Using Association Mapping in Teosinte to Investigate the Function of Maize Selection-Candidate Genes

BACKGROUND:Large-scale screens of the maize genome identified 48 genes that show the putative signature of artificial selection during maize domestication or improvement. These selection-candidate genes may act as quantitative trait loci (QTL) that control the phenotypic differences between maize and its progenitor, teosinte. The selection-candidate genes appear to be located closer in the genome to domestication QTL than expected by chance. METHODS AND FINDINGS:As a step toward defining the traits controlled by these genes, we performed phenotype-genotype association mapping in teosinte for 32 of the 48 plus three other selection-candidate genes. Our analyses assayed 32 phenotypic traits, many of which were altered during maize domestication or improvement. We observed several significant associations between SNPs in the selection-candidate genes and trait variation in teosinte. These included two associations that surpassed the Bonferroni correction and five instances where a gene significantly associated with the same trait in both of our association mapping panels. Despite these significant associations, when compared as a group the selection-candidate genes performed no better than randomly chosen genes. CONCLUSIONS:Our results suggest association analyses can be helpful for identifying traits under the control of selection-candidate genes. Indeed, we present evidence for new functions for several selection-candidate genes. However, with the current set of selection-candidate genes and our association mapping strategy, we found very few significant associations overall and no more than we would have found with randomly chosen genes. We discuss possible reasons that a large number of significant genotype-phenotype associations were not discovered

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Tidal modulation of Sr/Ca ratios in a Pacific reef coral

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 31 (2004): L16310, doi:10.1029/2004GL020600.The strontium-to-calcium ratio (Sr/Ca) of reef coral skeleton is an important tool for reconstructing past sea surface temperatures (SSTs). However, the accuracy of paleoSSTs derived from fossil coral Sr/Ca is challenged by evidence that physiological processes influence skeletal chemistry. Here we show that water level variations from tidal forcing are correlated with changes in coral Sr/Ca that cannot be accounted for by changes in SST. Ion microprobe measurements of Sr/Ca ratios in a Pacific Porites lutea reveal high-frequency variations at periods of ~6, ~10, and ~25 days. The relationship between Sr/Ca and temperature on these short timescales does not follow trends observed at longer periods, indicating that an additional forcing is required to explain our observations. We demonstrate that Sr/Ca is correlated with both tidal water level variations and SST, and that their contributions to the Sr/Ca content of the skeleton vary as a function of period. We propose that water level influences Sr/Ca indirectly via modulation of photosynthetically-active radiation (PAR) that drives large changes in zooxanthellate photosynthesis.This research was supported by WHOI Ocean Life Institute grant 25051316 to ALC; NSF grants EAR-9628749 and EAR-9904400 to the WHOI Northeast National Ion Microprobe Facility; DAMD 17-93-J-3052 supported ALC’s fieldwork on JA

Novel use of a Weerda laryngoscope for transoral excision of a cervical ganglioneuroma: a case report

<p>Abstract</p> <p>Introduction</p> <p>A ganglioneuroma is a benign neoplasm arising from neural crest cells of the sympathetic nerve fibers and is most commonly seen in the posterior mediastinum or retroperitoneum. Although very uncommon, ganglioneuromas must be included in the differential diagnosis of neck masses. In young adult women, neck incisions made for excision of these benign tumors should be avoided whenever possible.</p> <p>Case presentation</p> <p>We herein describe the case of a 19-year-old Japanese woman with a ganglioneuroma. The tumor was found in the parapharyngeal space, an unusual location. A fine-needle aspiration biopsy was performed but was considered inadequate to make a definitive diagnosis, so the asymptomatic lesion was surgically excised using a Weerda laryngoscope. The lesion measured 4 × 3 cm in size and was encapsulated. A pathological analysis showed the presence of two distinct cell types, ganglion cells and Schwann cells, embedded in a loose myxoid stroma. The final diagnosis was a ganglioneuroma.</p> <p>Conclusion</p> <p>A complete excision was made possible by using a transoral approach with a novel use of the Weerda laryngoscope. Although its applicability to specific cases depends on the location, size and nature of the tumor, we believe that the Weerda laryngoscope will continue to be useful for performing transoral surgery for cervical tumors.</p

Measurement of the flux of atmospheric muons with the CAPRICE94 apparatus

A new measurement of the momentum spectra of both positive and negative muons as function of atmospheric depth was made by the balloon-borne experiment CAPRICE94. The data were collected during ground runs in Lynn Lake on the 19-20th of July 1994 and during the balloon flight on the 8-9th of August 1994. We present results that cover the momentum intervals 0.3-40 GeV/c for negative muons and 0.3-2 GeV/c for positive muons, for atmospheric depths from 3.3 to 1000 g/cm**2, respectively. Good agreement is found with previous measurements for high momenta, while at momenta below 1 GeV/c we find latitude dependent geomagnetic effects. These measurements are important cross-checks for the simulations carried out to calculate the atmospheric neutrino fluxes and to understand the observed atmospheric neutrino anomaly.Comment: 28 pages, 13 Postscript figures, uses revtex.sty, to appear in Phys. Rev.

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.&lt;p&gt;&lt;/p&gt; Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.&lt;p&gt;&lt;/p&gt; Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.&lt;p&gt;&lt;/p&gt; Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.&lt;p&gt;&lt;/p&gt; Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.&lt;p&gt;&lt;/p&gt

Deglacial sea surface temperatures of the western tropical Pacific : a new look at old coral

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 19 (2004): PA4031, doi:10.1029/2004PA001084.Using Secondary Ion Mass Spectrometry (SIMS) ion microprobe techniques, we generated annual Sr/Ca cycles with subweekly resolution from chunks of Porites coral retrieved from a Tahiti barrier reef drill core (149°W, 17°S), representing the period 13,650 to 13,100 years B.P. The centers of pristine skeletal septa were selectively targeted with a 10 μm diameter ion beam spot, avoiding adjacent pore spaces occupied by secondary aragonite needles. Applying a Sr/Ca–sea surface temperature (SST) calibration equation derived from modern Tahiti Porites having the same low growth rate as the fossil specimens, we obtained SSTs ∼0.5°–1.5°C cooler during the Bølling-Allerod relative to the present day, with no significant change in seasonality. On the contrary, we estimate that analysis of bulk samples would yield excessively cool Sr/Ca-based SST estimates due to the occupation by secondary aragonite crystals of up to 50% of the skeletal pore space in the ancient samples. We find that growth rate effects on coral Sr/Ca further depress the apparent mean annual derived SSTs (by >3°C) and amplify the apparent seasonality by selectively enhancing wintertime cooling. Our microscale analysis of pristine skeleton and application of an appropriate growth-dependent calibration yield Sr/Ca-derived SSTs that are in good agreement with those derived from Mg/Ca ratios of calcitic foraminifera which indicate a continuous postglacial warming of the western tropical Pacific, in phase with the warming of the tropical Atlantic.Funds for this study were provided by NSF MG&G award number OCE-0241075

Measuring Organizational Power: Resources and Autonomy of Government Agencies

Although power is a major concern of organization theory, little research has focused on the horizontal dimension of power between organizations at relatively equal hierarchical levels. This study attempts to fill that void by operationalizing organizational power for 127 federal government agencies. The derived measure is subjected to tests for internal and external validity by empirically testing one promising theory of agency power.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline