Type VI Secretion System and Its Effectors PdpC, PdpD, and OpiA Contribute to; Francisella; Virulence in Galleria mellonella Larvae

Francisella tularensis causes the deadly zoonotic disease tularemia in humans and is able to infect a broad range of organisms including arthropods, which are thought to play a major role in; Francisella; transmission. However, while mammalian; in vitro; and; in vivo; infection models are widely used to investigate; Francisella; pathogenicity, a detailed characterization of the major; Francisella; virulence factor, a noncanonical type VI secretion system (T6SS), in an arthropod; in vivo; infection model is missing. Here, we use Galleria mellonella larvae to analyze the role of the; Francisella; T6SS and its corresponding effectors in F. tularensis subsp.; novicida; virulence. We report that G. mellonella larvae killing depends on the functional T6SS and infectious dose. In contrast to other mammalian; in vivo; infection models, even one of the T6SS effectors PdpC, PdpD, or OpiA is sufficient to kill G. mellonella larvae, while sheath recycling by ClpB is dispensable. We further demonstrate that treatment by polyethylene glycol (PEG) activates; Francisella; T6SS in liquid culture and that this is independent of the response regulator PmrA. PEG-activated IglC secretion is dependent on T6SS structural component PdpB but independent of putative effectors PdpC, PdpD, AnmK, OpiB; 1; , OpiB; 2; , and OpiB; 3; . The results of larvae infection and secretion assay suggest that AnmK, a putative T6SS component with unknown function, interferes with OpiA-mediated toxicity but not with general T6SS activity. We establish that the easy-to-use G. mellonella larvae infection model provides new insights into the function of T6SS and pathogenesis of; Francisella;

Paclitaxel-Coated Balloon for the Treatment of Infrainguinal Disease: 12-Month Outcomes in the All-Comers Cohort of BIOLUX P-III Global Registry

Purpose: To further investigate the safety and performance of the Passeo-18 Lux drug-coated balloon (DCB) for the treatment of atherosclerotic infrainguinal disease under real-world conditions. Materials and Methods: BIOLUX P-III is an international, prospective, observational registry (ClinicalTrials.gov identifier NCT02276313) conducted at 41 centers in Europe, Asia, and Australia with follow-up visits at 6, 12, and 24 months. Of 700 patients (mean age 70.0\ub110.2 years; 439 men) with 863 lesions in the all-comers cohort, 330 (47.1%) patients had diabetes and 234 (37.7%) had chronic limb-threatening ischemia. The majority (79.3%) of lesions were in the femoropopliteal segment; of all lesions, 645 (74.9%) were calcified and 99 (11.5%) had in-stent restenosis (ISR). The mean lesion length was 84.7\ub173.3 mm. The primary clinical endpoint was major adverse events (MAEs) within 6 months, a composite of device- and procedure-related mortality through 30 days, major target limb amputation, and clinically-driven target lesion revascularization (TLR). The primary performance endpoint was clinically-driven TLR within 12 months. Results: At 6 and 12 months, freedom from MAEs was 94.0% and 89.5% in the all-comers cohort: 95.0% and 91.2% in the femoropopliteal group and 95.3% and 88.0% in the ISR subgroup, respectively. Freedom from clinically-driven TLR at 12 months was 93.1% in the all-comers cohort, 93.9% in the femoropopliteal lesions, and 89.4% for ISR lesions. All-cause mortality was 6.1% in the all-comers cohort: 5.9% in both the femoropopliteal and ISR subgroups. There were no device- or procedure-related deaths at up to 12 months. The Rutherford category improved in >80% of all subgroups at 12 months. Conclusion: In a real-world patient population, the safety and performance of the Passeo-18 Lux DCB for the treatment of atherosclerotic infrainguinal lesions are maintained, with good performance outcomes and low complication rates at 12 months

Data and methods to calculate cut-off values for serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest.

