Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio]other antibodies of [gt-or-equal, slanted]2·0[ratio]1. The antiserum with the highest ratio (7·4[ratio]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [gt-or-equal, slanted]1000 HIU/ml, and a low absolute titre of other antibodies ([less-than-or-eq, slant]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event

Estimating the influence of different urban canopy cover types on atmospheric particulate matter (PM10) pollution abatement in London UK

In the urban environment atmospheric pollution by PM10 (particulate matter with a diameter less than 10 x 10-6 m) is a problem that can have adverse effects on human health, particularly increasing rates of respiratory disease. The main contributors to atmospheric PM10 in the urban environment are road traffic, industry and powerproduction. The urban tree canopy is a receptor for removing PM10s from the atmosphere due to the large surface areas generated by leaves and air turbulence created by the structure of the urban forest. In this context urban greening has long been known as a mechanism to contribute towards PM10 removal from the air, furthermore, tree canopy cover has a role in contributing towards a more sustainable urban environment.The work reported here has been carried out within the BRIDGE project (SustainaBle uRban plannIng Decision support accountinG for urban mEtabolism). The aim of this project is to assess the fluxes of energy, water, carbon dioxide and particulates within the urban environment and develope a DSS (Decision Support System) to aid urban planners in sustainable development. A combination of published urban canopy cover data from ground, airborne and satellite based surveys was used. For each of the 33 London boroughs the urban canopy was classified to three groups, urban woodland, street trees and garden trees and each group quantified in terms of ground cover. The total [PM10] for each borough was taken from the LAEI (London Atmospheric Emissions Inventory 2006) and the contribution to reducing [PM10] was assessed for each canopy type. Deposition to the urban canopy was assessed using the UFORE (Urban Forest Effects Model) approach. Deposition to the canopy, boundary layer height and percentage reduction of the [PM10] in the atmosphere was assessed using both hourly meterological data and [PM10] and seasonal data derived from annual models. Results from hourly and annual data were compared with measured values. The model was then applied to future predictions of annual [PM10] and future canopy cover scenarios for London. The contribution of each canopy type subjected to the different atmospheric [PM10] of the 33 London boroughs now and in the future will be discussed. Implementing these findings into a decision support system (DSS) for sustainable urban planning will also be discussed<br/

Mapping visual symbols onto spoken language along the ventral visual stream.

Reading involves transforming arbitrary visual symbols into sounds and meanings. This study interrogated the neural representations in ventral occipitotemporal cortex (vOT) that support this transformation process. Twenty-four adults learned to read 2 sets of 24 novel words that shared phonemes and semantic categories but were written in different artificial orthographies. Following 2 wk of training, participants read the trained words while neural activity was measured with functional MRI. Representational similarity analysis on item pairs from the same orthography revealed that right vOT and posterior regions of left vOT were sensitive to basic visual similarity. Left vOT encoded letter identity and representations became more invariant to position along a posterior-to-anterior hierarchy. Item pairs that shared sounds or meanings, but were written in different orthographies with no letters in common, evoked similar neural patterns in anterior left vOT. These results reveal a hierarchical, posterior-to-anterior gradient in vOT, in which representations of letters become increasingly invariant to position and are transformed to convey spoken language information

Distinct neural specializations for learning to read words and name objects

Understanding the neural systems that underpin reading acquisition is key if neuroscientific findings are to inform educational practice. We provide a unique window into these systems by teaching 19 adults to read 24 novel words written in unfamiliar letters and to name 24 novel objects while in an MRI scanner. Behavioral performance on trained items was equivalent for the two stimulus types. However, componential letter-sound associations were extracted when learning to read, as shown by correct reading of untrained words, whereas object-name associations were holistic and arbitrary. Activity in bilateral anterior fusiformgyri was greater during object name learning than learning to read, and ROI analyses indicated that left mid-fusiform activity was predictive of success in object name learning but not in learning to read. In contrast, activity in bilateral parietal cortices was predictive of success for both stimulus types but was greater during learning and recall of written word pronunciations relative to object names. We argue that mid-to-anterior fusiform gyri preferentially process whole items and contribute to learning their spoken form associations, processes that are required for skilled reading. In contrast, parietal cortices preferentially process componential visual-verbal mappings, a process that is crucial for early reading development

Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis

The DNA damage response (DDR) comprises multiple functions that collectively preserve genomic integrity and suppress tumorigenesis. The Mre11 complex and ATM govern a major axis of the DDR and several lines of evidence implicate that axis in tumor suppression. Components of the Mre11 complex are mutated in approximately five percent of human cancers. Inherited mutations of complex members cause severe chromosome instability syndromes, such as Nijmegen Breakage Syndrome, which is associated with strong predisposition to malignancy. And in mice, Mre11 complex mutations are markedly more susceptible to oncogene- induced carcinogenesis. The complex is integral to all modes of DNA double strand break (DSB) repair and is required for the activation of ATM to effect DNA damage signaling. To understand which functions of the Mre11 complex are important for tumor suppression, we undertook mining of cancer genomic data from the clinical sequencing program at Memorial Sloan Kettering Cancer Center, which includes the Mre11 complex among the 468 genes assessed. Twenty five mutations in MRE11 and RAD50 were modeled in S. cerevisiae and in vitro. The mutations were chosen based on recurrence and conservation between human and yeast. We found that a significant fraction of tumor-borne RAD50 and MRE11 mutations exhibited separation of function phenotypes wherein Tel1/ATM activation was severely impaired while DNA repair functions were mildly or not affected. At the molecular level, the gene products of RAD50 mutations exhibited defects in ATP binding and hydrolysis. The data reflect the importance of Rad50 ATPase activity for Tel1/ATM activation and suggest that inactivation of ATM signaling confers an advantage to burgeoning tumor cells

Comparing and validating methods of reading instruction using behavioural and neural findings in an artificial orthography.

There is strong scientific consensus that emphasizing print-to-sound relationships is critical when learning to read alphabetic languages. Nevertheless, reading instruction varies across English-speaking countries, from intensive phonic training to multicuing environments that teach sound- and meaning-based strategies. We sought to understand the behavioral and neural consequences of these differences in relative emphasis. We taught 24 English-speaking adults to read 2 sets of 24 novel words (e.g., /buv/, /sig/), written in 2 different unfamiliar orthographies. Following pretraining on oral vocabulary, participants learned to read the novel words over 8 days. Training in 1 language was biased toward print-to-sound mappings while training in the other language was biased toward print-to-meaning mappings. Results showed striking benefits of print-sound training on reading aloud, generalization, and comprehension of single words. Univariate analyses of fMRI data collected at the end of training showed that print-meaning relative to print-sound relative training increased neural effort in dorsal pathway regions involved in reading aloud. Conversely, activity in ventral pathway brain regions involved in reading comprehension was no different following print-meaning versus print-sound training. Multivariate analyses validated our artificial language approach, showing high similarity between the spatial distribution of fMRI activity during artificial and English word reading. Our results suggest that early literacy education should focus on the systematicities present in print-to-sound relationships in alphabetic languages, rather than teaching meaning-based strategies, in order to enhance both reading aloud and comprehension of written words. (PsycINFO Database Recor

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised