Bovine Staphylococcus aureus: Subtyping, evolution, and zoonotic transfer.

Staphylococcus aureus is globally one of the most important pathogens causing contagious mastitis in cattle. Previous studies using ribosomal spacer (RS)-PCR, however, demonstrated in Swiss cows that Staph. aureus isolated from bovine intramammary infections are genetically heterogeneous, with Staph. aureus genotype B (GTB) and GTC being the most prominent genotypes. Furthermore, Staph. aureus GTB was found to be contagious, whereas Staph. aureus GTC and all the remaining genotypes were involved in individual cow disease. In addition to RS-PCR, other methods for subtyping Staph. aureus are known, including spa typing and multilocus sequence typing (MLST). They are based on sequencing the spa and various housekeeping genes, respectively. The aim of the present study was to compare the 3 analytic methods using 456 strains of Staph. aureus isolated from milk of bovine intramammary infections and bulk tanks obtained from 12 European countries. Furthermore, the phylogeny of animal Staph. aureus was inferred and the zoonotic transfer of Staph. aureus between cattle and humans was studied. The analyzed strains could be grouped into 6 genotypic clusters, with CLB, CLC, and CLR being the most prominent ones. Comparing the 3 subtyping methods, RS-PCR showed the highest resolution, followed by spa typing and MLST. We found associations among the methods but in many cases they were unsatisfactory except for CLB and CLC. Cluster CLB was positive for clonal complex (CC)8 in 99% of the cases and typically positive for t2953; it is the cattle-adapted form of CC8. Cluster CLC was always positive for t529 and typically positive for CC705. For CLR and the remaining subtypes, links among the 3 methods were generally poor. Bovine Staph. aureus is highly clonal and a few clones predominate. Animal Staph. aureus always evolve from human strains, such that every human strain may be the ancestor of a novel animal-adapted strain. The zoonotic transfer of IMI- and milk-associated strains of Staph. aureus between cattle and humans seems to be very limited and different hosts are not considered as a source for mutual, spontaneous infections. Spillover events, however, may happen.

Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is frequent in stroke patients. Risk factors, treatment response, short-term and long-term outcome of SDB in stroke patients are poorly known. METHODS: We prospectively studied 152 patients (mean age 56+/-13 years) with acute ischemic stroke. Cardiovascular risk factors, Epworth sleepiness score (ESS), stroke severity/etiology, and time of stroke onset were assessed. The apnea-hypopnea index (AHI) was determined 3+/-2 days after stroke onset and 6 months later (subacute phase). Continuous positive airway pressure (CPAP) treatment was started acutely in patients with SDB (AHI > or =15 or AHI > or =10+ESS >10). CPAP compliance, incidence of vascular events, and stroke outcome were assessed 60+/-16 months later (chronic phase). RESULTS: Initial AHI was 18+/-16 (> or =10 in 58%, > or =30 in 17% of patients) and decreased in the subacute phase (P<0.001). Age, diabetes, and nighttime stroke onset were independent predictors of AHI (r2=0.34). In patients with AHI > or =30, age, male gender, body mass index, diabetes, hypertension, coronary heart disease, ESS, and macroangiopathic etiology of stroke were significantly higher/more common than in patients with AHI <10. Long-term incidence of vascular events and stroke outcome were similar in both groups. CPAP was started in 51% and continued chronically in 15% of SDB pts. Long-term stroke mortality was associated with initial AHI, age, hypertension, diabetes, and coronary heart disease. CONCLUSIONS: SDB is common particularly in elderly stroke male patients with diabetes, nighttime stroke onset, and macroangiopathy as cause of stroke; it improves after the acute phase, is associated with an increased poststroke mortality, and can be treated with CPAP in a small percentage of patients.

Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens

Fine particles (0.1-2.5 microm in diameter) may cause increased pulmonary morbidity and mortality. We demonstrate with a cell culture model of the human epithelial airway wall that dendritic cells extend processes between epithelial cells through the tight junctions to collect particles in the "luminal space" and to transport them through cytoplasmic processes between epithelial cells across the epithelium or to transmigrate through the epithelium to take up particles on the epithelial surface. Furthermore, dendritic cells interacted with particle-loaded macrophages on top of the epithelium and with other dendritic cells within or beneath the epithelium to take over particles. By comparing the cellular interplay of dendritic cells and macrophages across epithelial monolayers of different transepithelial electrical resistance, we found that more dendritic cells were involved in particle uptake in A549 cultures showing a low transepithelial electrical resistance compared with dendritic cells in16HBE14o cultures showing a high transepithelial electrical resistance 10 min (23.9% versus 9.5%) and 4 h (42.1% versus 14.6%) after particle exposition. In contrast, the macrophages in A549 co-cultures showed a significantly lower involvement in particle uptake compared with 16HBE14o co-cultures 10 min (12.8% versus 42.8%) and 4 h (57.4% versus 82.7%) after particle exposition. Hence we postulate that the epithelial integrity influences the particle uptake by dendritic cells, and that these two cell types collaborate as sentinels against foreign particulate antigen by building a transepithelial interacting cellular network.