The data and estimation methods presented in this article are associated with the research article, "Cut-off values of serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest: a retrospective multi-centre study" [1]. In this article we estimate recommended cut-off values for in-hospital triage with respect to extracorporeal rewarming. With only 6 survivors of 103 patients collected over a period of 20 years the ability to estimate reliable threshold values is limited. In addition, because the number of avalanche victims is also limited, a significantly larger dataset is unlikely to be obtained. We have therefore adapted two non-parametric estimation methods (bootstrapping and exact binomial distribution) to our specific needs and performed a simulations to confirm validity and reliability

Decomposition of semigroup algebras

Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

Safety of Novel Microbes for Human Consumption: Practical Examples of Assessment in the European Union

Novel microbes are either newly isolated genera and species from natural sources or bacterial strains derived from existing bacteria. Novel microbes are gaining increasing attention for the general aims to preserve and modify foods and to modulate gut microbiota. The use of novel microbes to improve health outcomes is of particular interest because growing evidence points to the importance of gut microbiota in human health. As well, some recently isolated microorganisms have promise for use as probiotics, although in-depth assessment of their safety is necessary. Recent examples of microorganisms calling for more detailed evaluation include Bacteroides xylanisolvens, Akkermansia muciniphila, fructophilic lactic acid bacteria (FLAB), and Faecalibacterium prausnitzii. This paper discusses each candidate's safety evaluation for novel food or novel food ingredient approval according to European Union (EU) regulations. The factors evaluated include their beneficial properties, antibiotic resistance profiling, history of safe use (if available), publication of the genomic sequence, toxicological studies in agreement with novel food regulations, and the qualified presumptions of safety. Sufficient evidences have made possible to support and authorize the use of heat-inactivated B. xylanisolvens in the European Union. In the case of A. muciniphila, the discussion focuses on earlier safety studies and the strain's suitability. FLAB are also subjected to standard safety assessments, which, along with their proximity to lactic acid bacteria generally considered to be safe, may lead to novel food authorization in the future. Further research with F. prausnitzii will increase knowledge about its safety and probiotic properties and may lead to its future use as novel food. Upcoming changes in EUU Regulation 2015/2283 on novel food will facilitate the authorization of future novel products and might increase the presence of novel microbes in the food market

Powers of componentwise linear ideals

We give criteria for graded ideals to have the property that all their powers are componentwise linear. Typical examples to which our criteria can be applied include the vertex cover ideals of certain finite graphs

Real-world experience with a Paclitaxel-Coated Balloon for the treatment of atherosclerotic infrainguinal arteries: 12-month interim results of the BIOLUX P-III registry first year of enrolment = Experiência real com balão revestido com paclitaxel para o tratamento de artérias infrainguinais ateroscleróticas: resultados após 12 meses do primeiro ano de seleção de pacientes para o registro BIOLUX P-III

