A dense ring of the trans-Neptunian object Quaoar outside its Roche limit.

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

Low Prevalence of Screen-Detected Colorectal Cancer in an Average-Risk Population: The New Normal.

Prior studies have reported the prevalence of colorectal cancer (CRC) in average-risk screening population ages 50-75 to be 0.7%-1.0%.1,2 However, no estimates from studies enrolling individuals undergoing screening colonoscopy have been reported. The experience of ongoing studies enrolling average-risk individuals is that the prevalence rates are substantially lower. A 2020 study from a community-based cohort undergoing CRC screening with fecal immunochemical testing followed by diagnostic colonoscopy reported a CRC prevalence rate of 1.46 per 1000, or 0.15%.3 The aim of our study is to report the screen-detected prevalence of CRC and advanced neoplasia in average-risk asymptomatic individuals from selected academic and community medical centers in the United States, Canada, and Germany and describe associated risk factors.

A radio-pulsing white dwarf binary star.

White dwarfs are compact stars, similar in size to Earth but approximately 200,000 times more massive. Isolated white dwarfs emit most of their power from ultraviolet to near-infrared wavelengths, but when in close orbits with less dense stars, white dwarfs can strip material from their companions and the resulting mass transfer can generate atomic line and X-ray emission, as well as near- and mid-infrared radiation if the white dwarf is magnetic. However, even in binaries, white dwarfs are rarely detected at far-infrared or radio frequencies. Here we report the discovery of a white dwarf/cool star binary that emits from X-ray to radio wavelengths. The star, AR Scorpii (henceforth AR Sco), was classified in the early 1970s as a δ-Scuti star, a common variety of periodic variable star. Our observations reveal instead a 3.56-hour period close binary, pulsing in brightness on a period of 1.97 minutes. The pulses are so intense that AR Sco's optical flux can increase by a factor of four within 30 seconds, and they are also detectable at radio frequencies. They reflect the spin of a magnetic white dwarf, which we find to be slowing down on a 107-year timescale. The spin-down power is an order of magnitude larger than that seen in electromagnetic radiation, which, together with an absence of obvious signs of accretion, suggests that AR Sco is primarily spin-powered. Although the pulsations are driven by the white dwarf's spin, they mainly originate from the cool star. AR Sco's broadband spectrum is characteristic of synchrotron radiation, requiring relativistic electrons. These must either originate from near the white dwarf or be generated in situ at the M star through direct interaction with the white dwarf's magnetosphere.

Community trial evaluating the integration of Indigenous healing practices and a harm reduction approach with principles of seeking safety in an Indigenous residential treatment program in northern Ontario.

OBJECTIVE: Our primary objective was to evaluate how the Indigenous Healing and Seeking Safety (IHSS) model impacted residential addiction treatment program completion rates. Our secondary objective was to evaluate health service use 6 months before and 6 months after residential treatment for clients who attended the program before and after implementing IHSS. METHODS: We observed clients of the Benbowopka Residential Treatment before IHSS implementation (from April 2013 to March 31, 2016) and after IHSS implementation (from January 1, 2018 - March 31, 2020). The program data were linked to health administration data, including the Ontario Health Insurance Plan (OHIP) physician billing, the Registered Persons Database (RPDB), the National Ambulatory Care Reporting System (NACRS), and the Discharge Abstract Database (DAD). Chi-square tests were used to compare patient characteristics in the no-IHSS and IHSS groups. We used logistic regression to estimate the association between IHSS and treatment completion. We used generalized estimating equation (GEE) regression model to evaluate health service use (including primary care visits, ED visits overall and for substance use, hospitalizations and mental health visits), Results: There were 266 patients in the no-IHSS group and 136 in the IHSS group. After adjusting for individual characteristics, we observed that IHSS was associated with increased program completion rates (odds ratio = 1.95, 95% CI 1.02-3.70). There was no significant association between IHSS patients' health service use at time one or time two. Primary care visits time 1: aOR 0.55, 95%CI 0.72-1.13, time 2: aOR 1.13, 95%CI 0.79-1.23; ED visits overall time 1: aOR 0.91, 95%CI 0.67-1.23, time 2: aOR 1.06, 95%CI 0.75-1.50; ED visits for substance use time 1: aOR 0.81, 95%CI 0.47-1.39, time 2: aOR 0.79, 95%CI 0.37-1.54; Hospitalizations time 1: aOR 0.78, 95%CI 0.41-1.47, time 2: aOR 0.76, 95%CI 0.32-1.80; Mental health visits time 1: aOR 0.66, 95%CI 0.46-0.96, time 2: aOR 0.92 95%CI 0.7-1.40. CONCLUSIONS: Our results indicate that IHSS positively influenced program completion but had no significant effect on health service use. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (identifier number NCT04604574). First registration 10/27/2020.

