Social Origins of Dictatorships: Elite Networks and Political Transitions in Haiti

Existing theories of democratic reversals emphasize that elites mount actions like coups when democracy is particularly threatening to their interests. However, existing theory has been largely silent on the role of elite social networks, which interact with economic incentives and may facilitate antidemocratic collective action. We develop a model where coups generate rents for elites and show that the effort an elite puts into a coup is increasing in their network centrality. We empirically explore the model using an original dataset of Haitian elite networks that we linked to firm-level data. We show that central families were more likely to be accused of participating in the 1991 coup against the democratic Aristide government. We then find that the retail prices of staple goods that are imported by such elites differentially increase during subsequent periods of nondemocracy. Our results suggest that elite social structure is an important factor in democratic reversals

Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.

Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system

Hypervelocity Star Candidates in the SEGUE G & K Dwarf Sample

We present 20 candidate hypervelocity stars from the Sloan Extension for Galactic Understanding and Exploration (SEGUE) G and K dwarf samples. Previous searches for hypervelocity stars have only focused on large radial velocities; in this study we also use proper motions to select the candidates. We determine the hypervelocity likelihood of each candidate by means of Monte Carlo simulations, considering the significant errors often associated with high proper motion stars. We find that nearly half of the candidates exceed their escape velocities with at least 98% probability. Every candidate also has less than a 25% chance of being a high-velocity fluke within the SEGUE sample. Based on orbits calculated using the observed six-dimensional positions and velocities, few, if any, of these candidates originate from the Galactic center. If these candidates are truly hypervelocity stars, they were not ejected by interactions with the Milky Way's supermassive black hole. This calls for a more serious examination of alternative hypervelocity-star ejection scenarios.Comment: 8 pages, 5 figures, published in ApJ, this version includes all figures as intende

Herbivory and Drought Generate Short‐Term Stochasticity and Long‐Term Stability in A Savanna Understory Community

Rainfall and herbivory are fundamental drivers of grassland plant dynamics, yet few studies have examined long‐term interactions between these factors in an experimental setting. Understanding such interactions is important, as rainfall is becoming increasingly erratic and native wild herbivores are being replaced by livestock. Livestock grazing and episodic low rainfall are thought to interact, leading to greater community change than either factor alone. We examined patterns of change and stability in herbaceous community composition through four dry periods, or droughts, over 15 years of the Kenya Long‐term Exclosure Experiment (KLEE), which consists of six different combinations of cattle, native wild herbivores (e.g., zebras, gazelles), and mega‐herbivores (giraffes, elephants). We used principal response curves to analyze the trajectory of change in each herbivore treatment relative to a common initial community and asked how droughts contributed to community change in these treatments. We examined three measures of stability (resistance, variability, and turnover) that correspond to different temporal scales and found that each had a different response to grazing. Treatments that included both cattle and wild herbivores had higher resistance (less net change over 15 years) but were more variable on shorter time scales; in contrast, the more lightly grazed treatments (no herbivores or wild herbivores only) showed lower resistance due to the accumulation of consistent, linear, short‐term change. Community change was greatest during and immediately after droughts in all herbivore treatments. But, while drought contributed to directional change in the less grazed treatments, it contributed to both higher variability and resistance in the more heavily grazed treatments. Much of the community change in lightly grazed treatments (especially after droughts) was due to substantial increases in cover of the palatable grass Brachiaria lachnantha. These results illustrate how herbivory and drought can act together to cause change in grassland communities at the moderate to low end of a grazing intensity continuum. Livestock grazing at a moderate intensity in a system with a long evolutionary history of grazing contributed to long‐term stability. This runs counter to often‐held assumptions that livestock grazing leads to directional, destabilizing shifts in grassland systems

Techniques for the isolation of high-quality RNA from cells encapsulated in chitosan hydrogels

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In addition, genomic DNA contamination during reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was observed in the hydrogels processed with the CTAB-based methods. Isolation methods using TRIzol® in combination with one of a Qiaex® gel extraction kit, an RNeasy® mini kit, or an extended solvent purification method extracted RNA suitable for gene amplification, with no evidence of genomic contamination. The latter two methods yielded the best results in terms of yield and amplification efficiency. Predigestion of the scaffolds with lysozyme was investigated as a possible means of enhancing RNA extraction from the polysaccharide gels, with no improvements observed in terms of the purity, yield, or amplification efficiency. Overall, this work highlights the application of a TRIzol®+extended solvent purification method for optimizing RNA extraction that can be applied to obtain reliable and accurate gene expression data in studies investigating cells seeded in chitosan-based scaffolds. © 2013 Mary Ann Liebert, Inc

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases.

