinery, suggesting that these factors cooperate to regulate translation in β cells. Conclusions: Our results identify a novel ERK/hnRNPK/DDX3X pathway that influences β cell survival and is activated under conditions associated with T2D. Keywords: RNA-Binding proteins, β cell, Stress, Translational regulation, Signaling

Objective: In type 2 diabetes (T2D), oxidative stress contributes to the dysfunction and loss of pancreatic β cells. A highly conserved feature of the cellular response to stress is the regulation of mRNA translation; however, the genes regulated at the level of translation are often overlooked due to the convenience of RNA sequencing technologies. Our goal is to investigate translational regulation in β cells as a means to uncover novel factors and pathways pertinent to cellular adaptation and survival during T2D-associated conditions. Methods: Translating ribosome affinity purification (TRAP) followed by RNA-seq or RT-qPCR was used to identify changes in the ribosome occupancy of mRNAs in Min6 cells. Gene depletion studies used lentiviral delivery of shRNAs to primary mouse islets or CRISPR-Cas9 to Min6 cells. Oxidative stress and apoptosis were measured in primary islets using cell-permeable dyes with fluorescence readouts of oxidation and activated cleaved caspase-3 and-7, respectively. Gene expression was assessed by RNA-seq, RT-qPCR, and western blot. ChIP-qPCR was used to determine chromatin enrichment. Results: TRAP-seq in a PDX1-deficiency model of β cell dysfunction uncovered a cohort of genes regulated at the level of mRNA translation, including the transcription factor JUND. Using a panel of diabetes-associated stressors, JUND was found to be upregulated in mouse islets cultured with high concentrations of glucose and free fatty acid, but not after treatment with hydrogen peroxide or thapsigargin. This induction of JUND could be attributed to increased mRNA translation. JUND was also upregulated in islets from diabetic db/db mice and in human islets treated with high glucose and free fatty acid. Depletion of JUND in primary islets reduced oxidative stress and apoptosis in β cells during metabolic stress. Transcriptome assessment identified a cohort of genes, including pro-oxidant and pro-inflammatory genes, regulated by JUND that are commonly dysregulated in models of β cell dysfunction, consistent with a maladaptive role for JUND in islets. Conclusions: A translation-centric approach uncovered JUND as a stress-responsive factor in β cells that contributes to redox imbalance and apoptosis during pathophysiologically relevant stress. Keywords: Translational regulation, Oxidative stress, Apoptosis, β cell

This article examines the prevalent state of river ecosystems in the forest-steppe area of Ukraine with special focus on preservation methods and revitalisation of river ecosystems in the coastal territories.

Background Drosanthemum, the only genus of the tribe Drosanthemeae, is widespread over the Greater Cape Floristic Region in southern Africa. With 114 recognized species, Drosanthemum, together with the highly succulent and species-rich tribe Ruschieae, constitute the ‘core ruschioids’ in Aizoaceae. Within Drosanthemum, nine subgenera have been described based on flower and fruit morphology. Their phylogenetic relationships, however, have not yet been investigated, hampering understanding of monophyletic entities and patterns of geographic distribution. Methods Using chloroplast and nuclear DNA sequence data, we performed network- and tree-based phylogenetic analyses of 73 species of Drosanthemum with multiple accessions for widespread species. A well-curated, geo-referenced occurrence dataset comprising the 134 genetically analysed and 863 further accessions was used to describe the distributional ranges of intrageneric lineages and the genus as a whole. Results Phylogenetic inference supports nine clades within Drosanthemum, seven of which group in two major clades, while the remaining two show ambiguous affinities. The nine clades are generally congruent to previously described subgenera within Drosanthemum, with exceptions such as cryptic species. In-depth analyses of sequence patterns in each gene region were used to reveal phylogenetic affinities inside the retrieved clades in more detail. We observe a complex distribution pattern including widespread, species-rich clades expanding into arid habitats of the interior (subgenera Drosanthemum p.p., Vespertina, Xamera) that are genetically and morphologically diverse. In contrast, less species-rich, genetically less divergent, and morphologically unique lineages are restricted to the central Cape region and more mesic conditions (Decidua, Necopina, Ossicula, Quastea, Quadrata, Speciosa). Our results suggest that the main lineages arose from an initial rapid radiation, with subsequent diversification in some clades.

Alzheimer’s disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer’s disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer’s disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.

Human memory is a selective process where details are often lost, yet some types of research relies heavily on human memorization. Studies have shown that photographs help enhance the memory significantly. This study envisions to create a low-cost, mass-scale system using cell phones and to handle the massive amount of data that live image capture tends to implicate.

The importance of glucokinase (GK) in the regulation of insulin secretion has been highlighted by the phenotypes of individuals with activating and inactivating mutations in the glucokinase gene (GCK). Here we report 10 individuals with congenital hyperinsulinism (HI) caused by eight unique activating mutations of GCK. Six are novel and located near previously identified activating mutations sites. The first recognized episode of hypoglycemia in these patients occurred between birth and 24 years, and the severity of the phenotype was also variable. Mutant enzymes were expressed and purified for enzyme kinetics in vitro. Mutant enzymes had low glucose half-saturation concentration values and an increased enzyme activity index compared with wild-type GK. We performed functional evaluation of islets from the pancreata of three children with GCK-HI who required pancreatectomy. Basal insulin secretion in perifused GCK-HI islets was normal, and the response to glyburide was preserved. However, the threshold for glucose-stimulated insulin secretion in perifused glucokinase hyperinsulinism (GCK-HI) islets was decreased, and glucagon secretion was greatly suppressed. Our evaluation of novel GCK disease-associated mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response. Article Highlights: Our evaluation of six novel and two previously published activating GCK mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response. These studies provide insights into the pathophysiology of GCK-hyperinsulinism and the dual role of glucokinase in β-cells and α-cells to regulate glucose homeostasis. [ABSTRACT FROM AUTHOR]

Objectives: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by “glucolipotoxicity.” Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets. Methods: Islets were cultured for 3 or 4 days at different glucose concentration with 0.5 mM palmitic acid (PA) or a 2:1 mixture of PA and oleic acid (OA) at 1% albumin (PA/BSA molar ratio 3.3). Afterwards, the response to glucose and acetylcholine were studied in perifusion experiments. Results: FA-induced impairment of insulin secretion and Ca2+ signaling depended strongly on the glucose concentrations of the culture medium. PA and OA in combination reduced acetylcholine potentiation of insulin secretion more than PA alone, both in mouse and human islets, with no evidence of a protective role of OA. In contrast, lipotoxicity was not observed with islets cultured for 3 days in medium containing less than 1 mM glucose and a mixture of glutamine and leucine (7 mM each). High glucose and FAs reduced endoplasmic reticulum (ER) Ca2+ storage capacity; however, preserving ER Ca2+ by blocking the IP3 receptor with xestospongin C did not protect islets from glucolipotoxic effects on insulin secretion. In contrast, an inhibitor of casein kinase 2 (CK2) protected the glucose dependent acetylcholine potentiation of insulin secretion in mouse and human islets against glucolipotoxicity. Conclusions: These results show that chronic FA treatment decreases acetylcholine potentiation of insulin secretion and that this effect is strictly glucose dependent and might involve CK2 phosphorylation of β-cell M3 muscarinic receptors.