Multiple lines of evidence suggest that Bordetella species have a significant life stage outside of the mammalian respiratory tract that has yet to be defined. The Bordetella virulence gene (BvgAS) ...two-component system, a paradigm for a global virulence regulon, controls the expression of many "virulence factors" expressed in the Bvg positive (Bvg+) phase that are necessary for successful respiratory tract infection. A similarly large set of highly conserved genes are expressed under Bvg negative (Bvg-) phase growth conditions; however, these appear to be primarily expressed outside of the host and are thus hypothesized to be important in an undefined extrahost reservoir. Here, we show that Bvg- phase genes are involved in the ability of Bordetella bronchiseptica to grow and disseminate via the complex life cycle of the amoeba Dictyostelium discoideum. Unlike bacteria that serve as an amoeba food source, B. bronchiseptica evades amoeba predation, survives within the amoeba for extended periods of time, incorporates itself into the amoeba sori, and disseminates along with the amoeba. Remarkably, B. bronchiseptica continues to be transferred with the amoeba for months, through multiple life cycles of amoebae grown on the lawns of other bacteria, thus demonstrating a stable relationship that allows B. bronchiseptica to expand and disperse geographically via the D. discoideum life cycle. Furthermore, B. bronchiseptica within the sori can efficiently infect mice, indicating that amoebae may represent an environmental vector within which pathogenic bordetellae expand and disseminate to encounter new mammalian hosts. These data identify amoebae as potential environmental reservoirs as well as amplifying and disseminating vectors for B. bronchiseptica and reveal an important role for the Bvg- phase in these interactions.
The ability of some bird species to pull up meat hung on a string is a famous example of spontaneous animal problem solving. The "insight" hypothesis claims that this complex behaviour is based on ...cognitive abilities such as mental scenario building and imagination. An operant conditioning account, in contrast, would claim that this spontaneity is due to each action in string pulling being reinforced by the meat moving closer and remaining closer to the bird on the perch. We presented experienced and naïve New Caledonian crows with a novel, visually restricted string-pulling problem that reduced the quality of visual feedback during string pulling. Experienced crows solved this problem with reduced efficiency and increased errors compared to their performance in standard string pulling. Naïve crows either failed or solved the problem by trial and error learning. However, when visual feedback was available via a mirror mounted next to the apparatus, two naïve crows were able to perform at the same level as the experienced group. Our results raise the possibility that spontaneous string pulling in New Caledonian crows may not be based on insight but on operant conditioning mediated by a perceptual-motor feedback cycle.
Background Sufficient evidence suggests that preoperative biliary stenting is associated with increased complication rates after pancreaticoduodenectomy. Methods Surveillance, Epidemiology, and End ...Results (SEER) and linked Medicare claims data (1992–2007) were used to identify patients with pancreatic cancer who underwent pancreaticoduodenectomy. We evaluated trends in the use of preoperative biliary stenting, timing of physician visits relative to stenting, and time to surgical resection and symptoms in stented and unstented patients. Results Pancreaticoduodenectomy was performed in 2,573 patients, and 52.6% of patients underwent preoperative biliary stenting ( N = 1,354). Of these, 75.3% underwent endoscopic stenting only, 18.9% received a percutaneous stent, and 5.8% underwent both procedures. The overall stenting rate increased from 29.6% of patients between 1992 and 1995 to 59.1% between 2004 and 2007 ( P < .0001). Preoperative stenting was more common in patients with jaundice, cholangitis, pruritus, or coagulopathy ( P < .05 for all). Of stented patients, 77.7% had had a stent placed prior to seeing a surgeon. Stenting prior to surgical consultation was associated with longer indwelling stent time compared to stenting after surgical consultation (37.3 vs 27.0 days, P < .0001). In addition, stented patients had longer times from surgeon visit to pancreatectomy than those who had not received stents (24.2 days vs 17.2 days, P < .0001). Conclusion Use of preoperative biliary stenting doubled between 1992 and 2007 despite evidence that stenting is associated with increased perioperative infectious complications. The majority of stenting occurred prior to surgical consultation and is associated with significant delay in time to operation. Surgeons should be involved early in order to prevent unnecessary stenting and improve outcomes.
Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence ...for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.
Management of deep-sea fisheries in areas beyond national jurisdiction by Regional Fisheries Management Organizations/Arrangements (RFMO/As) requires identification of areas with Vulnerable Marine ...Ecosystems (VMEs). Currently, fisheries data, including trawl and longline bycatch data, are used by many RFMO/As to inform the identification of VMEs. However, the collection of such data creates impacts and there is a need to collect non-invasive data for VME identification and monitoring purposes. Imagery data from scientific surveys satisfies this requirement, but there currently is no established framework for identifying VMEs from images. Thus, the goal of this study was to bring together a large international team to determine current VME assessment protocols and establish preliminary global consensus guidelines for identifying VMEs from images. An initial assessment showed a lack of consistency among RFMO/A regions regarding what is considered a VME indicator taxon, and hence variability in how VMEs might be defined. In certain cases, experts agreed that a VME could be identified from a single image, most often in areas of scleractinian reefs, dense octocoral gardens, multiple VME species’ co-occurrence, and chemosynthetic ecosystems. A decision flow chart is presented that gives practical interpretation of the FAO criteria for single images. To further evaluate steps of the flow chart related to density, data were compiled to assess whether scientists perceived similar density thresholds across regions. The range of observed densities and the density values considered to be VMEs varied considerably by taxon, but in many cases, there was a statistical difference in what experts considered to be a VME compared to images not considered a VME. Further work is required to develop an areal extent index, to include a measure of confidence, and to increase our understanding of what levels of density and diversity correspond to key ecosystem functions for VME indicator taxa. Based on our results, the following recommendations are made: 1. There is a need to establish a global consensus on which taxa are VME indicators. 2. RFMO/As should consider adopting guidelines that use imagery surveys as an alternative (or complement) to using bycatch and trawl surveys for designating VMEs. 3. Imagery surveys should also be included in Impact Assessments. And 4. All industries that impact the seafloor, not just fisheries, should use imagery surveys to detect and identify VMEs.