Sedimentary evolution and environmental history of Lake Van (Turkey) over the past 600,000 years

The lithostratigraphic framework of Lake Van, eastern Turkey, has been systematically analysed to document the sedimentary evolution and the environmental history of the lake during the past ca 600,000 years. The lithostratigraphy and chemostratigraphy of a 219 m long drill core from Lake Van serves to separate global climate oscillations from local factors caused by tectonic and volcanic activity. An age model was established based on the climatostratigraphic alignment of chemical and lithological signatures, validated by 40Ar/39Ar ages. The drilled sequence consists of ca 76% lacustrine carbonaceous clayey silt, ca 2% fluvial deposits, ca 17% volcaniclastic deposits and 5% gaps. Six lacustrine lithotypes were separated from the fluvial and event deposits, such as volcaniclastics (ca 300 layers) and graded beds (ca 375 layers), and their depositional environments are documented. These lithotypes are: (i) graded beds frequently intercalated with varved clayey silts reflect rising lake-levels during the terminations; (ii) varved clayey silts reflect strong seasonality and an intralake oxic–anoxic boundary, for example, lake-level highstands during interglacials/interstadials; (iii) CaCO3-rich banded sediments are representative of a lowering of the oxic-anoxic boundary, for example, lake-level decreases during glacial inceptions; (iv) CaCO3-poor banded and mottled clayey silts reflect an oxic–anoxic boundary close to the sediment-water interface, for example, lake-level low-stands during glacials/stadials; (v) diatomaceous muds were deposited during the early beginning of the lake as a fresh water system; and (vi) fluvial sands and gravels indicate the initial flooding of the lake basin. The recurrence of lithologies (i) to (iv) follows the past five glacial/interglacial cycles. A 20 m thick disturbed unit reflects an interval of major tectonic activity in Lake Van at ca 414 ka BP.

Cultural Diversity as a Concept of Global Law : Origins, Evolution and Prospects

“Cultural diversity” has become one of the latest buzzwords on the international policymaking scene. It is employed in various contexts – sometimes as a term close to “biological diversity”, at other times as correlated to the “exception culturelle” and most often, as a generic concept that is mobilised to counter the perceived negative effects of economic globalisation. While no one has yet provided a precise definition of what cultural diversity is, what we can observe is the emergence of the notion of cultural diversity as incorporating a distinct set of policy objectives and choices at the global level. These decisions are not confined, as one might have expected, to cultural policymaking, but rather spill over to multiple governance domains because of the complex linkages inherent to the simultaneous pursuit of economic and other societal goals that cultural diversity encompasses and has effects on. Accounting for these intricate interdependencies, the present article clarifies the origins of the concept of cultural diversity as understood in global law and traces its evolution over time. Observing the dynamics of the concept and the surrounding political and legal developments, the article explores its justification and overall impact on the global legal regime, as well as its discrete effects on different domains of policymaking, such as media, intellectual property and culture. While the analysis is legal in essence, the article is meant to speak also to a broader transdisciplinary public. The article is part of the speacial issue on ethnic diversity and cultural pluralism, which is available under the creative commons licence: http://www.mdpi.com/journal/diversity/special_issues/ethnic-diversity/.

Eco-Evolutionary Spatial Dynamics. Rapid Evolution and Isolation Explain Food Web Persistence

One of the current challenges in evolutionary ecology is understanding the long-term persistence of contemporary-evolving predator–prey interactions across space and time. To address this, we developed an extension of a multi-locus, multi-trait eco-evolutionary individual-based model that incorporates several interacting species in explicit landscapes. We simulated eco-evolutionary dynamics of multiple species food webs with different degrees of connectance across soil-moisture islands. A broad set of parameter combinations led to the local extinction of species, but some species persisted, and this was associated with (1) high connectance and omnivory and (2) ongoing evolution, due to multi-trait genetic variability of the embedded species. Furthermore, persistence was highest at intermediate island distances, likely because of a balance between predation-induced extinction (strongest at short island distances) and the coupling of island diversity by top predators, which by travelling among islands exert global top-down control of biodiversity. In the simulations with high genetic variation, we also found widespread trait evolutionary changes indicative of eco-evolutionary dynamics. We discuss how the ever-increasing computing power and high-resolution data availability will soon allow researchers to start bridging the in vivo–in silico gap.

Talking About Climate Change: The Ecological Crisis and Narrative Form

This article examines the issue of climate change in the context of ecocriticism. It analyzes some of the narrative forms employed in the mediation of climate change science, focusing on those used by mediators who are not themselves scientists in the transmission of scientific information to a nonspecialist readership or audience. It reviews four relevant works that combine the communication of scientific theories and facts with pedagogical and motivational impulses. These include David Guggenheimer’s documentary film An Inconvenient Truth, Fred Pearce’s book The Last Generation: How Nature Will Take Her Revenge for Climate Change and the climate change manuals The Live Earth Global Warming Survival Handbook and How to Save the Climate.

Endovascular Treatment of Acute Stroke: Evolution and Selection of Techniques and Instruments Based on Thrombus Imaging.

Mechanical thrombectomy provides higher recanalization rates than intravenous or intra-arterial thrombolysis. Finally this has been shown to translate into improved clinical outcome in six multicentric randomized controlled trials. However, within cohorts the clinical outcomes may vary, depending on the endovascular techniques applied. Systems aiming mainly for thrombus fragmentation and lacking a protection against distal embolization have shown disappointing results when compared to recent stent-retriever studies or even to historical data on local arterial fibrinolysis. Procedure-related embolic events are usually graded as adverse events in interventional neuroradiology. In stroke, however, the clinical consequences of secondary emboli have so far mostly been neglected and attributed to progression of the stroke itself. We summarize the evolution of instruments and techniques for endovascular, image-guided, microneurosurgical recanalization in acute stroke, and discuss how to avoid procedure-related embolic complications.

Disease evolution and outcomes in familial AML with germline CEBPA mutations

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.