The alpine flora on inselberg summits in the Maloti–Drakensberg Park, KwaZulu-Natal, South Africa

Background: Inselberg summits adjacent to the Maloti–Drakensberg escarpment occupy an alpine zone within the Drakensberg Alpine Centre (DAC). Inselbergs, the escarpment and surrounding mountains such as Platberg experience a severe climate; inselberg summits are distinct by being protected from human disturbance. Objectives: The aim of this article was to describe for the first time the flora of inselberg summits and to assess their potential contribution to conservation of DAC plant diversity. Method: We investigated whether the flora of inselberg summits formed a representative subset of the DAC flora in terms of shared, especially endemic or near endemic, species and representation of families. All species were listed for six inselbergs between Giant’s Castle and Sentinel, located in the Royal Natal National Park (RNNP) during November 2005. Comparisons, using literature, were made with floras of the DAC, as well as Platberg, an inselberg approximately 60 km north from Sentinel in the RNNP. Results: We recorded 200 species of pteridophytes and angiosperms on inselbergs, 114 DAC endemics or near endemics, one possible new species, and several range and altitudinal extensions. Asteraceae, Poaceae and Ericaceae comprised 42.1% of endemic and near endemic species, with Scrophulariaceae and Hyacinthaceae contributing 8.8%. Inselberg and DAC floras differed in respective rankings of Crassulaceae (8th vs. 15th), Polygalaceae, Apiaceae and Rosaceae (10th, 11th, 12th vs. 15th), Poaceae (2nd vs. 5th), Cyperaceae (3rd vs. 4th) and Scrophulariaceae (6th vs. 2nd). Growth forms on inselbergs were consistent with DAC flora. Inselbergs shared 40% of species with Platberg. Conclusion: Inselbergs, which supported 7.9% of species occurring in the DAC flora, are well protected from human impact, lack alien plants, but, despite this, are highly vulnerable to climate change. Conservation importance of inselbergs will increase as escarpment vegetation becomes increasingly degraded as a consequence of intensifying land use

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction

The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study

Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy

Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

SummaryCancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer

Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression

Chronic mucosal inflammation is associated with a greater risk of gastric cancer (GC) and, therefore, requires tight control by suppressive counter mechanisms. Gastrokine-2 (GKN2) belongs to a family of secreted proteins expressed within normal gastric mucosal cells. GKN2 expression is frequently lost during GC progression, suggesting an inhibitory role; however, a causal link remains unsubstantiated. Here, we developed Gkn2 knockout and transgenic overexpressing mice to investigate the functional impact of GKN2 loss in GC pathogenesis. In mouse models of GC, decreased GKN2 expression correlated with gastric pathology that paralleled human GC progression. At baseline, Gkn2 knockout mice exhibited defective gastric epithelial differentiation but not malignant progression. Conversely, Gkn2 knockout in the IL-11/STAT3-dependent gp130[superscript F/F] GC model caused tumorigenesis of the proximal stomach. Additionally, gastric immunopathology was accelerated in Helicobacter pylori–infected Gkn2 knockout mice and was associated with augmented T helper cell type 1 (Th1) but not Th17 immunity. Heightened Th1 responses in Gkn2 knockout mice were linked to deregulated mucosal innate immunity and impaired myeloid-derived suppressor cell activation. Finally, transgenic overexpression of human gastrokines (GKNs) attenuated gastric tumor growth in gp130[superscript F/F] mice. Together, these results reveal an antiinflammatory role for GKN2, provide in vivo evidence that links GKN2 loss to GC pathogenesis, and suggest GKN restoration as a strategy to restrain GC progression

Nanoantenna enhancement for telecom-wavelength superconducting single photon detectors

Superconducting nanowire single photon detectors are rapidly emerging as a key infrared photon-counting technology. Two front-side-coupled silver dipole nanoantennas, simulated to have resonances at 1480 and 1525 nm, were fabricated in a two-step process. An enhancement of 50 to 130% in the system detection efficiency was observed when illuminating the antennas. This offers a pathway to increasing absorption into superconducting nanowires, creating larger active areas, and achieving more efficient detection at longer wavelengths

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems

RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases

The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. The crystal structure of the N-terminal region of RavN revealed a U-box-like motif that was only remotely similar to other U-box domains, indicating that RavN is an E3 ligase relic that has undergone significant evolutionary alteration. Substitution of residues within the predicted E2 binding interface rendered RavN inactive, indicating that, despite significant structural changes, the mode of E2 recognition has remained conserved. Using hidden Markov model-based secondary structure analyses, we identified and experimentally validated four additional L. pneumophila effectors that were not previously recognized to possess E3 ligase activity, including Lpg2452/SdcB, a new paralog of SidC. Our study provides strong evidence that L. pneumophila is dedicating a considerable fraction of its effector arsenal to the manipulation of the host ubiquitylation pathway.Funding: This work was funded by the Intramural Research Program of the National Institutes of Health (to MPM)(Project Number: 1ZIAHD008893-07) and by the Spanish Ministry of Economy and Competitiveness Grant (to AH)(BFU2014-59759-R) and the Severo Ochoa Excellence Accreditation (to AH)(SEV-2016-0644). This study made use of the Diamond Light Source beamline I04 (Oxfordshire, UK) and ALBA synchrotron beamline BL13-XALOC, funded in part by the Horizon 2020 programme of the European Union, iNEXT (H2020 Grant # 653706). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Seasonality in Human Zoonotic Enteric Diseases: A Systematic Review

BACKGROUND: Although seasonality is a defining characteristic of many infectious diseases, few studies have described and compared seasonal patterns across diseases globally, impeding our understanding of putative mechanisms. Here, we review seasonal patterns across five enteric zoonotic diseases: campylobacteriosis, salmonellosis, vero-cytotoxigenic Escherichia coli (VTEC), cryptosporidiosis and giardiasis in the context of two primary drivers of seasonality: (i) environmental effects on pathogen occurrence and pathogen-host associations and (ii) population characteristics/behaviour. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed published literature from 1960-2010, resulting in the review of 86 studies across the five diseases. The Gini coefficient compared temporal variations in incidence across diseases and the monthly seasonality index characterised timing of seasonal peaks. Consistent seasonal patterns across transnational boundaries, albeit with regional variations was observed. The bacterial diseases all had a distinct summer peak, with identical Gini values for campylobacteriosis and salmonellosis (0.22) and a higher index for VTEC (Gini  0.36). Cryptosporidiosis displayed a bi-modal peak with spring and summer highs and the most marked temporal variation (Gini = 0.39). Giardiasis showed a relatively small summer increase and was the least variable (Gini = 0.18). CONCLUSIONS/SIGNIFICANCE: Seasonal variation in enteric zoonotic diseases is ubiquitous, with regional variations highlighting complex environment-pathogen-host interactions. Results suggest that proximal environmental influences and host population dynamics, together with distal, longer-term climatic variability could have important direct and indirect consequences for future enteric disease risk. Additional understanding of the concerted influence of these factors on disease patterns may improve assessment and prediction of enteric disease burden in temperate, developed countries