Global Burden of Animal Diseases: a novel approach to understanding and managing disease in livestock and aquaculture.

Investments in animal health and Veterinary Services can have a measurable impact on the health of people and the environment. These investments require a baseline metric that describes the burden of animal health and welfare in order to justify and prioritise resource allocation and from which to measure the impact of interventions. This paper is part of a process of scientific enquiry in which problems are identified and solutions sought in an inclusive way. It poses the broad question: what should a system to measure the animal disease burden on society look like and what value would it add? Moreover, it aims to do this in such a way as to be accessible by a wide audience, who are encouraged to engage in this debate. Given that farmed animals, including those raised by poor smallholders, are an economic entity, this system should be based on economic principles. These poor farmers are negatively impacted by disparities in animal health technology, which can be addressed through a mixture of supply-led and demand-driven interventions, reinforcing the relevance of targeted financial support from government and non-governmental organisations. The Global Burden of Animal Diseases (GBADs) Programme will glean existing data to measure animal health losses within carefully characterised production systems. Consistent and transparent attribution of animal health losses will enable meaningful comparisons of the animal disease burden to be made between diseases, production systems and countries, and will show how it is apportioned by people's socio-economic status and gender. The GBADs Programme will produce a cloud-based knowledge engine and data portal, through which users will access burden metrics and associated visualisations, support for decisionmaking in the form of future animal health scenarios, and the outputs of wider economic modelling. The vision of GBADs, strengthening the food system for the benefit of society and the environment, is an example of One Health thinking in action.

Les investissements réalisés en santé animale et dans les Services vétérinaires ont un impact mesurable sur la santé des personnes et de l'environnement. Le système de mesure appliqué à ces investissements doit reposer sur un référentiel de base décrivant l'impact de la santé et du bien-être animal de manière à justifier et classer par priorités les ressources allouées et à mesurer les effets des interventions. Les auteurs présentent une étude conduite dans le cadre d'une enquête scientifique destinée à identifier les problèmes et à rechercher des solutions de manière inclusive. L'étude pose la question de savoir à quoi devrait ressembler un système conçu pour mesurer l'impact sur la société des maladies animales, et quelle serait sa valeur ajoutée. En outre, l'étude est conduite de manière à être accessible à une large audience afin d'encourager cette dernière à participer aux discussions. Étant donné que les animaux d'élevage constituent une entité économique, y compris les animaux appartenant à des éleveurs pauvres, le système de mesure doit reposer sur des principes économiques. Les exploitants pratiquant une agriculture de subsistance subissent les effets négatifs des disparités entre les différentes technologies applicables à la santé animale, disparités auxquelles il est possible de remédier par le biais d'interventions associant des mesures dictées par l'offre et par la demande et en renforçant l'efficacité du soutien financier ciblé apporté par les organisations gouvernementales et non gouvernementales. Le Programme « L'impact mondial des maladies animales ¼ (GBADs) aura pour tâche de glaner les données existantes afin de mesurer les pertes associées à la santé animale au sein de systèmes de production qui auront été soigneusement caractérisés au préalable. Grâce à l'élucidation cohérente et transparente des pertes imputables à chaque problème de santé animale, des comparaisons pertinentes pourront être effectuées concernant l'impact des maladies animales par maladies, par systèmes de production et par pays, et la répartition de cet impact dans les populations concernées suivant le statut socio-économique et le genre des intéressés sera mieux comprise. Le Programme GBADs entend créer un moteur de recherche et un portail de données qui seront disponibles sur le Cloud et donneront aux utilisateurs l'accès à des outils de mesure de l'impact des maladies et à d'autres informations présentées sous forme graphique, ainsi qu'à des outils d'aide à la décision sous forme de scénarios prospectifs sur la santé animale et aux résultats d'études plus larges de modélisation économique. La vision du GBADs, renforcer le système de production de denrées alimentaires au profit de la société et de l'environnement, est un exemple de mise en oeuvre du concept Une seule santé.