Background: Endovascular management of atherosclerotic infrainguinal arteries recently shifted towards drug eluting devices, designed to locally prevent the restenosis process. Numerous clinical studies report an advantage of drug coated balloons over uncoated balloon angioplasty in treating lower extremity peripheral artery disease. However, as coating and balloon platforms are different, each device requires dedicated clinical evaluations. Objective: The aim of the study is to further investigate the safety and effectiveness of a Paclitaxel-Coated Balloon for the treatment of atherosclerotic infrainguinal arteries in a real-world setting. Methods: 203 patients out of a final sample of 882 were enrolled in this prospective multicenter, observational, all-comers registry during the first 12 months. The primary endpoints were major adverse events (defined as procedure or device related death within 30 days post index procedure, clinically-driven target lesion revascularization or major target limb amputation) at 6 months and freedom from clinically-driven target lesion revascularization at 12 months. Both endpoints were adjudicated by a Clinical Events Committee. Results: Mean patient age was 70.2\ub110.4 years (60.1% male). 47.3% of the patients were diabetic and 67.5% had a history of smoking. Severe claudication was reported in 37.4% and 40% had critical limb ischemia. 257 lesions, including 13.2% in the infrapopliteal territory, were treated with Passeo-18 Lux (mean lesion length 75.1 mm\ub169.4, 20% occlusions, 76.3% calcified). At 6 months, the rate of major adverse events was 5.5% (95%CI 3.1-9.7). Freedom from clinically-driven target lesion revascularization at 12 months was 93.2% (95%CI 89.1-95.8). All causes mortality was 6.5% (95%CI 3.8-11.0) and overall amputation rate was 4.2% (95%CI 2.1-8.3) at 12 months. Conclusion: In a real-world environment, the BIOLUX P-III registry preliminary results confirm the safety and efficacy of the Paclitaxel-Coated Passeo-18 Lux balloon as a stand-alone treatment option for atherosclerotic infrainguinal arteries.Contexto: O manejo endovascular de art\ue9rias infrainguinais ateroscler\uf3ticas recentemente tem mudado para dispositivos farmacol\uf3gicos, desenhados para impedir localmente o processo de reestenose. Numerosos estudos cl\uednicos descrevem uma vantagem da angioplastia com uso de bal\uf5es farmacol\uf3gicos sobre os bal\uf5es convencionais no tratamento de doen\ue7a arterial perif\ue9rica dos membros inferiores. No entanto, considerando que as plataformas do revestimento farmacol\uf3gico e dos bal\uf5es s\ue3o diferentes, cada dispositivo requer avalia\ue7\uf5es cl\uednicas espec\uedficas. Objetivo: Fazer investiga\ue7\ue3o adicional sobre a seguran\ue7a e efic\ue1cia de um bal\ue3o revestido com paclitaxel para o tratamento de art\ue9rias infrainguinais ateroscler\uf3ticas em um cen\ue1rio de mundo real. M\ue9todos: 203 pacientes de uma amostra final de 882 pacientes foram inclu\ueddos neste registro prospectivo observacional multic\ueantrico de inclus\ue3o sequencial, durante os primeiros 12 meses. Os desfechos prim\ue1rios foram eventos adversos maiores (definidos como morte relacionada ao procedimento ou ao dispositivo em at\ue9 30 dias ap\uf3s o procedimento-\uedndice, necessidade de revasculariza\ue7\ue3o da les\ue3o-alvo ou amputa\ue7\ue3o significativa do membro-alvo) em 6 meses e aus\ueancia de de revasculariza\ue7\ue3o da les\ue3o-alvo em 12 meses. Ambos os desfechos foram adjudicados por um comit\uea de eventos cl\uednicos. Resultados: A idade m\ue9dia foi 70,2\ub110,4 anos (60,1% sexo masculino). 47,3% dos pacientes eram diab\ue9ticos, e 67,5% tinham hist\uf3ria de tabagismo. Claudica\ue7\ue3o severa foi relatada em 37,4%, e 40% apresentava isquemia cr\uedtica de membro. 257 les\uf5es, incluindo 13,2% em territ\uf3rio infrapopl\uedteo, foram tratadas com o bal\ue3o Passeo-18 Lux (comprimento m\ue9dio das les\uf5es 75,1 mm\ub169,4, 20% oclus\uf5es, 76,3% calcificadas). Aos 6 meses, a taxa de eventos adversos maiores foi de 5,5% (95%CI 3,1-9,7). A aus\ueancia de revasculariza\ue7\ue3o da les\ue3o-alvo aos 12 meses foi de 93,2% (95%CI 89,1-95,8). Mortalidade por todas as causas foi de 6,5% (95%CI 3,8-11,0) e a taxa geral de amputa\ue7\ue3o foi de 4,2% (95%CI 2,1-8,3) aos 12 meses. Conclus\ue3o: Em um cen\ue1rio de mundo real, os resultados preliminares do registro BIOLUX P-III confirmam a seguran\ue7a e efic\ue1cia do bal\ue3o revestido com paclitaxel Passeo-18 Lux como op\ue7\ue3o de tratamento \ufanico para art\ue9rias infrainguinais ateroscler\uf3ticas

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language—the site of such integration seems to be the parietal and extending opercular cortices

Detection of triplex PCR for the modified qualitative soybean and maize genetically

A molecular screening method based on multiplex PCR that involves amplification of specific soybean or maize sequences from plant DNA (lectin or zein) and the amplification of 35S promoter and NOS terminator,for the detection of genetically modified soybean and maize was developed. The new method is proposed,for the simulicmeous cletcctimt of tree genetic elements in the.same run as reliable method for rapid detection of genetically, modified plants with sensitivity of 0.1%