Influence of age on the effectiveness of PCV2 vaccination in piglets with high levels of maternally derived antibodies

Two field studies were conducted to investigate the influence of age on the efficacy of vaccination against Porcine Circovirus Diseases (PCVD) in animals with high levels of maternally derived antibodies (MDA). A total of 416 piglets (Study 1) and 600 piglets (Study 2) were randomly allocated to one of three groups. Two groups in each study received a single dose of a PCV2 subunit vaccine, one group at 1 week old and the other at 3 weeks of age. The third group was left untreated. Animals vaccinated at 3 weeks of age showed a significantly higher average daily weight gain and significantly reduced viraemia following PCV2 infection than the respective control groups. This difference was not observed in pigs vaccinated at 1 week of age. Furthermore, only animals vaccinated at 3 weeks of age showed an increased serological response and a higher frequency of IgM-positive animals compared with controls. The data indicated that PCV2 vaccination in the presence of high MDA levels is efficacious when used in 3-week old but not in 1-week old pigs. As the range of MDA titres of pigs vaccinated at both 1 and 3 weeks of age were comparable, the data suggest that PCV2 vaccine efficacy was independent of the level of MDA. It appears that other age-related factors affecting the active and passive transfer of immunity may perhaps have interfered with the efficacy of the vaccine in 1-week old piglets. These findings have implications for future PCV2 vaccine testing and administration strategies.     

Strong association of de novo copy number mutations with autism

We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.     

Biomarker evidence for photosynthesis during neoproterozoic glaciation

Laterally extensive black shales were deposited on the S?o Francisco craton in southeastern Brazil during low-latitude Neoproterozoic glaciation approximately 740 to 700 million years ago. These rocks contain up to 3.0 weight % organic carbon, which we interpret as representing the preserved record of abundant marine primary productivity from glacial times. Extractable biomarkers reflect a complex and productive microbial ecosystem, including both phototrophic bacteria and eukaryotes, living in a stratified ocean with thin or absent sea ice, oxic surface waters, and euxinic conditions within the photic zone. Such an environment provides important constraints for parts of the "Snowball Earth" hypothesis.     

Time-critical social mobilization

The World Wide Web is commonly seen as a platform that can harness the collective abilities of large numbers of people to accomplish tasks with unprecedented speed, accuracy, and scale. To explore the Web's ability for social mobilization, the Defense Advanced Research Projects Agency (DARPA) held the DARPA Network Challenge, in which competing teams were asked to locate 10 red weather balloons placed at locations around the continental United States. Using a recursive incentive mechanism that both spread information about the task and incentivized individuals to act, our team was able to find all 10 balloons in less than 9 hours, thus winning the Challenge. We analyzed the theoretical and practical properties of this mechanism and compared it with other approaches.     

FGF-dependent mechanosensory organ patterning in zebrafish

During development, organ primordia reorganize to form repeated functional units. In zebrafish (Danio rerio), mechanosensory organs called neuromasts are deposited at regular intervals by the migrating posterior lateral line (pLL) primordium. The pLL primordium is organized into polarized rosettes representing proto-neuromasts, each with a central atoh1a-positive focus of mechanosensory precursors. We show that rosettes form cyclically from a progenitor pool at the leading zone of the primordium as neuromasts are deposited from the trailing region. fgf3/10 signals localized to the leading zone are required for rosette formation, atoh1a expression, and primordium migration. We propose that the fibroblast growth factor (FGF) source controls primordium organization, which, in turn, regulates the periodicity of neuromast deposition. This previously unrecognized mechanism may be applicable to understanding segmentation and morphogenesis in other organ systems.     

Video cameras on wild birds

New Caledonian crows (Corvus moneduloides) are renowned for using tools for extractive foraging, but the ecological context of this unusual behavior is largely unknown. We developed miniaturized, animal-borne video cameras to record the undisturbed behavior and foraging ecology of wild, free-ranging crows. Our video recordings enabled an estimate of the species' natural foraging efficiency and revealed that tool use, and choice of tool materials, are more diverse than previously thought. Video tracking has potential for studying the behavior and ecology of many other bird species that are shy or live in inaccessible habitats.     

The mutational landscape of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.     

Interfacial polygonal nanopatterning of stable microbubbles

Micrometer-sized bubbles are unstable and therefore difficult to make and store for substantial lengths of time. Short-term stabilization is achieved by the addition of amphiphilic molecules, which reduce the driving force for dissolution. When these molecules crystallize on the air/liquid interface, the lifetime of individual bubbles may extend over a few months. We demonstrated low gas-fraction dispersions with mean bubble radii of less than 1 micrometer and stability lasting more than a year. An insoluble, self-assembled surfactant layer covers the surface of the microbubbles, which can result in nanometer-scale hexagonal patterning that we explain with thermodynamic and molecular models. The elastic response of the interface arrests the shrinkage of the bubbles. Our study identifies a route to fabricate highly stable dispersions of microbubbles.     

Nervy links protein kinase a to plexin-mediated semaphorin repulsion

Cyclic nucleotides regulate axonal responses to a number of guidance cues through unknown molecular events. We report here that Drosophila nervy, a member of the myeloid translocation gene family of A kinase anchoring proteins (AKAPs), regulates repulsive axon guidance by linking the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) to the Semaphorin 1a (Sema-1a) receptor Plexin A (PlexA). Nervy and PKA antagonize Sema-1a-PlexA-mediated repulsion, and the AKAP binding region of Nervy is critical for this effect. Thus, Nervy couples cAMP-PKA signaling to PlexA to regulate Sema-1a-mediated axonal repulsion, revealing a simple molecular mechanism that allows growing axons to integrate inputs from multiple guidance cues.