Las inversiones en sanidad animal y en los Servicios Veterinarios pueden tener un efecto mensurable en la salud de las personas y el medio ambiente. Para efectuar estas inversiones se precisan parámetros que describan y cuantifiquen la situación de partida y el impacto de los problemas de sanidad y bienestar animales, a fin de poder, a partir de ahí, justificar y jerarquizar la asignación de recursos y medir los efectos de las intervenciones. Este artículo, inscrito en un proceso de indagación científica encaminado a detectar problemas y buscar soluciones de forma incluyente, plantea la cuestión general de cómo debería ser y qué valor añadido aportaría un sistema destinado a medir el impacto que imponen a la sociedad las enfermedades animales. Los autores, además, tratan de exponer la cuestión de manera que sea accesible a un público amplio, al que se alienta a participar en este debate. Dado que los animales de granja (incluidos los de pequeñas explotaciones) constituyen una entidad económica, tal sistema debería estar basado en principios económicos. Los productores que trabajan en régimen de subsistencia se ven negativamente afectados por las disparidades existentes en materia de tecnología zoosanitaria, disparidad que cabe corregir con una combinación de intervenciones marcadas por la oferta y otras marcadas por la demanda, dirigiendo así más selectivamente el apoyo económico de entidades gubernamentales y organizaciones no gubernamentales. El programa GBADs (El impacto global de las enfermedades animales) servirá para compilar datos ya existentes con el fin de medir las pérdidas zoosanitarias dentro de sistemas productivos cuidadosamente caracterizados. La atribución coherente y transparente de estas pérdidas zoosanitarias permitirá efectuar comparaciones significativas del impacto que representan las enfermedades animales en el caso de diferentes dolencias, sistemas productivos o países y pondrá de relieve cómo se distribuye este impacto en función del género y la condición socioeconómica de las personas. Por medio del programa GBADs se creará un motor de conocimiento y portal de datos ubicado en la nube que permita al usuario acceder a mediciones del impacto de enfermedades y representaciones gráficas conexas, a herramientas de apoyo a la adopción de decisiones, en forma de hipotéticas situaciones zoosanitarias futuras, y a los resultados de modelizaciones económicas más generales. La aspiración del programa GBADs ­ reforzar el sistema alimentario en beneficio de la sociedad y el medio ambiente ­ constituye un ejemplo de aplicación en la práctica del pensamiento en clave de Una sola salud.

A study protocol for a quasi-experimental community trial evaluating the integration of indigenous healing practices and a harm reduction approach with principles of seeking safety in an indigenous residential treatment program in Northern Ontario.

BACKGROUND: Indigenous communities in Canada face significant challenges with intergenerational trauma, which manifests in substance use disorders. There is consensus that connecting treatment approaches to culture, land, community, and spiritual practices is a pathway to healing trauma and substance use disorders for Indigenous peoples. Indigenous residential addiction treatment programs have been established as the primary intervention to provide healing for Indigenous peoples with substance use disorders and intergenerational trauma. However, there is limited evidence demonstrating the effectiveness of these programs. In collaboration with the Benbowopka Treatment Centre, this paper describes a study protocol which aims to evaluate the effectiveness of blending Indigenous Healing Practices and Seeking Safety for the treatment of Indigenous patients with intergenerational trauma and substance use disorders. METHODS: We will conduct a pre/post Quasi Experimental Community trial, to compare historical treatment outcomes for patients following the implementation of Indigenous Healing and Seeking Safety. We will conduct quantitative and qualitative analyses to understand the differences before and after the intervention is implemented. The pre- Indigenous Healing and Seeking Safety intervention study window will span from 2013 to 2016; n = 343, and the post-Indigenous Healing and Seeking Safety intervention study window from 2018 to 2020; n > 300. All participants will be enrolled in the Benbowopka residential treatment for the first time during the study periods. All data will be anonymized at the time of data entry. Propensity matching will be undertaken for patient characteristics, including sex/gender, age, and substance use type. RESULTS AND CONCLUSIONS: The study findings could be used to inform intergenerational trauma and substance use disorders residential treatment programming for Indigenous communities across Canada. Our work will contribute to the field of community-based intergenerational trauma and substance use disorders programming by addressing objectives that consider: (a) the patient perspective, (b) the program perspective, and (c) the community perspective. The study findings may validate an innovative approach for evaluating the effectiveness of residential addiction treatment and particularly the effective and appropriate care for Indigenous patients with intergenerational trauma and substance use disorders.

Antagonistic Interactions and Biofilm Forming Capabilities Among Bacterial Strains Isolated from the Egg Surfaces of Lake Sturgeon (Acipenser fulvescens).

Characterization of interactions within a host-associated microbiome can help elucidate the mechanisms of microbial community formation on hosts and can be used to identify potential probiotics that protect hosts from pathogens. Microbes employ various modes of antagonism when interacting with other members of the community. The formation of biofilm by some strains can be a defense against antimicrobial compounds produced by other taxa. We characterized the magnitude of antagonistic interactions and biofilm formation of 25 phylogenetically diverse taxa that are representative of isolates obtained from egg surfaces of the threatened fish species lake sturgeon (Acipenser fulvescens) at two ecologically relevant temperature regimes. Eight isolates exhibited aggression to at least one other isolate. Pseudomonas sp. C22 was found to be the most aggressive strain, while Flavobacterium spp. were found to be one of the least aggressive and the most susceptible genera. Temperature affected the prevalence and intensity of antagonism. The aggressive strains identified also inhibited growth of known fish pathogens. Biofilm formations were observed for nine isolates and were dependent on temperature and growth medium. The most aggressive of the isolates disrupted biofilm formation of two well-characterized isolates but enhanced biofilm formation of a fish pathogen. Our results revealed the complex nature of interactions among members of an egg associated microbial community yet underscored the potential of specific microbial populations as host probiotics.

Albedo and atmospheric constraints of dwarf planet Makemake from a stellar occultation.

Pluto and Eris are icy dwarf planets with nearly identical sizes, comparable densities and similar surface compositions as revealed by spectroscopic studies. Pluto possesses an atmosphere whereas Eris does not; the difference probably arises from their differing distances from the Sun, and explains their different albedos. Makemake is another icy dwarf planet with a spectrum similar to Eris and Pluto, and is currently at a distance to the Sun intermediate between the two. Although Makemake's size (1,420 ± 60 km) and albedo are roughly known, there has been no constraint on its density and there were expectations that it could have a Pluto-like atmosphere. Here we report the results from a stellar occultation by Makemake on 2011 April 23. Our preferred solution that fits the occultation chords corresponds to a body with projected axes of 1,430 ± 9 km (1σ) and 1,502 ± 45 km, implying a V-band geometric albedo p(V) = 0.77 ± 0.03. This albedo is larger than that of Pluto, but smaller than that of Eris. The disappearances and reappearances of the star were abrupt, showing that Makemake has no global Pluto-like atmosphere at an upper limit of 4-12 nanobar (1σ) for the surface pressure, although a localized atmosphere is possible. A density of 1.7 ± 0.3 g cm(-3) is inferred from the data.

Animal health economics: an aid to decisionmaking on animal health interventions - case studies in the United States of America.

For animal disease events the outcomes and consequences often remain unclear or uncertain, including the expected changes in benefits (e.g. profit to firms, prices to consumers) and in costs (e.g. response, clean-up). Moreover, the measurement of changes in benefits and costs across alternative interventions used to control animal disease events may be inexact. For instance, the economic consequences of alternative vaccination strategies to mitigate a disease can vary in magnitude due to trade embargoes and other factors. The authors discuss the economic measurement of animal disease outbreaks and interventions and how measurement is used in private and public decision-making. Two illustrative case studies in the United States of America are provided: a hypothetical outbreak of foot and mouth disease in cattle, and the 2014-2015 outbreak of highly pathogenic avian influenza in poultry.

