Regulation of surface architecture by symbiotic bacteria mediates host colonization

Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host–symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host–symbiont mutualism

Making the Case for New Research to Support the Integration of Small Unmanned Aircraft Systems into the National Airspace System

This paper describes the current state of sUAS regulation, their technical capabilities and the latest technologies that will allow for sUAS NAS integration. The research that is needed to demonstrate sUAS NAS integration capability is identified, and recommendations for conducting this necessary research are suggested

ARM Research in the Equatorial Western Pacific: A Decade and Counting

The tropical western Pacific (TWP) is an important climatic region. Strong solar heating, warm sea surface temperatures, and the annual progression of the intertropical convergence zone (ITCZ) across this region generate abundant convective systems, which through their effects on the heat and water budgets have a profound impact on global climate and precipitation. In order to accurately evaluate tropical cloud systems in models, measurements of tropical clouds, the environment in which they reside, and their impact on the radiation and water budgets are needed. Because of the remote location, ground-based datasets of cloud, atmosphere, and radiation properties from the TWP region have come primarily from short-term field experiments. While providing extremely useful information on physical processes, these short-term datasets are limited in statistical and climatological information. To provide longterm measurements of the surface radiation budget in the tropics and the atmospheric properties that affect it, the Atmospheric Radiation Measurement program established a measurement site on Manus Island, Papua New Guinea, in 1996 and on the island republic of Nauru in late 1998. These sites provide unique datasets now available for more than 10 years on Manus and Nauru. This article presents examples of the scientific use of these datasets including characterization of cloud properties, analysis of cloud radiative forcing, model studies of tropical clouds and processes, and validation of satellite algorithms. New instrumentation recently installed at the Manus site will provide expanded opportunities for tropical atmospheric science

Essentially English : Sherlock Holmes at the BBC

Sir Arthur Conan Doyle’s Sherlock Holmes stories, currently enjoying renewed popularity on television via the BBC’s Sherlock (2010- ), have been adapted for the screen countless times around the world. Arguably best remembered are Granada’s long-running strand with Jeremy Brett (1984-94), and the Universal film series of the 1940s, featuring Basil Rathbone and Nigel Bruce. Less frequently cited, however, are the two series produced by the BBC between 1965 and 1968, in which first Douglas Wilmer and later Peter Cushing took on the mantle of the Baker Street detective. Typically for the time – but against the wishes of the Conan Doyle estate - these programmes adopted a multi-camera studio model; a mode of production which made them less attractive to US networks than the single camera 35mm film output of commercial rivals such as ITC. Drawing upon material from the BBC’s Written Archives Centre, this article investigates the motivations underpinning the Corporation’s refusal to accommodate the estate’s exhortations to seek American co-production and utilise single camera filming, not least of which was the BBC’s stated desire to maintain the ‘essentially English’ quality of Sherlock Holmes. This decision would have significant repercussions for the series’ overseas saleability, and – despite impressive viewing figures and positive audience reaction at home in the UK – helped contribute to its ‘forgotten’ status with regard to the television canon

How well does neonatal neuroimaging correlate with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy?

BACKGROUND: In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear. METHODS: Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years. RESULTS: Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5-5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury. CONCLUSION: In the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes. IMPACT: Half of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia. Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment. Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI. Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes

Fabrication and characterization of dual function nanoscale pH-scanning ion conductance microscopy (SICM) probes for high resolution pH mapping