A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical significance of the mutation in this particular cancer type and therapeutic strategies are discussed.Key pointsTo our knowledge, this index case represents the first reported ALK translocation identified in an atypical carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible alternative platform for identifying sensitizing genomic alterations.Second-generation ALK inhibitors represent a new paradigm for treating ALK-positive patients with brain metastases

Synthesis and Evaluation of New Cathepsin D Inhibitors

Cathepsin D, a lysosomal aspartic protease, has been suggested to play a role in the metastatic potential of several types of cancer A high activated cathepsin D level in breast tumor tissue has been associated with an increased incidence of relapse and metastasis. High levels of active cathepsin D have also been found in colon cancer, prostate cancer, uterine cancer, and ovarian cancer. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases, such as cathepsin D and the HIV1 aspartyl protease. Also cathepsin D has recently been associated with the development of Alzheimer\u27s disease. Specific proteinase inhibitors, useful in investigations of the mechanisms and pathways of intracellular protein degradation, could lead to the development of therapeutic agents for treatment of many types of carcinomas as well as Alzheimer\u27s disease. The design and the synthesis of (hydroxyethyl)amine isostere inhibitors with the cyclic tertiary amines is described. The IC-50 and apparent Ki values for several cathepsin D inhibitors are reported

Herbivore Effects on Productivity Vary by Guild: Cattle Increase Mean Productivity While Wildlife Reduce Variability

Wild herbivores and livestock share the majority of rangelands worldwide, yet few controlled experiments have addressed their individual, additive, and interactive impacts on ecosystem function. While ungulate herbivores generally reduce standing biomass, their effects on aboveground net primary production (ANPP) can vary by spatial and temporal context, intensity of herbivory, and herbivore identity and species richness. Some evidence indicates that moderate levels of herbivory can stimulate aboveground productivity, but few studies have explicitly tested the relationships among herbivore identity, grazing intensity, and ANPP. We used a long- term exclosure experiment to examine the effects of three groups of wild and domestic ungulate herbivores (megaherbivores, mesoherbivore wildlife, and cattle) on herbaceous productivity in an African savanna. Using both field measurements (productivity cages) and satellite imagery, we measured the effects of different herbivore guilds, separately and in different combinations, on herbaceous productivity across both space and time. Results from both productivity cage measurements and satellite normalized difference vegetation index (NDVI) demonstrated a positive relationship between mean productivity and total ungulate herbivore pressure, driven in particular by the presence of cattle. In contrast, we found that variation in herbaceous productivity across space and time was driven by the presence of wild herbivores (primarily mesoherbivore wildlife), which significantly reduced heterogeneity in ANPP and NDVI across both space and time. Our results indicate that replacing wildlife with cattle (at moderate densities) could lead to similarly productive but more heterogeneous herbaceous plant communities in rangelands

Impact of age and race on outcomes of a program to prevent excess weight gain and disordered eating in adolescent girls

Interpersonal psychotherapy (IPT) prevents weight gain and reduces loss-of-control (LOC)-eating in adults. However, IPT was not superior to health-education (HE) for preventing excess weight gain and reducing LOC-eating over 1-year in adolescent girls at risk for excess weight gain and eating disorders. Limited data suggest that older and non-White youth may be especially responsive to IPT. In secondary analyses, we examined if age or race moderated weight and LOC-eating outcomes. The 113 participants (12–17 years; 56.6% White) from the original trial were re-contacted 3 years later for assessment. At baseline and follow-up visits through 3 years, we assessed BMI, adiposity by dual energy X-ray absorptiometry, and LOC-eating presence. In linear mixed models, baseline age moderated 3-year BMI outcome; older girls in IPT had the lowest 3-year BMI gain compared to younger girls in IPT and all girls in HE, p = 0.04. A similar pattern was observed for adiposity. Race moderated 3-year LOC-eating; non-White girls in IPT were most likely to abstain from LOC-eating at 3 years compared to all other girls, p = 0.04. This hypothesis-generating analysis suggests future studies should determine if IPT is especially efficacious at reducing LOC-eating in older, non-White adolescents