Knowing Which Foods Are Making Us Sick

Food Consumption/Nutrition/Food Safety, D18, I18,

Farmland and Open Space Preservation in Michigan: An Empirical Analysis

Part I of this Note describes the political and economic conditions that gave rise to the farmland and open space preservation enactments. It presents a brief political history of the support for this body of legislation and summarizes the economic arguments raised both for and against these preservation efforts. Part II describes the principal types of state farmland and open space preservation programs enacted during the past thirty years. Finally, Part III presents an empirical analysis of P.A. 116

Comparative expression analysis of Shox2 -deficient embryonic stem cell-derived sinoatrial node-like cells

The homeodomain transcription factor Shox2 controls the development and function of the native cardiac pacemaker, the sinoatrial node (SAN).Moreover, SHOX2 mutations have been associatedwith cardiac arrhythmias in humans. For detailed examination of Shox2-dependent developmentalmechanisms in SAN cells, we established a murine embryonic stem cell (ESC)-based model using Shox2 as a molecular tool. Shox2+/+ and Shox2−/− ESC clones were isolated and differentiated according to five different protocols in order to evaluate the most efficient enrichment of SAN-like cells. Expression analysis of cell subtype-specific marker genes revealed most efficient enrichment after CD166-based cell sorting. Comparative cardiac expression profiles of Shox2+/+ and Shox2−/− ESCs were examined by nCounter technology. Among other genes, we identified Nppb as a novel putative Shox2 target during differentiation in ESCs. Differential expression of Nppb could be confirmed in heart tissue of Shox2−/− embryos. Taken together, we established an ESC-based cardiac differentiation model and successfully purified Shox2+/+ and Shox2−/− SAN-like cells. This now provides an excellent basis for the investigation of molecular mechanisms under physiological and pathophysiological conditions for evaluating novel therapeutic approaches

The Ursinus Weekly, November 14, 1960

Focus on fraternities • Sixteen men accept bids on Nov. 7 to join four of U.C.\u27s local frats • WAA, Woodruff discuss possible ski weekend • Constitution is changed by Curtain Club members • U.C. groups hear Dr. Adams of Yale • Historical article by Dr. Armstrong printed in Church History • Whitians hold tea in Paisley for 50 women • Dr. Zucker to discuss disarming at International Relations Club • Frosh MSGA reps to prepare report on 1960 customs • Y introduces the Aetheneum Society • Juniors present The Bowery November 19 in T-G gym • ICG plans meeting for Nov. 4 in Bomberger chapel at 7 p.m. • Senior Ball set for December 2 • Pre-medders go to AED conference • Young Democrats got out vote, now drive for new membership • Newman Club schedules trip to Greek Catholic church • Bosniak, Dassler are selected 1962 Ruby editors • Harry Sprogall addresses forum • Shaw\u27s Androcles and the Lion subject of English Club meeting • French Club to be shown slides; Field trip discussion planned • Editorial: Forbearance • Letters to the editor • Review of the student concert • Novembers ago • Book review: We the living • Parting political shots: Meeting of minds; Not quite Lincoln and Douglas • Intramural corner • Soccer team drops three close games • Mariners best Bears; U.C. clobbers Fords • Lassies shut out Drexel, Beaver • French film to be shown at Franklin Institutehttps://digitalcommons.ursinus.edu/weekly/1326/thumbnail.jp

Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India.

The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had

Functional Characterization of Rare Variants in the SHOX2 Gene Identified in Sinus Node Dysfunction and Atrial Fibrillation

Sinus node dysfunction (SND) and atrial fibrillation (AF) often coexist; however, the molecular mechanisms linking both conditions remain elusive. Mutations in the homeobox-containing SHOX2 gene have been recently associated with early-onset and familial AF. Shox2 is a key regulator of sinus node development, and its deficiency leads to bradycardia, as demonstrated in animal models. To provide an extended SHOX2 gene analysis in patients with distinct arrhythmias, we investigated SHOX2 as a susceptibility gene for SND and AF by screening 98 SND patients and 450 individuals with AF. The functional relevance of the novel mutations was investigated in vivo and in vitro, together with the previously reported p.H283Q variant. A heterozygous missense mutation (p.P33R) was identified in the SND cohort and four heterozygous variants (p.G77D, p.L129=, p.L130F, p.A293=) in the AF cohort. Overexpression of the pathogenic predicted mutations in zebrafish revealed pericardial edema for p.G77D and the positive control p.H283Q, whereas the p.P33R and p.A293= variants showed no effect. In addition, a dominant-negative effect with reduced heart rates was detected for p.G77D and p.H283Q. In vitro reporter assays demonstrated for both missense variants p.P33R and p.G77D significantly impaired transactivation activity, similar to the described p.H283Q variant. Also, a reduced Bmp4 target gene expression was revealed in zebrafish hearts upon overexpression of the p.P33R mutant. This study associates additional rare variants in the SHOX2 gene implicated in the susceptibility to distinct arrhythmias and allows frequency estimations in the AF cohort (3/990). We also demonstrate for the first time a genetic link between SND and AF involving SHOX2. Moreover, our data highlight the importance of functional investigations of rare variants

Molecular Recognition of Glycan-Bearing Glycomacromolecules Presented at Membrane Surfaces by Lectins: An NMR View

Lectin–glycan interactions are at the heart of a multitude of biological events. Glycans are usually presented in a multivalent manner on the cell surface as part of the so-called glycocalyx, where they interact with other entities. This multivalent presentation allows us to overcome the typical low affinities found for individual glycan–lectin interactions. Indeed, the presentation of glycans may drastically impact their binding by lectins, highly affecting the corresponding binding affinity and even selectivity. In this context, we herein present the study of the interaction of a variety of homo- and heteromultivalent lactose-functionalized glycomacromolecules and their lipid conjugates with two human galectins. We have employed as ligands the glycomacromolecules, as well as liposomes decorated with those structures, to evaluate their interactions in a cell-mimicking environment. Key details of the interaction have been unravelled by NMR experiments, both from the ligand and receptor perspectives, complemented by cryo-electron microscopy methods and molecular dynamics simulations.M.H. and L.H. thank the DFG for support through the ViroCarb research consortium (HA5950/5-2) and the CeMSA@HHU (Center for Molecular and Structural Analytics @ Heinrich-Heine University) for recording the mass spectrometric and the NMR-spectroscopic data for the structural conformation of the glycomacromolecules and their lipid conjugates. The CIC bioGUNE EM platform is also thanked for infrastructural support during cryo-EM data collection. The group in Spain thank the European Research Council (RECGLYCANMR, Advanced grant no. 788143), MCIN/AEI/10.13039/501100011033 for grants PDI2021-1237810B-C21, PID2021-126130OB-I00, CEX2021-001136-S, and CIBERES, an initiative of Instituto de Salud Carlos III (ISCIII), Madrid, Spain, for generous funding

Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.

Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m(5)C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNA(Met)). Further, we demonstrate that m(5)C deficiency in mt-tRNA(Met) results in the lack of 5-formylcytosine (f(5)C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f(5)C in human mitochondrial RNA is generated by oxidative processing of m(5)C.This work was funded by the Medical Research Council (MRC; as part of the core funding for the Mitochondrial Biology Unit MC_U105697135 and by the G0801904 grant), the European Research Council (ERC; 310360), Cancer Research UK (CR-UK; C10701/ A15181), European Commission (FP7/2007-2013, under grant agreement number no.262055 (ESGI), as a Transnational Access project of the European Sequencing and Genotyping Infrastructure), core support grant from the Wellcome Trust and MRC to the Wellcome Trust-MRC Cambridge Stem Cell Institute, the European Commission (Horizon2020, under grant agreement number 633974), the Bundesministerium fur Bildung und Forschung (BMBF) (through the German Network for mitochondrial disorders (mitoNET, 01GM1113C) and through the European network for mitochondrial disorders (E-Rare project GENOMIT, 01GM1207)) and by EMBO (ALFT 701-2013).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1203

Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

Establishing gene regulatory networks during differentiation or reprogramming requires master or pioneer transcription factors (TFs) such as PU.1, a prototype master TF of hematopoietic lineage differentiation. To systematically determine molecular features that control its activity, here we analyze DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression. Although PU.1, in contrast to classical pioneer factors, is unable to access nucleosomal target sites in vitro, ectopic induction of PU.1 leads to the extensive remodeling of chromatin and redistribution of partner TFs. De novo chromatin access, stable binding, and redistribution of partner TFs both require PU.1's N-terminal acidic activation domain and its ability to recruit SWI/SNF remodeling complexes, suggesting that the latter may collect and distribute co-associated TFs in conjunction with the non-classical pioneer TF PU.1