Screening a panel of Bordetella bronchiseptica–defined mutants lacking various “virulence factors” revealed one completely unable to transmit between animals. Surprisingly, mutation of a locus ...associated with extracellular polysaccharide affected both shedding from infected animals and colonization of exposed animals.
Abstract
Background
The lack of animal models to experimentally study how infectious agents transmit between hosts limits our understanding of what makes some pathogens so contagious.
Methods
We recently developed a Bordetella bronchiseptica mouse model to study transmission and have used it to assess, for the first time, which of several well-studied “virulence factors” common to classical Bordetella species contribute to transmission.
Results
Among 13 mutants screened, a mutant lacking an extracellular polysaccharide (EPS) locus consistently failed to transmit. The loss of EPS had no obvious effect on in vitro characteristics of growth, adherence, cytotoxicity, or serum resistance, though it profoundly reduced the ability of the mutant to colonize the lower respiratory tract of mice. While wild-type B. bronchiseptica was shed from colonized mice and efficiently transmitted to cage-mates, the mutant colonized less efficiently, shed at lower numbers, and consequently did not transmit to naive animals.
Conclusions
These results have important implications for potential roles of polysaccharides in the pathogenesis and transmission of Bordetella species as well as other respiratory pathogens. Cases of pertussis (whooping cough) caused by Bordetella pertussis are on the rise, and understanding factors that contribute to their spread is critical to its control.
Detection of structural variants (SVs) is currently biased toward those that alter copy number. The relative contribution of inversions toward genetic disease is unclear. In this study, we analyzed ...genome sequencing data for 33,924 families with rare disease from the 100,000 Genomes Project. From a database hosting >500 million SVs, we focused on 351 genes where haploinsufficiency is a confirmed disease mechanism and identified 47 ultra-rare rearrangements that included an inversion (24 bp to 36.4 Mb, 20/47 de novo). Validation utilized a number of orthogonal approaches, including retrospective exome analysis. RNA-seq data supported the respective diagnoses for six participants. Phenotypic blending was apparent in four probands. Diagnostic odysseys were a common theme (>50 years for one individual), and targeted analysis for the specific gene had already been performed for 30% of these individuals but with no findings. We provide formal confirmation of a European founder origin for an intragenic MSH2 inversion. For two individuals with complex SVs involving the MECP2 mutational hotspot, ambiguous SV structures were resolved using long-read sequencing, influencing clinical interpretation. A de novo inversion of HOXD11-13 was uncovered in a family with Kantaputra-type mesomelic dysplasia. Lastly, a complex translocation disrupting APC and involving nine rearranged segments confirmed a clinical diagnosis for three family members and resolved a conundrum for a sibling with a single polyp. Overall, inversions play a small but notable role in rare disease, likely explaining the etiology in around 1/750 families across heterogeneous clinical cohorts.
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By analyzing genome sequencing data for 33,924 families from a heterogeneous rare-disease cohort, Pagnamenta et al. identified 45 families where inversions likely explain the etiology. In six instances, RNA-seq helped support the respective diagnoses, and exemplar cases include complex SVs involving MECP2 where long-read sequencing data influenced the clinical interpretation.
THE CONVECTIVE PRECIPITATION EXPERIMENT (COPE) Leon, David C.; French, Jeffrey R.; Lasher-Trapp, Sonia ...
Bulletin of the American Meteorological Society,
06/2016, Letnik:
97, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The Convective Precipitation Experiment (COPE) was a joint U.K.–U.S. field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that ...produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly as a result of the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the United States. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve numerical weather prediction (NWP) model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the U.K. BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360° volume scans over 10 elevation angles approximately every 5 min and was augmented by two Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper i) provides an overview of the COPE field campaign and the resulting dataset, ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone, and iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.
This case study is part of a project examining the Mount Arrowsmith Biosphere Region - a UNESCO-designated biosphere reserve on Vancouver Island, British Columbia. We aimed to understand the extent ...to which individuals in six communities experience psychological variables linked to pro-social and pro-environmental outcomes, such as sense of place - comprised of place attachment, place identity, and place dependence - and nature-relatedness. We also explored how these attitudes relate to residents' perceived views of, and walkable access to, nature. Overall, sense of place was neutral; nature relatedness and perceptions of views and access to nature were significantly stronger than sense of place. Although these two variables, as well as sense of place and perceptions of views and walkable access to nature correlated in the region on aggregate, significant associations were not revealed per community. Over 60% of responses to an open-ended item about physical features that contribute to sense of place concerned the natural environment - rather than social or built amenities. Municipal planners may capitalize on restorative effects that arise when community members form connections with nature, and concentrate funding or public engagement on trails, parks, and other natural features to bolster sense of place in coastal and mountainous communities.