Metacognition as Evidence for Evidentialism

Metacognition is the monitoring and controlling of cognitive processes. I examine the role of metacognition in ‘ordinary retrieval cases’, cases in which it is intuitive that via recollection the subject has a justified belief. Drawing on psychological research on metacognition, I argue that evidentialism has a unique, accurate prediction in each ordinary retrieval case: the subject has evidence for the proposition she justifiedly believes. But, I argue, process reliabilism has no unique, accurate predictions in these cases. I conclude that ordinary retrieval cases better support evidentialism than process reliabilism. This conclusion challenges several common assumptions. One is that non-evidentialism alone allows for a naturalized epistemology, i.e., an epistemology that is fully in accordance with scientific research and methodology. Another is that process reliabilism fares much better than evidentialism in the epistemology of memory

Forgetting memory skepticism

Memory skepticism denies our memory beliefs could have any notable epistemic good. One route to memory skepticism is to challenge memory’s epistemic trustworthiness, that is, its functioning in a way necessary for it to provide epistemic justification. In this paper we develop and respond to this challenge. It could threaten memory in such a way that we altogether lack doxastic attitudes. If it threatens memory in this way, then the challenge is importantly self-defeating. If it does not threaten memory in this way, then the challenge leaves a foundation for an inference to the best explanation response, one we articulate and support

Mammalian ANP32A and ANP32B proteins drive differential polymerase adaptations in avian influenza virus

ANP32 proteins, which act as influenza polymerase cofactors, vary between birds and mammals. In mammals, ANP32A and ANP32B have been reported to serve essential but redundant roles to support influenza polymerase activity. The well-known mammalian adaptation PB2-E627K enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbor this substitution. Here, we show that alternative PB2 adaptations, Q591R and D701N, also allow influenza polymerase to use mammalian ANP32 proteins, whereas other PB2 mutations, G158E, T271A, and D740N, increase polymerase activity in the presence of avian ANP32 proteins as well. Furthermore, PB2-E627K strongly favors use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs, and horses, where ANP32A proteins are the preferred cofactor. Using an experimental evolution approach, we show that the passage of viruses containing avian polymerases in human cells drove acquisition of PB2-E627K, but not in the absence of ANP32B. Finally, we show that the strong pro-viral support of ANP32B for PB2-E627K maps to the low-complexity acidic region (LCAR) tail of ANP32B. IMPORTANCE Influenza viruses naturally reside in wild aquatic birds. However, the high mutation rate of influenza viruses allows them to rapidly and frequently adapt to new hosts, including mammals. Viruses that succeed in these zoonotic jumps pose a pandemic threat whereby the virus adapts sufficiently to efficiently transmit human-to-human. The influenza virus polymerase is central to viral replication and restriction of polymerase activity is a major barrier to species jumps. ANP32 proteins are essential for influenza polymerase activity. In this study, we describe how avian influenza viruses can adapt in several different ways to use mammalian ANP32 proteins. We further show that differences between mammalian ANP32 proteins can select different adaptive changes and are responsible for some of the typical mutations that arise in mammalian-adapted influenza polymerases. These different adaptive mutations may determine the relative zoonotic potential of influenza viruses and thus help assess their pandemic risk

Systematic image-driven analysis of the spatial Drosophila embryonic expression landscape

We created innovative virtual representation for our large scale Drosophila insitu expression dataset. We aligned an elliptically shaped mesh comprised of small triangular regions to the outline of each embryo. Each triangle defines a unique location in the embryo and comparing corresponding triangles allows easy identification of similar expression patterns.The virtual representation was used to organize the expression landscape at stage 4-6. We identified regions with similar expression in the embryo and clustered genes with similar expression patterns.We created algorithms to mine the dataset for adjacent non-overlapping patterns and anti-correlated patterns. We were able to mine the dataset to identify co-expressed and putative interacting genes.Using co-expression we were able to assign putative functions to unknown genes

The transposable elements of the Drosophila melanogaster euchromatin: a genomics perspective.

BACKGROUND: Transposable elements are found in the genomes of nearly all eukaryotes. The recent completion of the Release 3 euchromatic genomic sequence of Drosophila melanogaster by the Berkeley Drosophila Genome Project has provided precise sequence for the repetitive elements in the Drosophila euchromatin. We have used this genomic sequence to describe the euchromatic transposable elements in the sequenced strain of this species. RESULTS: We identified 85 known and eight novel families of transposable element varying in copy number from one to 146. A total of 1,572 full and partial transposable elements were identified, comprising 3.86% of the sequence. More than two-thirds of the transposable elements are partial. The density of transposable elements increases an average of 4.7 times in the centromere-proximal regions of each of the major chromosome arms. We found that transposable elements are preferentially found outside genes; only 436 of 1,572 transposable elements are contained within the 61.4 Mb of sequence that is annotated as being transcribed. A large proportion of transposable elements is found nested within other elements of the same or different classes. Lastly, an analysis of structural variation from different families reveals distinct patterns of deletion for elements belonging to different classes. CONCLUSIONS: This analysis represents an initial characterization of the transposable elements in the Release 3 euchromatic genomic sequence of D. melanogaster for which comparison to the transposable elements of other organisms can begin to be made. These data have been made available on the Berkeley Drosophila Genome Project website for future analyses.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

An integrated computational pipeline and database to support whole-genome sequence annotation

We describe here our experience in annotating the Drosophila melanogaster genome sequence, in the course of which we developed several new open-source software tools and a database schema to support large-scale genome annotation. We have developed these into an integrated and reusable software system for whole-genome annotation. The key contributions to overall annotation quality are the marshalling of high-quality sequences for alignments and the design of a system with an adaptable and expandable flexible architecture

Coating mechanisms of single-walled carbon nanotube by linear polyether surfactants: insights from computer simulations

The noncovalent coating of carbon-based nanomaterials, such as carbon nanotubes, has important applications in nanotechnology and nanomedicine. The molecular modeling of this process can clarify its mechanism and provide a tool for the design of novel materials. In this paper, the coating mechanism of single-walled carbon nanotubes (SWCNT) in aqueous solutions by 1,2-dimethoxyethane oxide (DME), 1,2-dimethoxypropane oxide (DMP), poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) pentamers, and L64 triblock copolymer chains have been studied using molecular dynamics (MD) simulations. The results suggest a preferential binding to the SWCNT surface of the DMP molecules with respect to DME mainly driven by their difference in hydrophobicity. For the longer pentamers, it depends by the chain conformation. PPO isomers with radius of gyration larger than PEO pentamers bind more tightly than those with more compact conformation. In the case of the L64 triblock copolymer, the coating of the SWCNT surface produces a shell of PPO blocks with the PEO chains protruding into bulk water as expected from the so-called nonwrapping binding mechanism of SWCNT. In addition, the polymer coating, in qualitative agreement with experimental evidence on the poor capability of the L64 to disperse SWCNT, do not prevent the formation of CNT aggregates

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis

Species difference in ANP32A underlies influenza A virus polymerase host restriction.

Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals