Two key events associated with a transposable element burst occurred during rice domestication

Transposable elements shape genome evolution through periodic bursts of amplification. In this study we exploited knowledge of the components of the mPing/Ping/Pong TE family in four rice strains undergoing mPing bursts to track their copy numbers and distribution in a large collection of genomes from the wild progenitor Oryza rufipogon and domesticated Oryza sativa (rice). We characterized two events that occurred to the autonomous Ping element and appear to be critical for mPing hyperactivity. First, a point mutation near the end of the element created a Ping variant ( Ping16A ) with reduced transposition. The proportion of strains with Ping16A has increased during domestication while the original Ping (Ping16G) has been dramatically reduced. Second, transposition of Ping16A into a Stowaway element generated a locus ( Ping16A_Stow ) whose presence correlates with strains that have high mPing copies. Finally, demonstration that Pong elements have been stably silenced in all strains analyzed indicates that sustained activity of the mPing/Ping family during domestication produced the components necessary for the mPing burst, not the loss of epigenetic regulation

Junior Recital: Stephanie Zegadlo, Saxophone; Lu Liu, Piano; November 1, 2009

Kemp Recital HallNovember 01, 2009Sunday Evening6:00 p.m

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Caenorhabditis elegans RIG-I Homolog Mediates Antiviral RNA Interference Downstream of Dicer-Dependent Biogenesis of Viral Small Interfering RNAs.

Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection. However, it remains unclear if DRH-1 acts analogously to initiate antiviral RNAi in C. elegans Here, we performed a forward genetic screen to characterize antiviral RNAi in C. elegans Using a mapping-by-sequencing strategy, we uncovered four loss-of-function alleles of drh-1, three of which caused mutations in the helicase and C-terminal domains conserved in RLRs. Deep sequencing of small RNAs revealed an abundant population of Dicer-dependent virus-derived small interfering RNAs (vsiRNAs) in drh-1 single and double mutant animals after infection with Orsay virus, a positive-strand RNA virus. These findings provide further genetic evidence for the antiviral function of DRH-1 and illustrate that DRH-1 is not essential for the sensing and Dicer-mediated processing of the viral dsRNA replicative intermediates. Interestingly, vsiRNAs produced by drh-1 mutants were mapped overwhelmingly to the terminal regions of the viral genomic RNAs, in contrast to random distribution of vsiRNA hot spots when DRH-1 is functional. As RIG-I translocates on long dsRNA and DRH-1 exists in a complex with Dicer, we propose that DRH-1 facilitates the biogenesis of vsiRNAs in nematodes by catalyzing translocation of the Dicer complex on the viral long dsRNA precursors.IMPORTANCE The helicase and C-terminal domains of mammalian RLRs sense intracellular viral RNAs to initiate the interferon-regulated innate immunity against RNA virus infection. Both of the domains from human RIG-I can substitute for the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans, suggesting an analogous role for DRH-1 as an intracellular dsRNA sensor to initiate antiviral RNAi. Here, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in C. elegans Characterization of four distinct drh-1 mutants obtained from the screen revealed that DRH-1 did not function to initiate antiviral RNAi. We show that DRH-1 acted in a downstream step to enhance Dicer-dependent biogenesis of viral siRNAs in C. elegans As mammals produce Dicer-dependent viral siRNAs to target RNA viruses, our findings suggest a possible role for mammalian RLRs and interferon signaling in the biogenesis of viral siRNAs

The importance of preventive feedback: inference from observations of the stellar masses and metallicities of Milky Way dwarf galaxies

Dwarf galaxies are known to have remarkably low star formation efficiency due to strong feedback. Adopting the dwarf galaxies of the Milky Way as a laboratory, we explore a flexible semi-analytic galaxy formation model to understand how the feedback processes shape the satellite galaxies of the Milky Way. Using Markov-Chain Monte-Carlo, we exhaustively search a large parameter space of the model and rigorously show that the general wisdom of strong outflows as the primary feedback mechanism cannot simultaneously explain the stellar mass function and the mass--metallicity relation of the Milky Way satellites. An extended model that assumes that a fraction of baryons is prevented from collapsing into low-mass halos in the first place can be accurately constrained to simultaneously reproduce those observations. The inference suggests that two different physical mechanisms are needed to explain the two different data sets. In particular, moderate outflows with weak halo mass dependence are needed to explain the mass--metallicity relation, and prevention of baryons falling into shallow gravitational potentials of low-mass halos (e.g. "pre-heating") is needed to explain the low stellar mass fraction for a given subhalo mass.Comment: 14 pages, 4 figures, accepted for publication in Ap

Evaluating NGOs in international water development: a case study of H2O 4 ALL

With the introduction of the Millennium and Sustainable Development Goals, the level of sophistication required to measure the impact of international development has grown. However, evidence suggests that international non-governmental organizations (NGOs) have been slow to invest in development evaluation; instead of using evidence-based tools to enhance performance, such as logic models or benchmarks, NGOs engage in activities to demonstrate their good work (e.g., report writing, monitoring progress). In light of the current biophysical, socioeconomic, political, and human challenges that make the water-health nexus a “wicked problem,” this thesis addresses the knowledge gap in our understanding of factors that influence the measurable success of an NGO in water-based development. Using a case study design, evaluation frameworks were applied in the context of international water development. An evaluability assessment and process evaluation of the case study informed the creation of low cost evaluation tools that can be adapted and applied to other small NGOs with little or no formal evaluation training. By documenting the evaluation experience, facilitators and barriers to conducting an evaluation and embedding evaluative thinking in an NGO were also identified. As a whole, this thesis aimed to counteract the prioritization of individual projects with short-term impact. Findings support the need for theoretically grounded evaluations at the organizational level in order to address the complexity of global water needs, the diversity of individuals who lack access, civil society organizations and the constraints under which they work, and the work that remains to achieve Sustainable Development Goal 6: “Ensure availability and sustainable management of water and sanitation for all.

