To provide context for the diversifications of archosaurs, the group that includes crocodilians, dinosaurs and birds, we generated draft genomes of three crocodilians, Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the relatively rapid evolution of bird genomes represents an autapomorphy within that clade. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these new data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.

Abstract. In this paper, we give an overview of the BitBlaze project, a new approach to computer security via binary analysis. In particular, BitBlaze focuses on building a unified binary analysis platform and using it to provide novel solutions to a broad spectrum of different security problems. The binary analysis platform is designed to enable accurate analysis, provide an extensible architecture, and combines static and dynamic analysis as well as program verification techniques to satisfy the common needs of security applications. By extracting security-related properties from binary programs directly, BitBlaze enables a principled, root-cause based approach to computer security, offering novel and effective solutions, as demonstrated with over a dozen different security applications.

No abstract

Normal homeostatic functions of adult stem cells have rhythmic daily oscillations that are believed to become arrhythmic during aging. Unexpectedly, we find that aged mice remain behaviorally circadian and that their epidermal and muscle stem cells retain a robustly rhythmic core circadian machinery. However, the oscillating transcriptome is extensively reprogrammed in aged stem cells, switching from genes involved in homeostasis to those involved in tissue-specific stresses, such as DNA damage or inefficient autophagy. Importantly, deletion of circadian clock components did not reproduce the hallmarks of this reprogramming, underscoring that rewiring, rather than arrhythmia, is associated with physiological aging. While age-associated rewiring of the oscillatory diurnal transcriptome is not recapitulated by a high-fat diet in young adult mice, it is significantly prevented by long-term caloric restriction in aged mice. Thus, stem cells rewire their diurnal timed functions to adapt to metabolic cues and to tissue-specific age-related traits.

With the rapidly expanding availability of data from personal genomes, exomes and transcriptomes, medical researchers will frequently need to test whether observed genomic variants are novel or known. This task requires downloading and handling large and diverse datasets from a variety of sources, and processing them with bioinformatics tools and pipelines. Alternatively, researchers can upload data to online tools, which may conflict with privacy requirements. We present here Kaviar, a tool that greatly simplifies the assessment of novel variants. Kaviar includes: (i) an integrated and growing database of genomic variation from diverse sources, including over 55 million variants from personal genomes, family genomes, transcriptomes, SNV databases and population surveys; and (ii) software for querying the database efficiently.

The Cuatro Cié negas Basin (CCB) in the central part of the Chihuahan desert (Coahuila, Mexico) hosts a wide diversity of microorganisms contained within springs thought to be geomorphological relics of an ancient sea. A major question remaining to be answered is whether bacteria from CCB are ancient marine bacteria that adapted to an oligotrophic system poor in NaCl, rich in sulfates, and with extremely low phosphorus levels (<0.3 M). Here, we report the complete genome sequence of Bacillus coahuilensis, a sporulating bacterium isolated from the water column of a desiccation lagoon in CCB. At 3.35 Megabases this is the smallest genome sequenced to date of a Bacillus species and provides insights into the origin, evolution, and adaptation of B. coahuilensis to the CCB environment. We propose that the size and complexity of the B. coahuilensis genome reflects the adaptation of an ancient marine bacterium to a novel environment, providing support to a ''marine isolation origin hypothesis'' that is consistent with the geology of CCB. This genomic adaptation includes the acquisition through horizontal gene transfer of genes involved in phosphorous utilization efficiency and adaptation to high-light environments. The B. coahuilensis genome sequence also revealed important ecological features of the bacterial community in CCB and offers opportunities for a unique glimpse of a microbe-dominated world last seen in the Precambrian.evolution ͉ genomic adaptation ͉ horizontal gene transfer ͉ phosphorus stress ͉ sulfolipids T he Cuatro Ciénegas Basin (CCB) is located in a valley Ϸ740 m above sea level in the state of Coahuila, Mexico, that measures Ϸ30 km by 40 km and is surrounded by high mountains (Ͼ3,000 m) (Fig. 1). CCB is an enclosed evaporitic basin that receives Ϸ150 mm of annual precipitation. Despite the dry climate of the valley, the CCB harbors an extensive system of springs, streams, and pools (1). The CCB ecosystem is not only characterized by a high endemism of macrooganisms and biodiversity of microorganisms (1, 2), but also by extremely oligotrophic waters that are unable to sustain algal growth, making microbial mats the base of the food web (3). In particular, phosphorus (P) levels in CCB appear to be rather low, because they were below the level of detection of several methods used (0.3 M) and the extremely high biomass C:P and N:P ratios (Ͼ100 by moles) previously reported for CCB stromatolites (3, 4). Unlike the present sea, the Churince spring water is poor in NaCl and carbonates, but it is rich in sulfates, magnesium, and calcium (4). Characterization of the microbiological diversity by sequencing 16S rRNA genes revealed that nearly half of the phylotypes from the CCB were closely related to bacteria from marine environments (2). Bacillus coahuilensis is a free-living, spore-forming bacteria isolated from the water column of a shallow desiccation lagoon in the Churince system at CCB (4) (Fig. 1 A and B). A molecular phylogenetic analysis of 16S rRNA sequences indicates that B. coahuilensis is closely ...

No abstract

Vulnerability exploits remain an important mechanism for malware delivery, despite efforts to speed up the creation of patches and improvements in software updating mechanisms. Vulnerabilities in client applications (e.g., browsers, multimedia players, document readers and editors) are often exploited in spear phishing attacks and are difficult to characterize using network vulnerability scanners. Analyzing their lifecycle requires observing the deployment of patches on hosts around the world. Using data collected over 5 years on 8.4 million hosts, available through Symantec's WINE platform, we present the first systematic study of patch deployment in client-side vulnerabilities.We analyze the patch deployment process of 1,593 vulnerabilities from 10 popular client applications, and we identify several new threats presented by multiple installations of the same program and by shared libraries distributed with several applications. For the 80 vulnerabilities in our dataset that affect code shared by two applications, the time between patch releases in the different applications is up to 118 days (with a median of 11 days). Furthermore, as the patching rates differ considerably among applications, many hosts patch the vulnerability in one application but not in the other one. We demonstrate two novel attacks that enable exploitation by invoking old versions of applications that are used infrequently, but remain installed. We also find that the median fraction of vulnerable hosts patched when exploits are released is at most 14%. Finally, we show that the patching rate is affected by user-specific and applicationspecific factors; for example, hosts belonging to security analysts and applications with an automated updating mechanism have significantly lower median times to patch.