Lors d'un événement sanitaire, les résultats et les conséquences d'une intervention sont souvent incertains ou imprécis, y compris pour ce qui concerne l'évolution attendue des bénéfices (par ex. le profit pour les entreprises ou le prix payé par le consommateur) et des coûts (par ex. le coût de la réponse ou de l'assainissement). De plus, la mesure de l'évolution des bénéfices et des coûts suivant les différentes interventions utilisées pour lutter contre les maladies animales peut s'avérer inexacte. Par exemple, les conséquences économiques de différentes stratégies de vaccination visant à atténuer l'impact d'une maladie peuvent varier en ordre de grandeur du fait des restrictions imposées au commerce suite à la vaccination, ou d'autres facteurs. Les auteurs examinent l'évaluation économique des foyers de maladies animales et des interventions sanitaires ainsi que l'utilisation de ces évaluations dans les prises de décision du secteur privé et public. L'analyse est illustrée par deux études de cas aux États- Unis d'Amérique : l'hypothèse d'un foyer de fièvre aphteuse survenant dans la population bovine, et le foyer d'influenza aviaire hautement pathogène survenu en 2014­2015 chez les volailles.

A menudo los resultados o efectos de ciertos episodios zoosanitarios quedan poco claros o generan incertidumbre, por ejemplo sobre el modo en que en principio modifican los beneficios (réditos para las empresas, precios para el consumidor) y los costos (p.ej. de respuesta o de saneamiento de la explotación). Además, la medición de los cambios que experimenten los costos y beneficios a resultas de distintas intervenciones posibles para combatir un episodio zoosanitario puede resultar inexacta. Por ejemplo: las consecuencias económicas de estrategias alternativas de vacunación para mitigar una enfermedad pueden ser de magnitud variable dependiendo de la existencia de embargos comerciales u otros factores. Los autores examinan la cuantificación económica de los brotes de enfermedades animales y las intervenciones para combatirlos y explican cómo se utilizan esas mediciones para tomar decisiones en los sectores público y privado, ofreciendo como ejemplo casos situados en los Estados Unidos de América: un brote hipotético de fiebre aftosa en el ganado vacuno y el brote de influenza aviar altamente patógena que en 2014 y 2015 afectó a las aves de corral.

Bacterial community dynamics during industrial malting, with an emphasis on lactic acid bacteria.

Characterization of the microflora during malting is an essential step towards process management and optimization. Up till now, however, microbial characterization in the malting process has mostly been done using culture-dependent methods, probably leading to biased estimates of microbial diversity. The aim of this study was to characterize the bacterial communities using two culture-independent methods, including Terminal Restriction Fragment Length Polymorphism (T-RFLP) and 454 pyrosequencing, targeting the 16S rRNA gene. Studied samples originated from two harvest years and two malting houses malting the same batch of barley. Besides targeting the entire bacterial community (T-RFLP), emphasis was put on lactic acid bacteria (LAB) (T-RFLP and 454 pyrosequencing). The overall bacterial community richness was limited, but the community structure changed during the process. Zooming in on the LAB community using 454 pyrosequencing revealed a total of 47 species-level operational taxonomic units (OTUs). LAB diversity appeared relatively limited since 88% of the sequences were covered by the same five OTUs (representing members of Weissella, Lactobacillus and Leuconostoc) present in all samples investigated. Fluctuations in the relative abundances of the dominant LAB were observed with the process conditions. In addition, both the year of harvest and malting house influenced the LAB community structure.

Economic evaluation of lifestyle interventions to treat overweight or obesity in children.

OBJECTIVE: To estimate lifetime cost effectiveness of lifestyle interventions to treat overweight and obese children, from the UK National Health Service perspective. DESIGN: An adaptation of the National Heart Forum economic model to predict lifetime health service costs and outcomes of lifestyle interventions on obesity-related diseases. SETTING: Hospital or community-based weight-management programmes. POPULATION: Hypothetical cohorts of overweight or obese children based on body mass data from the National Child Measurement Programme. INTERVENTIONS: Lifestyle interventions that have been compared with no or minimal intervention in randomized controlled trials (RCTs). MAIN OUTCOME MEASURES: Reduction in body mass index (BMI) standard deviation score (SDS), intervention resources/costs, lifetime treatment costs, obesity-related diseases and cost per life year gained. RESULTS: Ten RCTs were identified by our search strategy. The median effect of interventions versus control from these 10 RCTs was a difference in BMI SDS of -0.13 at 12 months, but the range in effects among interventions was broad (0.04 to -0.60). Indicative costs per child of these interventions ranged from £108 to £662. For obese children aged 10-11 years, an intervention that resulted in a median reduction in BMI SDS at 12 months at a moderate cost of £400 increased life expectancy by 0.19 years and intervention costs were offset by subsequent undiscounted savings in treatment costs (net saving of £110 per child), though this saving did not emerge until the sixth or seventh decade of life. The discounted cost per life year gained was £13 589. Results were broadly similar for interventions aimed at children aged 4-5 years and which targeted both obese and overweight children. For more costly interventions, savings were less likely. CONCLUSION: Interventions to treat childhood obesity are potentially cost effective although cost savings and health benefits may not appear until the sixth or seventh decade of life.

Implementation and evaluation of a two-eyed seeing approach using traditional healing and seeking safety in an indigenous residential treatment program in Northern Ontario.

Indigenous clients in need of residential care for substance use disorders (SUD) often present with the diagnosis of substance use disorder (SUD) combined with intergenerational trauma (IGT) or both. SUD is exceedingly prevalent amongst Indigenous peoples due to the health impacts of colonisation, residential school trauma, and IGT on this population's health. We evaluated the effectiveness of a Two-Eyed Seeing approach in a four-week harm reduction residential treatment programme for clients with a history of SUD and IGT. This treatment approach blended Indigenous Healing practices with Seeking Safety based on Dr. Teresa Marsh's research work known as Indigenous Healing and Seeking Safety (IHSS). The data presented in this study was drawn from a larger trial. This qualitative study was undertaken in collaboration with the Benbowopka Treatment Centre in Blind River, Northern Ontario, Canada. Patient characteristic data were collected from records for 157 patients who had enrolled in the study from April 2018 to February 2020. Data was collected from the Client Quality Assurance Survey tool. We used the qualitative thematic analysis method to analyse participants' descriptive feedback about the study. Four themes were identified: (1) Motivation to attend treatment; (2) Understanding Benbowopka's treatment programme and needs to be met; (3) Satisfaction with all interventions; and (4) Moving forward. We utilised a conceptualised descriptive framework for the four core themes depicted in the medicine wheel. This qualitative study affirmed that cultural elements and the SS Western model were highly valued by all participants. The impact of the harm reduction approach, coupled with traditional healing methods, further enhanced the outcome. This study was registered with clinicaltrials.gov (identifier number NCT0464574).

The Ribosomal Database Project: improved alignments and new tools for rRNA analysis.

The Ribosomal Database Project (RDP) provides researchers with quality-controlled bacterial and archaeal small subunit rRNA alignments and analysis tools. An improved alignment strategy uses the Infernal secondary structure aware aligner to provide a more consistent higher quality alignment and faster processing of user sequences. Substantial new analysis features include a new Pyrosequencing Pipeline that provides tools to support analysis of ultra high-throughput rRNA sequencing data. This pipeline offers a collection of tools that automate the data processing and simplify the computationally intensive analysis of large sequencing libraries. In addition, a new Taxomatic visualization tool allows rapid visualization of taxonomic inconsistencies and suggests corrections, and a new class Assignment Generator provides instructors with a lesson plan and individualized teaching materials. Details about RDP data and analytical functions can be found at http://rdp.cme.msu.edu/.

Ribonuclease P catalysis differs from ribosomal RNA self-splicing.

Two RNA-catalyzed reactions have been described, the Tetrahymena self-splicing ribosomal RNA and ribonuclease P. The Tetrahymena self-splicing reaction proceeds through a transesterification cascade that is dependent upon nucleophilic attacks by ribose 3'-OH groups. Periodate oxidation of the catalytic (or substrate) RNA, which destroys the nucleophilicity of RNA 3' termini, did not inhibit ribonuclease P activity. Thus, catalysis by ribonuclease P differs from the self-splicing reaction.

Assessment of intraradicular bacterial composition by terminal restriction fragment length polymorphism analysis.

BACKGROUND: The aim of the study was to assess the bacterial community structures associated with endodontic infections using terminal restriction fragment length polymorphism (T-RFLP), and to investigate the correlation of whole community profiles with the manifestation of particular clinical features. METHODS: Intraradicular samples were collected from 34 subjects and classified into three study groups based on the observed clinical symptoms: acute (n = 16), sub-acute (n = 8), and asymptomatic (n = 10). Genomic DNA was extracted from each sample, submitted to polymerase chain reaction using a fluorescently labeled 16S ribosomal DNA forward primer, and digested with two tetrameric endonucleases (HhaI and MspI). The terminal restriction fragments (T-RFs) were subsequently discriminated in an automated DNA sequencer, and the results were filtered using a statistics-based criterion. RESULTS: Totals of 138 (HhaI) and 145 (MspI) unique T-RFs were detected (means 13.1 and 11.9) and there was high inter-subject variability in the bacterial assemblages. Odds-ratio analysis unveiled the existence of higher order groups of positively associated T-RFs, restating the concept that intricate ecological relationships may take place in the root canal space. A significantly greater T-RF prevalence was detected in acute cases, suggesting a straight correlation between species richness and spontaneous pain. CONCLUSION: Overall, no T-RFLP profile representing a specific bacterial consortium could be associated with the manifestation of symptoms of endodontic origin.

Terminal restriction fragment length polymorphism (T-RFLP): an emerging method for characterizing diversity among homologous populations of amplification products.

Terminal restriction fragment length polymorphism is a recent molecular approach that can assess subtle genetic differences between strains as well as provide insight into the structure and function of microbial communities. The technique has both high sensitivity and throughput making it ideal for comparative analyses.

The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows regular updates and the new prokaryotic taxonomy.

The Ribosomal Database Project-II (RDP-II) pro-vides data, tools and services related to ribosomal RNA sequences to the research community. Through its website (http://rdp.cme.msu.edu), RDP-II offers aligned and annotated rRNA sequence data, analysis services, and phylogenetic inferences (trees) derived from these data. RDP-II release 8.1 contains 16 277 prokaryotic, 5201 eukaryotic, and 1503 mitochondrial small subunit rRNA sequences in aligned and annotated format. The current public beta release of 9.0 debuts a new regularly updated alignment of over 50 000 annotated (eu)bacterial sequences. New analysis services include a sequence search and selection tool (Hierarchy Browser) and a phylogenetic tree building and visualization tool (Phylip Interface). A new interactive tutorial guides users through the basics of rRNA sequence analysis. Other services include probe checking, phylogenetic placement of user sequences, screening of users' sequences for chimeric rRNA sequences, automated alignment, production of similarity matrices, and services to plan and analyze terminal restriction fragment polymorphism (T-RFLP) experiments. The RDP-II email address for questions or comments is rdpstaff@msu.edu.

Oxidative pentose phosphate pathway inhibition is a key determinant of antimalarial induced cancer cell death.

Despite immense interest in using antimalarials as autophagy inhibitors to treat cancer, it remains unclear whether these agents act predominantly via autophagy inhibition or whether other pathways direct their anti-cancer properties. By comparing the treatment effects of the antimalarials chloroquine (CQ) and quinacrine (Q) on KRAS mutant lung cancer cells, we demonstrate that inhibition of the oxidative arm of the pentose phosphate pathway (oxPPP) is required for antimalarial induced apoptosis. Despite inhibiting autophagy, neither CQ treatment nor RNAi against autophagy regulators (ATGs) promote cell death. In contrast, Q triggers high levels of apoptosis, both in vitro and in vivo, and this phenotype requires both autophagy inhibition and p53-dependent inhibition of the oxPPP. Simultaneous genetic targeting of the oxPPP and autophagy is sufficient to trigger apoptosis in lung cancer cells, including cells lacking p53. Thus, in addition to reduced autophagy, oxPPP inhibition serves as an important determinant of antimalarial cytotoxicity in cancer cells.