The easy fabrication and use of nanoscale dual function pH-scanning ion conductance microscopy (SICM) probes is reported. These probes incorporate an iridium oxide coated carbon electrode for pH measurement and an SICM barrel for distance control, enabling simultaneous pH and topography mapping. These pH-SICM probes were fabricated rapidly from laser pulled theta quartz pipets, with the pH electrode prepared by in situ carbon filling of one of the barrels by the pyrolytic decomposition of butane, followed by electrodeposition of a thin layer of hydrous iridium oxide. The other barrel was filled with an electrolyte solution and Ag/AgCl electrode as part of a conductance cell for SICM. The fabricated probes, with pH and SICM sensing elements typically on the 100 nm scale, were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and various electrochemical measurements. They showed a linear super-Nernstian pH response over a range of pH (pH 2–10). The capability of the pH-SICM probe was demonstrated by detecting both pH and topographical changes during the dissolution of a calcite microcrystal in aqueous solution. This system illustrates the quantitative nature of pH-SICM imaging, because the dissolution process changes the crystal height and interfacial pH (compared to bulk), and each is sensitive to the rate. Both measurements reveal similar dissolution rates, which are in agreement with previously reported literature values measured by classical bulk methods

Adolescent Religiosity and Selective Exposure to Television

Relying on the Adolescent Media Practice Model and selective exposure theory, this study investigated whether religious adolescents watch less mature television entertainment programs than their less religious peers. Program maturity was measured using V-chip ratings, with higher maturity scores indicating content that included more sexuality, violence, and/or adult and sexual language. The responses from 1,335 16- to 18-year-olds who completed Wave 2 of the National Study of Youth and Religion (NSYR) survey were analyzed. Findings indicate that religiosity contributes to explaining the variance in television maturity means, with more religious adolescents indicating a preference for less mature television entertainment. Gender, race, income, and parents’ monitoring of teens’ media were also found to influence television maturity. Teens’ attitudes toward premarital sex appeared to mediate the effect of religiosity on their television entertainment choices

High on-off conductance switching ratio in optically-driven self-assembled conjugated molecular systems

A new azobenzene-thiophene molecular switch is designed, synthesized and used to form self-assembled monolayers (SAM) on gold. An "on/off" conductance ratio up to 7x1E3 (with an average value of 1.5x1E3) is reported. The "on" conductance state is clearly identified to the cis isomer of the azobenzene moiety. The high "on/off" ratio is explained in terms of photo-induced, configuration-related, changes in the electrode-molecule interface energetics (changes in the energy position of the molecular orbitals with respect to the Fermi energy of electrodes) in addition to changes in the tunnel barrier length (length of the molecules). First principles DFT calculations demonstrate a better delocalization of the frontier orbitals, as well as a stronger electronic coupling between the azobenzene moiety and the electrode for the cis configuration over the trans one. Measured photoionization cross-sections for the molecules in the SAM are close to the known values for azobenzene derivatives in solution.Comment: 1 file with main text, figure and suppementary informatio

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective

Relationships of Physical Performance Tests to Military-relevant Tasks in Women

Purpose: This investigation sought to determine the most predictive measures of performance on a repetitive box lifting task (RBLT) and load bearing task (LBT) among 123 women (aged 23±4 years, height 165±7 cm, body mass 64±10 kg). Methods: To determine the relationship of various predictors to performance on the RBLT and LBT, multiple regression analysis was conducted on body mass, height, leg cross-sectional area, upper and lower body muscular strength, lower body explosive power, upper and lower body local muscular endurance, and aerobic capacity. Results: The mean±SD (range) number of repetitions for the RBLT was 86±23 (20-159). The mean±SD (range) time to complete the LBT was 2,054±340 seconds (1,307-3,447). The following equations were generated: RBLT (number of repetitions)=57.4 + 0.2(peak jump power) + 0.4(number of pushups in 2 minutes) + 0.15(number of repetitions during the squat endurance test) + 1.39(one repetition maximal strength boxlift (kg)) – 0.04(2-mile run time (2MR) in seconds), R=0.81; standard error of the estimate (SEE)=14; LBT (in seconds)=1,831 – 4.28(number of repetitions during the squat endurance test) + 0.95(2MR in seconds) – 13.4(body mass), R=0.73; SEE=232. Conclusions: We found that the 2MR and squat endurance test were signifi cant predictive factors for performance on both load carriage tasks. These data also imply that women’s performance in combat-related tasks can be improved with training that targets muscular strength, power, and local muscular endurance in addition to aerobic capacity