"They Thought I was Just Joking About It": Experiences and Perceptions of Food Allergy in New Canadians from Asia

Perceived increased prevalence and levels of awareness of food allergy has become a global phenomenon, making it a major public health concern. Although little is known about its etiology or prevalence, substantial variation in prevalence on a global scale is evident. Studies on food allergy in Asia are reporting an increase in prevalence, particularly in economically developed regions like Hong Kong. Interestingly, risk perception studies have found that Canadians’ perceived prevalence of food allergy surpasses systematic estimates. Moreover, Canadian immigrants are more likely to rate the risk of food allergy as “high” compared to non-immigrants. To explore these issues further, qualitative interviews were conducted with key informants (n=3) and allergic individuals of Asian descent (n=18) in order to capture their lived experience with food allergies. Interviews lasted 30 minutes on average and they were tape recorded and transcribed verbatim for subsequent thematic analysis using QSR International’s NVivo 9. Results are organized around four major themes: perceived prevalence, risk perception, management and coping, and quality of life. With respect to perceived prevalence and risk, participants found food allergies to be more common in Canada than in Asia. Participants also agreed that having a food allergy is more manageable in Canada as a result of the policy environment (e.g., food labelling and school board policies). In addition, participants had dealt with skepticism and disbelief about their food allergy in Asia, impacting their quality of life. These findings demonstrate the need to recognize the varied impacts and experiences of food allergy among new Canadians, given that immigrants represent a large and growing proportion of the Canadian population.1 yea

The connection between the host halo and the satellite galaxies of the Milky Way

Many properties of the Milky Way's dark matter halo, including its mass assembly history, concentration, and subhalo population, remain poorly constrained. We explore the connection between these properties of the Milky Way and its satellite galaxy population, especially the implication of the presence of the Magellanic Clouds for the properties of the Milky Way halo. Using a suite of high-resolution $N$-body simulations of Milky Way-mass halos with a fixed final Mvir ~ 10^{12.1}Msun, we find that the presence of Magellanic Cloud-like satellites strongly correlates with the assembly history, concentration, and subhalo population of the host halo, such that Milky Way-mass systems with Magellanic Clouds have lower concentration, more rapid recent accretion, and more massive subhalos than typical halos of the same mass. Using a flexible semi-analytic galaxy formation model that is tuned to reproduce the stellar mass function of the classical dwarf galaxies of the Milky Way with Markov-Chain Monte-Carlo, we show that adopting host halos with different mass-assembly histories and concentrations can lead to different best-fit models for galaxy-formation physics, especially for the strength of feedback. These biases arise because the presence of the Magellanic Clouds boosts the overall population of high-mass subhalos, thus requiring a different stellar-mass-to-halo-mass ratio to match the data. These biases also lead to significant differences in the mass--metallicity relation, the kinematics of low-mass satellites, the number counts of small satellites associated with the Magellanic Clouds, and the stellar mass of Milky Way itself. Observations of these galaxy properties can thus provide useful constraints on the properties of the Milky Way halo.Comment: 20 pages, 12 figures, accepted for publication in ApJ. A new section on the effect of host halo mass-assembly history on the central galaxy stellar mass is adde

Practical Volume-Based Attacks on Encrypted Databases

Recent years have seen an increased interest towards strong security primitives for encrypted databases (such as oblivious protocols), that hide the access patterns of query execution, and reveal only the volume of results. However, recent work has shown that even volume leakage can enable the reconstruction of entire columns in the database. Yet, existing attacks rely on a set of assumptions that are unrealistic in practice: for example, they (i) require a large number of queries to be issued by the user, or (ii) assume certain distributions on the queries or underlying data (e.g., that the queries are distributed uniformly at random, or that the database does not contain missing values). In this work, we present new attacks for recovering the content of individual user queries, assuming no leakage from the system except the number of results and avoiding the limiting assumptions above. Unlike prior attacks, our attacks require only a single query to be issued by the user for recovering the keyword. Furthermore, our attacks make no assumptions about the distribution of issued queries or the underlying data. Instead, our key insight is to exploit the behavior of real-world applications. We start by surveying 11 applications to identify two key characteristics that can be exploited by attackers: (i) file injection, and (ii) automatic query replay. We present attacks that leverage these two properties in concert with volume leakage, independent of the details of any encrypted database system. Subsequently, we perform an attack on the real Gmail web client by simulating a server-side adversary. Our attack on Gmail completes within a matter of minutes, demonstrating the feasibility of our techniques. We also present three ancillary attacks for situations when certain mitigation strategies are employed.Comment: IEEE EuroS&P 202